Stick index of knots and links in the cubic lattice

The cubic lattice stick index of a knot type is the least number of sticks necessary to construct the knot type in the 3-dimensional cubic lattice. We present the cubic lattice stick index of various knots and links, including all (p,p+1)-torus knots, and show how composing and taking satellites can be used to obtain the cubic lattice stick index for a relatively large infinite class of knots. Additionally, we present several bounds relating cubic lattice stick index to other known invariants.Comment: 16 pages, 12 figure

The Science of Safety – An Emerging Concept in Medication Use and Research

Most published reports of patient safety in clinical practice focus largely on the culture of safety in complex health systems, separate from pre-approval and postmarketing research-related safety considerations for drugs, biologics, and other medical products. The science of safety requires a linked integrated perspective, i.e., an iterative process examining and relating safety concerns from drug or biologic discovery and development in preclinical stages, clinical trials and post-market use, research, surveillance, and potential regulatory changes. This commentary addresses the science of safety across the lifecycle of drug and biological products, regulatory considerations, barriers, and research needs. This paper provides a brief overview on how the functioning of healthcare systems affects the safety environment and describes how stakeholder involvement, research participation, and targeted education and training can help facilitate better safety measures and practices, provide improved quality of care to patients, and contribute to the science of safety. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties".   Type: Commentar

The Science of Safety – An Emerging Concept in Medication Use and Research

Most published reports of patient safety in clinical practice focus largely on the culture of safety in complex health systems, separate from pre-approval and postmarketing research-related safety considerations for drugs, biologics, and other medical products. The science of safety requires a linked integrated perspective, i.e., an iterative process examining and relating safety concerns from drug or biologic discovery and development in preclinical stages, clinical trials and post-market use, research, surveillance, and potential regulatory changes. This commentary addresses the science of safety across the lifecycle of drug and biological products, regulatory considerations, barriers, and research needs. This paper provides a brief overview on how the functioning of healthcare systems affects the safety environment and describes how stakeholder involvement, research participation, and targeted education and training can help facilitate better safety measures and practices, provide improved quality of care to patients, and contribute to the science of safety. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties".   Type: Commentar

Improving Anti-Hypertensive Medication Taking: the Direct and Interacting Effects of Perceived Adherence Difficulty, Adherence Knowledge, and Commitment to Adherence

Background Non-adherence to anti-hypertensive medications is prevalent, leading to increased hospital costs and preventable deaths and disabilities. Managing patient perceptions of adherence difficulties may be key to improving adherence. Objective This study examined the potential negative effect of patients’ perceived difficulties with anti-hypertensive medication taking on adherence, along with whether and how that effect could be reduced through patient knowledge of and commitment to adherence. Method 10,867 adult U.S. residents diagnosed with essential hypertension and prescribed anti-hypertensive medications participated in a cross-sectional online survey using self-reported behaviors and perceptions. Stepwise regressions and mean difference analyses were performed. Results Perceived adherence difficulty was negatively associated with adherence behaviors (b = -.443, p \u3c .001). This association was reduced by the moderating effects of adherence knowledge (b = .035, p \u3c .001) and commitment to adherence (b = .008, p = .037), and their direct effects on adherence behaviors (b = .075, p \u3c .001; b = .095, p \u3c .001, respectively). Some differences by patient race-ethnicity and income were observed

Fragile X syndrome: Diagnostic and carrier testing

The following are the recommendations of the American College of Medical Genetics (ACMG) Professional Practice and Guidelines Committee, convened to assist health care professionals in making decisions regarding genetic diagnosis and testing. The purpose of this document is to provide a brief overview of fragile X syndrome (FXS), and to make recommendations that can serve as general guidelines to aid clinicians in making referrals for diagnostic and carrier testing for this condition. Fragile X syndrome is the most common cause of inherited mental retardation and is caused by a mutation in the X-linked FMR1 gene. DNA studies are used for testing individuals with symptoms of FXS and individuals at risk for carrying the mutation. Genotypes are determined by examining the size of the trinucleotide repeat segment and the methylation status of the FMR1 gene. These guidelines supersede the 1994 ACMG statement of the same name

Progress and challenges in glacial lake outburst flood research (2017–2021):a research community perspective

