Journal articles: '658 : 658.14 /17 : 336.152' – Grafiati (2024)

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ZusammenfassungDas Ziel der Arbeit war, Referenzwerte für Blutparameter bei gesunden Meerschweinchen verschiedener Rassen mit einer für die Praxis geeigneten Blutentnahmemethode zu erstellen. Zur Sammlung der Daten wurde Blut von 101 klinisch gesunden Meerschweinchen, im Alter von sechs Wochen bis fünfeinhalb Jahren, aus der V. saphena lateralis entnommen. Für die folgenden Parameter wurden Referenzbereiche bestimmt: Hämatokrit (0,39-0,55 l/l), Hämoglobinkonzentration (7,26-10,51 mmol/l), Erythrozytenzahl (4,51-6,36 × 1012/l), Erythrozytenindices (MCHC: 18,1-19,7 mmol/l; MCH: 1,50-1,70 fmol/l; MCV: 80,3-89,1 fl), Leukozytenzahl (2910-14420 × 106/l), Differenzialblutbild (Monozyten: 0-657 × 106/l [0-9%]; Lymphozyten: 1401- 10665 × 106/l [28-84%]; stabkernige neutrophile Granulozyten: 0-72 × 106/l [0-1%]; segmentkernige neutrophile Granulozyten: 889-5097 × 106/l [12-62%]; eosinophile Granulozyten: 0-1563 × 106/l [0-14%]; basophile Granulozyten: 0-106 × 106/l [0-2%]) und Thrombozytenzahl (273-745 × 109/l), die Enzymaktivitäten der Alaninaminotransferase (ALT: 0-61 IU/l), alkalischen Phosphatase (AP: 0-418 IU/l), Aspartataminotransferase (AST: 0-90 IU/l), Glutamatdehydrogenase (GLDH: 0-17 IU/l), γ-Glutamyltransferase (γ-GT: 0-13 IU/l), Laktatdehydrogenase (LDH: 0-515 IU/l), Kreatinkinase (CK: 0-2143 IU/l), α-Amylase (0-3159 IU/l), Lipase (0-152 IU/l) und Cholinesterase (CHE: 0-8052 IU/l), die Konzentration der Substrate Glukose (4,95-15,95 mmol/l), Fruktosamin (134-271 µmol/l), Gesamteiweiß (44,4-65,8 g/l) mit Auftrennung durch Elektrophorese (Albumin: 25,5- 41,1 g/l [53,0-69,7%], α1-Globulin: 1,0-3,6 g/l [2,0-6,3%]; α2-Globulin: 7,9-14,8 g/l [16,3-27,1%]; β-Globulin: 2,5-6,8 g/l [4,8-11,4%]; γ-Globulin: 1,7-7,8 g/l [3,3-13,4%]), Cholesterin (0,31-1,67 mmol/l), Triglyzeride (0,33-2,35 mmol/l), Serum- gallensäuren (0,0-84,5 µmol/l), Bilirubin (0-1,59 µmol/l), Harnstoff (3,34-10,33 mmol/l) und Kreatinin (0-77 µmol/l) sowie der Elektrolyte Kalzium (2,4-3,1 mmol/l), Phosphat (1,03-6,98 mmol/l), Magnesium (0,99-2,56 mmol/l), Natrium (130-150 mmol/l), Kalium (4,5-8,8 mmol/l), Chlorid (94-111 mmol/l) und Eisen (26-76 µmol/l). Alters- (≤ 4 Monate und > 4 Monate) und Geschlechtsabhängigkeiten (männlich/ weiblich) wurden ermittelt.

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Abstract Background. Platelets (plt) prepared for transfusion contain multiple molecules that modulate immune function, mediate acute transfusion reactions, induce immune responses, and affect hemostasis. These cytokines/chemokines are secreted differentially from plt during storage (Transfusion2006;46:1184), and may be affected by processing, including pathogen inactivation. Aims. The INTERCEPT Blood System (IBS) for platelets utilizes amotosalen-HCl (S-59) with ultraviolet A (UVA) light to inactivate a broad spectrum of pathogens and leukocytes. This study was designed to evaluate the effects of photochemical treatment on in vitro release of immune modulation molecules after processing during 7 days (d) of storage. Methods. Platelet concentrates (n = 10) collected by aphaeresis (CPA) with process leuko-reduction (< 106) containing 8.15x1011 ± 0.8 platelets were suspended in 35% donor plasma and 65% platelet additive solution (Intersol, Baxter, France) and divided into two equal components. One served as an untreated control (C) and the other was prepared with 150 uM amotosalen and a 3 J/cm2 UVA photochemical treatment (PCT) and stored at 22°C with shaking for 7 days. Platelet concentration (106/uL), pH and levels of immune modulation factors were measured: CD62p(ng/mL), PDGF-AB(ng/mL), IL8(pg/mL), sCD40L(pg/mL), IL1β(pg/mL) and TNFα(pg/mL). The concentration of each factor was determined by specific enzyme linked immunosorbent assays in plt and supernatant (s) fractions isolated from stored PCT and C plt components. Mean values ± SD were calculated and compared by paired t-test. Results. Platelet content, pH and cytokine/chemokine content and release from CPA prepared with photochemical treatment were not statistically different (p > 0.05) from C during 7 d of storage (Table). From d1 to d7, the pH of PCT and C units decreased similarly, but remained within acceptable ranges. No detectable IL1β and TNFα were observed in PCT or C CPA. During platelet storage CD62p, PDGF-AB, IL8, and sCD40L increased similarly in supernatants of PCT and C units. The increase in supernatant levels correlated with a decrease of these cytokines in plt. Platelets in PCT and C retained measurable levels of CD62, IL8, sCD40L and PDGF-AB though 7 d. Levels of sCD40L demonstrated marked variation. Conclusions. Cytokines increased moderately in the supernatants of CPA and decreased in platelets during storage. After 7 d C and PCT platelets in CPA retained detectable levels of cytokines. PCT had no differential influence on release of immune modulation molecules in vitro over 7 d of storage. Day O O 5 5 7 7 Product C PCT C PCT C PCT pH 7.1 ±.1 7.1 ±.1 6.9 ±.1 6.8 ±.1 6.9 ±.1 6.8 ±.1 Plt ct 1.29 ±.3 1.30 ±.2 1.30 ±.3 1.19 ±.2 1.27 ±.2 1.18 ±.2 CD62p-s 89 ± 21 87 ± 17 110 ± 23 115 ± 27 117 ± 22 119 ± 25 CD62p-plt 149 ± 33 151 ± 33 141 ± 23 141 ± 25 139 ± 25 139 ± 26 PDGF-s 14.5 ± 3.5 13.6 ± 3.5 17.7 ± 2.4 15.8 ± 1.5 18.0 ± 2.1 17.5 ± 1.8 PDGF-plt 28.3 ± 3.5 30.3 ± 3.1 25.2 ± 3.6 24.9 ± 2.5 23.2 ± 4.0 23.3 ± 3.3 IL8-s 107 ± 17 108 ± 14 136 ± 42 116 ± 9 123 ± 20 120 ± 22 IL8-plt 135 ± 29 134 ± 28 110 ± 11 117 ± 12 103 ± 17 119 ± 32 CD40L-s 51 ± 86 66 ± 94 172 ± 157 237 ± 214 188 ± 198 201 ± 167 CD40L-plt 990 ± 805 1098 ± 747 485 ± 373 474 ± 331 346 ± 293 314 ± 282

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AbstractOscarkempffite, ideally Ag10Pb4(Sb17Bi9)∑=26S48, is a new mineral species found in old material (1929–30) from the Colorada vein, Animas mine, Chocaya Province, Department of Potosi, Bolivia. It is associated with aramayoite, stannite, miargyrite, pyrargyrite and tetrahedrite. Oscarkempffite forms anhedral grains and grain aggregates up to 10 mm across. The mineral is opaque, greyish black with a metallic lustre; it is brittle without any discernible cleavage. In reflected light oscarkempffite is greyish white, pleochroism is distinct, white to dark grey. Internal reflections are absent. In crossed polars, anisotropism is distinct with rotation tints in shades of grey. The reflectance data (%, air) are: 39.9, 42.6 at 470 nm, 38.6, 41.7 at 546 nm, 38.1, 41.2 at 589 nm and 37.3, 40.6 at 650 nm. Mohs hardness is 3–3½, microhardness VHN50 exhibits a range 189–208, with a mean value 200 kg mm–2. The average results of four electron-microprobe analyses in a grain are: Cu 0.24(7), Ag 14.50(8), Pb 11.16(14), Sb 28.72(16), Bi 24.56(17), S 20.87(5), total 100.05(6) wt.%, corresponding to Cu0.24Ag9.92Pb4.00Sb17.36Bi8.64S47.84 (on the basis of Me + S = 88 apfu). The simplified formula, Ag10Pb4Sb17Bi9S48, is in accordance with the results of a crystal-structure determination. The density, 5.8 g cm–3, was calculated using the ideal formula. Oscarkempffite has an orthorhombic cell with a = 13.199(2), b = 19.332(3), c = 8.249(1) Å, V = 2116.3(5) Å3, space group Pnca and Z = 1. The strongest eight lines in the (calculated) powder-diffraction pattern are [d in Å(I)hkl]: 3.66(35)(122), 3.37(70)(132), 3.34(100)(250), 2.982(55)(312), 2.881(86)(322), 2.733(29)(332), 2.073(27)(004) and 2.062(31)(182). Comparison with gustavite, andorite and roshchinite confirms its independence as a mineral species.

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Abstract Abstract 3125 Poster Board III-62 VTE is the most frequent complication of OS and it can be prevented through anticoagulant prophylaxis. Numerous studies have evaluated different agents for this purpose and there are new agents currently under development or recently approved for this indication. We conducted a systematic review of randomized controlled trials (RCT) evaluating administration of anticoagulants for VTE prophylaxis in OS and performed a MA of proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), symptomatic VTE and major bleeding episodes (as defined by the International Society on Thrombosis and Hemostasis). We included RCT comparing currently approved anticoagulants (head-to-head or placebo-controlled) for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, CT pulmonary angiography, or ventilation perfusion scan). Heterogeneity of proportions was evaluated using a chi2 test and pooled estimates of proportions were obtained using either a fixed or a random effects model in which the weights were estimated as proposed by Laird and Mosteller. We retrieved 74 studies including180 research arms and enrolling 71,012 patients. The total number of events and evaluable patients, percentage of events and 95% CI, and number of study arms included are shown in the table. We found differences in the percentage of VTE and bleeding events associated with the use of different anticoagulants for VTE prophylaxis after OS. Due to the nature of the analysis no effect measure can be estimated. These estimates might help to design future studies. Major VTE Total VTE Symptomatic VTE Major Bleeding Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) All patients LMWH 993/23692 5.96 (5.81, 6.11) 72 4068/22610 20.29 (20.04, 20.55) 80 193/19431 1.32 (1.27, 1.37) 35 476/28725 1.98 (1.93, 2.02) 70 UFH 234/2407 13.39 (12.86, 13.93) 14 596/2537 22.54 (22, 23.08) 17 11/339 3.24 (3.06, 3.43) 4 70/2849 2.75 (2.61, 2.89) 16 Warfarin 269/5677 6.28 (6.09, 6.46) 12 1317/4203 31.05 (30.44, 31.66) 12 71/4146 1.95 (1.83, 2.08) 6 96/6751 1.78 (1.69, 1.87) 12 Fonda 96/3673 3.81 (3.53, 4.09) 7 223/3477 6.82 (6.57, 7.07) 6 69/6398 1.06 (1.01, 1.1) 8 121/6576 1.63 (1.55, 1.71) 9 Riva 50/5025 2.02 (1.86, 2.19) 8 242/4595 13.05 (12.16, 13.94) 8 29/6252 0.46 (0.45, 0.48) 6 31/6643 0.63 (0.59, 0.68) 8 Dabi 149/4091 3.64 (3.59, 3.69) 6 834/4051 22.96 (21.91, 24.01) 6 26/3664 0.71 (0.67, 0.75) 4 67/5419 1.21 (1.17, 1.26) 6 Placebo 193/710 24.26 (23.17, 25.34) 10 379/816 49.35 (48.08, 50.62) 11 19/198 12.02 (10.32, 13.72) 3 12/753 1.59 (1.5, 1.68) 7 Total 1984/45275 129 7659/42289 140 418/40428 66 873/57716 128 Total Hip Arthroplasty LMWH 653/15978 6 (5.85, 6.16) 50 1817/14480 15.58 (15.35, 15.82) 55 81/11552 0.7 (0.69, 0.72) 19 306/18010 1.97 (1.92, 2.02) 45 UFH 187/1739 14.3 (13.64, 14.96) 11 354/1836 20.13 (19.46, 20.8) 13 11/246 4.47 (4.21, 4.73) 3 52/1451 3.2 (3.01, 3.39) 11 Warfarin 77/2758 4.28 (4.08, 4.48) 6 265/1273 20.82 (20.59, 21.04) 6 32/1833 1.75 (1.69, 1.81) 2 47/2856 2.23 (2.09, 2.37) 5 Fonda 28/1799 2.96 (2.58, 3.33) 3 85/1695 5.01 (4.91, 5.12) 2 15/2255 0.67 (0.63, 0.7) 2 69/2349 2.94 (2.87, 3.01) 3 Riva 25/2938 2.21 (1.95, 2.46) 5 73/2749 9.72 (8.92, 10.53) 5 10/3468 0.29 (0.27, 0.31) 3 14/3795 0.49 (0.44, 0.54) 5 Dabi 72/1803 3.99 (3.88, 4.11) 2 124/1766 7.02 (6.77, 7.27) 2 21/2293 0.92 (0.91, 0.93) 2 38/2309 1.65 (1.58, 1.72) 2 Placebo 105/414 26.01 (24.76, 27.27) 7 174/418 45.43 (43.74, 47.13) 7 4/147 2.72 (2.46, 2.98) 2 3/388 0.77 (0.69, 0.86) 5 Total 1147/27429 84 2892/24217 90 174/21794 33 529/31158 76 Total Knee Arthroplasty LMWH 277/6916 4.45 (4.34, 4.55) 25 2062/7326 30.72 (30.37, 31.07) 32 83/4902 1.69 (1.66, 1.73) 11 89/7808 1.14 (1.12, 1.16) 26 UFH 42/638 6.58 (6.39, 6.78) 3 226/638 35.42 (35.05, 35.79) 3 0/93 NE 1 3/318 0.94 (0.84, 1.05) 2 Warfarin 192/2919 8.1 (7.88, 8.32) 9 1052/2930 39.36 (38.69, 40.02) 9 39/2056 1.9 (1.84, 1.96) 3 28/3407 0.82 (0.79, 0.85) 8 Fonda 23/452 9.3 (7.93, 10.67) 2 45/361 12.47 (12.12, 12.81) 1 3/517 0.58 (0.51, 0.65) 1 12/601 2 (1.88, 2.11) 2 Riva 25/2087 1.2 (1.15, 1.24) 3 169/1846 18.55 (16.47, 20.63) 3 19/2784 0.68 (0.65, 0.71) 3 17/2848 0.6 (0.57, 0.63) 3 Dabi 77/2288 3.37 (3.32, 3.41) 4 710/2285 30.98 (30.42, 31.55) 4 5/1371 0.36 (0.32, 0.41) 2 29/3110 0.93 (0.89, 0.98) 4 Placebo 88/296 27.12 (24.54, 29.7) 4 205/398 55.19 (53.53, 56.84) 5 15/51 29.41 (28.16, 30.66) 1 9/365 2.47 (2.31, 2.62) 4 Total 724/15596 50 4469/15784 57 164/11774 22 187/18457 49 LMWH Low molecular weight heparin, UFH unfractionated heparin, Riva Rivaroxaban, Dabi Dabigatran etexilate Disclosures Lazo-Langner: Boehringer Ingelheim: Honoraria. Rodger:Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding.

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Background:Comorbidities in rheumatic diseases (RDs) have been associated with increased morbidity and mortality. Evidence on prevalence of comorbidities in antiphospholipid syndrome (APS) and its difference from high comorbidity burden RDs is limited.Objectives:To compare the prevalence of common comorbidities between APS [primary (PAPS) and Systemic lupus erythematosus (SLE)-APS] and Rheumatoid arthritis (RA) patients.Methods:326 APS patients from the Greek registry (237 women, mean age 48.7±13.4 years, 161 PAPS) were matched 1:2 for age and sex with 652 RA patients from Greek RA Registry. Prevalence of cardiovascular (CV) risk factors, stroke, coronary artery disease (CAD), osteoporosis, diabetes mellitus (DM), Chronic obstructive pulmonary disease (COPD), depression and neoplasms were compared between APS and RA using logistic regression analysis.Results:Regarding CV burden, hyperlipidemia and obesity (ΒMI≥30) were comparable while hypertension, smoking, CAD and stroke were more prevalent in APS compared to RA patients (Table 1). Osteoporosis and depression were more frequent in APS while DM, COPD and neoplasms were comparable between two groups. Comparison of APS subgroups to 1:2 matched RA patients revealed that smoking and stroke were more prevalent in PAPS and SLE-APS vs RA. Hypertension, CAD and osteoporosis were more prevalent only in SLE-APS vs. RA while DM was less prevalent in PAPS vs. RA patients.Table 1.Comparison of comorbidities between Antiphospholipid syndrome (APS) vs. matched Rheumatoid Arthritis (RA) patients and between primary APS (PAPS) or Systemic Lupus Erythematosus-APS (SLE-APS) vs matched RA patientsAPSRAOR*PAPSRAORSLE-APSRAORn (%)326652161322165330Hypertension97 (29.8)136 (21)1.61 (1.19-2.18)40 (25)75 (23.3)1.09 (0.70-1.69)57 (34.6)61 (18.5)2.33 (1.52-3.56)Smoking175 (53.7)264 (40.5)1.70 (1.30-2.22)87 (54)142 (44)1.49 (1.02-2.18)88 (53.3)122 (37)1.95 (1.33-2.85)Hyperlipidemia79 (24.2)135 (20.7)1.23 (0.89-1.68)40 (24.8)62 (19.3)1.39 (0.88-2.18)39 (23.6)73 (22)1.09 (0.70-1.70)Obesity48 (20.5)105 (19.5)1.06 (0.73-1.56)20 (17)51 (19)0.86 (0.49-1.52)28 (24)54 (19.7)1.28 (0.76-2.15)Stroke±66 (20.3)9 (1.4)13.8 (6.5-29.1)36 (22.4)4 (1.2)19.9 (6.6-59.9)30 (18.2)5 (1.5)7.8 (2.7-22.6)Coronary disease±16 (4.9)13 (2)3.14 (1.17-8.45)2 (1.2)7 (2.2)0.46 (0.04-4.77)14 (8.5)6 (1.8)10.9 (2.7-44.3)Osteoporosis×66 (20.3)92 (14)1.45 (1.01-2.06)19 (11.8)42 (13)0.96 (0.54-1.73)47 (28.5)50 (15)1.91 (1.20-3.05)Diabetes×18 (5.5)58 (9)0.58 (0.33-1.01)5 (3)29 (9)0.34 (0.13-0.89)13 (8)29 (9)0.88 (0.44-1.79)COPD≠11 (3.4)14 (2.2)1.26 (0.56-2.84)3 (1.9)6 (2)0.96 (0.23-4.0)8 (5)8 (2.4)1.28 (0.44-3.72)Depression#53 (16.3)66 (10)1.70 (1.15-2.53)23 (14)30 (9.3)1.69 (0.93-3.05)30 (18.2)36 (10.9)1.65 (0.96-2.84)Neoplasms˅14 (4.3)27 (4.1)1.05 (0.54-2.06)5 (3)12 (3.7)0.84 (0.28-2.52)9 (5.5)15 (4.6)1.31 (0.55-3.1)*OR: Odds ratio, crude or adjusted for: ± age, sex, smoking, hypertension, hyperlipidemia, BMI, corticosteroid (Cs) duration × Cs duration ≠ smoking, Cs duration #sex, disease duration, Cs duration ˅ age, disease durationConclusion:Comorbidity burden in APS (PAPS and SLE-APS) is comparable or even higher to that in RA, entailing a high level of diligence for CV risk prevention, awareness for depression and corticosteroid exposure minimization.Disclosure of Interests:Stylianos Panopoulos: None declared, Konstantinos Thomas: None declared, Georgios Georgiopoulos: None declared, Dimitrios Boumpas Grant/research support from: Unrestricted grant support from various pharmaceutical companies, Christina Katsiari: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Alexandros Drosos: None declared, Kyriaki Boki: None declared, Theodoros Dimitroulas: None declared, Alexandros Garyfallos Grant/research support from: MSD, Aenorasis SA, Speakers bureau: MSD, Novartis, gsk, Charalambos Papagoras: None declared, PELAGIA KATSIMPRI: None declared, Apostolos Tziortziotis: None declared, Christina Adamichou: None declared, Evripidis Kaltsonoudis: None declared, Evangelia Argyriou: None declared, GEORGIOS VOSVOTEKAS Grant/research support from: MSD, Janssen, Consultant of: MSD, Novartis, Roche, UCB pharma, Bristol-Myers Squibb, AbbVie, Speakers bureau: UCB pharma, Menarini, Bristol-Myers Squibb, MSD, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Dimitrios Vassilopoulos: None declared, Maria Tektonidou Grant/research support from: AbbVie, MSD, Novartis and Pfizer, Consultant of: AbbVie, MSD, Novartis and Pfizer

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Background:Four clinical phenotypes of IgG4-Related Disease (IgG4-RD) have been recently identified by Latent Class Analysis (LCA) - Pancreato/biliary (Group 1); Retroperitoneum/Aortitis (Group 2); Head-and-neck limited (Group 3); Mickulicz/Systemic (Group 4) - but the relevance of this classification for patient management remains unknown (1,2).Objectives:We aimed to assess whether clinical judgment can replicate LCA classification and to evaluate potential differences in epidemiological features, serological findings, and disease outcomes between disease phenotypes.Methods:The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA derived phenotypes based on clinical judgment. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD Responder Index (RI); history of atopy, diabetes, osteoporosis, relapses, and tumors; cumulative dose of glucocorticoids and use of rituximab.Results:Clinical judgment recapitulated LCA classification with strong agreement between IgG4-RD experts (κ= 0.841, p < 0.0005). Group 1 showed the highest levels of serum IgG4 and IgE. Group 2 and 4 had the lowest and highest IgG4-RD RI, respectively (Table 1). Increased cumulative doses of glucocorticoids and higher relapse rate were observed in Group 3 (Fig 1). A higher incidence of diabetes mellitus was observed in Group 1 and 4.Table 1Clinical and serological characteristics of patients cohort.Group 1(59 pts - 45%)Group 2(29 pts - 22%)Group 3(25 pts - 19%)Group 4(18 pts - 14%)P valueFemale n° (%)12 (20%)8 (28%)11 (44%)5 (28%)0.18Age67 (61-73)61 (56-70)52 (40-62)57 (51-62)<0.0001Serum IgG4 (mg/dL)331 (184-575)155 (49-258)150 (80-255)282 (166-460)0.0009IgG4-RD RI9 (6-9)6 (6-9)9 (6-12)9 (6-13)0.004Definite diagnosis n° (%)20 (34%)18 (62%)20 (80%)10 (55%)0.0008Probable diagnosis n° (%)1 (0.59%)0 (0%)1 (0.19%)1 (0.14%)0.6Possible diagnosis n° (%)38 (64%)10 (34%)4 (16%)7 (39)0.0003Emergency Department n° (%)37 (63%)14 (48%)7 (28%)10 (55%)0.03History of atopy n° (%)7 (12%)4 (14%)7 (28%)6 (23%)0.09ESR (mm/h)20 (8-39)40 (14-59)38 (14-54)12 (8-21)0.04CRP (mg/L)5 (2-8)10 (3-52)8 (3-28)3 (2-6)0.03Eosinophils (cell/mm3)200 (200-500)200 (100-275)300 (200-475)200 (100-500)0.3IgE (U/mL)283 (97-723)69 (28-264)120 (41-412)219 (54-657)0.02Plasmablast (cell/mL)1765 (627-4000)1890 (1020- 4000)2000 (370- 4780)2690 (140-5130)0.99Diagnostic delay (months)4 (2-9)7 (4-12)10 (3-18)11 (2-38)0.04Starting prednisone dose(mg, range)60 (37-70)50 (40-75)65 (40-90)40 (30-70)0.8Diabetes at disease onset10 (17%)1 (3%)2 (8%)2 (11%)0.09Figure 1.Relapse free survival of the four different IgG4-RD phenotypes.Conclusion:Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.References:[1]Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS. 2018;126:459-476.[2]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78:406-412.Disclosure of Interests:Marco Lanzillotta: None declared, Emanuel Della Torre: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gaia Mancuso: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

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Background:Abatacept (ABA) is a selective T-cell co-stimulatory modulator. After its approval, changes in therapeutic recommendations, the arrival of new drugs (e.g., biosimilars or Janus kinase inhibitors) and growing focus on comprehensive patient care may have changed prescription patterns, channeling ABA use towards specific patient subtypes. To date, studies analyzing these aspects in clinical practice settings are scarce.Objectives:We aimed to evaluate the epidemiological profile of ABA users and compare it to other DMARD groups included in the register.Methods:We performed an observational study based on the nationwide Spanish register BIOBADASER, which includes patients with rheumatic diseases receiving biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) from 28 tertiary centers. For this analysis, all RA patients included from December 2015 to December 2020 were examined. Baseline features were analyzed descriptively grouping all b/tsDMARDs by mode of action. Clinical effectiveness was assessed through drug survival obtained by the Kaplan-Meier method. Patients were right-censored if data were not available if they were still on treatment at the time of data analysis. The safety profile was assessed by the adverse events (AE) and serious AE incidence rates (IR) expressed as events per 1000 patient-years.Results:There were 628 ABA-treated patients, 471 (75%) using the subcutaneous presentation. Only 142 (23%) were on first-line while 381 (61%) were on third or later-line therapy. ABA users were older and more likely to present certain comorbidities compared to the other b/tsDMARD groups. The biggest relative differences were seen for interstitial lung disease (ILD), chronic obstructive pulmonary disease (COPD), diabetes and ischemic heart disease. (Table 1)Table 1.This 12-month interim analysis includes 496 patients (336 with axSpA, 98 with RA and 62 with PsA)NABAIL-6CD20JAKiTNFi6287861816691787Mean age, years (SD)64.1 (12.0)50.7 (12.7)63.2 (12.3)59.6 (12.3)60.7 (13.1)Female sex, n (%)482 (77)652 (83)135 (75)537 (80)1418 (79)Median disease duration (p25-p75)10.1 (5.1-16.5)9.4 (4.6-15.9)13.3 (8.3-20.6)10.4 (5.0-17.2)7.4 (3.2-13.7)ACPA, n (%)352 (72)425 (71)113 (79)407 (70)875 (70)RF, n (%)380 (77)454 (75)124 (86)411 (70)915 (72)Current smokers, n (%)98 (16)137 (17)338 (19)90 (20)259 (18)ILD, n (%)64 (13)21 (3)25 (2)8 (2)19 (2)COPD, n (%)38 (6)23(3)52 (3)14 (3)43 (3)Chronic Kidney Disease, n (%)18 (3)13 (2)19 (1)13 (3)18 (1)Diabetes73 (12)66 (8)13 (7)46 (10)100 (7)Ischemic Heart Disease, n (%)36 (6)23 (3)012 (3)30 (2)Hypertension, n (%)197 (31)198 (25)416 (23)131 (30)338 (23)Heart Failure, n (%)19 (4)12 (2)10 (1)6 (2)5 (1)Osteoporosis, n (%)133 (21)141 (18)26 (14)72 (16)215 (15)IL-6: Tocilizumab and Sarilumab; CD20: Rituximab and biosimilars; JAKi: Janus kinase inhibitors (Tofacitinib and Baricitinib); TNFi: TNF inhibitors and biosimilars; ACPA: anti-citrullinated peptide antibodies; RF: rheumatoid factor; ILD: interstitial lung disease; COPD: chronic obstructive pulmonary disease.Overall, 63% of patients remained on ABA at 1 year, 48% at 2 and 31% at 5 years after drug initiation. The corresponding proportions were 79%, 65% and 52% for bionaïve and 59%, 43% and 30% for those in third or later-line therapy. From 394 total discontinuations, loss of efficacy in 225 (57%) and AE in 98 (25%) were the main reasons. This trend was consistent among all therapy lines.The total IR of AE was 886.5 (837.3-938.5) and 156.4 (136.5-179.2) for SAE. Infections were the most frequent AE overall, IR 44.4 (34.4-57.3), and the highest IR was seen among bionaïve patients (69.6 (44.9-107.9)).Conclusion:ABA-treated RA patients in Spain are older and have more comorbidities (vs other b/tsDMARDs), especially ILD, COPD, ischemic heart disease and diabetes and receive ABA as third or later-line therapy. Although these features are associated with worse response to treatment and a higher risk of infection, ABA presents a good drug survival and infectious AE are not the main cause of discontinuation.Acknowledgements:On behalf of the BIOBADASER Working groupDisclosure of Interests:Sebastián C Rodriguez-García Speakers bureau: Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Janssen, Consultant of: Bristol-Myers-Squibb, Galápagos, Carlos Sánchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Roche, Sanofi, MSD, UCB-Pharma, Bristol-Myers-Squibb, Novartis, Lilly, and Pfizer., Dolores Ruiz-Montesinos: None declared, Manuel Pombo: None declared, Fernando Sánchez-Alonso: None declared, Juan J. Gómez-Reino Consultant of: Pfizer, Grant/research support from: Abbvie, Lilly, MSD, Pfizer, Roche, and UCB.

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5039 Background: Plasma ctDNA is a promising minimally invasive biomarker in mCRPC. Pre-treatment high levels of ctDNA reflect poor prognosis (Romanel et al, Sci Transl Med 2015; Annala et al, Cancer Discov 2018). However, the role of plasma ctDNA in prostate tumour monitoring is largely unexplored. We aimed to determine if monitoring tumour response by quantifying ctDNA levels in plasma could enable early assessment of therapy efficacy for mCRPC. Methods: Between January 2011 and June 2016, 132 sequential plasma samples from 54 mCRPC patients (pts) (30 pre- and 24 post-chemotherapy) treated with abiraterone (abi) were collected. Targeted next-generation sequencing was performed on the PGM Ion Torrent using a 316 or 318 Chip to account for 1000X expected coverage per target. We estimated the global tumour content for each sequential plasma sample from study patients by using the approach developed in (Carreira et al, Sci Trasl Med 2014; Romanel et al, Sci Transl Med 2015 ), which extends the CLONET framework (Prandi et al, Genome Biol 2014). Prostate Cancer Working Group -3 (PCWG3) criteria were used to assess clinical, biochemical (PSA) and radiographic (RAD) progression disease (PD). We considered ctDNA PD any increase of ctDNA from baseline value. Results: In our cohort of 54 pts (median age: 75 years, range 70-78), we observed 17 (31.5%) PD, 14 (25.9%) stable disease, and 23 (42.6%) partial/complete response after the first 3 months (mo) abi therapy. The odds ratio (OR) for PD having any increase in ctDNA and a PSA decline < 50% at ~3-mo therapy was 10.83, 95% CI 2.55-45.95, P = 0.001, and 3.27, 95% CI 0.89-12.3, P = 0.074, respectively. In addition, we assessed all 3 types of median PD time from starting abi treatment, suggesting the ability of ctDNA variation to predict overall PD [RAD PD = 6.8 mo, PSA PD = 4.4 mo, and ctDNA PD = 3.0 mo, P = 0.008). An increase of ctDNA levels during the first 3-mo abi treatment was significantly associated with a long-term androgen deprivation therapy (ADT) before plasma sample collection (previous ADT > 24 mo vs 12 > previous ADT ≤23 mo vs < 12 mo: P = 0.036). Conclusions: In mCRPC, an early change in ctDNA fraction may be considered as a predictive biomarker playing a key role in individualized disease monitoring. Prospective evaluation of treatment decisions based on ctDNA is now required.

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Abstract Background: chronic lymphocytic leukemia (CLL) is characterized by progressive immunodeficiency with high prevalence of infections, autoimmune phenomena and secondary malignancies. The immune deregulation may be due to the disease itself or it may be a consequence of the treatment performed. Despite the use of highly effective chemo-immunotherapy, CLL remains incurable nowadays, even if the availability of new drugs is improving life expectancy. Aims: to evaluate the incidence of second cancers in CLL patients, and to investigate their relationship with disease features and therapy lines. Methods: 514 CLL patients diagnosed and followed from 1983 until 2014 at our Institution were retrospectively evaluated. Secondary cancers were categorized according to the originating organ or tissue; skin cancers were divided into melanoma and non-melanoma. History of neoplasia preceding CLL diagnosis was also registered. Results: clinical, hematological and biological characteristics at CLL diagnosis are listed in Table 1. During the follow up 88 patients (17%) developed secondary cancers, with a mean time from diagnosis to secondary neoplasia of 9 years. Considering tumor site, we observed 9 hematological malignancies, 9 lung, 5 breast, 19 uro-genital tract (5 kidney, 10 prostate, 4 bladder, 2 uterus, and 2 ovarian), 15 gastro-enteric tract (12 colon, 2 gastric and 1 tongue), 4 pancreas, 3 melanoma and 15 skin cancers other than melanoma. No significant differences were observed according to age, gender, Rai/Binet stage and hematologic parameters in patients with or without secondary tumors (Table 1). Considering prognostic features, no association was found with 13q deletion, chromosome 12 trisomy, VHIG mutational status, or with ZAP-70 and CD-38 positivity. On the contrary, the development of second cancers was associated with the presence of chromosome 17p (8% with secondary neoplasia versus 6% without, p=0.05) and 11q deletions (13% versus 9%, p=0.08). Medical history was positive for malignancies in 70 patients (13%): 2 hematological malignancies, 3 airways (2 lower and 1 upper), 3 breast, 6 uro-genital tract (3 bladder, 3 prostate, 2 uterus and 1 ovarian), 3 gastro-enteric tract, 3 skin cancers other than melanoma, and 3 melanoma. As regards treatment, 46/88 (52.3%) and 219/426 (51.4%) patients with or without secondary cancers, underwent at least one therapy line. Eighty-six patients were treated with fludarabine containing regimens, of whom 11 developed a secondary cancer; 180 patients received chlorambucil and 34 developed a secondary tumor. Among 65 patients who underwent alemtuzumab treatment, 10 were later diagnosed with a second cancer. During the follow up, 121 patients died, 18 with secondary malignancy. Of note, 41 patients died from CLL progression, 2 from thrombotic events, 11 from infections and 8 from secondary malignancy. Conclusions: secondary malignancies are not infrequent in patients with CLL and their occurrence is not clearly related to biologic markers or to the treatment performed. A careful clinical follow up, encompassing sex and age adjusted tumors screening, is advisable for an early diagnosis and appropriate treatment of secondary malignancies in CLL. Table 1. clinical and laboratory features of 514 CLL patients with or without secondary malignancies. Data are expressed as median (range) or absolute number (%). Secondary malignancies Yes (N=88) No (N=426) Age years 64 (39-80) 63 (31-90) Gender M/F 57/31 250/176 Follow-up years 12 (0-30) 12 (1-25) Rai/Binet<C/III> C/III 85 (97) 3 (3) 401 (94) 25 (6) WBC x10e3/mmc 18.74 (3.6-138) 17.3 (3-384) ALC x10e3/mmc 12.63 (1.8-91.8) 11.9 (1.4-381) Hb g/dL 14 (9-17) 14 (8-18) PLT x10e3/mmc 198 (77-608) 184 (58-472) LDH U/L 325 (144-838) 334 (142-795) Beta2microglobulin mg/L 2 (1-23) 2 (0-10) FISH*Del11qDel13qDel17p+12 6 (13) 19 (40) 4 (8) 6 (13) 23 (9) 101 (40) 15 (6) 38 (15) VHIG unmutated** 15 (42) 80 (39) ZAP-70 positive*** 14 (39) 73 (36) CD-38 positive**** 15 (42) 76 (37) *Tested in 48 and 252 patients respectively. **Tested in 36 and 205 patients respectively. ***Tested in 33 and 182 patients respectively. ****Tested in 56 and 291 patients respectively. Disclosures No relevant conflicts of interest to declare.

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Modeling using structural equations, is a second generation statistical data analysis technique, it has been positioned as the methodological options most used by researchers in various fields of science. The best known method is the covariance-based approach, but it presents some limitations for its application in certain cases. Another alternative method is based on the variance structure, through the analysis of partial least squares, which is an appropriate option when the research involves the use of latent variables (for example, composite indicators) prepared by the researcher, and where it is necessary to explain and predict complex models. This article presents a brief summary of the structural equation modeling technique, with an example on the relationship of constructs, sustainability and competitiveness in iron mining, and is intended to be a brief guide for future researchers in the engineering sciences. Keywords: Competitiveness, Structural equations, Iron mining, Sustainability. References [1]J. Hair, G. Hult, C. Ringle and M. Sarstedt. A Primer on Partial Least Square Structural Equation Modeling (PLS-SEM). California: United States. Sage, 2017. [2]H. Wold. Model Construction and Evaluation when Theoretical Knowledge Is Scarce: An Example of the Use of Partial Least Squares. Genève. Faculté des Sciences Économiques et Sociales, Université de Genève. 1979. [3]J. Henseler, G. Hubona & P. Ray. “Using PLS path modeling new technology research: updated guidelines”. Industrial Management & Data Systems, 116(1), 2-20. 2016. [4]G. Cepeda and Roldán J. “Aplicando en la Práctica la Técnica PLS en la Administración de Empresas”. Congreso de la ACEDE, Murcia, España, 2004. [5]D. Garson. Partial Least Squares. Regresión and Structural Equation Models. USA. Statistical Associates Publishing: 2016. [6]D. Barclay, C. Higgins & R. Thompson. “The Partial Least Squares (PLS) Approach to Causal Modeling: Personal Computer Adoption and Use as an Illustration”. Technology Studies. Special Issue on Research Methodology. (2:2), pp. 285-309. 1995. [7]J. Medina, N. Pedraza & M. Guerrero. “Modelado de Ecuaciones Estructurales. Un Enfoque de Partial Least Square Aplicado en las Ciencias Sociales y Administrativas”. XIV Congreso Internacional de la Academia de Ciencias Administrativas A.C. (ACACIA). EGADE – ITESM. Monterrey, México, 2010. [8]J. Medina & J. Chaparro. “The Impact of the Human Element in the Information Systems Quality for Decision Making and User Satisfaction”. Journal of Computer Information Systems. (48:2), pp. 44-52. 2008. [9]D. Leidner, S. Carlsson, J. Elam & M. Corrales. “Mexican and Swedish Managers’ Perceptions of the Impact of EIS on Organizational Intelligence, Decisión Making, and Structure”. Decision Science. (30:3), pp. 633-658. 1999.[10]W. Chin. “The partial least squares approach for structural equation modeling”. Chapter Ten, pp. 295-336 in Modern methods for business research. Edited by Macoulides, G. A., New Jersey: Lawrence Erlbaum Associates, 1998. [11]M. Höck & C. Ringle M. “Strategic networks in the software industry: An empirical analysis of the value continuum”. IFSAM VIIIth World Congress, Berlin 2006. [12]J. Henseler, Ch. Ringle & M. Sarstedt. Handbook of partial least squares: Concepts, methods and applications in marketing and related fields. Berlin: Springer, 2012. [13]S. Daskalakis & J. Mantas. “Evaluating the impact of a service-oriented framework for healthcare interoperability”. Studies in Health Technology and Informatics. pp. 285-290. 2008. [14]C. Fornell & D. Larcker: “Evaluating Structural Equation Models with Unobservable Variables and Measurement Error”, Journal of Marketing Research, vol. 18, pp. 39-50. Februay 1981. [15]C. Fornell. A Second Generation of Multivariate Analysis: An Overview. Vol. 1. New York, U.S.A. Praeger Publishers: 1982. [16]R. Falk and N. Miller. A Primer for Soft Modeling. Ohio: The University of Akron. 1992. [17]M. Martínez. Aplicación de la técnica PLS-SEM en la gestión del conocimiento: un enfoque técnico práctico. Revista Iberoamericana para Investigación y el Desarrollo Educativo. Vol. 8, Núm. 16. 2018. [18]S. Geisser. “A predictive approach to the random effects model”. Biometrika, Vol. 61(1), pp. 101-107. 1974. [19]J. Cohen. Statistical power analysis for the behavioral sciences. Mahwah, NJ: Lawrence Erlbaum, 1988. [20]GRI (2013). G4 Sustainability Reporting Guidelines. Global Reporting Initiative. Available: www.globalreporting.org

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Abstract Abstract 3830 In myeloid malignancies, genetic abnormalities in key apoptosis pathway genes (eg., p53) are associated with poor responses to conventional cytotoxic therapy. In pre-clinical models, non-cytotoxic, DNA methyltransferase 1 (DNMT1) depleting regimens of the deoxycytidine analogue decitabine relieve aberrant epigenetic repression of key late-differentiation genes and induce cell cycle exit by p53-independent differentiation pathways (CEBPE, MXD1, p27/CDKN1B) (Ng et al, Leukemia 2011). To translate these observations into practice, a clinical trial is being conducted in MDS, using decitabine at minimum doses required to deplete DNMT1 (0.1–0.2 mg/kg [5–10 mg/m2]), administered by the subcutaneous (SC) route to avoid high peak levels that cause apoptosis, and using a metronomic schedule (1-3X/week for ≥1y) to increase exposure time for S-phase specific depletion of DNMT1. To evaluate mechanism of action, correlative studies include quantification of pH2AX (DNA damage marker) and DNMT1 levels in bone marrow by flow-cytometry, and immunohistochemical evaluation by ImageQuant of p27/CDKN1B and KI67 expression, expected to vary directly and inversely respectively with terminal differentiation. A two-stage Simon design was used, and results from the first stage (n=15, patient characteristics table 1) are reported (median follow-up 330 days, range 142–180). Anti-emetics were not required, and there were no administration related adverse events. Neutropenic fever (NF) occurred in 11 patients, 7 of whom did not have NF prior to therapy (median time to nadir 40 days). By IWG criteria, complete hematologic and cytogenetic remissions (CR) with persistent dysplasia occurred in 2 subjects, hematologic improvement (HI) occurred in 4 subjects (overall response rate, ORR=40%), and stable disease in 7. Median response duration for HI/CR is 243 days, with 5 of 6 responses ongoing (range 74–292). Complete cytogenetic responses occurred even in patients with highly complex chromosome abnormalities (table 1). Bone marrow cell pH2AX expression decreased non-significantly from pre-treatment to week 6 to week 12 (median values 1.2, 0.5 and 0.4% respectively, p=0.27 Wilcoxon test), with a >3-fold reduction in mean percentage of cells expressing DNMT1 in the same period (Turkey-Kramer test p<0.001). Consistent with differentiation-mediated cell cycle exit, median p27/CDKN1B expression increased from 26.8 to 66.2 to 78.7% of bone marrow cells (p<0.001), with a concomitant decrease in median KI67 expression from 65.8 to 46.2 to 28.7% (p<0.001) (table 1). ORR of only 40% despite major p27 and cytogenetic responses and stable disease in almost all subjects (table 1), suggested that relief of cytopenia may require a threshold of normal stem cell reserve and a supportive marrow microenvironment. Accordingly, in HI/CR versus other subjects, median duration of disease was 855 versus 1350 days (p=0.15), and median pre-treatment bone marrow cellularity was 65 versus 30% (p=0.14). In conclusion, this study provides clinical proof of principle that a decitabine regimen rationalized for non-cytotoxic epigenetic-differentiation effects is active in myeloid malignancy, correlates with molecular markers of terminal differentiation, and has potentially important safety and efficacy advantages over cytotoxic therapy that warrant further evaluation and optimization. All subjects: baseline and response characteristics BM blasts: <5%/≥5%/≥10% Median Age (range) Prev. 5aza or lenali-domide (%) Prev. chemotx and XRT (%) Median disease duration (days) M/FM CR (%) HI (%) HI and CR (%) Cyto CR (%) Cyto PR (%) HI, CR and stable disease (%) 9/3/3 72 (46–83) 7 (46) 2 (13) 1080 (90–4680) 10/5 2/15 (13) 4/15 (26) 6/15 (40) 4/7 (57) 1/7 (14) 13/15 (87) Subjects with cytogenetic abnormalities pH2AX% KI67% p27 (CDKN1B) % Patient Number Pre-Tx Cyto. Abn. Best cyto Resp. Pre-Tx Wk 6 Wk 12 Pre-Tx Wk 6 Wk 12 Pre-Tx Wk 6 Wk 12 1 20q- 6/20 meta-phases Norm. 20/20 7 1 0.8 42 17 31 14 79 58 2 -7 19/20 meta. -7 6/20 0.2 0.2 0.2 71 65 36 30 57 78 8 del3, -5, -7, +22 4/20 meta. Norm. 20/20 3.4 1.8 0.2 66 50 24 44 69 71 9 +mar 2/20 meta. Norm. 20/20 0.7 1.6 0 74 39 27 13 55 88 11 -4,del5,-17,add19/45, add19),+19, +mar1/-6,+inv6,-7,-10,+del10, -14,+add14, -15,-22,t(15;22), +mar2 16/20 meta. Norm. 20/20 3.5 0.5 0.4 71 46 20 30 66 79 14 -Y 20/20 meta. -Y 16/20 4.3 0.2 0.2 70 54 47 86 15 -Y in 3/20 metaphases -Y 7/20 1.7 0.4 0.4 81 50 18 71 Disclosures: No relevant conflicts of interest to declare.

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Abstract Introduction: Romiplostim is a thrombopoietin receptor agonist approved for use in adult pts with ITP. Pooled analyses of combined pt data from romiplostim ITP clinical studies have previously been reported. Here we report updated safety and efficacy data according to baseline splenectomy status. Methods: Data from adult pts in 13 completed ITP studies with romiplostim were analysed up to June 2014. Pts received romiplostim, placebo or medical standard of care (SOC) and data from the placebo/SOC arms were pooled. All 13 studies were included in analyses of baseline pt characteristics and safety endpoints; 4 early dose-finding studies were excluded from analyses of efficacy endpoints as they do not reflect the current dosing of romiplostim. Adverse events were adjusted for time spent on study and reported as rates per 100 pt-years. For pts who started their parent study in the placebo/SOC group and then went on to receive romiplostim in an extension study, all data from the first dose of romiplostim were included in the romiplostim group. A platelet response was defined as a platelet count ≥50x109/L without rescue medication in the previous 8 weeks; a platelet response for 9 out of any 12 consecutive weeks on-study was considered a sustained platelet response. All analyses were descriptive and no statistical testing was performed. Results: Data from 1,111 pts were analysed, 395 splenectomized and 716 nonsplenectomized. The splenectomized and nonsplenectomized groups were similar in age (median 52 vs 53 years) and sex (female 64% vs 60%), but in the splenectomized group median baseline platelet counts were slightly lower (14 vs 19x109/L) and a higher proportion of pts were known to have received >3 prior ITP treatments (38% vs 12%) than the nonsplenectomized group. Rates of AEs, serious AEs, fatal AEs, treatment-related AEs, thrombotic events, and hemorrhages were lower in nonsplenectomized than splenectomized pts and were in general lower in romiplostim than placebo/SOC-treated pts in both groups. Bone marrow reticulin occurred in 17 romiplostim-treated pts and one placebo-treated pt, at a slightly increased rate in splenectomized vs nonsplenectomized pts. Bone marrow collagen was reported in one romiplostim-treated nonsplenectomised pt. Data from 1,024 pts were analysed for efficacy (376 splenectomized, 648 nonsplenectomized). The median (Q1, Q3) most frequent weekly dose was 4 µg/kg (2, 9) in splenectomized and 3 µg/kg (2, 7) in nonsplenectomized pts. A platelet response was achieved in 82% of splenectomized and 91% of nonsplenectomized pts and a sustained platelet response in 66% and 79%, respectively. The median time to first response was 2.1 weeks for splenectomized and 2.0 weeks for nonsplenectomized pts. Platelet responses were maintained in those who responded: after the first response the median (Q1, Q3) proportion of time with a response was 97% (79%, 100%) for splenectomized and 100% (91%, 100%) for nonsplenectomized pts. Conclusions: A relatively large number of nonsplenectomized pts have received romiplostim in clinical studies. Safety of romiplostim was comparable in splenectomized and nonsplenectomized patients with no new safety signals observed, and platelet response rates were high and of sustained duration in both groups. Abstract 4199. Table Number of events (rate per 100 pt-years) Splenectomized Nonsplenectomized Placebo/SOC N=27 Pt-yr=11.2 Romiplostim N=391 Pt-yr=702.0 Placebo/SOC N=106 Pt-yr=97.7 Romiplostim N=655 Pt-yr=1129.7 All AE 208 (1861.1) 8609 (1226.3) 1028 (1052.6) 9624 (851.9) Serious AE 15 (134.2) 478 (68.1) 92 (94.2) 498 (44.1) Fatal AE 3 (26.8) 11 (1.6) 5 (5.1) 31 (2.7) Treatment-related AE 15 (134.2) 864 (123.1) 152 (155.6) 928 (82.1) Treatment-related serious AE 0 (0) 65 (9.3) 18 (18.4) 59 (5.2) Treatment-related fatal AE 0 (0) 2 (0.3) 0 (0) 3 (0.3) Thrombotic events 1 (8.9) 44 (6.3) 5 (5.1) 52 (4.6) Hemorrhage events 54 (483.2) 1868 (266.1) 233 (238.6) 1591 (140.8) Fatal hemorrhage events 1 (3.7) 0 (0) 0 (0) 5 (0.8) Bone marrow reticulin /collagen events* 1 (8.9) 11 (2.0) 0 (0) 7 (0.8) Hematologic malignancies/MDS 0 (0) 6 (0.9) 4 (4.1) 8 (0.7) Any malignancies 0 (0) 24 (3.4) 9 (9.2) 43 (3.8) * Bone marrow collagen reported in one romiplostim-treated nonsplenectomized pt. Excludes study NCT00907478 as bone marrow evaluations were collected differently than in other studies; in the romiplostim arms the N/pt-yrs were 331/560.6 for splenectomised and 546/866.7 for nonsplenectomised pts. Disclosures Rodeghiero: GSK: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Suppremol: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Steurer:Amgen: Honoraria. Godeau:Amgen: Consultancy. Carpenter:Amgen: Employment, Equity Ownership. Kreuzbauer:Amgen: Employment, Equity Ownership.

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Abstract Background Crohn’s disease (CD) is a progressive inflammatory disease that often results in intestinal complications such as small bowel (SB) strictures. SB strictures are frequently associated with substantial morbidity and may require surgery. The natural history of SB strictures in the era of biologic treatments has not been well characterized. Aims To determine the proportion of patients with SB strictures who develop complicated stricturing disease and to identify clinical factors associated with this outcome. Methods We performed a retrospective observational study between January 1, 2009, and May 31, 2019. Adults (&gt;17 years) with CD who underwent an abdominal CT scan or MRI were identified from our institutional data warehouse using the ICD-10 code K50* and local imaging codes. Reports were reviewed to determine the imaging protocol and the presence of SB strictures. We included CT or MR enterography studies that reported SB strictures and excluded encounters with incomplete records, diverting ostomies, ileal J-pouches, and patients evaluated for pre-surgical planning. Each imaging study was included as a separate encounter in our analysis. Our primary endpoint was the development of complicated stricturing disease defined as stricture-related hospitalization or surgery. Time to event was estimated using Kaplan–Meier analysis and associated factors were assessed by multivariable Cox proportional hazard models adjusted for age, sex, exposure to biologics and corticosteroids. Results A total of 6583 unique imaging studies were identified: 926 (14%) studies reported SB strictures without penetrating complications, and 568 (9%) studies reported penetrating complications. A total of 503 (8%) studies, performed on 330 patients, met our inclusion criteria: mean age 42 (SD, 15.1) years and 166 (50%) males. Overall, 144 (44%) patients developed complicated stricturing disease: 106 (32%) patients required surgery and 132 (40%) patients were hospitalized for stricture related complications. Of the patients who underwent surgery, the mean time to surgery was 13 months (SD, 18.3) and among patients who required hospitalization, mean time to hospitalization was 15 months (SD, 17.8) (Figure 1). On multivariable analysis, exposure to corticosteroids (aHR 2.11; 95% CI, 1.54–2.90; p&lt;0.001) but not biologics (aHR 1.1; 95% CI, 0.84–1.43; p&lt;0.48) at the time of the imaging study was independently associated with the development of complicated stricturing disease. Conclusions In our single center study, complicated stricturing disease occurred in 44% of patients with CD who had a SB stricture and was associated with corticosteroids but not biologics.These findings, along with additional clinical and radiologic factors may help in the development of clinical support tools to identify patients at highest risk of developing complicated stricturing disease. Figure 1. Kaplan-Meier estimates of the time to complicated stricturing disease (surgery or hospitalization) after an imaging encounter documenting SB stricture(s). Funding Agencies None

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Abstract Management of hemostasis with factor IX replacement during surgical procedures on patients with hemophilia B is vital to patient safety. A recombinant factor IX (rFIX, nonacog gamma, RIXUBIS, BAX 326) presents a treatment alternative for hemophilia B; nonacog gamma is manufactured with no materials of human or animal origin, and includes as two-step virus inactivation (solvent/detergent treatment and nanofiltration). This multi-national clinical trial was conducted to investigate the efficacy and safety of nonacog gamma for perioperative use in previously-treated patients with severe (FIX level < 1%) or moderately severe (FIX level 1-2%) hemophilia B. Interim results of 14 (11 major) surgeries showed that nonacog gamma is safe and effective in maintaining hemostasis in the surgical setting;1 the results of all 38 surgeries are presented here. Previously-treated hemophilia B immunocompetent patients aged 12 to 65 years with no evidence of a history of FIX inhibitors were eligible for participation if they were either: 1) participating in another trial with nonacog gamma and required an emergency or elective major or minor surgical, dental, or other invasive procedure; or 2) if not participating in any other nonacog gamma clinical study, they required elective major surgery and had been treated previously with plasma-derived and/or recombinant FIX concentrate(s) for a minimum of 150 exposure days. Pre-operative FIX levels were targeted at 80%-100% of normal for major, and 30%-60% of normal for minor surgeries, through an individualized nonacog gamma dosing approach. Hemostatic efficacy was evaluated intra- and post-operatively by determination of actual versus predicted blood loss and a semi-quantitative 4-point hemostatic efficacy rating scale (excellent, good, fair, none); safety was assessed in terms of the occurrence of adverse events. Thirty patients participated in this study, 10 of whom underwent multiple surgeries and were re-enrolled for each surgery. Of a total of 38 surgeries performed, 21 were major (14 orthopedic) and 17 were minor. Hemostatic efficacy for 37/38 surgeries (including 20/21 major surgeries) had a rating of 'excellent' and one was 'good' (a knee joint replacement). At drain removal (n=14), the ratings for all major surgeries were either 'excellent' (10/14) or 'good' (4/14). On postoperative day 3, 6 of 7 major surgeries where no drain was employed had a rating of 'excellent', and one had a rating of 'good'. At discharge from hospital, 12/21 were 'excellent', 7/21 were 'good' and 2 were 'fair' (both had ratings of 'excellent' intraoperatively and at drain removal). For 16/21 major surgeries, the actual blood loss was below (n=8) or equal to (n=8) the average predicted blood loss and the mean post-operative blood loss was 552.4 mL (range: 11-1100 mL) in subjects who had a drain placed. For 12/17 minor surgeries, actual intraoperative blood loss was below the average predicted blood loss, for 4/17 minor surgeries, the actual intraoperative blood loss matched the average predicted blood loss, and for 1 minor surgery (intra-articular infiltration) actual blood loss was between the average predicted and maximum predicted blood loss. Nonacog gamma was safe and well tolerated. One possibly related AE (hemorrhagic anemia) was reported. This event was resolved at the completion of the study. No thrombogenic events or severe allergic reactions, nor induction of inhibitory antibodies to FIX or total binding antibodies to FIX were observed. Conclusion: Nonacog gamma provides a safe and effective treatment alternative for perioperative management of hemostasis in hemophilia B patients in a variety of surgical settings. References 1 Windyga J, Lissitchkov T, Stasyshyn O, et al. Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective, open-label, uncontrolled, multicentre, phase III study. Haemophilia. 2014 Sep;20(5):651-8. Disclosures Windyga: CSL Behring: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Biogen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Nordisk: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Aspen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Sanofi: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Baxalta, now part of Shire: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Investigator Clinical Studies, Patents & Royalties, Research Funding, Speakers Bureau; Octapharma: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding, Speakers Bureau; Alexion: Other: Speaker's honorarium. Mamonov:Baxalta (Now part of Shire): Research Funding. Chapman:Baxalta (Now part of Shire): Employment, Equity Ownership. Tangada:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Abbuehl:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership.

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Background: It is well known that coronary artery bypass graft (CABG) is considered as gold standard treatment of left main (LM) stem disease. Over the years PCI of left main (LM) stem disease, proved its non-inferiority to CABG in treating LM stem disease Objectives: Exact data of LM stem PCI and its procedural success, in-hospital, and post-procedural one-year survival outcome in-terms of repeat hospitalization due to re-infarction, LVF and death, in our population not known clearly. Therefore, we have carried out this prospective observational cohort to see the overall outcomes of LM Stem, PCI in our population Methods and materials: Patients who underwent elective CAG and found LM stem disease and planned for PCI, were enrolled in this non-randomized observational study between November 2013 to September 2019. Total 146 patient (F 29; Male 117) were enrolled in this study. Results: Out of 146 patients, female :19.8% (n=29) vs Male: 80.1% (n=117). Among, these patient females were more obese (BMI: Female 29.8 ± 3.6 vs male 26.8 ± 3.8). Male patients were older than female; Male 59 yrs. vs female 56 yrs. Among the CAD risk factors Hypertension (HTN) 67.8% (n=99), dyslipidemia 56.2% (n=82), Diabetes Mellitus (DM) 51.4% (n=75), smoking 31.5% (n=46), Family history of CAD (FH) 21.2% (n=31). In this study, 19.2%(n=28) patient had CABG in the past. Common Stented territories were ostial LM 6.8%(n=10), shaft of LM 28.8% (n=42), distal LMLAD 47.3% (n=69), distal LM-LCX 15.1% (n=22) and distal LM-RI 2.7% (n=4). Common DES were Everolimus 69.9% (n=102), Sirolimus 12.3% (n=18), Zotarolimus 9.6%(n=14), BMS 4.8% (n=7), Sirolimus with Epithelial Progenitor Cell 3.4% (n=5), and Biolimus 2.1% (n=3). In terms of post procedural dual antiplatelet therapy (DAPT), patients receiving Clopidogrel were 57.5% (n=85), Ticagrelor 28.8% (n=42), and Prasugrel 13.7% (n=20). Total 12 patient died due to acute, sub-acute stent thrombosis or reinfarction with or without arrhythmia. Relook CAG done was only in 14.4% (n=21) patients, Stent patency 80.9% (n=17), significant ISR, later went to CABG 14.3%(n=3) and mild ISR 4.7% (n=1). IVUS guided PCI were done only in 10.9% (n=16) patients. Major adverse cardiac events in terms of periprocedural MI, repeat hospitalization or death were not common in this study. Conclusion: PCI of LM stem disease is one of the important treatment modalities over CABG in our patient population. Very few patients developed re-stenosis, that needs repeat revascularization either by PCI or CABG. Thus, we may conclude, PCI of LM stem disease might be an alternative to CABG and needs comparative multicenter study to justify its superiority outcome in our patient population. Bangladesh Heart Journal 2020; 35(2) : 78-86

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Background:Heterogeneity is a hallmark of psoriatic arthritis (PsA), which is reflected in diverse clinical, imaging and molecular features that may reflect disease course and response to treatment. We hypothesized that specific molecular pathways underlie the various manifestations of PsA.Objectives:To create a model for accurate and biologically meaningful sub-phenotyping of PsA using imaging and molecular data. Specifically, we aimed to identify imaging sub-phenotypes in patients with PsA and determine their association with whole blood mRNA expression markers.Methods:55 patients with PsA ready to initiate treatment for active disease were prospectively recruited. An ultrasound assessment of the extent of musculoskeletal inflammation in 64 joints, 34 tendons and 16 entheses was performed. Sonographic inflammation (in greyscale and Doppler) of the following domains was graded for: a) synovitis; b) peri-tendonitis; c) tenosynovitis; and d) enthesitis. A global inflammatory score was calculated for each tissue domain. Peripheral blood was profiled with RNAseq, and gene expression data were obtained. Analyses were performed in two stages: 1) Unsupervised cluster analysis was performed using hierarchial and k-means to define imaging sub-phenotypes in PsA that reflected the predominant tissue involved; 2) Principal component analysis with ellipses was used to determine the association between imaging-defined clusters and peripheral blood gene expression profile.Results:The patients could be divided into 3 groups based on unsupervised hierarchical and k-means clustering of images indicating the predominant involved tissue (Figure 1): 1) Enthesitis predominant (N=13 [24%]); 2) Peri-tendonitis predominant (N=11 [20%]); 3); Synovitis predominant (N=31 [56%]). Patients in the synovitis predominant group had more nail involvement, while those in the peri-tendonitis group had the highest number of clinically active joints (Table 1). Unsupervised clustering of gene expression data identified three clusters that partially overlapped with the imaging clustering (Figure 2). Overall, 344 genes were differentially expressed (p<0.05) in two of the three comparisons between the imaging clusters.Table 1.Clinical Features by Imaging ClusteringVariableEnthesitis predominantcluster(N=13)Peritendonitis predominant cluster(N=11)Synovitis predominant cluster(N=31)Age (years)47 (14)49 (16)45 (20)Sex: Female8 (61.5%)5 (45.5%)15 (48.4%)PsA duration (years)1.2 (1.5)1.6 (11.5)0.8 (3.7)BMI29.4 (6.8)25 (8.1)26.1 (8.4)Nail lesions3 (23.1%)5 (45.5%)17 (54.8%)PASI1.2 (2.7)1.2 (3.2)2.8 (7.8)Tender joint count6 (9)11 (5)3 (6)Swollen joint count2 (6)10 (7)3 (6)Dactylitis3 (23.1%)4 (36.4%)7 (22.6%)Enthesitis count3 (3)1 (4)0 (2)Enthesitis12 (92.3%)7 (63.6%)15 (48.4%)hsCRP2.9 (8.8)8.5 (21.5)3.6 (9.4)Median (IQ range) and frequencies (%)Bolded=Statistically different between the 3 groups (p<0.05)Conclusion:We identified three different imaging clusters based on the predominant tissue involved in patients with active PsA. Distinct gene expression profiles may underlie these imaging clusters seen in PsA.Acknowledgments:The study was supported by a Discovery Grant from the National Psoriasis Foundation.Disclosure of Interests:Lihi Eder Grant/research support from: Abbvie, Lily, Janssen, Amgen, Novartis, Consultant of: Janssen, Speakers bureau: Abbvie, Lily, Janssen, Amgen, Novartis, Quan Li: None declared, Sara Rahmati: None declared, Iris Eshed: None declared, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Igor Jurisica Grant/research support from: IBM, Vinod Chandran Grant/research support from: Abbvie, Celgene, Consultant of: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lily, Janssen, Novartis, Pfizer, UCB, Employee of: Spouse employed by Eli Lily

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Background:Most autoimmune diseases are more prevalent in women. Symptom severity, disease progression, response to therapy and overall survival differ between males and females with rheumatic diseases.Objectives:To identify the characteristics of autoimmune diseases presentation and treatment between male and female population using information from the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort that collects the information of patients using biologic and biosimilar drugs since 2016. For this study we included all patients enrolled in the registry and compared baseline clinical and disease characteristics, treatment and presence of adverse events between genders. We used logistic regression to analyze univariable associations.Results:A total of 655 participants were analysed, of which 82% were female (Table 1). We found women were older with a median of 53 years compared to 46 years in men (OR 1.02, CI 1.0-1.1). Smoking was higher in men (16%) compared to women (5%), (OR 0.3, CI 0.2-0.6). Women had longer disease duration, 9 years compared to 7 years in men (OR 1, CI 1.0-1.1). Rheumatoid arthritis (RA) was more prevalent in women (OR 2.7, CI 1-6.9), while ankylosing spondylitis (AS) and psoriatic arthritis (PsA) were more prevalent in men (OR 0.2, CI 0.1-0.4, and OR 0.3, CI 0.1-0.9 respectively). Women had more comorbidities than men (OR 1.8, CI 1.1-2.8) and used steroids more frequently (OR 1.7, CI 1.1-2.7). Differences in disease activity were not found, however we noticed high activity scores among participants.Table 1.Baseline characteristics in the cohort by sexWomenn=532 (82%)Menn=123 (18%)UnivariableaOR(95%CI)Age, median (IQR)53 (44-60)47 (34-55)1.02 (1.0-1.1)*Body Mass Index, median (IQR)27 (23-31)26 (23-30)1.0 (0.9-1.1)Smoking, n(%)28 (5)18 (16)0.3 (0.2- 0.6)*Disease duration, median (IQR)9 (4-16)7 (2-13)1.0 (1.0-1.1)*Diagnosis, n(%): RA414 (78)37 (30)2.4 (1.0-5.7)* AIJ12 (2)5 (4)0.5 (0.1-1.9) AS37 (7)56 (46)0.1 (0.1-0.4)* PsA19 (4)15 (12)0.3 (0.1-0.8)* SLE17 (3)3 (2)1.2 (0.3-5.2) Others33 (6)7 (6)1Disease Activity indexes, median (IQR) DAS28a4.9 (3.6-5.9)4.9 (3.0-5.9)1.1 (0.9-1.3) BASDAIb4.8 (2.9-8)5.3 (2.8-7.5)0.9 (0.8- 1.1) ASDASc3.2 (1.9-4.5)3.9 (2.5-4.7)0.8 (0.6-1.2) SLEDAId14.5 (5.0-19.5)25 (25.0-31.0)0.6 (0.4-1.1)High blood pressure, n(%)77 (15)14 (12)1.3 (0.7-2.4)Diabetes mellitus, n(%)46 (9)7 (6)1.5 (0.7-3.5)High cholesterol, n(%)41 (8)8 (7)1.2 (0.4-2.6)Other comorbidities, n(%):173 (33)26 (21)1.8 (1.1 -2.8)*Use of previous biologic, n(%):216 (40)44 (36)1.2 (0.8- 1.8)Use of steroids, n(%):215 (42)34 (29)1.7 (1.1 -2.7)*Use of DMARD, n(%):418 (79)89 (72)1.4 (0.9-2.2)Adverse eventsb, n(%):69 (13)14 (11)1.2 (0.7-2.1) Severeb, n(%):12 (17)3 (21)0.8 (0.2-3.1)Univariable logistic regression analysis. *p<0.05.an=469,bn=99,cn=71,dn=19,Table 1.Analysis of association between change (Δ) in FMD and relevant parameters by univariate and multivariate linear regression analysis.UnivariateRho (p)MultivariateBeta (p)Δ FMD (%)(r2=0.30)ChangeADMA (µmol/l)-0.63 (<0.001)-0.25 (0.01)MDA (nmol/ml)-0.58 (<0.001)-0.18 (0.02)SOD (U/ml)0.48 (<0.001)NSGSH (U/ml)0.02 (0.75)NSHOMA-0.21 (0.001)NSeGFR (ml/min/ 1.73 m2)-0.03 (0.62)NShsCRP (mg/l)-0.45 (<0.001)NSPTX3 (ng/ml)-0.49 (<0.001)-0.21 (0.01)SBP (mmHg)-0.26 (<0.001)NSDBP (mmHg)-0.11 (0.12)NSHemoglobin (g/dl)0.07 (0.32)NSTotal Cholesterol (mg/dl)-0.05 (0.49)NSTriglyceride (mg/dl)-0.11 (0.12)NSLDL (mg/dl)-0.12 (0.07)NSHDL (mg/dl)0.02 (0.82)NSHbA1c (%)-0.26 (<0.001)NSFigure 1.Scatter-plot graphs between FMD and ADMA, MDA, CuZn-SOD, PTX-3.Conclusion:In our study we found sex differences regarding age and disease duration, being higher in women. As expected, the prevalence of RA was higher in women and AS and PsA in men. Overall, women used more steroids than men. An interesting finding was that patients had high disease activity. Future longitudinal analyses will allow us to analyse sex differences in disease progression and treatment response.References:[1] Ortona E et al. Ann Ist Super Sanita 2016;52(2):205-12[2] Ngo ST et al. Front Neuroendocrinol 2014;3(3):347-69Disclosure of Interests:Vijaya Rivera Teran: None declared, Deshire Alpizar-Rodriguez: None declared, Sandra Sicsik: None declared, Fedra Irazoque-Palazuelos Consultant of: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche and UCB, Dafhne Miranda: None declared, David Vega-Morales: None declared, Julio Cesar Casasola: None declared, Sandra Carrilo: None declared, angel castillo: None declared, Sergio Duran Barragan: None declared, Omar Muñoz: None declared, Aleni Paz: None declared, Angélica Peña: None declared, Alfonso Torres: None declared, Daniel Xavier Xibille Friedmann Consultant of: Lilly, Abbvie, Speakers bureau: Lilly, Abbvie, Azucena Ramos: None declared, José Francisco Moctezuma: None declared, Francisco Aceves: None declared, Estefania Torres: None declared, Natalia Santana: None declared, Miguel Vazquez: None declared, Erick Zamora: None declared, Francisco Guerrero: None declared, Claudia Zepeda: None declared, Melanea Rivera: None declared, Kitzia Alvarado: None declared, Cesar Francisco Pacheco Tena: None declared

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Abstract Introduction: There has been little improvement in cancer survival of adolescent and young adult (AYA) patients, ages 18-39, possibly reflecting different disease biology in this subgroup. Myelodysplastic syndrome (MDS) is mainly a disease of the elderly. The characteristics, outcomes and response to treatment are not well described among AYA population. Patients and Methods: Retrospective review of patients from the Moffitt Cancer Center MDS database. We compared baseline characteristics and outcomes of AYA population to older patients. Descriptive statistics were used for baseline characteristics. Chi-square test was used for categorical variables, and t-test for continuous variables comparison. Kaplan-Meier estimates were used for overall survival (OS), and cox regression method for multivariable analysis. Results: We identified 51 AYA and 1,897 older MDS patients. Table-1 summarizes baseline characteristics. More females and Hispanics were noted in AYA group. The AYA patients had higher risk disease, more circulating myeloblasts and more hypoplastic MDS. Autoimmune disorders were more prevalent in older patients. The median OS was 47 months (mo) in the AYA group versus 40 mo in the older group (p 0.26). The median OS was 47 mo versus 56 months in lower risk (low and intermediate-1(int-1)) IPSS MDS AYA group and older group respectively (p 0.46). In the higher risk IPSS group (int-2 and high), median OS was 82 mo in AYA group compared to 17 mo in older group (p 0.001). Thirty individuals were transplanted in the AYA versus 241 in the older group. The median OS for transplanted patients was 55 mo in the AYA group and 46 mo in the older (p 0.4). Whereas, in the non-transplanted patients median survival was 31 months for AYA and 39 months for the older group (p 0.9). The rate of AML transformation was 37% versus 28% in AYA and older group respectively (p 0.17). No difference in use or response to hypomethylating agents was observed. Lenalidomide therapy was seldom used in younger patients. In AYAs, poor karyotype was the only variable strongly associated with worse outcome. Fifteen patients had poor risk karyotype. The median OS was 47 months, not reached and 29 months among patients with good, intermediate and poor risk cytogenetics, respectively (p 0.035) Conclusion: MDS is rare and tends to be more aggressive in the AYA population. The karyotype was the most important prognostic factor. The differences in underlying disease biology should be further explored. Allogeneic stem cell transplant offered younger patients best outcomes. Table 1. Baseline characteristics of AYA and Older Patient Characteristic AYA (18-39) (N= 51) Older Patients (> 39 years old) (N=1,897) P value Gender Female 25 (49%) 655 (34.5%) 0.025 Race White Black Hispanic Other 34 (66.7%) 2 (3.9%) 13 (25.5%) 2 (3.9%) 1,736 (91.5%) 47 (2.5%) 57 (3%) 41 (2.2%) 0.000 t-MDS Yes 10 (19.6%) 359 (18.9%) 0.902 WHO Subtype RA RARS RCMD Deletion 5q RAEB-1 RAEB-2 AML CML MDS-U MDS/MPN 3 (5.9%) 1 (2%) 22 (43.1%) 0 (0%) 11 (21.6%) 10 (19.6%) 0 (0%) 0 (0%) 1 (2%) 2 (3.9%) 196 (10.4%) 151 (8%) 583 (30.8%) 51 (2.7%) 372 (19.7%) 336 (17.7%) 1 (0.1%) 60 (3.2%) 44 (2.3%) 94 (5%) 0.188 IPSS Lower risk Higher risk 28 (59.6%) 19 (40.4%) 1,264 (68.2%) 590 (31.8%) IPSS-R Very low/low Intermediate High/very high 13 (30.1%) 14 (32.6%) 16 (37.3%) 826 (45.3%) 394 (21.6%) 602 (33%) Hypoplastic BM Yes 11 (23.4%) 178 (9.8%) 0.009 LGL clone Yes 0 (0%) 159 (8.4%) 0.033 Autoimmune disease Yes 8 (15.7%) 500 (26.4%) 0.055 Karyotype Good Intermediate Poor 24 (50%) 9 (18.8%) 15 (31.3%) 1120 (60.4%) 300 (16.2%) 434 (23.4%) 0.324 Peripheral Blasts Yes 14 (29.8%) 246 (13.2%) 0.003 RBC Transfusion Dependent 36 (70.6%) 1274 (67.3%) 0.372 Disclosures Shah: Seattle Genetics: Research Funding; Rosetta Genomics: Other: Grant support; Acetylon: Other: Advisory board; Plexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Other: Advisory board, Speakers Bureau; Bayer: Honoraria; Celgene: Other: Advisory board, Speakers Bureau; DeBartolo Institute for personalized medicine: Other: Grant support. Lancet:Pfizer: Consultancy; Kalo-Bios: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding. List:Celgene Corporation: Honoraria, Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding.

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Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.

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Abstract Abstract 650 INTRODUCTION. The most prominent clinical problem in CB transplant is a slower engraftment kinetic, as compared to the conventional SC sources. Engraftment failure is usually defined in CB transplantation as a lack of PMN recovery 60 days after transplant, whilst a definition of late engraftment is currently lacking. A late engraftment is a major cause of transplant-related mortality (TRM), due to the prolonged exposure of the recipient to the infective and hemorrhagic risk. After the HSCT, the probability of engraftment at each time interval tends to increase up to a maximum and then gradually decreases, which is typically represented by a sinusoid curve. The decrease of engraftment probability after transplant results in a rapidly increasing risk of TRM; therefore such a turning point should be considered the beginning of a risk phase for late/no engraftment. Therefore, it is important to find the time point after UCBT in which the probability of engraftment will decrease in order to help taking a decision for rescue with a second transplant. We analyzed the clinical expectations beyond this time in a hom*ogenous population of CB recipients. PATIENTS AND METHODS. We investigated the engraftment kinetic in a population of 1215 patients who received a single, unrelated CB transplant for Acute Leukemia (AL) in Complete Remission (CR) following a Myeloablative Conditioning Regimen (MAC). All patients were transplanted in EBMT Centers and reported to the Eurocord Registry from 1994 to 2010. Ratio Lymphoid/Myeloid Leukemias was 769/445, reflecting a major proportion of pediatric patients over adults (857/357). Patients were transplanted in first (43.4%), second (46,6%), or third or subsequent remission (10%), respectively. Median (range) age at transplant was 9.5 (0.3-63) years. Median weight (Kg) at transplant was 33 (5-112). Out of 1089 patients evaluable for HLA-matching, 601 (55.2%) were mismatched for 0–1 loci, 448 (41.1%) for 2 loci and 40 (3.6%) for more than 2 loci. Fifty percent of the patients had a TBI-based myeloablative regimen. Data on TNC counts at freezing of transplanted CBU were available in 963 cases: median and range were 5 (1.1-41.83)x107/Kg. RESULTS. The median FU was 30 months (1-174). At 24 months overall survival was 49±2%, TRM was 32±2%. Median time of engraftment was 24 days (10-133) with a cumulative incidence of 86±1% at day 60. Analyzing the cumulative curve of engraftment, we considered the engraftment probability within intervals of five days after the transplant; in fact the highest probability of engraftment was at day 25 and dropped of 50% at day 42. Among 167 patients (13.7%) who did not engraft at this time, 63 patients (38%) experienced a late engraftment with a median time of 47 days (43-131) after transplant. The cumulative incidence of engraftment at 120 days was 37% and 38% at day 180 without any further increasing later on. Out of the 104 patients who never engrafted, 74 died and major causes of death were bacterial (17%), viral (10%) and fungal (9%) infections, respectively, whilst 30 patients are alive at the last follow up. Information of graft failure treatment was available for 84 patients. Twenty eight did not receive any treatment (25 died at a median time of 80 days form UCBT), 24 had an autologous back up and 32 underwent a second allogeneic HSCT (14 second UCBT, 9 Haplo PBSC and 9 unrelated BMT). Of those 32, 17 patients engrafted, 5 relapsed; 24 died, 8 are alive at last follow up. CONCLUSIONS: The maximum probability of engraftment after UCBT for patients with AL in remission is at day 25 and halves at day 42, thus suggesting that a clinical decision should be made within this period. In particular, rescue actions, such as infusion of another graft, either allogeneic of autologous, should be considered. Such a model can be applied to different subsets of patients and is particularly useful in transplant at high risk of late engraftment such as UCBT. Disclosures: No relevant conflicts of interest to declare.

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Background:DISCOVER 1 & 2, two double-blind, phase-3, psoriatic arthritis (PsA) trials of guselkumab (GUS, an IL-23 inhibitor), demonstrated significant improvement with GUS vs placebo (PBO) in signs and symptoms of PsA, with good tolerability, at week (w) 24 during the PBO-controlled period.1,2 Beyond w24, all patients (pts) switched to GUS. Continued treatment maintained efficacy through w52.3,4Objectives:To describe pooled safety results from the DISCOVER 1 & 2 trials through 1-year of GUS treatment.Methods:Adults with active PsA (DISCOVER 1: ≥3 tender/swollen joints and C-Reactive protein [CRP] ≥0.3 mg/dL; DISCOVER 2: ≥5 tender/swollen joints and CRP ≥0.6 mg/dL) were randomized to subcutaneous GUS 100 mg at w0, w4, then every 8 w (q8w); GUS 100 mg q4w; or PBO. At w24, PBO pts switched to GUS 100 mg q4w. Pts were biologic naive except ~30% pts in DISCOVER 1. Safety was reported through w60 in DISCOVER 1 and through w52 in DISCOVER 2.Results:Baseline characteristics were similar between treatment groups in the pooled studies. Through w24 and 1 year, numbers of pts per 100 patient years with ≥1 event were similar among treatment groups for adverse events (AEs), serious AEs, infections, serious infections, and discontinuations due to AE (Table 1). At 1 year, there were no cases of active tuberculosis, opportunistic infections (including candida), or inflammatory bowel disease in GUS-treated pts; 2 deaths in PBO pts; and low incidences that were similar across treatment groups for malignancy, major adverse cardiac events, and injection-site reactions. Incidence of anti-GUS antibodies was 4.5%, and most were not neutralizing. Mild elevations in serum hepatic transaminases and decreases in neutrophil counts were consistent at 1 year with the results at w24 (Table 1).Conclusion:GUS regimens of q8w and q4w were well tolerated in PsA pts through 1 year of treatment in the phase-3 DISCOVER trials, consistent with the w24 results. No meaningful differences between incidences of AEs were reported in the q8w and q4w groups. The safety profile of GUS in PsA pts is generally comparable with the previously established safety profile of GUS.References:[1]Deodhar A et al. Lancet. 2020;395:1115[2]Mease P et al. Lancet. 2020;395:1126[3]Ritchlin C et al. EULAR 2020 # SAT0397[4]McInnes I et al. EULAR 2020 # SAT0402Table 1.Number of Patients with AEs per 100 PY and Incidence of AEs of InterestTime Period24 Weeks1 Year*Treatment GroupPBOGUS SC 100 mgPBO to GUS‡GUS SC 100 mgDosing ScheduleMatchingq8wq4wGUSCombined†q4wq8wq4wGUSCombined‡ N3723753737483523753731100Total PY Follow-Up173173172346204384385589Patients with AEs per 100 PY, n (95% CI)≥1 AE143 (123, 166)148 (127, 171)154 (132, 178)151 (136, 167)92 (77, 108)114 (100, 130)115 (101, 131)109 (100, 117)≥1 Serious AE7.1 (3.7, 12)4.1 (1.6, 8.4)4.7 (2.0, 9.3)4.4 (2.5, 7.3)7.0 (3.8, 11.8)4.8 (2.9, 7.6)4.0 (2.2, 6.6)4.9 (3.6, 6.6)≥1 Infection50 (39, 62)47 (37, 59)52 (42, 65)49 (42, 58)39 (31, 49)41 (34, 48)38 (31, 45)39 (35, 44)≥1 Serious Infection1.7 (0.4, 5.1)0.6 (0.0, 3.2)1.8 (0.4, 5.1)1.2 (0.3, 3.0)2.5 (0.8, 5.8)1.3 (0.4, 3.1)0.8 (0.2, 2.3)1.3 (0.7, 2.3)Discontinued due to AE4.1 (1.6, 8.4)2.9 (1.0, 6.8)4.7 (2.0, 9.3)3.8 (2.0, 6.5)3.5 (1.4, 7.1)2.1 (0.9, 4.1)2.6 (1.3, 4.8)2.6 (1.7, 3.8)AEs of Interest§, n (%)Death2 (0.5)0000000Malignancy1 (0.3)2 (0.5)02 (0.3)1 (0.3)2 (0.5)03 (0.3)Major Adverse Cardiac Events1 (0.3)01 (0.3)1 (0.1)001 (0.3)1 (0.1)Opportunistic Infections00000000Tuberculosis00000000Inflammatory Bowel Disease1 (0.3)0000000Injection-Site Reaction1 (0.3)5 (1.3)4 (1.1)9 (1.2)4 (1.1)6 (1.6)9 (2.4)19 (1.7)Anti-GUS Antibody+-6/373 (1.6)9/371 (2.4)15/744 (2.0)14/350 (4.0)18/373 (4.8)17/371 (4.6)49/1094 (4.5)*Through w60 for DISCOVER 1 and w52 for DISCOVER 2; †Combined GUS q8w and q4w; ‡For patients who switched from PBO to GUS, only data on and after first GUS administration were included in this group; §PBO N=370.AE, adverse event; CI, confidence interval; GUS, guselkumab; PBO, placebo; PY, patient year; q4w, every 4 weeks; q8w, every 8 weeks; SC, subcutaneous; w, weekDisclosure of Interests:Christopher T. Ritchlin Grant/research support from: Received grant/research support from UCB Pharma, AbbVie, Amgen, consultation fees from UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Wolf-Henning Boehncke Consultant of: Received consultation fees from Janssen, Grant/research support from: Received grant/research support from Janssen Research & Development, LLC, Iain McInnes Consultant of: Received consultation fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Received grant/research support from Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Alice B Gottlieb Speakers bureau: Received speakers fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Consultant of: Received consultation fees from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Grant/research support from: Received grant/research support from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB, Shelly Kafka Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xie L Xu Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, May Shawi Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.

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Abstract Background: The control of hemoglobin F (Hb F) expression has proven an elusive puzzle with several postulated but not mutually exclusive hypotheses. A silencing mechanism hypothesis, which predicts the existence of a regulatory element that suppresses HbF expression, has been supported by recent investigations into a 3.5 kb region upstream from the delta globin gene (HBD). To test this hypothesis, we have investigated our historical case files in a tertiary care high-throughput clinical laboratory and compared the patient phenotype (Hgb, MCV, MCH, RDW, Hb F %, and flow cytometry Hb F distribution) with the status of this 3.5 kb region. Methods: A query of clinical testing patient files from Mayo Clinic Metabolic Hematology Laboratory yielded 179 patients confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA) to contain large deletions located within the epsilon through beta globin genes. Of these, 27 unrelated patients with breakpoints between the pseudobeta (HBBP1) and HBD genes were identified. Four additional MLPA probe pairs were placed in this region and the patient phenotypes were compared. Results: The interior two (of the four added) probes between HBBP1 and HBD stratified all 27 cases. The other two (flanking) probes were never discriminatory, thus refining the area of interest to 2.4 kb. Sixteen cases showed breakpoints within hg19 g.5260154-5259135 (5' region) and eleven cases showed breakpoints within hg19 g.5259136-5257692 (3' region) upstream of HBD. Patients who displayed a phenotype of HPFH (n = 9) contained breakpoints in the 5' region whereas those with a delta beta thalassemia (DBT) phenotype (n = 11) were associated with breakpoints in the 3' region. A subset (n = 7) with breakpoints in the 5' region had indefinite phenotypic features, but of these, all but one showed hom*ocellular Hb F distribution. Conclusion: Our molecular and phenotypic correlation of 27 patients with large deletional breakpoints between HBBP1 and HBD supports the hypothesis of a silencing element located upstream of HBD and further narrows the area that segregates many HPFH and DBT patient phenotypes from 3.5 kb to 2.4 kb. Several potential silencing effectors with binding sites in this region include HDAC1, GATA1 and H3K27me3; interestingly, the BCL11A binding site may be outside of the regulatory area. Table 1. Phenotypic data of patients with deletions between HBBP1 and HBD. Case Age/Sex Hb F Hb A2 Hb X Hgb RBC MCV MCH MCHC RDW Hb F Flow (Y) (%) (%) (%) (g/dL) ( 10^12/L) (fL) (pg/cell) (hg/cell) (%) 3' Region 1 47 M 25.5 2.1 16.7 6.3 81.4 26.7 32.8 15.7 H 2 5 M 28.3 2.4 12.5 4.9 74.6 25.4 34 15.9 H 3 24 F 30.3 1.7 11.6 4.23 92.7 27.4 29.6 15.2 H 4 9 F 36.3 2.2 S = 62 13.1 5.2 69.9 NA NA 14.8 5 24 F 37.3 2.1 C = 61 12.9 5.1 72.9 25.5 35 14.3 6 3 M 39.7 2.1 12.4 4.4 88.7 28.1 31.7 16.3 7 27 F 40.2 3.4 S = 56 12.2 4.4 79.7 27.8 34.9 15 8 16 M 43.7 2.2 S = 54 15.9 6.8 71.5 23.5 32.9 14.1 9 7m M 100.0* 0.0 12.8 4.8 76 26.5 34.9 16.8 3' Region 10 28 F 20.9 2 10.11 4.4 70.9 22.7 32.1 19 H 11 64 M 21.4 2.3 10.51 4.1 81.1 25.8 31.8 18.1 12 2.5 M 24 2.1 10.21 5.3 59.4 19.3 32.5 20.9 H 13 58 F 24 2.1 9.51 4.4 72.2 21.5 29.8 17.7 H 14 14 F 25.4 1.5 10.81 4.9 69.4 22 31.8 17.6 H 15 52 F 26.9 1.8 8.42 3.6 72 23.5 32.7 19.4 T 16 34 M 38.7 1.7 S = 60 11.4 4.7 71.6 NA NA 21.6 5' Region 17 24 F 2.7 2.9 12.3 6.1 62.2 20 32.2 18.2 18 32 F 6.1 2.7 10.2 5.1 61.3 19.9 32.5 19.3 19 27 F 7.2 2.9 11 5.1 72.9 21.7 29.8 19.9 20 29 F 7.8 2.7 10.2 4.7 72.2 21.7 30 20.5 21 15 M 7.8 2.5 12.7 6.2 64.7 20.4 31.5 21.2 22 42 M 7.8 3.1 10.6 4.9 75.1 21.5 28.6 23.7 23 60 M 10.1 2.5 11 4.5 74.8 24.7 33 23.4 24 41 M 10.7 2.8 8.6 4.1 73.3 21.2 29 26.8 25 30 F 11.5 2.7 12.1 5.5 67.4 21.9 32.5 21.8 26 25 F 13.2 2.8 12.1 5.3 68.4 22.8 33.3 21.6 27 3 F 18.3 2.6 11.9 5.79 63.6 20.6 32.3 22.7 T Normal values <1 2-3.3 0 H = hom*ocellular; T= heterocellular; I = indeterminate; *hom*ozygous deletion -- = no deletion; + = deletion present (all alpha deletions were single -3.7 kb 'rightward' deletions) 1 = Suspected Fe deficiency; 2 = recent transfusion Disclosures No relevant conflicts of interest to declare.

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Целью данной работы является синтез и исследование свойств синтетического айкинита, PbCuBiS3.Синтез проводили в откачанных кварцевых ампулах в течение 7–8 ч, максимальная температура составляла 1250–1325 К. Далее образцы охлаждали и выдерживали при 600 К в течение недели. Потом ампулы вскрывали, образцы тщательно перетирали и после плавки отжигали при 600–800 К в зависимости от состава не менее двух недель для приведения образцов в равновесное состояние. Отожженные образцы исследовали методами дифференциально-термического (ДТА), рентгенофазового (РФА), микроструктурного (МСА) анализов, а также измерением микротвердости и определением плотности. РФА проводили на рентгеновском приборе модели Д 2 PHASER с использованием CuKa- излучении Ni-фильтр.Комплексом методов физико-химического анализа изучены разрезы CuBiS2–PbS, Cu2S–PbCuBiS3, Bi2S3–PbCuBiS3, PbBi2S4–PbCuBiS3, PbBi4S7–PbCuBiS3 квазитройной системы Cu2S–Bi2S3–PbS и построены их фазовые диаграммы.Установлено, что кроме сечения PbBi2S4–PbCuBiS3 все разрезы квазибинарные и характеризуются наличием ограниченных областей растворимости на основе исходных компонентов.При изучении разреза CuBiS2–PbS установлено образование четверного соединения состава PbCuBiS3, встречающееся в природе в виде минерала айкинита, плавящегося конгруэнтно при 980 К. Установлено, что соединение PbCuBiS3 кристаллизуется в ромбической сингонии с параметрами решетки: а = 1.1632, b = 1.166, с = 0.401 нм, прост. группа Pnma, Z = 4. Методами ДТА и РФА установлено, что соединение PbCuBiS3 является фазой переменного состава с областью гомогенности от 45 до 52 мол. % PbS. Соединение PbCuBiS3 является дырочным полупроводником с шириной запрещенной зоны ΔЕ = 0.84 эВ. ЛИТЕРАТУРА 1. Zhang Y-X., Ge Z-H., Feng J. Enhanced thermoelectric properties of Cu1.8S via introducing Bi2S3 andBi2S3/Bi core-shell nanorods. Journal of Alloys and Compounds. 2017;727: 1076–1082. DOI: https://doi.org/10.1016/j.jallcom.2017.08.2242. Mahuli N., Saha D., Sarkar S. K. Atomic layer deposition of p-type Bi2S3. Journal of Physical ChemistryC. 2017;121(14): 8136–8144. DOI: https://doi.org/10.1021/acs.jpcc.6b126293. Ge Z-H, Qin P., He D, Chong X., Feng D., Ji Y-H., Feng J., He J. Highly enhanced thermoelectric propertiesof Bi/Bi2S3 nano composites. ACS Applied Materials & Interfaces. 2017;9(5): 4828–4834. DOI: https://doi.org/10.1021/acsami.6b148034. Savory C. N., Ganose A. M., Scanlon D. O. Exploring the PbS–Bi2S3 series for next generation energyconversion materials. Chemistry of Materials. 2017;29(12): 5156–5167. DOI: https://doi.org/10.1021/acs.chemmater.7b006285. 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The debate about diagnoses and treatment of attention deficit hyperactive disorder (ADHD) in children continue to range on between the developmental and biological perspectives. While there is increasing evidence that support the biological susceptibility of the disorder, a number of researches also emphasized the significant effect of environment on the syndrome. This study used developmental perspectives to evaluate and bring together various bio-psychosocial factors that impact on children diagnosed with ADHD. The study explored and integrated the existing and advancing study on ADHD to a more refined pattern that embraced developmental perspectives. The study also discussed how the linkage in childhood ADHD fits within the developmental psychopathology perspective. The study revealed that ADHD as a developmental disorder is influenced by prenatal, biological and psychosocial environmental risk factors, and suggested that better understanding of genomic susceptibilities, family environment and parental characteristics would transform the pathway for development of ADHD in children. References American Psychiatric Association.(2000). Diagnostic and StatisticalManual of MentalDisorders. 4th ed. Washington, DC: American Psychiatric Association. American Psychiatric Association.(2013). Diagnostic and StatisticalManual of MentalDisorders.5th ed. Washington, DC: American Psychiatric Association. Arnsten, A.F, (2007). Catecholamine and second messenger influenceson prefrontalcortical networks of “representational knowledge”:a rational bridge between genetics andthe symptoms of mental illness. Cerebral Cortex, 17, i6–i15. Arnsten, A.F, & Pliszka, S.R. (2011). 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Agustini, N. K. R., & Merkusiwati, N. K. L. A. (2016). Pengaruh Tekanan Ketaatan, Senioritas Auditor Dan Tekanan Anggaran Waktu Terhadap Audit Judgment. Universitas Udayana, 15, 433–462. Akhtar, S., bin Arshad, M. A., Mahmood, A., & Ahmed, A. (2015). Spiritual Quotient and Ethical Values towards Organizational Sustainability. International Letters of Social and Humanistic Sciences, 58(2001), 1–7. https://doi.org/10.18052/www.scipress.com/ilshs.58.1 Anggriawan, E. F. (2014). Summary for Policymakers. In Intergovernmental Panel on Climate Change (Ed.), Climate Change 2013 - The Physical Science Basis (Vol. 3, pp. 1–30). https://doi.org/10.1017/CBO9781107415324.004 Anwar Prabu, M. (2015). Mangkunegaran, Anwar Prabu. 2009. Manajemen Sumber Daya Manusia Perusahaan. (12th ed.). Bandung: PT Remaja Rosa Karya. Bodnar, G. H., & Hopwood, W. S. (2012). Accounting Information System. Pearson - Prentice Hall. Broberg, P., Tagesson, T., Argento, D., Gyllengahm, N., & Mårtensson, O. (2017). 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This paper presents some results of rainfall forecast in the monsoon onset period in South Vietnam, with the use of ensemble Kalman filter to assimilate observation data into the initial field of the model. The study of rainfall forecasts are experimented at the time of Southern monsoon outbreaks for 3 years (2005, 2008 and 2009), corresponding to 18 cases. In each case, there are five trials, including satellite wind data assimilation, upper-air sounding data assimilation, mixed data (satellite wind+upper-air sounding data) assimilation and two controlled trials (one single predictive test and one multi-physical ensemble prediction), which is equivalent to 85 forecasts for one trial. Based on the statistical evaluation of 36 samples (18 meteorological stations and 18 trials), the results show that Kalman filter assimilates satellite wind data to forecast well rainfall at 48 hours and 72 hours ranges. With 24 hour forecasting period, upper-air sounding data assimilation and mixed data assimilation experiments predicted better rainfall than non-assimilation tests. The results of the assessment based on the phase prediction indicators also show that the ensemble Kalman filter assimilating satellite wind data and mixed data sets improve the rain forecasting capability of the model at 48 hours and 72 hour ranges, while the upper-air sounding data assimilation test produces satisfactory results at the 72 hour forecast range, and the multi-physical ensemble test predicted good rainfall at 24 hour and 48 hour forecasts. The results of this research initially lead to a new research approach, Kalman Filter Application that assimilates the existing observation data into input data of the model that can improve the quality of rainfall forecast in Southern Vietnam and overall country in general.References Bui Minh Tuan, Nguyen Minh Truong, 2013. 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Куликовская битва 8 сентября 1380 г. по праву считается одним из известнейших сражений русской военной истории. В тот день русская рать под началом великого князя московского и владимирского Дмитрия Ивановича нанесло сокрушительное поражение войску могущественного ордынского темника и некоронованного властителя немалой части Золотой Орды Мамая. В последующие десятилетия усилиями нескольких поколений русских книжников сложился «куликовский миф», нашедший свое отражение в произведениях, летописных и литературных, «куликовского цикла». Этот миф оказал колоссальное влияние на последующую традицию изучения Куликовской битвы и кампании 1380 г. в отечественной исторической литературе. В данной статье автор предлагает взглянуть с учетом новых тенденций и методик в изучении русского венного дела эпохи позднего Средневековья – раннего Нового времени на одну из составляющих этого «мифа» – бытующие в научной и в особенности в популярной литературе «тьмочисленные» оценки численности русского войска, давшего в тот день бой ордынцам. На основе имеющихся прямых и косвенных свидетельств автор приходит к выводу, что полки Дмитрия Ивановича на Куликовом поле насчитывали порядка 10-12 тыс. конных воинов. Библиографические ссылки Азбелев С.Н. Численность и состав войск на Куликово поле // Древняя Русь. Вопросы медиевистики. 2015. № 4(62). С. 23−29. Алексеев Ю.Г. Аграрная и социальная история Северо-Восточной Руси XV – XVI вв.. Переяславский уезд // Алексеев Ю.Г. Аграрная и социальная история России XV – XVI вв. СПб.: Изд-во Олега Абышко. 2019. С. 21−264. Амелькин А.О., Селезнев Ю.В. Куликовская битва в свидетельствах современников и памяти потомков. М.: Квадрига, 2010. 384 с. 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RESUMENLos monasterios femeninos nacen en beaterios en muchos casos. Así los beaterios son el primer paso de la reclusión pero, al mismo tiempo el modelo de rechazo. Por otro lado, con el Concilio de Trento, la Contrarreforma fue la imposición de la reforma religiosa con una renovación espiritual, pero reproduce la subordinación femenina y la clausura. Nuevamente se renuevan los rechazos en este caso el modelo son los conventos de Toledo y el monasterio de San Clemente. Este estudio examina la importancia de los beaterios en las fundaciones conventuales en Toledo.Y analiza la oposición y acciones de rechazo de las beatas y monjas de las distintas comunidades monásticas y mendicantes frente a las reformas de vida claustral, incluido la normativa del Concilio de Trento. Utilizando para ello las fuentes documentales localizadas durante la elaboración de mi tesis doctoral.PALABRAS CLAVE: Beaterios, conventos, oposición, Toledo, Edad ModernaABSTRACTWomen’s monasteries often began as beatorios. These beaterios were thus the first step in confinement but at the same time the model of rejection. Meanwhile the Council of Trent and Counterreformation represented the imposition of religious reform with spiritual renewal, but reproduced female subordination and cloister. Again renew rejects in this case the model are convents in Toledo and the monastery of Saint Clemens. This study examines the importance of beaterios in the founding of convents in Toledo. And it analyses how pious women and nuns of the different monastic and mendicant orders opposed and rejected resist reforms of cloistered life, including the Council of Trent legislation. 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Introdução: Disfunção Temporomandibular (DTM) é o termo para designar um quadro de desorganização neuromuscular identificada pela presença de cefaleias crônicas, sons na articulação temporomandibular, restrições dos movimentos mandibulares, hiperestesia e dor nos músculos da mastigação, da cabeça e do pescoço. Objetivo: realizar uma revisão de literatura sobre a DTM. Material e Método: foi feita uma seleção de artigos científicos a partir das bases de dados LILACS e SCIELO utilizando os descritores “Articulação Temporomandibular”, “Transtornos da Articulação Temporomandibular” e “Dor Facial”, usando como critérios de inclusão trabalhos brasileiros e inglês publicados em português e inglês no período de 2000 a 2018. Dos 798 artigos encontrados e delimitados pelos critérios inclusivos, foram selecionados 56 artigos como amostra, que apresentaram a temática elencada para a pesquisa e que foram discutidos nas seguintes sessões: a) Conceitos e epidemiologia; b) Etiologia; c) Sintomatologia; d) Diagnóstico; e) Tratamento. Conclusão: as causas da DTM são multifatoriais e seu diagnóstico deve ser minucioso. Observa-se a importância da anamnese para coleta de dados sintomatológicos da doença e o estudo de cada caso para melhor adequar a técnica de tratamento a ser utilizada. Há a necessidade de avaliações clínicas multidisciplinares nos indivíduos identificados com DTM para que o tratamento seja otimizado, minimizando a morbidade e diminuindo os custos do tratamento. Descritores: Articulação Temporomandibular; Transtornos da Articulação Temporomandibular; Dor Facial. Referências Capellini VK, Souza GS, Faria CRS. Massage therapy in the management of myogenic TMD: a pilot study. 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Behavioural changes and occlusal splints are effective in the management of masticatory myofascial pain: a short-term evaluation. Journal of Oral Rehabilitation. 2012;39(10):754-60. John MT, Reissmann DR, Schierz O, Wassell RW. Oral health-related quality of life in patients with temporo­mandibular disorders. J Orofac Pain. 2007;21(1):46-54. Barros VMM, Seraidarian PI, Côrtes MI, Paula LV. The impact of orofacial pain on the quality of life of pa­tients with temporomandibular disorder. J Orofac Pain. 2009;23(1):28-37. Schierz O, John MT, Reissmann DR, Mehrstedt M, Sz­entpétery A. Comparison of perceived oral health in patients with temporomandibular disorders and dental anxiety using oral health-related quality of life profiles. Qual Life Res. 2008;17(6):857-66. Dahlström L, Carlsson GE. Temporomandibular disor­ders and oral health-related quality of life. A systematic review. Acta Odontol Scand. 2010;68(2):80-85. Lemos GA, Paulino MR, Forte FDS, Beltrão RTS, Ba­tista AUD. Influence of temporomandibular disorder presence and severity on oral health-related quality of life. Rev Dor. 2015;16(1):10-14. Ballegaard V, Thede-Schmidt-Hansen P, Svensson P, Jensen R. Are headache and temporomandibular disorders related? A blinded study. Cephalalgia. 2008;28(8):832-41. Plesh O, Noonan C, Buchwald DS, Goldberg J, Afari N. Temporomandibular disorder-type pain and migraine headache in women: A preliminary twin study. J Orofac Pain. 2012;26(2):91-8. Melo GM, Barbosa JFS. Parafunção x DTM: a influ­ência dos hábitos parafuncionais na etiologia das de­sordens temporomandibulares. POS. 2009; 1(1):43-8. Guhur MLP, Alberto RN, Carniatto N. Influências bio­lógicas, psicológicas e sociais do vestibular na adoles­cência. Roteiro. 2010;35(1):115-38. Cuccia AM, Caradonna C, Caradonna D. Manual Therapy of the mandibular accessory ligaments for the management of temporomandibular joint disorders. JAOA. 2011;111(2):102-12. Pasinato F, Souza JA, Corrêa ECR, Silva AMT. Temporomandibular disorder and generalized jointhypermobility: app lication of diagnostic criteria. Braz J Otorhinolaryngol. 2011;77(4):418-425. Sabatke S, Bonotto D, Cunali PA. Disfunção têm poro-mandibular (DTM) e cefaleia: associação frequente. Migrâneas cefaleias. 2006,9(3):78-9. Fikackova H, Dostalova L, Vosicka R, Peterova V, Navratil L, Lesak J. Arthralgia of the temporomandibular joint and low-lewel laser therapy. Photomed Laser Surg. 2006;21(1):522-7. Catão MHCV, Oliveira PS, Costa RO, Carneiro VSM. Avaliação da eficácia do laser de baixa intensidade no tratamento das disfunções temporomandibular: estudo clínico randomizado. Rev CEFAC. 2013;15(6):1601-8.

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Abstract Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 10 9 /L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group. Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). Study registration ISRCTN66726260.

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Abstract Background Ureteroarterial fistula (UAF) is a rare but potentially life threatening disease. The aim of this study was to evaluate the outcome of endovascular therapy for UAF treatment. Methods This retrospective case series evaluates a single center experience of percutaneous stent graft (SG) angioplasty and/or coil embolization for UAF. Patient follow-up included technical and early clinical success, complications and revisional procedures. We also conducted a systematic review of the literature reporting on endovascular UAF management. Results We identified 17 UAF in 16 patients (12 male, 4 female, mean age 69.8 ± 11.3 years) who underwent endovascular UAF therapy at our tertiary hospital. All patients presented with hematuria. 5/17 (29.4%) presented with flank pain, in 7 (41.2%) cases patients were in hypovolemic shock. Risk factors of UAF included chronic indwelling ureteral stents in all fistulas, major pelvic surgery in 13 cases (76.5%). In 6 cases (35.3%) SG were placed from the common iliac artery (CIA) to the external iliac artery (EIA) following coil embolization of the proximal internal iliac artery (IIA). SG placement without previous coil embolization was performed in 10 fistulas (58.8%). In one case only coil embolization of the IIA was performed. Mean follow-up was 654 (range: 1–3269) days. All procedures were technically successful and no procedure related deaths occurred during follow-up. During the initial hospital stay hematuria disappeared in 14/17 cases (82.4%). Overall, four patients suffered recurrent hematuria, which in three cases resolved after a secondary intervention. One recurrent UAF related death occurred during follow-up 229 days after initial treatment. A total of 152 UAF cases were additionally analyzed from our systematic literature review: SG placement with or without embolization was performed in 140 cases (92.1%) while embolization alone was done in 12 cases (7.9%). Complications included UAF recurrence (18/152, 11.8%), SG thrombosis (7/140, 5%), and SG infections (5/140, 3.6%) with an overall complications rate of 13.8%. Five patients died due to UAF (3.3%). Conclusion Endovascular therapy offers high technical success rates and rapid bleeding control of UAF. Severe complications like SG occlusions or SG infections are rare but significant. Antibiotic treatment and single anti-platelet therapy improve SG durability as well as close and long follow-up to timely perform repeated endovascular or surgical treatment if necessary. Evidence-based medicine Level 4, case series.

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Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty‐nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10‐year mean phenylalanine concentration, 924±330 µmol/L) and 39 age‐ and sex‐matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten‐year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end‐diastolic thickness, 7.0±17 versus 8.8±1.7 mm [ P <0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [ P =0.004]), more dilated left ventricular cavity (end‐diastolic volume, 87±14 versus 80±14 mL/m 2 [ P =0.0178]; end‐systolic volume, 36±9 versus 29±8 mL/m 2 [ P <0.001]), lower ejection fraction (59±6% versus 64±6% [ P <0.001]), reduced systolic deformation (global circumferential strain, −29.9±4.2 % versus −32.2±5.0 % [ P =0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m 2 [ P <0.001]). T1 native values were decreased (936±53 versus 996±26 ms [ P <0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine ( P =0.013) and tyrosine ( P =0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early‐stage cardiomyopathy. Regular cardiology follow‐up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

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Abstract Background Diet is an important risk factor for cancer that is amenable to intervention. Estimating the cancer burden associated with diet informs evidence-based priorities for nutrition policies to reduce cancer burden in the United States. Methods Using a comparative risk assessment model that incorporated nationally representative data on dietary intake, national cancer incidence, and estimated associations of diet with cancer risk from meta-analyses of prospective cohort studies, we estimated the annual number and proportion of new cancer cases attributable to suboptimal intakes of seven dietary factors among US adults ages 20 years or older, and by population subgroups. Results An estimated 80 110 (95% uncertainty interval [UI] = 76 316 to 83 657) new cancer cases were attributable to suboptimal diet, accounting for 5.2% (95% UI = 5.0% to 5.5%) of all new cancer cases in 2015. Of these, 67 488 (95% UI = 63 583 to 70 978) and 4.4% (95% UI = 4.2% to 4.6%) were attributable to direct associations and 12 589 (95% UI = 12 156 to 13 038) and 0.82% (95% UI = 0.79% to 0.85%) to obesity-mediated associations. By cancer type, colorectal cancer had the highest number and proportion of diet-related cases (n = 52 225, 38.3%). By diet, low consumption of whole grains (n = 27 763, 1.8%) and dairy products (n = 17 692, 1.2%) and high intake of processed meats (n = 14 524, 1.0%) contributed to the highest burden. Men, middle-aged (45–64 years) and racial/ethnic minorities (non-Hispanic blacks, Hispanics, and others) had the highest proportion of diet-associated cancer burden than other age, sex, and race/ethnicity groups. Conclusions More than 80 000 new cancer cases are estimated to be associated with suboptimal diet among US adults in 2015, with middle-aged men and racial/ethnic minorities experiencing the largest proportion of diet-associated cancer burden in the United States.

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This paper presents an analytical approach to postbuckling behaviors of functionally graded multilayer nanocomposite plates reinforced by a low content of graphene platelets (GPLs) using the first order shear deformation theory, stress function and von Karman-type nonlinear kinematics and include the effect of an initial geometric imperfection. The weight fraction of GPL nano fillers is assumed to be constant in each individual GPL-reinforced composite (GPLRC). The modified Halpin-Tsai micromechanics model that takes into account the GPL geometry effect is adopted to estimate the effective Young’s modulus of GPLRC layers. The plate is assumed to resting on Pasternak foundation model and subjected to mechanical and thermal loads. The results show the influences of the GPL distribution pattern, weight fraction, geometry, elastic foundations, mechanical and temperature loads on the postbuckling behaviors of FG multilayer GPLRC plates. Keywords: Postbuckling; Graphene nanocomposite plate; First order shear deformation plate theory. References [1] K.S. Novoselov, A.K. Geim, S.V. Morozov, D. Jiang, Y. Zhang, S.V. Dubonos, I.V. Grigorieva, A. Firsov, Electric filed effect in atomically thin carbon films, Science 306 (2004) 666–669. http://doi.org/ 10.1126/science.1102896.[2] K.S. Novoselov, D. Jiang, F. Schedin, T.J. Booth, V.V. Khotkevich, S.V. Morozov, A.K. Geim, Two-dimensional atomic crystals, Proceedings of the National Academy of Sciences of the United States of America 102 (2005) 10451–10453. https://doi.org/10.1073/pnas.0502848102.[3] C.D. Reddy, S. Rajendran, K.M. Liew, Equilibrium configuration and continuum elastic properties of finite sized graphene, Nanotechnology 17 (2006) 864-870. https://doi. org/10.1088/0957-4484/17/3/042.[4] C. Lee, X.D. Wei, J.W. Kysar, J. Hone, Measurement of the elastic properties and intrinsic strength of monolayer graphene, Science 321 (2008) 385–388. http://doi.org/10.1126/ science.1157996.[5] F. Scarpa, S. Adhikari, A.S. Phani, Effective elastic mechanical properties of single layer graphene sheets, Nanotechnology 20 (2009) 065709. https://doi.org/10.1088/0957-4484/20/6/ 065709.[6] Y.X. Xu, W.J. Hong, H. Bai, C. Li, G.Q. Shi, Strong and ductile poly(vinylalcohol)/graphene oxide composite films with a layered structure, Carbon 47 (2009) 3538–3543. https://doi.org/ 10.1016/j.carbon.2009.08.022.[7] J.R. Potts, D.R. Dreyer, C.W. Bielawski, R.S. Ruoff, Graphene-based polymer nanocomposites, Polymer 52 (2011) 5-25. https://doi.org/10.1016/j .polymer.2010.11.042.[8] T.K. Das, S. Prusty, Graphene-based polymer composites and their applications, Polymer-Plastics Technology and Engineering 52 (2013) 319-331. https://doi.org/10.1080/03602559.2012. 751410.[9] M. Song, J. Yang, S. Kitip*rnchai, W. Zhud, Buckling and postbuckling of biaxially compressed functionally graded multilayer graphene nanoplatelet-reinforced polymer composite plates, International Journal of Mechanical Sciences 131–132 (2017) 345–355. https://doi.org/10.1016/j.ijmecsci.2017.07.017.[10] H.S. Shen, Y. Xiang, F. Lin, D. Hui, Buckling and postbuckling of functionally graded graphene-reinforced composite laminated plates in thermal environments, Composites Part B 119 (2017) 67-78. https://doi.org/10.1016/j.compositesb.2017. 03.020.[11] H. Wu, S. Kitip*rnchai, J. Yang, Thermal buckling and postbuckling of functionally graded graphene nanocomposite plates, Materials and Design 132 (2017) 430–441. https://doi.org/10. 1016/j.matdes.2017.07.025.[12] J. Yang, H. Wu, S. Kitip*rnchai, Buckling and postbuckling of functionally graded multilayer graphene platelet-reinforced composite beams, Composite Structures 161 (2017) 111–118. https://doi.org/10.1016/j.compstruct.2016.11.048.[13] H.S. Shen, Y. Xiang, Y. Fan, Postbuckling of functionally graded graphene-reinforced composite laminated cylindrical panels under axial compression in thermal environments, International Journal of Mechanical Sciences 135 (2018) 398–409. https://doi.org/10.1016/j.ijme csci.2017.11.031.[14] M.D. Rasool, B. Kamran, Stability analysis of multifunctional smart sandwich plates with graphene nanocomposite and porous layers, International Journal of Mechanical Sciences 167 (2019) 105283. https://doi.org/10.1016/j.ijmecs ci.2019.105283.[15] J.J. Mao, W. Zhang, Buckling and post-buckling analyses of functionally graded graphene reinforced piezoelectric plate subjected to electric potential and axial forces, Composite Structures 216 (2019) 392–405. https://doi.org/10.1016/j. compstruct.2019.02.095.[16] P.H. Cong, N.D. Duc, New approach to investigate nonlinear dynamic response and vibration of functionally graded multilayer graphene nanocomposite plate on viscoelastic Pasternak medium in thermal environment, Acta Mechanica 229 (2018) 651-3670. https://doi.org/ 10.1007/s00707-018-2178-3.[17] N.D. Duc, N.D. Lam, T.Q. Quan, P.M. Quang, N.V. Quyen, Nonlinear post-buckling and vibration of 2D penta-graphene composite plates, Acta Mechanica (2019), https://doi.org/10. 1007/s00707-019-02546-0.[18] N.D. Duc, P.T. Lam, N.V. Quyen, V.D. Quang, Nonlinear Dynamic Response and Vibration of 2D Penta-graphene Composite Plates Resting on Elastic Foundation in Thermal Environments, VNU Journal of Science: Mathematics-Physics 35(3) (2019) 13-29. https:// doi.org/10.25073/2588-1124/vnumap. 4371.[19] J.N. Reddy, Mechanics of laminated composite plates and shells; theory and analysis, Boca Raton: CRC Press, 2004.[20] H.S. Shen, A two-step perturbation method in nonlinear analysis of beams, plates and shells, John Wiley & Sons Inc., 2013.

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Abstract: In this study, the effect of tides and storm surges on storm waves at the Northern coastal area of Vietnam is investigated by a coupled model of surge wave and tide (called: SuWAT). In particular, tide and storm surge are simulated by two-dimensional long wave equations taking into account the wave radiation stress, obtained from the SWAN model. The numerical was then applied to simulate storm waves and surges for typhoon Frankie (7/1996), Washi (7/2005) and Doksuri (9/2017). In the case of the super typhoon, the intensity of typhoon Washi is increased to level 16 (super typhoon level) but remains the same trajectory and operating time. The numerical results showed relatively well with observation data on storm surge and wave height. In general, the wave height is higher in the region near the coast and lower at offshore when considering the effect of tide and storm surge on storm wave. It also indicated that the effect of storm surge on storm wave is more significant than the tide. The results of the study are the basis for proposing to improve the wave forecasting technology in the study area. Keywords: Storm wave, tides, storm surge, super typhoon. References: [1] Đ. Đ. Chiến, N. B. Thủy, N.T. Sáo, T.H. Thái, S. Kim. Nghiên cứu tương tác sóng và nước dâng do bão bằng mô hình số trị, Tạp chí Khí tượng Thủy văn, 647 (2014) 19-24.[2] T.Q. Tiến, P.K. Ngọc. Kết nối mô hình SWAN với mô hình WAM thành hệ thống dự báo sóng biển cho vùng Vịnh Bắc Bộ, Tạp chí Khí tượng Thủy văn, 651 (2014) 21-26.[3] Y.Funakoshi, S.C.Hagen, P.Bacopoulos. Coupling of hydrodynamic and wave models: case study for Hurricane Floyd (1999) Hindcast, Journal of Waterway, Port, Coastal and Ocean Engineering, 134 (2008) 321 – 335.[4] S.Y. Kim, T. Yasuda, H. Mase. Wave set-up in the storm surge along open coasts during Typhoon Anita, Coastal Engineering, 57 (2010) 631-642.[5] X. Bertin, K. Li, A. Roland, and J.R. Bidlot. The contribution of short waves in storm surges: two recent examples in the central part of the bay of Biscay, Continental Shelf Research 96 (2015) 1-15.[6] H.Đ. Cường, N.B. Thủy, N.V. Hưởng, D.Đ. Tiến. Đánh giá nguy cơ bão và nước dâng do bão tại ven biển Việt Nam, Tạp chí khí tượng thủy văn, 684 (2018) 29-36.[7] Delf University of Technology. SWAN Cycle III Verion 40.31, User Guide. Delf, 2004.[8] N.B. Thủy, H.Đ. Cường, D.Đ. Tiến, Đ.Đ. Chiến, S.Kim. Đánh giá diễn biến nước biển dâng do bão số 3 năm 2014 và vấn đề dự báo, Tạp chí Khí tượng Thủy văn, 647 (2014).14-18.[9] N.B. Thuy, S. Kim, D.D. Chien, V.H. Dang, H.D. Cuong, C. Wettre and L. R. Hole. Assessment of Storm Surge along the Coast of Central Vietnam, Coastal researcher Journal, 33 (2017) 518-530.[10] V.H. Đăng, N.B. Thủy, Đ.Đ. Chiến, S. Kim. Nghiên cứu đánh giá định lượng các thành phần nước dâng trong bão bằng mô hình số trị, Tạp chí khoa học công nghệ biển. 17 (2017) 132-138.[11] T. Fujita. Pressure distribution within typhoon, Geophysical Magazine, 23 (1952). 437-451.

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Mesona chiensis Benth. is a natural and safe pharmaceutical ingredient with many nutrients and special medical functions. The aim of this study was to investigate the prevention and treatment effect of ethanol extract from Mesona chiensis Benth. on the plasma lipid concentration of high fat diet-induced obesity mice. Male white mice (Mus musculus) 5 - 6 weeks of age were fed a high-fat diet including standard pellets (65% in weight) and boiled lard (35% in weight) for 6 weeks model obese mice. The study was divided into 2 periods: the prevention period for 4 weeks and the treatment period for 15 days. Prevention group (normal-weight mice) received ethanol extract of Mesona chinensis Benth. (400 mg/kg bw) and be fed a high-fat diet for 4 weeks. Treatment group (obese mice) received ethanol extract of Mesona chinensis Benth. (400 mg/kg bw) and be fed a high-fat diet for 15 days. The finding of the present investigation showed that mice fed a high-fat diet had significantly higher levels of TC, TG and TC/HDL-C compared to those in mice fed a normal diet. Body weight (bw) was significantly and positively correlated to TG (r = 0.53, P < 0.05) and TC (r = 0.33, P < 0.05) levels. After 4 weeks of receiving ethanol extract of Mesona chinensis Benth., the TG concentration and TC/HDL-C of the prevention group were significantly lower than those of the control group. After 15 days of treatment with obese mice, no statistically significant differences in blood lipid concentrations were observed compared with mice receiving fenofibrat and NaCl. In conclusion, ethanol extract of Mesona chinensis Benth. has the effect of preventing hyperlipidemia in mice fed a high-fat diet. Keywords Mesona chiensis Benth., hypolipidemic, high fat diet, obesity mice. References [1] A.D. Smith, S.P. Datta, G.H. Smith, Oxford dictionary of biochemistry and molecular biology, Oxford University Press, UK, 1997.[2] T. Akiyama, I. Tachibana, H. Shirohara, N. Watanabe and M. Otsuki, High-fat hypercaloric diet induces obesity, glucose intolerance and hyperlipidemia in normal adult male Wistar rat, Diabetes research and clinical practice. 31 (1996) 27-35. [3] T. Kelly, W. Yang, C.S. Chen, K. Reynolds, J. He, Global burden of obesity in 2005 and projections to 2030, International journal of obesity. 32 (2008) 1431-1437.[4] E. Bonora, S. Kiechl, J. Willeit, F. Oberhollenzer, G. Egger, R. Bonadonna and M. Muggeo, Carotid atherosclerosis and coronary heart disease in the metabolic syndrome, Diabetes Care. 26 (2003) 1251-1257.[5] P. Paramsothy, R. Knopp, Management of dyslipidaemias, Heart 92 (2006) 1529-1534. [6] M.F. Asaolu, S.S. Asaolu, A.O. Oyeyemi and B.T. Aluko, Hypolipemic effects of methanolic extract of Persea americana seeds in hypercholesterolemic rats, J Med Medical Sci 1 (2010) 126-128.[7] T. Zhou, D. Luo, X. Li and Y. Luo, Hypoglycemic and hypolipidemic effects of flavonoids from lotus (Nelumbo nuficera Gaertn) leaf in diabetic mice, Journal of Medicinal Plants Research 3 (2009) 290-293.[8] R. Subramanian, M.Z. Asmawi and A. Sadikun, Effect of ethanolic extract of Andrographis paniculata (Burm. F.) nees on a combination of fat-fed diet and low dose streptozotocin induced chronic insulin resistance in rats, Diabetologia Croatica 37 (2008) 13-22.[9] R. Gupta, R.S. Gupta, Effect of Pterocarpus marsupium in streptozotocin-induced hyperglycemic state in rats: comparison with glibenclamide, Diabetologia Croatica. 38 (2009) 39-45.[10] N.S. El-Shenawy, I.M. Abdel-Nabi, Hypoglycemic effect of Cleome droserifolia ethanolic leaf extract in experimental diabetes, and on non-enzymatic antioxidant, glycogen, thyroid hormone and insulin levels, Diabetologia Croatica. 35 (2006) 15-22.[11] J.C. Russell, S.D. Proctor, Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis, Cardiovasc. Pathol. 15 (2006) 318-330.[12] W. Yin, E. Carballo-Jane, D.G. McLaren, V.H. Mendoza, K. Gagen, N.S. Geoghagen and M. Wolff, Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia, Journal of lipid research. 53 (2012) 51-65.[13] Z. Zhao, Y. Shi, N. Huang, C. Fu, F. Tang, Q. Jiang, The research advances on Mesona chinensis Benth in China, Journal of Southern Agriculture. 42 (2011) 657-660.[14] S. Hailan, H. Yingzhen, C. Jingying, Comparative analysis of amino acids content in Mesona chinensis from different producing areas, Chinese Wild Plant Resour 5 (2011) 19-23.[15] Y.F. Liu, H.T. Xia, S.P. Yang, Quantitative Determination of Total Flavonoids in Sisal Flower by UV Spectrophotometry, Food Science. 9 (2005) 107-112.[16] C. Chusak, T. Thilavech, S. Adisakwattana, Consumption of Mesona chinensis attenuates postprandial glucose and improves antioxidant status induced by a high carbohydrate meal in overweight subjects, The American journal of Chinese medicine. 42 (2014) 315-336.[17] N.H. Linh, M.D. Quynh, M.T.T. Le, B.T.T. Thuy, V.T.M. Hong, N.T.H. Hanh, Effects of Mesona chinensis Benth. extract on obesity treatment in mice, Journal of Science and Technology of Thai Nguyen University. 164 (2017), 195-199 [Article in Vietnamese].[18] T.T.C. Mai, N.T. Ha, P.T. Ngoc, Effect of green tea (Camellia sinensis) polyphenol on blood antioxydant status in streptozocin induced diabetic rats, Journal of Medical Research. 5 (2005) 27-33 [Article in Vietnamese].[19] N.Q. Trung, P.T. Ngoc, Study on the effect of reducing dyslipidemia of mulberry leaf extract powder in dyslipidemia and diabetes white rats, Journal of Medical Research. 4 (2007) 107-115 [Article in Vietnamese]. [20] B. Enkhmaa, K. Shiwaku, T. Katsube, Mulberry (Murus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atheroscletotic lesion development in LDL recepror-deficient mice, The Journal of Nutrition. 135 (2005) 729-734. [21] E.C. Aguilar, M.D.G.M.N. Queiroz, D.A.D. Oliveira and N.J.F.D. Oliveira, Serum lipid profile and hepatic evaluation in mice fed diet containing pequi nut or pulp (Caryocar brasiliense Camb.), Food Science and Technology. 31 (2011) 879-883.[22] T.T.M. Loan, T.Q. 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Objetivo: verificar a distribuição espacial e o perfil epidemiológico dos casos notificados da violência contra a mulher em um município do nordeste brasileiro, no biênio 2012-2013. Metodologia: foi realizado um estudo transversal, de base populacional, quantitativo, descritivo, no município de Campina Grande – PB, com base nas notificações da violência junto ao SINAN. O instrumento para a coleta dos dados foi construído com base nos campos disponíveis para as respostas da ficha de notificação, dividido em sete blocos. A análise estatística dos dados foi desenvolvida baseando-se em frequências absolutas e relativas, sendo construído um gráfico de espalhamento de Moran a fim de verificar a distribuição espacial da violência nos bairros de Campina Grande. As análises foram realizadas com auxílio do software estatístico R (RStudio) Resultados: Foram analisadas 109 notificações de violência contra a mulher. Prevaleceram mulheres adultas, não gestantes, pardas, com baixa escolaridade. Houve predominância da violência psicológica e física. Os bairros mais afetados pela violência foram Velame, Malvinas, Bodocongó, Dinamérica, Santa Rosa, Centenário, Catolé e José Pinheiro. Conclusão: foi possível traçar o perfil mais envolvido com a violência contra a mulher na cidade de Campina Grande, devendo ser voltado um olhar mais atencioso à violência doméstica, sobretudo entre pares, com o objetivo de encorajar essas mulheres a denunciarem violências vivenciadas.Descritores: Violência; Notificação de Abuso; Prevalência.ReferênciasMalta DC, Minayo MCS, Soares Filho AM, Silva MMA, Montenegro MMS, Ladeira RM et al. Mortalidade e anos de vida perdidos por violências interpessoais e autoprovocadas no Brasil e Estados: análise das estimativas do Estudo Carga Global de Doença, de 1990 e 2015. Rev bras epidemiol.2017;20(suppl 1):142-56,Haagsma JA, Graetz N, Bolliger I, Naghavi M, Higashi H, Mullany EC et al. The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of disease study 2013. Inj Prev. 2016;22(1):3-18.Silva LEL, Oliveira MLC. Características epidemiológicas da violência contra a mulher no Distrito Federal, 2009 a 2012. Epidemiol Serv Saúde. 2016; 25(2):331-42.Santos TMB, Cardoso MD, Pitangui ACR, Santos YGC, Paiva SM, Melo JPR et al. Completitude das notificações de violência perpetrada contra adolescentes em Pernambuco, Brasil. Ciênc saúde coletiva. 2016;21(12):3907-16.Rates SMM, Melo EM, Mascarenhas MDM, Malta DC, et al. Violence against children: an analysis of mandatory reporting of violence, Brazil 2011. Ciênc saúde coletiva. 2015; 20(3):655-65.Assunção RM. Statistical assessment of câncer cluster evidence – in search of a middle ground. International. J Epidemiol. 2013;42(2):453-55.Mendonça MFS, Silva APSC, Castro CCL. A spatial analysis of urban transit accidents assited by Emergency Mobile Care Service: an analysis of space and time. Rev Bras Epidemiol. 2017;20(4):727-41.Bivand R, Piras G. Comparing implementations of estimation methods for spatial econometrics. J Stat Softw. 2015;63(18):1-36.Marconi MA, Lakatos EM. Fundamentos da Metodologia Científica. 5. ed. São Paulo: Atlas; 2003.Brasil. Instituto Brasileiro de Geografia e Estatística. 2017 Disponível em: http://cidades. ibge.gov.br/xtras/perfil.php?codmun=250400 Acesso em: 10/09/2018Romero DE, Cunha AB. Avaliação da qualidade das variáveis epidemiológicas e demográficas do Sistema de Informações sobre Nascidos Vivos, 2002. Cad Saúde Pública. 2007;23(3):701-14.R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org/. 2014.Carter PM, Walton MA, Goldstick J, Epstein-Ngo QM, Zimmerman MA, Mercado MC et al. Violent firearm-related conflicts among high-risk youth: An event-leveland daily calendar analysis. Prev Med. 2017;102:112-19.Deslandes SF, Assis SG, Santos NC. Violência envolvendo crianças no Brasil: um plural estruturado e estruturante. In: Brasil. Ministério da Saúde (MS), organizador. Impacto da violência na saúdedos brasileiros. Brasília: MS; 2005. p. 43-78.Assis SG, Avanci JQ, Pesce RP, Pires TO, Gomes DL. Notificações de violência doméstica, sexual e outras violências contra crianças no Brasil. Ciênc saúde colet. 2012;17(9):2305-17. Bozzo ACB, Matos GC, Beraldi LP, Souza MD. Violência doméstica contra a mulher: caracterização dos casos notificados em um município do interior paulista. Rev enferm UERJ. 2017; 25:e11173.Almeida FSJ, Coutinho EC, Duarte JC, Chaves CMB, Nelas PAB, Amaral OP et al. Domestic violence in pregnancy: prevalence and characteristics of the pregnant woman. J Clin Nurs. 2017;26(15-16):2417-25.Koenig LJ, Whitaker DJ, Royce RA, Wilson TE, Ethier K, Fernandez I. Physical and sexual violence during pregnancy and after delivery: a prospective multistate study of women with or at risk for HIV infection. Am J Public Health. 2006;96(6):1052-59.de Macedo Bernardino I, Santos LM, Ferreira AVP, de Almeida Lima TLM, da Nóbrega LM, d’Avila S. Intimate partner violence against women, circ*mstances of aggressions and oral-maxillofacial traumas: A medical-legal and forensic approach. Leg Med (Tokyo). 2018;31:1-6.Minayo MCS. Conceitos, teorias e tipologias de violência: a violência faz mal à saúde individual e coletiva. In: Sousa ER, organizadores. Curso impactos da violência na saúde. Rio de Janeiro: EAD/ENSP; 2007. p. 24-35.Veloso MMX, Magalhães CMC, Dell’Aglio DD, Cabral IR, Gomes MM. Notificação da violência como estratégia de vigilância em saúde: perfil de uma metrópole do Brasil. Ciênc saúde colet. 2013;18(5):1263-72.Cezar PK, Arpini DM. Registros de notificação compulsória de violência envolvendo crianças e adolescentes. Psicol ciênc prof. 2017;37(2):432-45.Sena CA, Silva MA, Falbo Neto, GH. Incidência da violência sexual em crianças e adolescentes em Recife/Pernambuco no biênio 2012-2013. Ciênc saúde colet. 2018;23(5):1122-24.Oliveira JR, Costa COM, Amaral MTR, Santos CA, Assis SG, Nascimento OC. Violência sexual e coocorrências em crianças e adolescentes: estudo das incidências ao longo de uma década. Cien saude colet. 2014;19(3):759-71.Bezerra KS, Araújo Neto F. A violência doméstica contra a mulher no município de Campina Grande – PB. Rev Dat@venia. 2014;6(1):10-15.

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Red bayberry (Myrica rubra (Lour.) Siebold & Zucc.), small trees, evergreen, dioecious, natively grows in evergreen broad-leaved forests at elevation of 1580-1875 m a.s.l., and can survive in low nutrient soil at Cao Ma Po commune, Quan Ba district, Ha Giang province. Some data on morphology, phenology, population structure, natural regeneration and distribution of Red baybery, climatic characteristics, physical and chemical properties of soil, and vegetation structure of forests having Myrica rubra occurrence are presented in this paper. Keywords Red bayberry, Myrica rubra, biology, ecology, conservation, Ha Giang, Vietnam References [1] Lu A. & Bornstein A. J., Myricaceae in Wu Z. Y. & Raven P. H. (eds.). Flora of China Vol. 4, Science Press & Missouri Botanical Garden Press, Beijing & St. Louis, 1999, pp. 275-276.[2] He X. H., Chen L. G., Asghar S. & Chen Y., Red Bayberry (Myrica rubra), a Promising Fruit and Forest Tree in China, Journal of the American Pomological Society, 58(3), 2004, pp. 163- 168.[3] Joyce D., Khurshid T., Liu S., McGregor G., Li J. & Jiang Y., Red Bayberry-A New and Exciting Crop for Australia? An investigation of the potential for commercialisation of Myrica rubra Sieb. and Zucc. (Yang mei) in Australia, RIRDC Publication No. 05/081, 2005, 26 pp. [4] Sharpe R. H. & Knapp F. W., The Straberry tree, Myrica rubra Sieb. and Zucc., Florida State Horticultural Society, 1972, pp. 326-328. [5] Chai C. Y. & Chen Y. F., Introduction of Yangmei Elite Varieties in California, World Journal of Forestry, 5(1), 2016, pp. 1-6.[6] Fang Z. X., Zhang M., Tao G. J., Sun Y. F. & Sun J. C., Chemical composition of clarified bayberry (Myrica rubra Sieb et Zucc.) juice sediment, Journal of Agriculture and Food Chemistry, 54(20), 2006, pp. 7710-7716.[7] Cheng J. Y., Ye X. Q., Chen J. C., Liu D. H. & Zhou S. H., Nutritional composition of underutilized bayberry (Myrica rubra Sieb. et Zucc.) kernels, Food Chemistry, 107(4), 2008, pp. 1674-1680.[8] Joyce D. & Sanewski G., The Commercial Potential of Red Bayberry in Australia, RIRDC Publication No. 10/200, 2010, 36 pp.[9] Zhang X. N., Huang H. Z., Zhao X. Y., Lu Q., Sun C. D., Li X., Chen K. S., Effects of flavonoids-rich Chinese bayberry (Myrica rubra Sieb. et Zucc.) pulp extracts on glucose consumption in human HepG2 cells, Journal of Functional Foods, 14, 2015, pp. 144-153.[10] Tong Y., Zhou X. M., Wang S. J., Yang Y. & Cao Y. L., Analgesic activity of myricetin isolated from Myrica rubra Sieb. et Zucc. leaves, Archives of Pharmacal Research, 2(4), 2009, pp. 527-533. [11] Zhang Y., Zhou X. Z., Tao W. Y., Li L. Q., Wei C. Y., Duan J., Chen S. G. & Ye X. Q., Antioxidant and antiproliferative activities of proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves, Journal of Functional Foods, 27, 2016, pp. 645-654.[12] Kim H. H., Kim D. H., Kim M. H., Oh M. H., Kim S. R., et al., Flavonoid constituents in the leaves of Myrica rubra Sieb. et Zucc. with anti-inflammatory activity, Archives of Pharmacal Research, 36(12), 2013, pp. 1533-1540.[13] Kuo P. L., Hsu Y. L., Lin T. C., Lin L. T. & Lin C. C., Induction of apoptosis in human breast adenocarcinoma MCF-7 cells by prodelphinidin B-2 3,3'-di-O-gallate from Myrica rubra via Fas-mediated pathway, Journal of Pharmacy and Pharmacology 56(11), 2004, pp. 1399-1406.[14] Sun C. D., Zheng Y. X., Chen Q. J., Tang X. L., Jiang M., Zhang J. K., Li X. & Chen K. S., Purification and anti-tumour activity of cyanidin-3-O-glucoside from Chinese bayberry fruit, Food Chemistry, 131(4), 2012, pp. 1287-1294.[15] Sun C. D., Huang H. Z., Xu C. J., Li X. & Chen K. S., Biological activities of extracts from Chinese bayberry (Myrica rubra Sieb. et Zucc.): A review, Plant Foods for Human Nutrition, 68(2), 2013, pp. 97-106.[16] Langhansova L., Hanusova V., Rezek J., Stohanslova B., Ambroz M., et al., Essential oil from Myrica rubra leaves inhibits cancer cell proliferation and induces apoptosis in several human intestinal lines, Industrial Crops Products ,59, 2014, pp. 20-26.[17] Ambrǒz M., Bousǒvá I., Skarka A., Hanusǒvá V., Králová V., et al., The Influence of Sesquiterpenes from Myrica rubra on the Antiproliferative and Pro-Oxidative Effects of Doxorubicin and Its Accumulation in Cancer Cells, Molecules, 20(8), 2015, pp. 15343-15358.[18] Lê Mộng Chân và Lê Thị Huyền, Thực Vật Rừng, Nxb Nông nghiệp, Hà Nội, 2000, tr. 149-150.[19] Xia N. H., Myricaceae in Hu Q. M. & Wu D. L. (eds.), Flora of Hong Kong Vol. 1, Agriculture, Fisheries and Conservation Department, Hong Kong, 2007, pp. 125-126.[20] Nguyễn Sinh Khang, Bùi Hồng Quang, Vũ Tiến Chính, Nguyễn Tiến Hiệp, Nguyễn Quang Hiếu, Nguyễn Thành Sơn, Xia Nian He & Davidson Christopher, Myrica rubra (Lour.) Siebold & Zucc. (Myricaceae): A useful plant resource in Vietnam, Hội nghị Khoa học toàn quốc lần thứ 7 về Sinh thái và Tài nguyên sinh vật, Viện Sinh thái và Tài nguyên sinh vật, Nxb Nông nghiệp, Hà Nội, 2017, pp. 226-232. [21] Nguyễn Nghĩa Thìn, Các phương pháp nghiên cứu thực vật, Nxb. Đại học Quốc gia Hà Nội, Hà Nội, 2007.[22] Liesner R., Field Techniques Used by Missouri Botanical Garden, 2018, http://www.mobot.org/MOBOT/molib/fieldtechbook/welcome.shtml [23] Bộ Khoa học và Công nghệ, Tiêu chuẩn Việt Nam TCVN 7538-2:2005 (ISO 10381 - 2 : 2002) về Chất lượng đất - Lấy mẫu - Phần 2: Hướng dẫn kỹ thuật lấy mẫu.[24] Phạm Hoàng Hộ, Cây cỏ Việt Nam, tập 1, Nxb Trẻ, TP. Hồ Chí Minh, 1999.[25] Phạm Hoàng Hộ, Cây cỏ Việt Nam, tập 2, Nxb Trẻ, TP. Hồ Chí Minh, 2003.[26] Phạm Hoàng Hộ, Cây cỏ Việt Nam, tập 3, Nxb Trẻ, TP. Hồ Chí Minh, 2000.[27] http://www.efloras.org/flora_page.aspx?flora_id=2 [28] http://www.theplantlist.org/[29] http://www.iucnredlist.org/ [30] Bộ Khoa học và Công nghệ, Viện Khoa học và Công nghệ Việt Nam, Sách Đỏ Việt Nam. Phần II: Thực vật, Nxb. Khoa học Tự nhiên và Công nghệ, Hà Nội, 2007, 612 tr.[31] Nguyễn Khánh Vân, Nguyễn Thị Hiền, Phan Kế Lộc và Nguyễn Tiến Hiệp, Các biểu đồ sinh khí hậu Việt Nam, Nxb. Đại học Quốc gia Hà Nội, 2000, tr. 45, 48, 120, 121.[32] Averyanov L. V., Lộc P. K., Hiệp N. T. & Harder D. K., Phytogeographic Review of Vietnam and Adjacent Areas of Eastern Indochina, Komarovia, 3, 2003, pp. 1-83.[33] Tsujino R. & Yumoto T., Topography-specific seed dispersal by Japanese macaques in a lowland forest on Yakushima Island, Japan, Journal of Animal Ecology, 78, 2009, pp. 119-125.[34] Đỗ Đình Sâm, Ngô Đình Quế, Nguyễn Tử Siêm và Nguyễn Ngọc Bình, Cẩm nang ngành Lâm nghiệp, Chương Đất và Dinh dưỡng đất, Bộ NN&PTNT, Chương trình hỗ trợ ngành Lâm nghiệp và đối tác, 2006, 143 tr.[35] Li Z. L., Zhang S. L. & Chen D. M., Red bayberry (Myrica rubra Sieb. & Zucc.): A valuable evergreen tree fruit for tropical and subtropical areas, Acta Horticulture 321, 1992, pp.112-121.[36] Sasakawa H., 1995: Effect of Frankia Inoculation on Growth and Nitrogen-Fixing Activity of Myrica rubra Seedlings Prepared Aseptically, Soil Science and Plant Nutrition 41(4): 691-698.[37] Tian X. R., Shu L. F. & He Q. T., Selection of fire-resistant Tree Species for Southwestern China, Forestry Studies in China, 3(2), 2001, pp. 32-38.[38] Deng C. N., Pan X. M., Zhang H. Y. & Pan X. L., Fire-resistance of six tree species to fire probed by chlorophyll fluorescence, Journal of Food, Agriculture & Environment, 10(2), 2012, pp. 1329-1333.[39] Nguyễn Tiến Bân (Chủ biên), Danh lục các loài Thực vật Việt Nam, tập 2, Nxb. Nông nghiệp, 2003, 1203 tr.[40] Nguyễn Tiến Bân (Chủ biên), Danh lục các loài Thực vật Việt Nam, tập 3, Nxb. Nông nghiệp, 2005, 1248 tr.

