Auswahl der wissenschaftlichen Literatur zum Thema „306.436 62“

Introduction: Replacement factor VIII (FVIII) products have been administered to achieve desired FVIII levels for bleed treatment, perioperative management, or routine prophylaxis. Individual variability in pharmacokinetics (PK) has resulted in dosing ranges, rather than fixed doses. N8-GP (ESPEROCT®) is an extended half-life recombinant FVIII product. The pathfinder trials evaluated routine prophylaxis and bleed treatment in previously treated adolescents/adults (pathfinder 2) and children (pathfinder 5) with severe hemophilia A and perioperative management of major surgery (pathfinder 3). Methods: Adolescents/adults (aged ≥12 y) were administered 50 IU/kg N8-GP every 4 days (Q4D) as routine prophylaxis in the main phase; alternative weekly dosing was explored in 2 extension phases. For the on-demand treatment arm, patients were to be given 20 to 70 IU/kg, depending on bleed severity and desired FVIII levels. Children (aged <12 y) on prophylaxis were administered a target of 60 (50-75) IU/kg N8-GP twice weekly. For surgery, a pre-trial test dose of 50 IU/kg was administered with PK assessment and then dosing in the study was to achieve desired FVIII suggested by World Federation of Hemophilia guidelines. Results: Pathfinder 2 enrolled 186 patients (46 from the US) with 128 (69%) completing the second extension phase encompassing 785 patient-years (66,577 exposure days) with 2,758 treated bleeds. On-demand patients (n=12) treated for a total of 37 patient-years of exposure reported 1,270 (46%) bleeds. In the main phase, 105 of 175 adolescents/adults on prophylaxis (50 IU/kg Q4D) experienced 436 bleeds with a median annualized bleeding rate (ABR) of 1.2. Through the study (mean 3.5 years), 177 adolescents/adults on doses of ~52 IU/kg Q4D had a median ABR of 0.99 and mean (95% CI) FVIII trough levels of 3.1 (2.6-3.4) IU/dL. Treatment of bleeding through extension 1 is described in Table; the median dose for mild/moderate bleeds was 42 IU/kg. For participants who were in the on-demand arm, the median initial dose was 28 IU/kg, with 88.4% of bleeds treated with a single dose. In subjects receiving prophylaxis, the median initial dose matched the prophylaxis dose (52 IU/kg), and 76% of bleeds received a single dose. For 15 severe bleeds, the median total dose was 111 IU/kg per episode. Pathfinder 5 enrolled 68 children (34 aged 0-5 y, 34 aged 6-11 y), 95% previously on prophylaxis; 62 completed the extension, amounting to 306 patient-years (32,138 exposure days) with mean exposure of 4.5 years. Overall, 55 patients (81%) reported 330 bleeds; most were traumatic (67%). Median ABR in the main phase (0.48 years) was 2.0 and through the entire study was 0.8 with mean (95% CI) FVIII trough activity of 1.9 (1.6-2.5) IU/dL. The mean prophylaxis dose was 64.7 IU/kg at a mean interval of 3.5 days, likely reflecting rounding the targeted 60 IU/kg twice weekly dose. For 70 bleeds in the main phase, 88% of bleeds were treated with 1 to 2 injections; median utilization for bleeds was 68 IU/kg (Table). Pathfinder 3 evaluated 45 surgeries in 33 adolescents/adults; 96% were reported as excellent/good efficacy. Median preoperative dose mirrored test dose (52 IU/kg) with median total dose per surgery of 702 IU/kg (until 14 days post-surgery). Postoperative dosing was at ~24-hour intervals with the number of doses and treatment duration dependent on procedure (Table). Conclusion: The pathfinder trials demonstrate effective prophylaxis was achieved with very consistent prophylaxis dosing for both adolescents/adults (~50 IU/kg Q4D) and children (~65 IU/kg twice weekly). Bleeds were generally treated for patients on prophylaxis with a single prophylactic dose (~50 or ~65 IU/kg). Dosing intervals in severe bleeding and surgery were ~24 hours, including in children. Disclosures Escobar: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wheeler:uniQure: Membership on an entity's Board of Directors or advisory committees; BioMarin: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk Inc: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Lentz:Novo Nordisk Inc.: Consultancy, Honoraria, Research Funding. Clausen:Novo Nordisk A/S: Employment. Cooper:Novo Nordisk Inc.: Employment.

This study aimed to identify the molecular mechanisms regulated by a combined vaccine against Aeromonas salmonicida and Vibrio anguillarum (O1 serotype). These bacteria cause furunculosis and vibriosis, respectively, and are associated with a high mortality in rainbow trout in Korea. The vaccine upregulated gene expression of TCRα, T-bet, sIgM, and mIgM, markers of an activated adaptive immune response. On days 1, 3, and 5, transcriptome analysis revealed 862 (430 up- and 432 downregulated), 492 (204 up- and 288 downregulated), and 741 (270 up- and 471 downregulated) differentially expressed genes (DEGs), respectively. Gene ontology (GO) enrichment analysis identified 377 (108 MF, 132 CC, 137 BP), 302 (60 MF, 180 CC, 62 BP), and 314 (115 MF, 129 CC, 70 BP) GOs at days 1, 3, and 5, respectively. Kyoto Encyclopedia of Genetic and Genomic enrichment analysis identified eight immune system-related pathways like cytokine-cytokine receptor interaction, NF-kappaB signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, cytosolic DNA sensing pathway, cell adhesion molecule, complement and coagulation cascade, and antigen processing and presentation. In the analysis of the protein–protein interaction of immune-related DEGs, a total of 59, 21, and 21 interactional relationships were identified at days 1, 3, and 5, respectively, with TNF having the highest centrality at all three time points.

Abstract Abstract 5014 Exposure to toxic compounds and pesticides leads to an increased risk to develop Multiple Myeloma (MM). The metabolism and the excretion of xenobiotics are mediated by the enzymes and transporters acting in the detoxifying/elimination process. The nuclear receptors NR1I2 (or PXR) and NR1I3 (or CAR) act as xenosensor activating the detoxifying/elimination process in response to the intracellular levels of xenobiotics. It has been hypothesized that part of the individual variability in drug metabolism efficiency could be due to the genetic variations within these regulator genes affecting their expression and/or function. To investigate the impact of genetic variation within these genes on MM susceptibility, we selected and genotyped 10 tag Single Nucleotide Polymorphisms (SNPs) in the PXR gene and 7 tag SNPs in the CAR gene in 627 MM cases (320 males and 307 females) and 883 (459 males and 424 females) controls from different European populations. All the SNPs were in Hardy-Weinberg equilibrium (p>0.001), with the exception of the PXR SNP rs2461818 that was therefore excluded from the analysis. We found no association of any of the genotyped SNPs with MM risk. In the same way, haplotype distribution showed no differences between cases and controls. This was the first comprehensive investigation of genetic variation in xenobiotic regulators genes PXR and CAR in relation to MM risk and our data suggest that common variants in these genes have no impact in modifying MM risk. Table I. Genotype distribution of the PXR and CAR SNPs among MM cases and controls. SNP (rs) Cases (%) Controls (%) OR* 95%C.I. p-value p-trend PXR C/C 429 (69.5) 623 (70.7) 1.00 Ref 0.423 rs10511395 A/C 160 (25.9) 228 (25.9) 1.02 0.81 – 1.30 0.851 A/A 28 (4.6) 30 (3.4) 1.38 0.81 – 2.35 0.232 PXR C/C 452 (74.0) 656 (74.8) 1.00 Ref 0.451 rs1054190 C/T 137 (22.4) 200 (22.8) 1.00 0.78 – 1.28 0.993 T/T 22 (3.6) 21 (2.4) 1.56 0.84 – 2.88 0.155 PXR C/C 412 (65.9) 591 (67.2) 1.00 Ref 0.819 rs11917714 C/T 190 (30.4) 250 (28.5) 1.07 0.85 – 1.35 0.535 T/T 23 (3.7) 38 (4.3) 0.84 0.49 – 1.44 0.536 PXR C/C 223 (36.3) 296 (33.7) 1.00 Ref 0.126 rs12488820 C/T 289 (47.0) 407 (46.4) 0.93 0.74 – 1.18 0.574 T/T 103 (16.7) 175 (19.9) 0.79 0.58 – 1.06 0.119 PXR G/G 430 (69.6) 593 (67.4) 1.00 Ref 0.807 rs13071341 A/G 166 (26.9) 269 (30.6) 0.85 0.67 – 1.07 0.158 A/A 22 (3.5) 18 (2.0) 1.70 0.90 – 3.22 0.102 PXR A/A 352 (58.7) 516 (39.4) 1.00 Ref 0.981 rs3237359 A/G 209 (34.8) 291 (33.5) 1.04 0.83 – 1.30 0.720 G/G 39 (6.5) 62 (7.1) 0.90 0.59 – 1.37 0.619 PXR C/C 255 (41.2) 383 (43.6) 1.00 Ref 0.815 rs13059232 C/T 299 (48.3) 390 (44.4) 1.16 0.93 – 1.44 0.192 T/T 65 (10.5) 106 (12.0) 0.94 0.66 – 1.33 0.711 PXR A/A 300 (48.7) 437 (49.7) 1.00 Ref 0.258 rs3732357 A/G 240 (39.0) 361 (41.0) 0.94 0.75 – 1.17 0.589 G/G 76 (12.3) 82 (9.3) 1.31 0.92 – 1.85 0.130 PXR T/T 328 (53.6) 463 (52.9) 1.00 Ref 0.424 rs1357459 C/T 249 (40.7) 345 (39.4) 1.02 0.82 – 1.27 0.850 C/C 35 (5.7) 67 (7.7) 0.75 0.49 – 1.17 0.206 CAR A/A 218 (35.4) 335 (38.1) 1.00 Ref 0.571 rs3003596 A/G 296 (48.0) 393 (44.7) 1.16 0.93 – 1.46 0.191 G/G 102 (16.6) 151 (17.2) 1.04 0.77 – 1.41 0.799 CAR G/G 264 (42.7) 371 (42.0) 1.00 Ref 0.642 rs3813627 G/T 276 (44.7) 392 (44.4) 0.98 0.79 – 1.23 0.882 T/T 78 (12.6) 120 (13.6) 0.91 0.66 – 1.26 0.581 CAR A/A 441 (73.1) 635 (73.5) 1.00 Ref 0.911 rs11265571 A/T 147 (24.4) 207 (24.0) 1.01 0.79 – 1.29 0.911 T/T 15 (2.5) 22 (2.5) 0.97 0.49 – 1.89 0.921 CAR T/T 404 (64.2) 575 (65.7) 1.00 Ref 0.836 rs2307418 G/T 193 (31.1) 268 (30.6) 1.02 0.81 – 1.27 0.879 G/G 23 (3.7) 32 (3.7) 1.05 0.60 – 1.83 0.863 CAR C/C 348 (56.6) 508 (57.7) 1.00 Ref 0.527 rs2502805 C/T 220 (35.8) 313 (35.6) 1.05 0.84 – 1.30 0.693 T/T 47 (7.6) 59 (6.7) 1.16 0.77 – 1.74 0.484 CAR A/A 245 (39.8) 346 (39.4) 1.00 Ref 0.770 rs4073054 A/C 291 (47.2) 412 (46.9) 0.98 0.78 – 1.22 0.855 C/C 80 (13.0) 120 (13.7) 0.94 0.68 – 1.31 0.720 CAR C/C 360 (57.6) 524 (59.8) 1.00 Ref 0.391 rs4233368 A/C 225 (36.0) 302 (34.4) 1.09 0.88 – 1.36 0.439 A/A 40 (6.4) 51 (5.8) 1.15 0.74 – 1.78 0.538 Genotype distribution among MM cases and controls in the overall population. * OR are adjusted for age, gender and region of origin. Differences in samples numbers are due to failures in genotyping. Disclosures: No relevant conflicts of interest to declare.

Introduction. Circadian rhythms are an adaptational mechanism to day-night cycle. At the cellular level rhythms are supported by oscillations of transcription of Bmal1, 2, Clock and Npas2, Per1-3, Cry1, 2 clock genes; in the organism rhythms are synchronized with melatonin, the "hormone of darkness". Reliable data have been obtained that disruption of biological "clocks" at the cellular and/or organism level are associated with carcinogenesis, but the experimental results in this direction remain incomplete. Aim. Assessment of the continuous lighting and melatonin administration effects on chemically induced carcinogenesis in mice and expression of clock genes and proteins in normal and tumor lung tissue. Materials and methods. Lung tumors were induced by urethane in 120 male SHR mice. Animals were kept at constant (LL) or standard (LD) light; half of the animals received melatonin (MT) daily at 20 mg/l at night with water for 45 weeks of experiment. At the end of the experiment, the frequency and multiplicity of lung tumours of different size were assessed. Expression of clock genes Clock, Bmal1, Cry1 was assessed in tumor samples and normal lung tissue by real-time PCR; protein content of BMAL1, CLOCK, CRY1 and PER2 was determined by immunohistochemistry. Statistical data were processed using the programs MS Excel 2007, GraphPad Prism 6.0 with commonly used statistical criteria. Results. The number of animals with lung tumors was between 89 and 100% in different groups. Large tumors (>2 mm) were more frequently observed in LL group (62 tumors out of 294, 21,1%) than in LD group (59 tumors out of 405, 14,6%, p=0,0245). Administration of exogenous melatonin at constant lighting statistically significantly reduced the frequency of large tumors (28 tumors out of 320, 8.8%, p=0,0001 in comparison with LL). In normal lung tissue of animals kept at constant lighting (LL) the increase in relative expression of clock genes in comparison with LD group was revealed: Bmal1 by 3,1 times (p=0,02) and Cry1 by 3,6 times (p=0,0002). No such differences were found for Clock gene. The relative content of BMAL1 and CLOCK proteins in all experimental conditions was higher in adenomas and adenocarcinomas compared to normal tissue. Conclusion. Constant lighting promotes the development of chemically induced lung tumors, and melatonin administration inhibits carcinogenesis under constant lighting. The content of BMAL1 and CLOCK transcription activator proteins in lung tumors was found to increase in comparison with normal tissue, whereas no increase in the expression level of corresponding genes in tumors was observed.

279 Background: The University of Utah opened a cancer specific ICU (HICU) in 2011 admitting medical and surgical cancer pts. Prior to this, medical cancer pts were admitted to the MICU while the SICU admitted both and medical and surgical pts. The primary objective of this study was to compare the quality metrics of mortality and length of stay (LOS). Methods: Pts with a cancer diagnosis and admitted to the MICU or SICU from 2009-2011 or the HICU from 2011-2013 were evaluated. Pts were stratified by ICU type and the HICU was also analyzed by excluding post-operative pts (HICU-MED). Survival from admission, hospital and ICU mortality, and LOS was assessed. Results: A total of 1,375 pts were included with 259 (19%), 416 (30%), and 700 (51%) pts admitted to the MICU, SICU, and HICU, respectively. The median age was 62 years (range 18-91 years) and 57% (n = 787) were male; no significant differences in age (p = 0.1975) and sex (p = 0.7681) were observed between ICU’s. Cancer classification was oncology (65%, n = 888), hematology (32%, n = 435), and BMT (4%, n = 52). Of all pts admitted to the HICU, 44% (n = 308) were post-operative and excluded from HICU-MED (n = 392). See table for survival and LOS comparisons. Conclusions: No differences in overall survival and hospital morality (ICU and out-of-ICU) were observed comparing pts admitted to the HICU vs SICU and HICU-MED vs MICU. ICU-free days were significantly shorter resulting in shorter hospitalizations for the HICU vs SICU, which may have contributed to the reduced 30-day mortality in pts admitted to the HICU. [Table: see text]

Teknologi ponsel pintar khususnya dengan sistem operasi android berkembang sangat pesat, termasuk dalam perkembangan aplikasi yang berbasis android. Perkembangan teknologi tersebut mencakup berbagai bidang dalam kehidupan sehari-hari, salah satunya dalam bidang olahraga kesehatan. Tujuan penelitian ini adalah untuk memberikan gambaran tentang persepsi dan minat masyarakat olahraga di Daerah Istimewa Yogyakarta terhadap aplikasi android kategori kebugaran dan kesehatan. Penelitian ini merupakan penelitian deskriptif dengan metode survei. Instrumen yang digunakan dalam penelitian ini adalah angket berbasis web. Penelitian dilakukan dengan melakukan survei terhadap para praktisi keolahragaan, akademisi di bidang olahraga kesehatan, serta masyarakat umum yang berjumlah 62 responden. Hasil penelitian menunjukkan bahwa persepsi responden terhadap aplikasi ponsel pintar sistem operasi android kategori kesehatan dan kebugaran pada kategori Baik Sekali sebesar 4,8%, Baik sebesar 37,2%, Cukup sebesar 22,6%, Kurang sebesar 30,6%, dan Sangat Kurang sebesar 4,8%. Minat responden terhadap aplikasi ponsel pintar sistem operasi android kategori kesehatan dan kebugaran pada kategori Baik Sekali sebesar 12,9%, Baik sebesar 43,6%, Cukup sebesar 29%, Kurang sebesar 11,3%, dan Sangat Kurang sebesar 3,2%. Secara umum, hasil penelitian menunjukkan bahwa persepsi dan minat para praktisi keolahragaan, akademisi di bidang olahraga kesehatan, serta masyarakat umum terhadap aplikasi ponsel pintar sistem operasi android kategori kesehatan dan kebugaran adalah baik. Android application in sport and health: How are societies’s perception and interest? AbstractThe aim of this research was to identify societies’s perception and interest of sport and health android application. It was a descriptive research with survey metode, used web based questionare as the research instruments. The research had done with surveyed sport health professionals, sport health academicians, and the citizens. The number of the subject was 62 respondents. The result of this research showed that societies’s perception of sport and health android application are Very Good at 4,8%, Good at 37,2%, Enough at 22,6%, Less at 30,6%, and Very Less at 4,8%. Societies’s interest of sport and health android application are Very Good at 12,9%, Good at 43,6%, Enough at 29%, Less at 11,3%, and Very Less at 3,2%. In general, the results of the study show that the perceptions and interests of sport health professionals, sport health academicians, and the citizens of sport and health android application is good.

The material grain size changes significantly during machining of hardened steels, and this must be taken into account for improved modeling of surface integrity effects resulting from machining. Grain size changes induced during orthogonal cutting of hardened AISI 52100 (62 HRC) are modeled using the Finite Element (FE) method; in particular, a user subroutine involving a hardness-based flow stress model is implemented in the FE code and empirical models are utilized for describing the phase transformation conditions to simulate formation of white and dark layers. Furthermore, a procedure utilizing the Zener-Hollomon relationship is implemented in the above-mentioned user subroutine to predict the evolution in material grain size at different cutting speeds (300, 600, 900 SFPM). All simulations were performed for dry cutting conditions using a low CBN-content insert (Kennametal KD050 grade, ANSI TNG-432 geometry). The model is validated by comparing the predicted results with experimental evidence available in the literature.

Abstract Juvenile chinook salmon were sampled from August 1986 to March 1987 at stations near Prince George and Quesnel, influenced by sewage and pulp mill discharges. Maximum densities of 0.2 fish·mࢤ2 were recorded. Salmon were collected at reference sites in November 1986 and at Agassiz in April 1987. Fingerling chinook were exposed at 0.7°C to a commercial wood preservative containing 2,3,4,6 - tetrachlorophenol (TeCP) and pentachlorophenol (PCP) in the laboratory to simulate winter conditions in the upper Fraser River. Fish exposed for 62 days to 2 ug·Lࢤ1 contained a mean of 224 ng·gࢤ1 TeCP and 431 ng·gࢤ1 PCP. Chlorophenol uptake in feral fish was low. However, 3,4,5-trichloro-guaiacol levels to 304 ng·gࢤ1 and tetrachloroguaiacol values to 136 ng·gࢤ1 were measured in March. Fish from Agassiz, 518 km downstream of Quesnel, also contained these two substances. Thus chinook salmon can bioconcentrate persistent chlorophenols and chloroguaiacols directly from cold water (< 1°C). The biological consequences are uncertain.

Blue agave (Agave tequilana F.A.C. Weber var. Azul) is an important crop for Mexico, from which tequila is made. In 2018 1,138,800 t of agave were produced under aproduction system where the use of agrochemicals has become widespread; in particular, the excessive use of chemical fertilizers generates problems of environmental impact in the producing areas. An alternative to solve this problem is the use of soil microbial resources to reduce this impact. The use of arbuscular mycorrhizal fungi (AMF) as biofertilizers is a functional alternative in other crops that could be implemented in the production of blue agave. The aim of this research was to evaluate the effect of native mycorrhizal consortia isolated from the rhizosphere of A. cupreata from Michoacán on the growth of blue agave. An experiment was conducted under a randomized complete blocks design where eight AMF consortia, a commercial inoculum (Rhizophagus intraradices) and a control (without AMF) were evaluated on A. tequilana seedlings. The experiment was maintained for 300 d under greenhouse conditions and, at the end, growth and microbiological variables were analyzed; in addition, mycorrhizal dependency and the Dickson index were calculated as parameters of plant quality. Significant differences (Tukey, P ≤ 0.05) were found in the growth traits of agave plants when inoculated with AMF consortia compared to control plants. The agave plants inoculated with the native consortium Barranca de las Nueces showed greater growth and Dickson index, with a mycorrhizal colonization of 49 % and a mycorrhization dependency of 62 %, as well as the highest spore density (244 spores 100 g-1 of substrate). Results suggest that AMF could be a biotechnology alternative in the agricultural production process of blue agave.

BackgroundTofacitinib, an oral Janus Kinase inhibitor, is indicated for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA).ObjectivesTo describe the safety profile of Tofacitinib in a French prospective observational study DeFacTo.MethodsThe safety profile of tofacitinib was assessed using interim data from a descriptive analysis of patients who took at least one dose of tofacitinib in the DeFacTo study.ResultsAmong 314 patients enrolled in the study, 306 received tofacitinib and were included in the safety analysis, including 274 patients with a follow-up ≥ 18 months (POP2) on 03/15/22 date of analysis) with a median exposure duration of 538 [Q1; Q3: 381; 554] days. 113 patients (41.2%) were still on tofacitinib (39 discontinued, 122 missing data regarding prescription). At inclusion, 78.3% of the 306 pts were women with a mean (± standard deviation) age of 59.5 ± 11.5 years, median disease duration of 8.9 years [Q1; Q3: 4.1; 18.9]. There was a history of cardiovascular (CV) disease in 11.9% of cases (including 4.6% myocardial infarction (MI), 5.0% stroke/transient ischemic attack (TIA), 1.7% heart failure, and 1.7% peripheral arterial disease); 5.6% history of cancer, 16.8% history of infection, and 46.6% smoker/former smoker. Tofacitinib was prescribed in combination with a csDMARD in 61.1% of patients and corticosteroids in 56.2% of cases. The results showed that adverse events (AEs) were reported in 54.2% of the 306 patients, 14.4% were considered as serious. Infections were found in 22.2% of patients, no deaths were reported (Table 1).Table 1.Real-life and age-specific safety data for tofacitinibN, (%)< 65 ans (n=193)≥ 65 ans (n=111)Total (n=306*)Adverse events (AEs)104 (53.9)62 (55.9)166 (54.2)Serious adverse events21 (10.9)23 (20.7)44 (14.4)Infection41 (21.2)27 (24.3)68 (22.2)Herpes Zoster6 (3.1)6 (5.4)12 (3.9)Serious AEs of special interestSerious infection5 (2.6)4 (3.6)9 (2.9)Herpes zosterTuberculosis1 (0.5)0 (0.0)0 (0.0)2 (1.8)1 (0.3)2 (0.7)Cancer1 (0.5)1 (0.9)2 (0.7)CV eventⴕ1 (0.5)1 (0.9)2 (0.7)VTEⱡ0 (0.0)2 (1.8)2 (0.7)Death0 (0.0)0 (0.0)0 (0.0)*2 patients with missing age but counted in the total. ⴕ cardiovascular event (Evt): non-fatal MI and stroke + CV death. ⱡ VTE (venous thromboembolic disease): deep vein thrombosis + pulmonary embolism.ConclusionThese intermediate, descriptive results show a safety profile of tofacitinib in real-life RA similar to the one previously reported in clinical and observational studies.[1-2]References[1]Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89https://doi.org/10.1186/s13075-019-1866-2[2]Kremer et al. ACR Open Rheumatology 2021. DOI 10.1002/acr2.11232AcknowledgementsThis study was sponsored by Pfizer.Disclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Yves Brault Shareholder of: Pfizer, Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer.

Abstract The longest selection in the Reader is excerpted from an extended interview with Kenneth Leish, arranged in twelve parts (392 double-spaced pages of typescript and a two-page index of names). Although only the first four parts include dates, It is clear from references to current productions at places like the Music Theater at Lincoln Center that the final portions of the interview did not extend much beyond Summer and Fall 1968.* In a portion of the Reminiscences not reprinted here readers learn that the press suppressed Hart’s excessive drinking as well as his homosexuality, not because Rodgers threatened the publisher of a scandal rag when confronted with questions about Hart’s sexuality, but “because the newspaper people were all crazy about him” (p. 200}. Also in this section Rodgers discloses that For the archivally curious this footnote offers topics, dates (when provided in the interviews), and page numbers for each section: (I) Rodgers’s current activities (December I4, I967), I-39; (2) Background (December I9, I967), 40-84; (3) Producing Avanti and The Garrick Gaieties through A Connecticut Yankee (February 2I, I968), 85-u8; (4) I927-I932 (March I, I968), II9-43; (5) I932-I936, I44-67; (6) Working with Hart, I68-203 [marked on the title page “closed during lifetime”]; (7) Pal Joey and Oklahoma!, 204-46; (8) State Fair and Carousel, 247-78; (9) Allegro and South Pacific, 279-307; (IO) The King and I, Victory at Sea, and Me and Juliet, 308-36; (II) Pipe Dream and The Sound of Music, 337-62; (I2) After Hammerstein, 363-92.