Glacial lake outburst floods (GLOFs) are among the most concerning consequences of retreating glaciers in mountain ranges worldwide. GLOFs have attracted significant attention amongst scientists and practitioners in the past 2 decades, with particular interest in the physical drivers and mechanisms of GLOF hazard and in socioeconomic and other human-related developments that affect vulnerabilities to GLOF events. This increased research focus on GLOFs is reflected in the gradually increasing number of papers published annually. This study offers an overview of recent GLOF research by analysing 594 peer-reviewed GLOF studies published between 2017 and 2021 (Web of Science and Scopus databases), reviewing the content and geographical focus as well as other characteristics of GLOF studies. This review is complemented with perspectives from the first GLOF conference (7-9 July 2021, online) where a global GLOF research community of major mountain regions gathered to discuss the current state of the art of integrated GLOF research. Therefore, representatives from 17 countries identified and elaborated trends and challenges and proposed possible ways forward to navigate future GLOF research, in four thematic areas: (i) understanding GLOFs - timing and processes; (ii) modelling GLOFs and GLOF process chains; (iii) GLOF risk management, prevention and warning; and (iv) human dimensions of GLOFs and GLOF attribution to climate change.Fil: Emmer, Adam. University of Graz; AustriaFil: Allen, Simon K.. Universitat Zurich; Suiza. Universidad de Ginebra; SuizaFil: Carey, Mark. University of Oregon; Estados UnidosFil: Frey, Holger. Universitat Zurich; SuizaFil: Huggel, Christian. Universitat Zurich; SuizaFil: Korup, Oliver. Universitat Potsdam; AlemaniaFil: Mergili, Martin. University of Graz; AustriaFil: Sattar, Ashim. Universitat Zurich; SuizaFil: Veh, Georg. Universitat Potsdam; AlemaniaFil: Chen, Thomas Y.. Columbia University; Estados UnidosFil: Cook, Simon J.. University Of Dundee; Reino Unido. Unesco. Centre For Water Law, Policy And Science; Reino UnidoFil: Correas Gonzalez, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Das, Soumik. Jawaharlal Nehru University; IndiaFil: Diaz Moreno, Alejandro. Reynolds International Ltd; Reino UnidoFil: Drenkhan, Fabian. Pontificia Universidad Católica de Perú; PerúFil: Fischer, Melanie. Universitat Potsdam; AlemaniaFil: Immerzeel, Walter W.. Utrecht University; Países BajosFil: Izagirre, Eñaut. Universidad del País Vasco; EspañaFil: Joshi, Ramesh Chandra. Kumaun University India; IndiaFil: Kougkoulos, Ioannis. American College Of Greece; GreciaFil: Kuyakanon Knapp, Riamsara. University of Oslo; Noruega. University of Cambridge; Estados UnidosFil: Li, Dongfeng. National University Of Singapore; SingapurFil: Majeed, Ulfat. University Of Kashmir; IndiaFil: Matti, Stephanie. Haskoli Islands; IslandiaFil: Moulton, Holly. University of Oregon; Estados UnidosFil: Nick, Faezeh. Utrecht University; Países BajosFil: Piroton, Valentine. Université de Liège; BélgicaFil: Rashid, Irfan. University Of Kashmir; IndiaFil: Reza, Masoom. Kumaun University India; IndiaFil: Ribeiro De Figueiredo, Anderson. Universidade Federal do Rio Grande do Sul; BrasilFil: Riveros, Christian. Instituto Nacional de Investigación En Glaciares y Ecosistemas de Montaña; PerúFil: Shrestha, Finu. International Centre For Integrated Mountain Development Nepal; NepalFil: Shrestha, Milan. Arizona State University; Estados UnidosFil: Steiner, Jakob. International Centre For Integrated Mountain Development Nepal; NepalFil: Walker-Crawford, Noah. Colegio Universitario de Londres; Reino UnidoFil: Wood, Joanne L.. University of Exeter; Reino UnidoFil: Yde, Jacob C.. Western Norway University Of Applied Sciences; Suiz

Consumption of a soy drink has no effect on cognitive function but may alleviate vasomotor symptoms in post-menopausal women; a randomised trial

Purpose: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. Methods: 101 post-menopausal women, aged 44–63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene’s Climacteric Scale. Results: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: − 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). Conclusions: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women

Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping

Human CD8+ T cell cross-reactivity across influenza A, B and C viruses

Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8+ T cells confer cross-protection against IAV strains, however the responses of CD8+ T cells to IBV and ICV are understudied. We investigated the breadth of CD8+ T cell cross-recognition and provide evidence of CD8+ T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8+ T cell epitopes from IBVs that were protective in mice and found memory CD8+ T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8+ T cells displayed tissue-resident memory phenotypes. Notably, CD38+Ki67+CD8+ effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8+ T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction