Opposing patterns in self-reported and measured physical activity levels in middle-aged adults

Physical activity brings significant health benefits to middle-aged adults, although the research to date has been focused on late adulthood. This study aims to examine how ageing affects the self-reported and accelerometer-derived measures of physical activity levels in middle-aged adults. We employed the data recorded in the UK Biobank and analysed the physical activity levels of 2,998 participants (1381 men and 1617 women), based on self-completion questionnaire and accelerometry measurement of physical activity. We also assessed the musculoskeletal health of the participants using the dual-energy X-ray absorptiometry (DXA) measurements provided by the UK Biobank. Participants were categorised into three groups according to their age: group I younger middle-aged (40 to 49 years), group II older middle-aged (50 to 59 years), and group III oldest middle-aged (60 to 69 years). Self-reported physical activity level increased with age and was the highest in group III, followed by group II and I (P?<?0.05). On the contrary, physical activity measured by accelerometry decreased significantly with age from group I to III (P?<?0.05), and the same pertained to the measurements of musculoskeletal health (P?<?0.05). It was also shown that middle-aged adults mostly engaged in low and moderate intensity activities. The opposing trends of the self-reported and measured physical activity levels may suggest that middle-aged adults over-report their activity level as they age. They should be aware of the difference between their perceived and actual physical activity levels, and objective measures would be useful to prevent the decline in musculoskeletal health.

     

北京市三级甲等医院结直肠癌患者就医流向规律分析

目的 分析不同特征的结直肠癌患者就医行为选择在中医院（含中西医结合医院）、西医院及肿瘤专科医院间的差异，为合理引导结直肠癌患者适宜就医及制订相关政策提供依据。方法 收集北京地区2018年1月-2019年12月17家三级甲等医院21894例首诊结直肠癌成年住院患者的病案首页数据，采用EmpowerStats 2.0对数据进行描述性分析。结果 21894例结直肠癌患者中就诊于中医院的有862例（3.93%），西医院的有8723例（39.85%），肿瘤专科医院的有12309例（56.22%）。对于不同医疗机构，男性占比均大于女性，58-68岁患者占比最大。且结直肠癌患者年龄、医疗付款方式及肿瘤分期在不同医疗机构间的分布存在差异（P<0.001）。西医院及肿瘤专科医院结直肠癌Ⅲ期患者占比最大，而就诊于中医院患者中结直肠癌Ⅳ期最多。从地域分布来看，异地就诊比例（57.32%）大于本地，且就诊于肿瘤专科医院的患者中73.66%来自外地。患者来源前三名分别是北京市、河北省及内蒙古自治区。而在北京市内，西医院患者主要来源于朝阳区、海淀区及西城区，中医院患者主要来源于海淀区、朝阳区及丰台区，肿瘤专科医院则主要来源于朝阳区、海淀区及丰台区。结论 应大力倡导年轻以及早期结直肠癌患者向中医院分流，充分施展中医药在结直肠癌患者中的治疗优势；发挥三级医院带动作用，建立对口帮扶医院，减少不必要的跨省流动及提倡结直肠癌的早筛早治，以降低结直肠癌死亡率。     

A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders

PurposeUnderstanding the value of genetic screening and testing for monogenic disorders requires high-quality, methodologically robust economic evaluations. This systematic review sought to assess the methodological quality among such studies and examined opportunities for improvement.MethodsWe searched PubMed, Cochrane, Embase, and Web of Science for economic evaluations of genetic screening/testing (2013-2019). Methodological rigor and adherence to best practices were systematically assessed using the British Medical Journal checklist.ResultsAcross the 47 identified studies, there were substantial variations in modeling approaches, reporting detail, and sophistication. Models ranged from simple decision trees to individual-level microsimulations that compared between 2 and >20 alternative interventions. Many studies failed to report sufficient detail to enable replication or did not justify modeling assumptions, especially for costing methods and utility values. Meta-analyses, systematic reviews, or calibration were rarely used to derive parameter estimates. Nearly all studies conducted some sensitivity analysis, and more sophisticated studies implemented probabilistic sensitivity/uncertainty analysis, threshold analysis, and value of information analysis.ConclusionWe describe a heterogeneous body of work and present recommendations and exemplar studies across the methodological domains of (1) perspective, scope, and parameter selection; (2) use of uncertainty/sensitivity analyses; and (3) reporting transparency for improvement in the economic evaluation of genetic screening/testing.     

Fibroblast growth factor receptors in cancer: genetic alterations,diagnostics, therapeutic targets and mechanisms of resistance

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...