The aim was to explore user experiences of using a telehealth system (Telekit) designed for the Danish TeleCare North trial. Telekit is designed for patients diagnosed with chronic obstructive pulmonary disease (COPD) in order to manage the disease and support patient empowerment. This article sums up COPD-participants' user experiences in terms of increased sense of freedom, of security, of control, and greater awareness of COPD symptoms. A consecutive sample of sixty participants (27 women, 33 men) were recruited from the TeleCare North trial. At home the participants completed a non-standardised questionnaire while a researcher was present. The questionnaire identified their health status, their use of specific technologies, and their user experiences with the telehealth system. Results from the questionnaire indicate that the majority of participants (88%) considered the Telekit system as easy to use. 43 (72%) participants felt increased sense of security, and 37 (62%) participants felt increased sense of control by using the system. 30 (50%) participants felt greater awareness of their COPD symptoms, but only 16 (27%) participants felt increased freedom. The study has provided a general picture of COPD participants' user experiences which is important to emphasise as it has a bearing on whether a given implementation will be successful or not.

За дендрометричними і санітарними характеристиками та показника- ми декоративності з’ясовували сучасний стан вікових екземплярів дубу звичайного на території парку культури та відпочинку ім. Федора Мер- шавцева (м. Кривий Ріг). В межах території парку виявлено 64 екземп- ляри вікових дерев дубу звичайного. Вони згруповані у чотири локації: Фундатори Криворіжжя (чотири дерева), Криворізька діброва (46 дерев), Криворізький квартет (п’ять дерев), Гданцівські дуби (дев’ять дерев). Ві- кові дерева парку характеризуються: 1) унікальними дендрометричними показниками висоти дерева (від 14 м до 38 м, в середньому 25 м) та ді- аметру стовбуру (від 37 см до 102 см, в середньому 62 см); 2) задовіль- ним санітарним станом та високою естетичністю; 3) наявністю вікових (100–200 років) та багатовікових (200–1000 років) екземплярів (вік двох дерев перевищує 300 р., вік восьми дерев перевищує офіційний вік на- шого міста – 245 р.). Рекомендовано створення ботанічної пам’ятки природи «Вікові дерева дубу звичайного парку імені Федора Мершавцева (м. Кривий Ріг)».

Between April 2020 and January 2022, the Food Standards Agency (FSA) commissioned a quarterly survey on consumer handwashing. Key findings from this survey are: Across all waves of the handwashing tracker, participants were most likely to report washing their hands with soap and warm water. However, the proportion who reported handwashing with soap and warm water ‘always’ or ‘most of the time’ declined over time (79% April 2020, compared to 68% in January 2022). Most participants reported washing their hands for between 20 and 24 seconds across all waves. However, the proportion who reported this significantly declined over time (was 35% in April 2020, down to 27% in January 2022). Over time, there was a significant decrease in the proportion of participants who reported ‘always’ washing their hands in the following scenarios inside the home: before cooking/preparing food (72% in April 2020, 62% in January 2022) before eating (48% in April 2020, 42% in January 2022) after handling rubbish (73% in April 2020, 65% in January 2022) when arriving home, after a trip outside of the home (55% in April 2020, 47% in January 2022) Reported handwashing after contact with animals (including pets) remained broadly stable over time. On average, across all waves, 36% of participants with a pet reported washing their hands ‘always’ after contact with animals, (whilst 26% reported doing this ‘most of the time’, 30% reported doing this ‘sometimes’ and 7% reported ‘never’ washing their hands after contact with animals). Over time, there was a significant decrease in the proportion of participants who reported ‘always’ washing their hands in the following scenarios outside of the home: when eating a picnic (35% in July 2020, 29% in January 2022) when consuming a takeaway outside of the home (35% in July 2020, 30% in January 2022) Since a peak in October 2020 (43%), the proportion of participants who reported ‘always’ washing their hands after blowing their nose, sneezing or coughing into their hands gradually declined and was significantly lower in January 2022 (35%). The proportion of participants who reported ‘always’ washing their hands after using the toilet also declined over time. In April 2020 87% of participants reported ‘always’ washing their hands after using the toilet, decreasing significantly to 80% in January 2022. Across all waves, most participants reported carrying and using hand sanitising gel as a hand washing alternative in a range of scenarios, but the proportion who reported doing this declined over time. For example: 55% of participants reported using hand sanitising gel after using public transport in October 2020, declining significantly to 44% in January 2022 54% of participants reported using hand sanitising gel when attending a social event in October 2020, declining significantly to 45% January 2022.