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Rice bran is an important source of nutrients that have many good bioactive compounds. This study examined the extraction of bran rice oil using supercritical carbon dioxide. Free fatty acids contained in bran rice were stabilized at 5.25% for 8 months by fluid bed dryer equipment. Supercritical carbon dioxide extraction of rice bran oil at pressure of 400 bar, temperature of 60 oC, CO2 flow rate of 20 g/min for 120 minutes yielded 14.84% oil. The concentration of γ-oryzanol in rice bran oil extracted by supercritical carbon dioxide (0.50%) was higher than in rice bran oil derived from hexane Soxhlet extraction (0.42%). The effect of pressure and temperature on extraction yield and the concentration of γ-oryzanol contained in rice bran oil was observed. Keywords Rice bran, rice bran oil, γ-oryzanol, free fatty acid, supercritical carbon dioxide. References [1] A. A. Wani, P. Singh, M. A. Shah, U. S. Weisz, K. Gul, I. A. Wani, Rice Starch Diversity: Effects on Structural, Morphological, Thermal, and Physicochemical Properties -A Review, Comprehensive Reviews in Food Science and Food Safety, Vol. 11, No. 5, 2012, pp. 417-436, https://doi.org/10.1111/j.1541-4337.2012.00193.x.[2] K. Gul, B. Yousuf, A. K. Singh, P. Singh, A. A. Wani, Rice Bran: Nutritional Values and Its Emerging Potential for Development of Functional Food - A Review, Bioactive Carbohydrates and Dietary Fibre, Vol. 6, No. 1, 2015, pp. 24-30, https://doi.org/10.1016/j.bcdf.2015.06.002.[3] G. Hua, S. Huang, S. Cao, Z. Ma, Effect of Enrichment with Hemicellulose from Rice Bran on Chemical and Functional Properties of Bread, Food Chemistry, Vol. 115, No. 3, 2009, pp. 839-842, https://doi.org/10.1016/j.foodchem.2008.12.092.[4] T. S. Shin, J. S. Godber, Changes of Endogenous Antioxidants and Fatty Acid Composition in Irradiated Rice Bran during Storage, Journal of Agricultural Food Chemistry, Vol. 44, 1996, pp. 567-573, https://doi.org/10.1021/jf950386a.[5] B. O. Juliano, P. A. Hicks, Rice Functional Properties and Rice Food Products, Food Reviews International, Vol. 12, No. 1, 1996, pp. 71-103, https://doi.org/10.1080/87559129609541068.[6] M. Ghosh, Review on Recent Trends in Rice Bran Oil Processing, J Amer Oil Chem Soc,Vol. 84, 2007, pp. 315-324, https://doi.org/10.1007/s11746-007-1047-3.[7] M. Sugano, E. Tsuji, Rice Bran Oil and Cholesterol Metabolism, Journal of Nutrition, Vol. 127, No. 3, 1997, pp. 521-524, https://doi.org/10.1093/jn/127.3.521S.[8] G. S. Seetharamaiah, N. Chandrasekhara, Studies on Hypocholesterolemic Activity of Rice Bran Oil, Atherosclerosis, Vol. 78, No. 2-3, 1989, pp. 219-223, https://doi.org/10.1016/0021-9150(89)90226-8.[9] J. K. Duve, P. J. White, Extraction and Identification of Antioxidants in Oats, Journal of American Oil Chemists Society, Vol. 68, No. 6, 1991, pp. 365-37, https://doi.org/10.1007/BF02663751.[10] L. Xu, X. Zhan, Z. Zeng, R. Chen, H. Li, T. Xie, S. Wang, Recent Advances on Supercritical Fluid Extraction of Essential Oils, African Journal of Pharmacy and Pharmacology, Vol. 5, No. 9, 2011, pp. 1196-1211, https://doi.org/10.5897/AJPP11.228.[11] C. R. Chen, C. H. Wang, L. Y. Wang, Z. H. Hong, S. H. Chen, W. J. Ho, C. M. J. Chang, Supercritical Carbon Dioxide Extraction and Deacidification of Rice Bran Oil, J. of Supercritical Fluids, Vol. 45, No. 3, 2008, pp. 322-331, https://doi.org/10.1016/j.supflu.2008.01.006.[12] K. Tomita, S. Machmudah, Wahyudiono, R. f*ckuzato, H. Kanda, A. T. Quitain, M. Sasaki, M. Goto, Extraction of Rice Bran Oil by Supercritical Carbon Dioxide and Solubility Consideration, Separation and Purification Technology, Vol. 125, No. 7, 2014, pp. 319-325, http://dx.doi.org/10.1016/j.seppur.2014.02.008.[13] F. Malekian, R. M. Rao, W. Prinyawiwatkul, W. E. Marshall, M. Windhauser, M. Ahmedna, Lipase and Lipoxygenase Activity, Functionality, and Nutrient Losses in Rice Bran During Storage, Bull. La. Agric. Exp. Stn. LSU Agric. Cent., Vol. 870, 2000, pp. 1-68.[14] S. Akter, M. Ahiduzzaman, Effect of Storage Life of Rice Bran on the Quality of Oil, Journal of Food and Nutrition Sciences, Vol. 5, No. 1, 2017, pp. 11-15, https://doi.org/10.11648/j.jfns.20170501.12.[15] H. R. Sharma, G. S. Chauhan, K. Agrawal, Physico-Chemical Characteristics of Rice Bran Processed by Dry Heating and Extrusion Cooking, International Journal of Food Properties, Vol. 7, No. 3, 2004, pp. 603-614, https://doi.org/10.1081/JFP-200033047.[16] N. R. Lakkakula, M. Lima, T. Walker, Rice Bran Stabilization and Rice Bran Oil Extraction using Ohmic Heating, Bioresource Technology, Vol. 92, No. 2, 2004, pp. 157-161, https://doi.org/10.1016/j.biortech.2003.08.010.[17] D. Martin, J. S. Gober, G. Selhako, L. Verma, J. H. Wells, Optimizing Rice Bran Stabilization by Extrusion Cooking, Lousiana Agraculture, Vol. 30, 1993, pp. 13.[18] R. N. Sayre, R. M. Saunders, R. V. Enochian, W. G. Shultz, E. C. Beagle, Review of Rice Bran Stabilization Systems with Emphasis on Extrusion Cooking, Cereal Food World, Vol. 7, 1982, pp. 317.[19] M. S. Kuk, M. K. Dowd, Supercritical CO2 Extraction of Rice Bran, J. Am. Oil Chem. Soc, Vol. 75, 1998, pp. 623-628.[20] Y. T. Chen, Y. H. Ling, An Overview of Supercritical Fluid Extraction in Chinese Herbal Medicine: from Preparation to Analysis, J. Food Drug Anal, Vol. 8, No. 4, 2000, pp. 235-247, https://doi.org/10.38212/2224-6614.2815.[21] S. R. S. Ferreira, Z. L. Nikolov, L. K. Doraiswamy, M. A. A. Meireles, A. J. 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Lepsius, Susanne / Friedrich Vollhardt / Oliver Bach (Hrsg.), Von der Allegorie zur Empirie. Natur im Rechtsdenken des Spätmittelalters und der Frühen Neuzeit (Abhandlungen zur rechtswissenschaftlichen Grundlagenforschung. Münchener Universitätsschriften. Juristische Fakultät, 100), Berlin 2018, Schmidt, VI u. 328 S., € 79,95. (Peter Oestmann, Münster) Baumgärtner, Ingrid / Nirit Ben-Aryeh Debby / Katrin Kogman-Appel (Hrsg.), Maps and Travel in the Middle Ages and the Early Modern Period. Knowledge, Imagination, and Visual Culture (Das Mittelalter. Beihefte, 9), Berlin / Boston 2019, de Gruyter, IX u. 412 S. / Abb., € 119, 95. (Gerda Brunnlechner, Hagen) Damen, Mario / Jelle Hamers / Alastair J. Mann (Hrsg.), Political Representation. Communities, Ideas and Institutions in Europe (c. 1200 – c. 1690) (Later Medieval Europe, 15), Leiden / Boston 2018, Brill, XIV, 332 S. / Abb., € 143,00. (Olaf Mörke, Kiel) Erkens, Franz-Reiner, Sachwalter Gottes. Der Herrscher als „christus domini“, „vicarius Christi“ und „sacra majestas“. Gesammelte Aufsätze. Zum 65. Geburtstag hrsg. v. Martin Hille / Marc von Knorring / Hans-Cristof Kraus (Historische Forschungen, 116), Berlin 2017, Duncker &amp; Humblot, 564 S., € 119,90. (Ludger Körntgen, Mainz) Scheller, Benjamin / Christian Hoffarth (Hrsg.), Ambiguität und die Ordnung des Sozialen im Mittelalter (Das Mittelalter. Beihefte, 10), Berlin / Boston 2018, de Gruyter, 236 S. / Abb., € 99,95. (Frank Rexroth, Göttingen) Jaspert, Nikolas / Imke Just (Hrsg.), Queens, Princesses and Mendicants. Close Relations in European Perspective (Vita regularis, 75), Wien / Zürich 2019, Lit, VI u. 301 S. / graph. Darst., € 44,90. (Christina Lutter, Wien) Schlotheuber, Eva, „Gelehrte Bräute Christi“. Religiöse Frauen in der mittelalterlichen Gesellschaft (Spätmittelalter, Humanismus, Reformation, 104), Tübingen 2018, Mohr Siebeck, IX u. 340 S., € 99,00. (Christine Kleinjung, Potsdam) Caflisch, Sophie, Spielend lernen. Spiel und Spielen in der mittelalterlichen Bildung (Vorträge und Forschungen, Sonderband 58), Ostfildern 2018, Thorbecke, 468 S., € 46,00. (Benjamin Müsegades, Heidelberg) Bolle, Katharina / Marc von der Höh / Nikolas Jaspert (Hrsg.), Inschriftenkulturen im kommunalen Italien. Traditionen, Brüche, Neuanfänge (Materiale Textkulturen, 21), Berlin / Boston 2019, de Gruyter, VIII u. 334 S. / Abb., € 79,95. (Eberhard J. Nikitsch, Mainz) Gamberini, Andrea, The Clash of Legitimacies. The State-Building Process in Late Medieval Lombardy (Oxford Studies in Medieval European History), Oxford / New York 2018, Oxford University Press, VIII u. 239 S. / Abb., £ 65,00. (Tom Scott, St Andrews) Roth, Prisca, Korporativ denken, genossenschaftlich organisieren, feudal handeln. Die Gemeinden und ihre Praktiken im Bergell des 14.–16. Jahrhunderts, Zürich 2018, Chronos, 427 S. / Abb., € 58,00. (Beat Kümin, Warwick) Hardy, Duncan, Associative Political Culture in the Holy Roman Empire. Upper Germany, 1346 – 1521, Oxford 2018, Oxford University Press, XIII u. 320 S. / Abb., £ 75,00. (Christian Hesse, Bern) Pelc, Ortwin (Hrsg.), Hansestädte im Konflikt. Krisenmanagement und bewaffnete Auseinandersetzung vom 13. bis zum 17. Jahrhundert (Hansische Studien, 23), Wismar 2019, callidus, XIII u. 301 S., € 38,00. (Ulla Kypta, Hamburg) Bähr, Matthias / Florian Kühnel (Hrsg.), Verschränkte Ungleichheit. Praktiken der Intersektionalität in der Frühen Neuzeit (Zeitschrift für Historische Forschung, Beiheft 56), Berlin 2018, Duncker &amp; Humblot, 372 S., € 79,90. (Andrea Griesebner, Wien) Miller, Peter N., History and Its Objects. Antiquarianism and Material Culture since 1500, Ithaca / London 2017, Cornell University Press, VIII u. 300 S. / Abb., $ 39,95. (Sundar Henny, Bern) Behringer, Wolfgang / Eric-Oliver Mader / Justus Nipperdey (Hrsg.), Konversionen zum Katholizismus in der Frühen Neuzeit. Europäische und globale Perspektiven (Kulturelle Grundlagen Europas, 5), Berlin 2019, Lit, 333 S. / Abb., € 39,90. (Christian Mühling, Würzburg) Cañizares-Esguerra, Jorge / Robert A. Maryks / Ronnie Po-chia Hsia (Hrsg.), Encounters between Jesuits and Protestants in Asia and the Americas (Jesuit Studies, 14; The Boston College International Symposia on Jesuit Studies, 3), Leiden / Boston 2018, Brill, IX u. 365 S. / Abb., € 135,00. (Fabian Fechner, Hagen) Flüchter, Antje / Rouven Wirbser (Hrsg.), Translating Catechisms, Translating Cultures. The Expansion of Catholicism in the Early Modern World (Studies in Christian Mission, 52), Leiden / Boston 2017, Brill, VI u. 372 S., € 132,00. (Markus Friedrich, Hamburg) Županov, Ines G. / Pierre A. 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(Michael Ströhmer, Paderborn) Harst, Joachim / Christian Meierhofer (Hrsg.), Ehestand und Ehesachen. Literarische Aneignungen einer frühneuzeitlichen Institution (Zeitsprünge, 22, H. 1/2), Frankfurt a. M. 2018, Klostermann, 211 S., € 54,00. (Pia Claudia Doering, Münster) Peck, Linda L., Women of Fortune. Money, Marriage, and Murder in Early Modern England, Cambridge [u. a.] 2018, Cambridge University Press, XIV u. 335 S. / Abb., £ 26,99. (Katrin Keller, Wien) Amussen, Susan D. / David E. Underdown, Gender, Culture and Politics in England, 1560 – 1640. Turning the World Upside Down (Cultures of Early Modern Europe), London [u. a.] 2017, Bloomsbury Academic, XV u. 226 S., £ 95,00. (Daniela Hacke, Berlin) Raux, Sophie, Lotteries, Art Markets and Visual Culture in the Low Countries, 15th – 17th Centuries (Studies in the History of Collecting and Art Markets, 4), Leiden / Boston 2018, Brill, XVII u. 369 S. / Abb., € 125,00. (Tilman Haug, Essen) Kullick, Christian, „Der herrschende Geist der Thorheit“. Die Frankfurter Lotterienormen des 18. Jahrhunderts und ihre Durchsetzung (Studien zu Policey, Kriminalitätsgeschichte und Konfliktregulierung), Frankfurt a. M. 2018, Klostermann, VII u. 433 S. / Abb., € 69,00. (Tilman Haug, Essen) Barzman, Karen-edis, The Limits of Identity. Early Modern Venice, Dalmatia, and the Representation of Difference (Art and Material Culture in Medieval and Renaissance Europe, 7), Leiden / Boston 2017, Brill, XVII u. 315 S. / Abb., € 139,00. (Stefan Hanß, Manchester) Deutsche Reichstagsakten unter Maximilian I., Bd. 10: Der Reichstag zu Worms 1509, bearb. v. Dietmar Heil (Deutsche Reichstagsakten. Mittlere Reihe, 10), Berlin / Boston 2017, de Gruyter Oldenbourg, 874 S., € 169,95. (Thomas Kirchner, Aachen) Deutsche Reichstagsakten unter Maximilian I., Bd. 11: Die Reichstage zu Augsburg 1510 und Trier/Köln 1512, 3 Bde., bearb. v. Reinhard Seyboth (Deutsche Reichstagsakten. Mittlere Reihe, 11), Berlin / Boston 2017, de Gruyter Oldenbourg, 2822 S., € 349,00. (Thomas Kirchner, Aachen) Fitschen, Klaus / Marianne Schröter / Christopher Spehr / Ernst-Joachim Waschke (Hrsg.), Kulturelle Wirkungen der Reformation / Cultural Impact of the Reformation. Kongressdokumentation Lutherstadt Wittenberg August 2017, 2 Bde. (Leucorea-Studien zur Geschichte der Reformation und der Lutherischen Orthodoxie, 36 u. 37), Leipzig 2018, Evangelische Verlagsanstalt, 639 S. / Abb.; 565 S. / Abb., je € 60,00. (Ingo Leinert, Quedlinburg) Johnson, Carina L. / David M. Luebke / Marjorie E. Plummer / Jesse Spohnholz (Hrsg.), Archeologies of Confession. Writing the German Reformation 1517 – 2017 (Spektrum, 16), New York / Oxford 2017, Berghahn, 345 S., £ 92,00. (Markus Wriedt, Frankfurt a. M.) Lukšaitė, Ingė, Die Reformation im Großfürstentum Litauen und in Preußisch-Litauen (1520er Jahre bis zum Beginn des 17. Jahrhunderts), übers. v. Lilija Künstling / Gottfried Schneider, Leipzig 2017, Leipziger Universitätsverlag, 662 S. / Abb., € 49,00. (Alfons Brüning, Nijmegen) Beutel, Albrecht (Hrsg.), Luther Handbuch, 3., neu bearb. u. erw. Aufl., Tübingen 2017, Mohr Siebeck, XVI u. 611 S., € 49,00. (Olaf Mörke, Kiel) Frank, Günter (Hrsg.), Philipp Melanchthon. Der Reformator zwischen Glauben und Wissen. Ein Handbuch, Berlin / Boston 2017, de Gruyter, XI u. 843 S. / Abb., € 149,95. (Olaf Mörke, Kiel) Tuininga, Matthew J., Calvin’s Political Theology and the Public Engagement of the Church. Christ’s Two Kingdoms (Law and Christianity), Cambridge [u. a.] 2017, Cambridge University Press, XIV u. 386 S., £ 27,99. (Volker Reinhardt, Fribourg) Becker, Michael, Kriegsrecht im frühneuzeitlichen Protestantismus. Eine Untersuchung zum Beitrag lutherischer und reformierter Theologen, Juristen und anderer Gelehrter zur Kriegsrechtsliteratur im 16. und 17. 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(Hans Medick, Göttingen) Zurbuchen, Simone (Hrsg.), The Law of Nations and Natural Law 1625 – 1800 (Early Modern Natural Law, 1), Leiden / Boston 2019, Brill, X u. 337 S., € 131,00. (Miloš Vec, Wien) Mishra, Rupali, A Business of State. Commerce, Politics, and the Birth of the East India Company (Harvard Historical Studies, 188), Cambridge / London 2018, Harvard University Press, VII u. 412 S., $ 35,00. (Christina Brauner, Tübingen) Towsey, Mark / Kyle B. Roberts (Hrsg.), Before the Public Library. Reading, Community, and Identity in the Atlantic World, 1650 – 1850 (Library of the Written Word, 61; The Handpress World, 46), Leiden / Boston 2018, Brill, XVII u. 415 S., € 145,00. (Stefan Hanß, Manchester) Rosenmüller, Christoph, Corruption and Justice in Colonial Mexico, 1650 – 1755 (Cambridge Latin America Studies, 113), Cambridge / New York 2019, Cambridge University Press, XV u. 341 S. / Abb., £ 75,00. (Tobias Schenk, Wien) Tricoire, Damien, Der koloniale Traum. 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(Ulrich Niggemann, Augsburg) Boswell, Caroline, Disaffection and Everyday Life in Interregnum England (Studies in Early Modern Cultural, Political and Social History, 29), Woodbridge 2017, The Boydell Press, XII u. 285 S., £ 65,00. (Philip Hahn, Tübingen) Kinsella, Eoin, Catholic Survival in Protestant Ireland, 1660 – 1711. Colonel John Browne, Landownership and the Articles of Limerick (Irish Historical Monographs), Woodbridge 2018, The Boydell Press, XVI u. 324 S. / Abb., £ 75,00. (Matthias Bähr, Dresden) Mansel, Philip, King of the World. The Life of Louis XIV, [London] 2019, Allen Lane, XIII u. 604 S. / Abb., £ 30,00. (William D. Godsey, Wien) Gräf, Holger Th. / Christoph Kampmann / Bernd Küster (Hrsg.), Landgraf Carl (1654 – 1730). Fürstliches Planen und Handeln zwischen Innovation und Tradition (Veröffentlichungen der Historischen Kommission für Hessen, 87), Marburg 2017, Historische Kommission für Hessen, XIII u. 415 S. / Abb., € 29,00. (Alexander Schunka, Berlin) Schriften zur Reise Herzog Friedrichs von Sachsen-Gotha nach Frankreich und Italien 1667 und 1668. Eine Edition, 3 Bde., Bd. 1: Reiseberichte; Bd. 2: Planung, Landeskunde, Rechnungen; Bd. 3: Briefe, hrsg. v. Peter-Michael Hahn / Holger Kürbis (Schriften des Staatsarchivs Gotha, 14.1 – 3), Wien / Köln / Weimar 2019, Böhlau, XLVI u. 546 S. / Abb.; 660 S.; 374 S., € 200,00. (Michael Kaiser, Köln) Mulsow, Martin, Radikale Frühaufklärung in Deutschland 1680 – 1720, Bd. 1: Moderne aus dem Untergrund; Bd. 2: Clandestine Vernunft, Göttingen 2018, Wallstein, 502 bzw. 624 S. / Abb., € 59,90. (Helmut Zedelmaier, München) Göse, Frank / Jürgen Kloosterhuis (Hrsg.), Mehr als nur Soldatenkönig. Neue Schlaglichter auf Lebenswelt und Regierungswerk Friedrich Wilhelms I. (Veröffentlichungen aus den Archiven Preußischer Kulturbesitz. Forschungen, 18), Berlin 2020, Duncker &amp; Humblot, 398 S. / Abb., € 89,90. 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Edelmayer, Friedrich / Gerhard Pfeisinger (Hrsg.), Ozeane. Mythen, Interaktionen und Konflikte (Studien zur Geschichte und Kuktur der iberischen und iberoamerikanischen Länder, 16), Münster 2017, Aschendorff, 336 S. / Abb., € 49,00. (Ruth Schilling, Bremen / Bremerhaven) Jaynes, Jeffrey, Christianity beyond Christendom. The Global Christian Experience on Medieval Mappaemundi and Early Modern World Maps (Wolfenbütteler Forschungen, 149), Wiesbaden 2018, Harrassowitz in Kommission, 483 S. / Abb., € 128,00. (Gerda Brunnlechner, Hagen) Weltecke, Dorothea (Hrsg.), Essen und Fasten. Interreligiöse Abgrenzung, Konkurrenz und Austauschprozesse / Food and Fasting. Interreligious Differentiations, Competition and Exchange (Beihefte zum Archiv für Kulturgeschichte, 81), Köln / Weimar / Wien 2017, Böhlau, 130 S., € 30,00. (Helmut W. Klug, Graz) Dirmeier, Artur (Hrsg.), Essen und Trinken im Spital. Ernährungskultur zwischen Festtag und Fasttag (Studien zur Geschichte des Spital-‍, Wohlfahrts- und Gesundheitswesens, 13), Regensburg 2018, Pustet, 287 S. / Abb., € 34,95. (Josef Matzerath, Dresden) Widder, Ellen / Iris Holzwart-Schäfer / Christian Heinemeyer (Hrsg.), Geboren, um zu herrschen? Gefährdete Dynastien in historisch-interdisziplinärer Perspektive (Bedrohte Ordnungen, 10), Tübingen 2018, Mohr Siebeck, VIII u. 307 S. / Abb., € 59,00. (Lennart Pieper, Münster) Füssel, Marian / Philip Knäble / Nina Elsemann (Hrsg.), Wissen und Wirtschaft. Expertenkulturen und Märkte vom 13. bis 18. Jahrhundert, Göttingen / Bristol 2017, Vandenhoeck &amp; Ruprecht, 418 S. / Abb., € 70,00. (Justus Nipperdey, Saarbrücken) Whittle, Jane (Hrsg.), Servants in Rural Europe. 1400 – 1900, Woodbridge 2017, Boydell &amp; Brewer, XIII u. 271 S., £ 19,99. (Werner Troßbach, Witzenhausen) Rutz, Andreas, Die Beschreibung des Raums. 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В соединениях, кристаллизующихся в структурном типе пирохлора (пр. гр. симм. Fd3m) общей формулы А2В2X6X’, на месте катионов A могут находиться двух- или трёхзарядные ионы, на месте B – четырёх- или пятизарядные ионы. В большом количестве работ рассматриваются вопросы формирования таких структур в зависимости от природы и размеров катионов A и B, мало внимания уделяется определению температурных интервалов их устойчивости. Поэтому целью данной работы являлось исследование термолиза твердых растворов замещения H2Sb2–xVxO6·nH2Oв интервале температур 25–700 °С, определение влияния природы катиона B (Sb, V) на устойчивость структуры типа пирохлора при нагревании.Твердые растворы замещения были получены методом соосаждения. В качестве объектов исследования выбраны образцы H2Sb2–xVxO6·nH2O, содержащие по данным элементного анализа 0; 5 (x = 0.10); 15 (x = 0.30); 20 (x = 0.40); 24 (x = 0.48) ат.% ванадия. С помощью метода ИК-спектроскопии анализировали изменение протонгидратной подрешетки в образцах, содержащих различное количество V+5. Рентгенофазовый и термогравиметрический анализ образцов позволил смоделировать процесс термолиза и определить состав фаз на каждой стадии.Показано, что при температурах 25–400 °С происходит удаление протонсодержащих группировок из гексагональных каналов структуры типа пирохлора. Увеличение количества ионов V+5 в твердых растворах изменяет энергию связи протонов с ионами кислорода [BO3]–-октаэдра, что приводит к смещению границ стадий: ионы оксония и молекулы воды удаляются при более высоких температурах, а гидроксид-ионы при более низких температурах. Повышениетемпературы выше 500 °С приводит к разрушению структуры по причине удаления кислорода из [BO3]–-октаэдров.Предложена модель заполнения атомами кристаллографических позиций структуры типа пирохлора для фаз, которые образуются при термолизе H2Sb2–xVxO6·nH2O при температурах 25–400 °С.Установлены структурные формулы твердых растворов - (H3O)Sb2-xVxO5(OH)·nH2O, где 0 < x≤ 0.48, 0 <n≤ 1.1. Показано, что на температурные интервалы стадий термолиза влияет энергия связи протонов с ионами кислорода [BO3]–-октаэдров, где B = V, Sb, формирующих каркас структуры. При этом в рамках структуры типа пирохлора исследуемые твердые растворы устойчивы до 400 °С. ЛИТЕРАТУРА Subramanian M. A., Aravamudan G., Rao G. V. S. Oxide pyrochlores — A review. Progress in Solid State Chemistry. 1983;15(2): 55–143. DOI: https://doi.org/10.1016/0079-6786(83)90001-8 Krasnov A. G., Piir I. V., Koroleva M. S., Sekushin N. A., Ryabkov Y. I., Piskaykina M. M., Sadykov V. A., Sadovskaya E. M., Pelipenko V. V., Eremeev N. F. The conductivity and ionic transport of doped bismuth titanate pyrochlore Bi1.6МxTi2O7–d (М– Mg, Sc, Cu). Solid State Ionics. 2017;302: 118–125. DOI: https://doi.org/10.1016/j.ssi.2016.12.019 Cherednichenko L. A., Moroz Ya. A. Catalytic properties of heteropolytungstates with 3d elementsand their thermolysis products. Kinetics and Catalysis. 2018;59(5): 572–577. DOI: https://doi.org/10.1134/S0023158418050038 Krasnov A. G., Kabanov A. A., Kabanova N. A., Piir I. V., Shein I. R. Ab initio modeling of oxygen ionmigration in non-stoichiometric bismuth titanate pyrochlore Bi1.5Ti2O6.25. Solid State Ionics. 2019;335: 135–141. DOI: https://doi.org/10.1016/j.ssi.2019.02.023 Farlenkov A. S., Khodimchuk A. V., Eremin V. A., Tropin E. S., Fetisov A. V., Shevyrev N. A., Leonidov I. I., Ananyev M. V. Oxygen isotope exchange in doped lanthanum zirconates. Journal of Solid State Chemistry. 2018;268: 45–54. DOI: https://doi.org/10.1016/j.jssc.2018.08.022 Rejith R. S., Thomas J. 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Eine Biographie, Beck 2017, München, 253 S. / Abb., € 24,95. (Georg Eckert, Wuppertal) Home, Roderick W. / Isabel M. Malaquias / Manuel F. Thomaz (Hrsg.), For the Love of Science. The Correspondence of J. H. de Magellan (1722 – 1790), 2 Bde., Bern [u. a.] 2017, Lang, 2002 S. / Abb., € 228,95. (Lisa Dannenberg-Markel, Aachen) Wendt-Sellin, Ulrike, Herzogin Luise Friederike von Mecklenburg-Schwerin (1722 – 1791). Ein Leben zwischen Pflicht, Pläsir und Pragmatismus (Quellen und Studien aus den Landesarchiven Mecklenburg-Vorpommerns, 19), Köln / Weimar / Wien 2017, Böhlau, 468 S. / Abb., € 60,00. (Britta Kägler, Trondheim) Oehler, Johanna, „Abroad at Göttingen“. Britische Studenten als Akteure des Kultur- und Wissenstransfers 1735 bis 1806 (Veröffentlichungen der Historischen Kommission für Niedersachsen und Bremen, 289), Göttingen 2016, Wallstein, 478 S. / graph. Darst., € 39,90. (Michael Schaich, London) Düwel, Sven, Ad bellum Sacri Romano-Germanici Imperii solenne decernendum: Die Reichskriegserklärung gegen Brandenburg-Preußen im Jahr 1757. Das Verfahren der „preußischen Befehdungssache“ 1756/57 zwischen Immerwährendem Reichstag und Wiener Reichsbehörden, 2 Teilbde., Münster 2016, Lit, 985 S. / Abb., € 79,90 (Bd. 3 als Download beim Verlag erhältlich). (Martin Fimpel, Wolfenbüttel) Pufelska, Agnieszka, Der bessere Nachbar? Das polnische Preußenbild zwischen Politik und Kulturtransfer (1765 – 1795), Berlin / Boston 2017, de Gruyter Oldenbourg, VIII u. 439 S., € 74,95. (Maciej Ptaszyński, Warschau) Herfurth, Stefan, Freiheit in Schwedisch-Pommern. Entwicklung, Verbreitung und Rezeption des Freiheitsbegriffs im südlichen Ostseeraum zum Ende des 18. Jahrhunderts (Moderne europäische Geschichte, 14), Göttingen 2017, Wallstein, 262 S. / Abb., € 29,90. (Axel Flügel, Bielefeld) Boie, Heinrich Christian / Luise Justine Mejer, Briefwechsel 1776 – 1786, hrsg. v. 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Bihrer, Andreas / Miriam Czock / Uta Kleine (Hrsg.), Der Wert des Heiligen. Spirituelle, materielle und ökonomische Verflechtungen (Beiträge zur Hagiographie, 23), Stuttgart 2020, Steiner, 234 S. / Abb., € 46,00. (Carola Jäggi, Zürich) Leinsle, Ulrich G., Die Prämonstratenser (Urban Taschenbücher; Geschichte der christlichen Orden), Stuttgart 2020, Kohlhammer, 250 S. / Abb., € 29,00. (Joachim Werz, Frankfurt a. M.) Gadebusch Bondio, Mariacarla / Beate Kellner / Ulrich Pfisterer (Hrsg.), Macht der Natur – gemachte Natur. Realitäten und Fiktionen des Herrscherkörpers zwischen Mittelalter und Früher Neuzeit (Micrologus Library, 92), Florenz 2019, Sismel, VI u. 345 S. / Abb., € 82,00. (Nadine Amsler, Berlin) Classen, Albrecht (Hrsg.), Pleasure and Leisure in the Middle Ages and Early Modern Age. Cultural-Historical Perspectives on Toys, Games, and Entertainment (Fundamentals of Medieval and Early Modern Culture, 23), Berlin / Boston 2019, de Gruyter, XIII u. 751 S. / Abb., € 147,95. (Adrina Schulz, Zürich) Potter, Harry, Shades of the Prison House. A History of Incarceration in the British Isles, Woodbridge 2019, The Boydell Press, XIII u. 558 S. / Abb., £ 25,00. (Gerd Schwerhoff, Dresden) Müller, Matthias / Sascha Winter (Hrsg.), Die Stadt im Schatten des Hofes? Bürgerlich-kommunale Repräsentation in Residenzstädten des Spätmittelalters und der Frühen Neuzeit (Residenzenforschung. Neue Folge: Stadt und Hof, 6), Ostfildern 2020, Thorbecke, 335 S. / Abb., € 64,00. (Malte de Vries, Göttingen) De Munck, Bert, Guilds, Labour and the Urban Body Politic. Fabricating Community in the Southern Netherlands, 1300 – 1800 (Routledge Research in Early Modern History), New York / London 2018, Routledge, XIV u. 312 S. / Abb., £ 115,00. (Philip Hoffmann-Rehnitz, Münster) Sonderegger, Stefan / Helge Wittmann (Hrsg.), Reichsstadt und Landwirtschaft. 7. Tagung des Mühlhäuser Arbeitskreises für Reichsstadtgeschichte, Mühlhausen 4. bis 6. März 2019 (Studien zur Reichsstadtgeschichte, 7), Petersberg 2020, Imhof, 366 S. / Abb., € 29,95. (Malte de Vries, Göttingen) Israel, Uwe / Josef Matzerath, Geschichte der sächsischen Landtage (Studien und Schriften zur Geschichte der sächsischen Landtage, 5), Ostfildern 2019, Thorbecke, 346 S. / Abb., € 26,00. (Thomas Fuchs, Leipzig) Unverfehrt, Volker, Die sächsische Läuterung. Entstehung, Wandel und Werdegang bis ins 17. Jahrhundert (Studien zur europäischen Rechtsgeschichte, 317; Rechtsräume, 3), Frankfurt a. M. 2020, Klostermann, X u. 321 S., € 79,00. (Heiner Lück, Halle) Jones, Chris / Conor Kostick / Klaus Oschema (Hrsg.), Making the Medieval Relevant. How Medieval Studies Contribute to Improving Our Understanding of the Present (Das Mittelalter. Beihefte, 6), Berlin / Boston 2020, VI u. 297 S. / graph. Darst., € 89,95. (Gabriela Signori, Konstanz) Lackner, Christina / Daniel Luger (Hrsg.), Modus supplicandi. Zwischen herrschaftlicher Gnade und importunitas petentium (Veröffentlichungen des Instituts für Österreichische Geschichtsforschung, 72), Wien / Köln / Weimar 2019, Böhlau, 224 S. / Abb., € 40,00. (Jörg Voigt, Rom) Andermann, Kurt / Enno Bünz (Hrsg.), Kirchenvogtei und adlige Herrschaftsbildung im europäischen Mittelalter (Vorträge und Forschungen, 86), Ostfildern 2019, Thorbecke, 469 S., € 55,00. (Markus Müller, München) Deigendesch, Roland / Christian Jörg (Hrsg.), Städtebünde und städtische Außenpolitik. Träger, Instrumentarien und Konflikte während des hohen und späten Mittelalters. 55. Arbeitstagung in Reutlingen, 18.–20. November 2016 (Stadt in der Geschichte, 44), Ostfildern 2019, Thorbecke, 322 S. / Abb., € 34,00. (Evelien Timpener, Gießen) Müller, Monika E. / Jens Reiche, Zentrum oder Peripherie? Kulturtransfer in Hildesheim und im Raum Niedersachsen (12.–15. Jahrhundert) (Wolfenbütteler Mittelalter-Studien, 32), Wiesbaden 2017, Harrassowitz in Kommission, 544 S. / Abb., € 88,00. (Harald Wolter-von dem Knesebeck, Bonn) Hill, Derek, Inquisition in the Fourteenth Century. The Manuals of Bernard Gui and Nicholas Eymerich (Heresy and Inquisition in the Middle Ages, 7), Woodbridge 2019, York Medieval Press, X u. 251 S., £ 60,00. (Thomas Scharff, Braunschweig) Peltzer, Jörg, Fürst werden. Rangerhöhungen im 14. Jahrhundert – Das römisch-deutsche Reich und England im Vergleich (Historische Zeitschrift. Beihefte (Neue Folge), 75), Berlin / Boston 2019, de Gruyter Oldenbourg, 150 S. / Abb., € 64,95. (Kurt Andermann, Karlsruhe / Freiburg i. Br.) Wilhelm von Ockham, De iuribus Romani imperii / Das Recht von Kaiser und Reich. III.2 Dialogus. Lateinisch – Deutsch, 2 Bde., übers. und eingel. v. Jürgen Miethke (Herders Bibliothek der Philosophie des Mittelalters, 49), Freiburg i. Br. / Basel / Wien 2020, Herder, 829 S., € 54,00 bzw. € 58,00. (Christoph Mauntel, Tübingen) Dokumente zur Geschichte des Deutschen Reiches und seiner Verfassung 1360, bearb. v. Ulrike Hohensee / Mathias Lawo / Michael Lindner / Olaf B. Rader (Monumenta Germaniae Historica. Constitutiones et acta publica imperatorum et regum, 13.1), Wiesbaden 2016, Harrassowitz, L u. 414 S., € 120,00. (Martin Bauch, Leipzig) Dokumente zur Geschichte des Deutschen Reiches und seiner Verfassung 1361, bearb. v. Ulrike Hohensee / Mathias Lawo / Michael Lindner / Olaf B. Rader (Monumenta Germaniae Historica. Constitutiones et acta publica imperatorum et regum, 13.2), Wiesbaden 2017, Harrassowitz, VI u. 538 S. (S. 415 – 952), € 140,00. (Martin Bauch, Leipzig) Forcher, Michael / Christoph Haidacher (Hrsg.), Kaiser Maximilian I. Tirol. Österreich. Europa. 1459 – 1519, Innsbruck / Wien 2018, Haymon Verlag, 215 S. / Abb., € 34,90. (Jörg Schwarz, Innsbruck) Weiss, Sabine, Maximilian I. Habsburgs faszinierender Kaiser, Innsbruck / Wien 2018, Tyrolia-Verlag, 400 S. / Abb., € 39,95. (Jörg Schwarz, Innsbruck) Christ-von Wedel, Christine, Erasmus of Rotterdam. A Portrait, Basel 2020, Schwabe, 175 S. / Abb., € 36,00. (Jan-Hendryk de Boer, Essen) Schmidt, Bernward / Simon Falch (Hrsg.), Kilian Leib (1471 – 1553). Prediger – Humanist – Kontroverstheologe (Katholisches Leben und Kirchenreform im Zeitalter der Glaubensspaltung, 80), Münster 2020, Aschendorff, 187 S. / Abb., € 24,90. (Jan-Hendryk de Boer, Essen) Gehrt, Daniel / Kathrin Paasch (Hrsg.), Friedrich Myconius (1490 – 1546). Vom Franziskaner zum Reformator (Gothaer Forschungen zur Frühen Neuzeit, 15), Stuttgart 2020, Steiner, 392 S. / Abb., € 66,00. (Eike Wolgast, Heidelberg) Klarer, Mario (Hrsg.), Piracy and Captivity in the Mediterranean. 1550 – 1810 (Routledge Research in Early Modern History), London / New York 2019, Routledge, XIII u. 281 S. / Abb., £ 120,00. (Josef J. Schmid, Mainz / Manubach) Fischer-Kattner, Anke / Jamel Ostwald (Hrsg.), The World of the Siege. Representations of Early Modern Positional Warfare (History of Warfare, 126), Leiden / Boston 2019, Brill, IX u. 316 S. / Abb., € 105,00. (Marian Füssel, Göttingen) Dörfler-Dierken, Angelika (Hrsg.), Reformation und Militär. Wege und Irrwege in fünf Jahrhunderten, Göttingen 2019, Vandenhoeck &amp; Ruprecht, 320 S. / Abb., € 35,00. (Marianne Taatz-Jacobi, Halle) Schönauer, Tobias / Daniel Hohrath (Hrsg.), Formen des Krieges. 1600 – 1815 (Kataloge des Bayerischen Armeemuseums, 19), Ingolstadt 2019, Bayerisches Armeemuseum, 248 S. / Abb., € 15,00. (Thomas Weißbrich, Berlin) Goetze, Dorothée / Lena Oetzel (Hrsg.), Warum Friedenschließen so schwer ist. Frühneuzeitliche Friedensfindung am Beispiel des Westfälischen Friedenskongresses (Schriftenreihe zur Neueren Geschichte, 39; Schriftenreihe zur Neueren Geschichte. Neue Folge, 2), Münster 2019, Aschendorff, IX u. 457 S. / Abb., € 62,00. (Benjamin Durst, Augsburg) Rohrschneider, Michael (Hrsg.), Frühneuzeitliche Friedensstiftung in landesgeschichtlicher Perspektive. Unter redaktioneller Mitarbeit v. Leonard Dorn (Rheinisches Archiv, 160), Wien / Köln / Weimar 2020, Böhlau, 327 S. / Abb., € 45,00. (Benjamin Durst, Augsburg) Richter, Susan (Hrsg.), Entsagte Herrschaft. Mediale Inszenierungen fürstlicher Abdankungen im Europa der Frühneuzeit, Wien / Köln / Weimar 2019, Böhlau, 223 S. / Abb., € 45,00. (Andreas Pečar, Halle) Astorri, Paolo, Lutheran Theology and Contract Law in Early Modern Germany (ca. 1520 – 1720) (Law and Religion in the Early Modern Period / Recht und Religion in der Frühen Neuzeit, 1), Paderborn 2019, Schöningh, XX u. 657 S., € 128,00. (Cornel Zwierlein, Berlin) Prosperi, Adriano, Justice Blindfolded. The Historical Course of an Image (Catholic Christendom, 1300 – 1700), übers. v. John Tedeschi / Anne C. Tedeschi, Leiden / Boston 2018, Brill, XXIV u. 260 S., € 105,00. (Mathias Schmoeckel, Bonn) Ceglia, Francesco Paolo de (Hrsg.), The Body of Evidence. Corpses and Proofs in Early Modern European Medicine (Medieval and Early Modern Philosophy and Science, 30), Leiden / Boston 2020, Brill, X u. 355 S., € 154,00. (Robert Jütte, Stuttgart) Río Parra, Elena del, Exceptional Crime in Early Modern Spain. Taxonomic and Intellectual Perspectives (The Medieval and Early Modern Iberian World, 68), Leiden / Boston 2019, Brill, XI u. 218 S. / Abb., € 95,00. (Ralf-Peter Fuchs, Essen) Moreno, Doris (Hrsg.), The Complexity of Hispanic Religious Life in the 16th–18th Centuries (The Iberian Religious World, 6), Leiden / Boston 2020, Brill, 225 S. / Abb., € 165,00. (Joël Graf, Bern) Kaplan, Benjamin J., Reformation and the Practice of Toleration. Dutch Religious History in the Early Modern Era (St Andrews Studies in Reformation History), Leiden / Boston 2019, Brill, IX u. 371 S. / Abb., € 128,00. (Olaf Mörke, Kiel) Cecere, Domenico / Chiara De Caprio / Lorenza Gianfrancesco / Pasquale Palmieri (Hrsg.), Disaster Narratives in Early Modern Naples. Politics, Communication and Culture, Rom 2018, Viella, 257 S. / Abb., € 45,00. (Cornel Zwierlein, Berlin) Prak, Maarten / Patrick Wallis (Hrsg.), Apprenticeship in Early Modern Europe, Cambridge [u. a.] 2020, Cambridge University Press, XII u. 322 S. / Abb., £ 75,00. (Patrick Schmidt, Rostock) Bracht, Johannes / Ulrich Pfister, Landpacht, Marktgesellschaft und agrarische Entwicklung. Fünf Adelsgüter zwischen Rhein und Weser, 16. bis 19. Jahrhundert (Vierteljahrschrift für Sozial- und Wirtschaftsgeschichte. Beihefte, 247), Stuttgart 2020, Steiner, 364 S. / Abb., € 59,00. (Nicolas Rügge, Hannover) Kenny, Neil, Born to Write. Literary Families and Social History in Early Modern France, Oxford / New York 2020, Oxford University Press, XII u. 407 S. / Abb., £ 65,00. (Markus Friedrich, Hamburg) Capp, Bernard, The Ties That Bind. Siblings, Family, and Society in Early Modern England, Oxford / New York 2018, Oxford University Press, 222 S., £ 60,00. (Margareth Lanzinger, Wien) Huber, Vitus, Die Konquistadoren. Cortés, Pizarro und die Eroberung Amerikas (C. H. Beck Wissen, 2890), München 2019, Beck, 128 S. / Abb., € 9,95. (Horst Pietschmann, Hamburg) Stolberg, Michael, Gelehrte Medizin und ärztlicher Alltag in der Renaissance, Berlin / Boston 2021, de Gruyter Oldenbourg, VIII u. 580 S. / Abb., € 89,95. (Robert Jütte, Stuttgart) Lüneburg, Marie von, Tyrannei und Teufel. Die Wahrnehmung der Inquisition in deutschsprachigen Druckmedien im 16. Jahrhundert, Wien / Köln / Weimar 2020, Böhlau, 234 S. / Abb., € 45,00. (Wolfgang Reinhard, Freiburg i. Br.) Krey, Alexander, Wirtschaftstätigkeit, Verwaltung und Lebensverhältnisse des Mainzer Domkapitels im 16. Jahrhundert. Eine Untersuchung zu Wirtschaftsstil und Wirtschaftskultur einer geistlichen Gemeinschaft (Schriften zur Sozial- und Wirtschaftsgeschichte, 35), Hamburg 2020, Dr. Kovaç, 530 S. / graph. Darst., € 139,80. (Maria Weber, München) Fuchs, Gero, Gewinn als Umbruch der Ordnung? Der Fall des Siegburger Töpfers Peter Knütgen im 16. Jahrhundert (Rechtsordnung und Wirtschaftsgeschichte, 19), Tübingen 2019, Mohr Siebeck, XIII u. 195 S. / Abb., € 59,00. (Anke Sczesny, Augsburg) Lotito, Mark A., The Reformation of Historical Thought (St Andrews Studies in Reformation History), Leiden / Boston 2019, Brill, XX u. 542 S. / Abb., € 160,00. (Andreas Bihrer, Kiel) Georg III. von Anhalt, Abendmahlsschriften, hrsg. v. Tobias Jammerthal / David B. Janssen (Anhalt‍[er]‌kenntnisse), Leipzig 2019, Evangelische Verlagsanstalt, 440 S., € 48,00. (Eike Wolgast, Heidelberg) Bauer, Stefan, The Invention of Papal History. Onofrio Panvinio between Renaissance and Catholic Reform (Oxford-Warburg Studies), Oxford 2020, Oxford University Press, VIII u. 262 S. / Abb., £ 70,00. (Marco Cavarzere, Venedig) Murphy, Neil, The Tudor Occupation of Boulogne. Conquest, Colonisation and Imperial Monarchy, 1544 – 1550, Cambridge [u. a.] 2019, Cambridge University Press, XVIII u. 296 S. / Abb., £ 75,00. (Martin Foerster, Hamburg) Mills, Simon, A Commerce of Knowledge. Trade, Religion, and Scholarship between England and the Ottoman Empire, c. 1600 – 1760, Oxford 2020, Oxford University Press, XII u. 332 S. / Abb., £ 65,00. (Stefano Saracino, Jena / München) Karner, Herbert / Elisabeth Loinig / Martin Scheutz (Hrsg.), Die Jesuiten in Krems – die Ankunft eines neuen Ordens in einer protestantischen Stadt im Jahr 1616. Die Vorträge der Tagung des Instituts für kunst- und musikhistorische Forschungen der Österreichischen Akademie der Wissenschaften, des Niederösterreichischen Instituts für Landeskunde und des Instituts für Österreichische Geschichtsforschung der Universität Wien, Krems, 28. bis 29. Oktober 2016 (Studien und Forschungen aus dem Niederösterreichischen Institut für Landeskunde, 71), St. Pölten 2018, Verlag Niederösterreichisches Institut für Landeskunde, 432 S. / Abb., € 25,00. (Markus Friedrich, Hamburg) Die „litterae annuae“ der Gesellschaft Jesu von Otterndorf (1713 bis 1730) und von Stade (1629 bis 1631), hrsg. v. Christoph Flucke / Martin J. Schröter, Münster 2020, Aschendorff, 154 S. / Abb., € 24,90. (Markus Friedrich, Hamburg) Como, David R., Radical Parliamentarians and the English Civil War, Oxford 2018, Oxford University Press, XV u. 457 S. / Abb., £ 85,00. (Torsten Riotte, Frankfurt a. M.) Corens, Liesbeth, Confessional Mobility and English Catholics in Counter-Reformation Europe, Oxford / New York 2019, Oxford University Press, XII u. 240 S. / Abb., £ 60,00. (Ulrich Niggemann, Augsburg) Asche, Matthias / Marco Kollenberg / Antje Zeiger (Hrsg.), Halb Europa in Brandenburg. Der Dreißigjährige Krieg und seine Folgen, Berlin 2020, Lukas, 244 S. / Abb., € 20,00. (Michael Rohrschneider, Bonn) Fiedler, Beate-Christine / Christine van den Heuvel (Hrsg.), Friedensordnung und machtpolitische Rivalitäten. Die schwedischen Besitzungen in Niedersachsen im europäischen Kontext zwischen 1648 und 1721 (Veröffentlichungen des Niedersächsischen Landesarchivs, 3), Göttingen 2019, Wallstein, 375 S. / Abb., € 29,90. (Niels Petersen, Göttingen) Prokosch, Michael, Das älteste Bürgerbuch der Stadt Linz (1658 – 1707). Edition und Auswertung (Quelleneditionen des Instituts für Österreichische Geschichtsforschung, 18), Wien / Köln / Weimar 2019, Böhlau, 308 S. / Abb., € 50,00. (Beate Kusche, Leipzig) Häberlein, Mark / Helmut Glück (Hrsg.), Matthias Kramer. Ein Nürnberger Sprachmeister der Barockzeit mit gesamteuropäischer Wirkung (Schriften der Matthias-Kramer-Gesellschaft zur Erforschung der Geschichte des Fremdsprachenerwerbs und der Mehrsprachigkeit, 3), Bamberg 2019, University of Bamberg Press, 221 S. / Abb., € 22,00. (Helga Meise, Reims) Herz, Silke, Königin Christiane Eberhardine – Pracht im Dienste der Staatsraison. Kunst, Raum und Zeremoniell am Hof der Frau Augusts des Starken (Schriften zur Residenzkultur 12), Berlin 2020, Lukas Verlag, 669 S. / Abb., € 70,00. (Katrin Keller, Wien) Schaad, Martin, Der Hochverrat des Amtmanns Povel Juel. Ein mikrohistorischer Streifzug durch Europas Norden der Frühen Neuzeit (Histoire, 176), Bielefeld 2020, transcript, 249 S., € 39,00. (Olaf Mörke, Kiel) Overhoff, Jürgen, Johann Bernhard Basedow (1724 – 1790). Aufklärer, Pädagoge, Menschenfreund. Eine Biografie (Hamburgische Lebensbilder, 25), Göttingen 2020, Wallstein, 200 S. / Abb., € 16,00. (Mark-Georg Dehrmann, Berlin) Augustynowicz, Christoph / Johannes Frimmel (Hrsg.), Der Buchdrucker Maria Theresias. Johann Thomas Trattner (1719 – 1798) und sein Medienimperium (Buchforschung, 10), Wiesbaden 2019, Harrassowitz, 173 S. / Abb., € 54,00. (Mona Garloff, Innsbruck) Beckus, Paul, Land ohne Herr – Fürst ohne Hof? Friedrich August von Anhalt-Zerbst und sein Fürstentum (Quellen und Forschungen zur Geschichte Sachsen-Anhalts, 15), Halle 2018, Mitteldeutscher Verlag, 604 S. / Abb., € 54,00. (Michael Hecht, Halle) Whatmore, Richard, Terrorists, Anarchists and Republicans. The Genevans and the Irish in Time of Revolution, Princeton / Oxford, Princeton University Press 2019, XXIX u. 478 S. / Abb., £ 34,00. (Ronald G. Asch, Freiburg i. Br.) Elster, Jon, France before 1789. The Unraveling of an Absolutist Regime, Princeton / Oxford 2020, Princeton University Press, XI u. 263 S. / graph. Darst., £ 34,00. (Lars Behrisch, Utrecht) Hellmann, Johanna, Marie Antoinette in Versailles. Politik, Patronage und Projektionen, Münster 2020, Aschendorff, X u. 402 S. / Abb., € 57,00. (Pauline Puppel, Berlin) Müchler, Günter, Napoleon. Revolutionär auf dem Kaiserthron, Darmstadt 2019, wbg Theiss, 622 S. / Abb., € 24,00. (Hans-Ulrich Thamer, Münster) Prietzel, Sven, Friedensvollziehung und Souveränitätswahrung. Preußen und die Folgen des Tilsiter Friedens 1807 – 1810 (Quellen und Forschungen zur Brandenburgischen und Preußischen Geschichte, 53), Berlin 2020, Duncker &amp; Humblot, 408 S., € 99,90. (Nadja Ackermann, Bern) Christoph, Andreas (Hrsg.), Kartieren um 1800 (Laboratorium Aufklärung, 19), Paderborn 2019, Fink, 191 S. / Abb., € 69,00. (Michael Busch, Rostock / Schwerin)

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