Prattmahoney8727

The understanding of the benefit risk profile, and relative effectiveness of a new medicinal product, are initially established in a circumscribed patient population through clinical trials. There may be uncertainties associated with the new medicinal product that cannot be, or do not need to be resolved before launch. Post-licensing or post-launch evidence generation (PLEG) is a term for evidence generated after the licensure or launch of a medicinal product to address these remaining uncertainties. PLEG is thus part of the continuum of evidence development for a medicinal product, complementing earlier evidence, facilitating further elucidation of a product's benefit/risk profile, value proposition and/or exploring broader aspects of disease management and provision of healthcare. PLEG plays a role in regulatory decision making, not only in the European Union (EU) but also in other jurisdictions including the United States and Japan. PLEG is also relevant for downstream decision-making by Health Technology Assessment bodies (HTAb) and payers. PLEG comprises studies of different designs, based on data collected in observational or experimental settings. Experience to date in the EU has indicated a need for improvements in PLEG. Improvements in design and research efficiency of PLEG could be addressed through more systematic pursuance of Scientific Advice on PLEG with single or multiple decision makers. To date, limited information has been available on the rationale, process, or timing for seeking PLEG advice from regulators or HTAb. This article sets out to address these issues and to encourage further uptake of PLEG advice. This article is protected by copyright. All rights reserved.Workers of many species of social Hymenoptera have functional ovaries and are capable of laying haploid, unfertilized eggs, at least in the absence of a queen. Except for honeybees, it remains largely unknown whether worker-produced males have the same quality as queen-produced males and whether workers benefit in direct fitness by producing their sons. Previous studies in the monogynous ant Temnothorax crassispinus revealed that a high proportion of males in natural and laboratory colonies are worker offspring. Here, we compare longevity, body size, sperm length and sperm viability between queen- and worker-produced males. We either split queenright colonies into queenright and queenless halves or removed the queen from a fraction of the queenright colonies and then examined the newly produced males. Male quality traits varied considerably among colonies but differed only slightly between queen- and worker-produced males. Worker-produced males outnumbered queen-produced males and also had a longer lifespan, but under certain rearing conditions sperm from queen-produced males had a higher viability. © 2020 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.The recently discovered twisted graphene has aroused considerable interest. We have found a simple chemical route to prepare twisted graphene by covalently linking layers of exfoliated graphene containing surface carboxyl groups with an amine-containing linker ( trans -1,4-diaminocyclohexane). The twisted graphene shows the expected selected area electron diffraction pattern with sets of diffraction spots out with different angular spacings, unlike graphene which shows a hexagonal pattern. Twisted multilayer graphene oxide could be prepared by the above procedure. Twisted boron nitride, prepared by cross-linking layers of BN containing surface amino groups with oxalic acid linker, exhibits a diffraction pattern comparable to that of twisted graphene. Linsitinib ic50 First-principles DFT calculations throw light on the structures and the nature of interactions associated with twisted graphene/BN obtained by covalent linking of layers. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This study explored the relationships between the decline in sexual function and psychological burdens and life satisfaction in older men with the aim of providing prospective targets for interventions. From January 2016 to January 2019, we selected 1,326 men aged over 50 years old. We adopted the International Index of Erectile Function-5 (IIEF-5), self-estimated intravaginal ejaculatory latency time (IELT), the premature ejaculation diagnostic tool (PEDT), the General Anxiety Disorder-7 (GAD-7), the Patients Health Questionnaire-9 (PHQ-9), the satisfaction with life scale and the control, autonomy, self-realisation and pleasure scale (CASP-19) to measure premature ejaculation, erectile dysfunction and well-being (including, depression, anxiety, and life quality and satisfaction) respectively. The individuals were divided into two main groups the decline group and the no-decline group. The incidences of erectile dysfunction (ED), premature ejaculation (PE), anxiety and depression in men who reported a declinine in sexuality. © 2020 Blackwell Verlag GmbH.The Iroquois homeobox gene 5 (IRX5), one of the members of the Iroquois homeobox family, has been identified to correlate with worse prognosis in many cancers, including colorectal cancer (CRC). In this study, upregulation of IRX5 revealed a great reduction in the proliferation of CRC colorectal cancer cell line SW480 and DLD-1, which was accompanied by G1/S arrest, increased expression in cyclin E1, P21, and P53 and a decrease in cyclin A2, B1, and D1. Furthermore, IRX5-mediated an increase expression of RH2A protein, the biomarker of DNA damage. Consequently, the SA-β-gal level is higher in IRX5-overexpression cells compared to control ones, which showed elevated DNA damage triggered cellular senescence. Recapitulating the above findings, IRX5 exhibited higher levels of genomic instability. IRX5 may be a perspective target for cancer therapy and it deserves further investigation. © 2020 Wiley Periodicals, Inc.An embryonic lethal mutation in chicken named cleft primary palate (cpp) is inherited in an autosomal recessive mode and results in a severely truncated upper beak. In this study, genotyping and sequencing techniques were employed to advance our genetic and genomic knowledge of the mutation's chromosomal location, candidate region and possible causative element using a congenic inbred line. Herein, the candidate region for the cpp developmental mutation was established as a ca. 5.1 Mb region of chicken chromosome 11 (GGA 11) through the use of a 600K Affymetrix SNP array. The SNPs identified from this array linked to cpp were used to genotype individuals from the congenic inbred line over several generations and thereby fine-map the causative region resulting in an approximately 200 kb size reduction. This candidate region (4.9 Mb) was sequenced via capture array in a cohort of 24 individuals, including carriers, mutants and their wild type (wt) siblings. Interestingly, the GGA 11 region for cpp encompasses the predicted centromere location and is thus unlikely to be highly disrupted by further recombination.