Heat production (HP) or energy expenditure for activity (EEa) is of fundamental nutritional importance for livestock because it determines the proportion of ingested nutrients available for productive functions. Previous estimates of EEa are unreliable and vary widely with different indirect methodologies. This leads to erroneous nutritional strategies, especially when intake on pasture does not meet nutritional requirements and supplementation is necessary for acceptable production. Therefore, the objective of this project was to measure EEa in different classes of livestock (beef cattle and goats) over a wide range of ecological and management conditions to develop and evaluate simple means of prediction. In the first study in Israel, small frame (SF) and large frame (LF) cows (268 and 581 kg) were monitored during spring, summer, and autumn. Feed intake by SF cows per unit of metabolic weight was greater (P < 0.001) than that by LF cows in both spring and summer and their apparent selection of higher quality herbage in spring was greater (P < 0.10) than that of LF cows. SF cows grazed more hours per day and walked longer distances than the LF cows during all seasons. The coefficient of specific costs of activities (kJ•kg BW-0.75•d-1) and of locomotion (J•kg BW-0.75•m-1) were smaller for the SF cows. In the second study, cows were monitored in March, May, and September when they grazed relatively large plots, 135 and 78 ha. Energy cost coefficients of standing, grazing, and horizontal locomotion derived were similar to those of the previous study based on data from smaller plots. However, the energy costs of walking idle and of vertical locomotion were greater than those found by Brosh et al. (2006) but similar to those found by Aharoni et al. (2009). In the third study, cows were monitored in February and May in a 78-ha plot with an average slope of 15.5°, whereas average plot slopes of the former studies ranged between 4.3 and 6.9°. Energy cost coefficients of standing, grazing, and walking idle were greater than those calculated in the previous studies. However, the estimated energy costs of locomotion were lower in the steeper plot. A comparison on a similar HP basis, i.e., similar metabolizable energy (ME) intake, shows that the daily energy spent on activities in relation to daily HP increased by 27% as the average plot slope increased from 5.8 and 6.02 to 15.5°. In the fourth study, cows grazing in a woodland habitat were monitored as in previous studies in December, March, and July. Data analysis is in progress. In the first US experiment, Boer and Spanish does with two kids were used in an experiment beginning in late spring at an average of 24 days after kidding. Two does of each breed resided in eight 0.5-ha grass/forb pastures. Periods of 56, 60, 63, 64, and 73 days in length corresponded to mid-lactation, early post-weaning, the late dry period, early gestation, and mid-gestation. EEa expressed as a percentage of the ME requirement for maintenance plus activity in confinement (EEa%) was not influenced by stocking rate, breed, or period, averaging 49%. Behavioral activities (e.g., time spent grazing, walking, and idle, distance traveled) were not highly related to EEa%, although no-intercept regressions against time spent grazing/eating and grazing/eating plus walking indicated an increase in EEa% of 5.8 and 5.1%/h, respectively. In the second study, animal types were yearling Angora doeling goats, yearling Boer wether goats, yearling Spanish wether goats, and Rambouilletwether sheep slightly more than 2 yr of age. Two animals of each type were randomly allocated to one of four pastures 9.3, 12.3, 4.6, and 1.2 ha in area. The experiment was conducted in the summer with three periods, 30, 26, and 26 days in length. EEa% was affected by an interaction between animal type and period (Angora: 16, 17, and 15; Boer: 60, 67, and 34; Spanish: 46, 62, and 42; sheep: 22, 12, and 22% in periods 1, 2, and 3, respectively (SE = 6.1)). EEa% of goats was predicted with moderate accuracy (R2 = 0.40-0.41) and without bias from estimates of 5.8 and 5.1%/h spent grazing/eating and grazing/eating plus walking, respectively, determined in the first experiment; however, these methods were not suitable for sheep. These methods of prediction are simpler and more accurate than currently recommended for goats by the National Research Council.

The survey presented in this report reveals that Nordic citizens are concerned about climate change. Many people are willing to increase efforts to fight climate change, even if this entails a personal contribution in terms of higher taxes or behavioural change. The survey shows that different social groups perceive the impacts of climate change and climate mitigation policies in different ways. In general, attitudes towards climate policies and perceptions regarding their fairness are conditioned by socio-demographic factors such as gender, age, employment status, type of housing and transport behaviour. General attitudes towards climate change and climate policies The first part of this report explores general attitudes towards climate change and climate policies. This section shows that seven in ten (71%) respondents think that climate change is a serious or very serious problem, particularly among the youngest age group (18-29 years). Three in four (74%) interviewed persons in this group share this view. Those with a university degree are more concerned about climate change (83%) than those with primary or secondary education (57% and 62%, respectively). Approximately half (48-51%) of respondents in all age groups agree that more financial resources should be invested in preventing climate change, even if this would imply an increase in taxes. The survey results show that women in the Nordic Region are more concerned about climate change than men (79% compared to 64%). It also reveals that people living in urban areas are more worried about climate change (82%) than those who live in towns and suburbs (68%) or in rural areas (62%). Urban dwellers are also more positive about investing more resources in preventing climate change (59%) than those who live in rural areas (39%) and in towns and suburbs (46%). More than half of the respondents (52%) agree that taking further action on climate change would be beneficial for the economy. Students, unemployed and retired people are more likely to agree with this view (55%, 57% and 55%, respectively) than those currently in employment, including the self-employed (50%). Those employed in carbon-intensive sectors are less positive about the expected economic impact of climate policies than those who work in other economic sectors (41% compared to 55%). They are also more concerned about the risk of job losses during the transition to a low-carbon economy than those employed in sectors with lower carbon intensity (37% compared to 24%). Concerns about this issue are also higher among those who live in rural areas (31%) or towns and suburbs (30%) compared to those who live in cities (22%). Present and future effects of climate change mitigation policies on individuals and households The central part of the survey explores perceptions regarding the present and future impacts of climate policies. Such challenges are perceived differently depending on specific sociodemographic conditions. Nearly one fourth (23%) of respondents state that high energy costs mean they are struggling to keep their homes at a comfortable temperature. Those living in houses report being more impacted (27%) than those living in apartments (18%), and those using fossil fuels to heat their homes are most affected (44%). The risk of energy poverty is also higher among non-EU immigrants to the Nordic Region. Those who say they are struggling to keep their homes at a comfortable temperature range from 23% among Nordic-born citizens to 37% among non-EU immigrants. Nearly three in ten respondents (28%) have modified their transportation behaviour during the last year due to high fuel costs. This proportion is substantially greater among those living in towns and suburbs (32%) compared to those who live in rural areas (29%) or cities (23%). The majority of the Nordic population (52%) states that current climate policies have a neutral effect on their household economies. However, 28% of respondents say they are negatively impacted by climate policies in economic terms. Men report being negatively affected more frequently than women (33% vs 22%, respectively). People who live in houses are more likely to claim they are being negatively impacted than people who live in apartments (31% and 23%, respectively). Nearly half (45%) of the respondents in the Nordic Region agree that climate initiatives will improve health and well-being, and half of the respondents (50%) think that climate change initiatives will lead to more sustainable lifestyles in their area. However, half (51%) of the Nordic population expect to see increases in prices and the cost of living as a consequence of climate policies, and those who believe that climate policies will create jobs and improve working conditions in the areas where they live (31% and 24%, respectively) are outnumbered by those who believe the opposite (35% and 34%, respectively). Fairness of climate policies The last section of the report looks at how the Nordic people perceive the fairness of climate policies in distributional terms. In the survey, the respondents were asked to judge to what extent they agree or disagree that everyone in their country or territory is equally affected by initiatives to fight climate change regardless of personal earnings, gender, age, country of origin and where they live – cities or rural areas. The results show that the Nordic people believe climate change initiatives affect citizens in different ways depending on their demographic, socioeconomic and territorial backgrounds. More than half of the respondents (56%) disagree that everyone is equally affected by initiatives to fight climate change regardless of earnings. Only 22% agree with this statement. Younger age groups are more pessimistic than older age groups on this point (66% in the 18-29 age group compared to 41% in the 65+ group). Almost half of respondents (48%) agree that climate policies are fair from a gender perspective, while 25% disagree with this statement and 23% are neutral. Roughly one in three (30%) respondents in the Nordic Region agree that people are equally affected by climate change initiatives regardless of age, 41% disagree with this statement and 25% are neutral. More than one third (35%) of the Nordic population agree that everyone is equally affected by initiatives to fight climate change regardless of the country of origin, while 34% of them disagree. More than half of respondents (56%) think that the impact of climate initiatives differs between rural and urban areas, while only 22% think that all areas are equally affected. Respondents who live in cities are more likely to respond that climate policy impacts differ between rural and urban areas (60%) than respondents who live in rural areas (55%) and towns and suburbs (53%). One third (33%) of respondents in the survey think that the Sámi population is affected by climate change initiatives to the same extent as the rest of the population. In Greenland, a majority of the population (62%) agrees that the indigenous population in Greenland is equally affected by measures to combat climate change. The results from this survey conducted in the autumn of 2022, show that the population in the Nordic Region perceive the impacts of climate mitigation policies in different ways. These results can raise awareness and stimulate debate about the implementation of climate mitigation policies for a just green transition.

MGR recorded 1355 violent incidents during May 2024, mostly triggered by politics, access to resources, and other socio-economic factors. More than 243 deaths and 1345 injuries have been recorded from these incidents. The highest number of violent incidents have been recorded in the form of clashes and attacks (432). Some 280 incidents are directly political violence, protests and arrests which resulted in 24 deaths. Geographically, Chittagong (316) scores the highest number of violence followed by Dhaka (314), Rajshahi (245) and Barishal (152). There were 62 protests and demonstrations and only 27 of protests were triggered by politics. While some 18.77% of political violence contributed by Bangladesh Awami League & affiliates, Bangladesh Nationalist Party (BNP) scored only 1.54% of political violence in the month of May. Law and security forces conducted 3.60% of political violence. Intra-party violence within the Awami League showed a surge in May, count of 27. Whereas 79% political incidents were rural, 21% of political violence incidents took place in urban areas. MGR data team has come across upazila local elections and post-election violence. Supporters and candidates were beaten, assault, injured and killed during elections and post-election time. Some 173 electoral violence and irregularities has been recorded from all over the Bangladesh.