Effect of thong style flip-flops on children’s barefoot walking and jogging kinematics

BACKGROUND: Thong style flip-flops are a popular form of footwear for children. Health professionals relate the wearing of thongs to foot pathology and deformity despite the lack of quantitative evidence to support or refute the benefits or disadvantages of children wearing thongs. The purpose of this study was to compare the effect of thong footwear on children’s barefoot three dimensional foot kinematics during walking and jogging. METHODS: Thirteen healthy children (age 10.3 ± 1.6 SD years) were recruited from the metropolitan area of Sydney Australia following a national press release. Kinematic data were recorded at 200 Hz using a 14 camera motion analysis system (Cortex, Motion Analysis Corporation, Santa Rosa, USA) and simultaneous ground reaction force were measured using a force platform (Model 9281B, Kistler, Winterthur, Switzerland). A three-segment foot model was used to describe three dimensional ankle, midfoot and one dimensional hallux kinematics during the stance sub-phases of contact, midstance and propulsion. RESULTS: Thongs resulted in increased ankle dorsiflexion during contact (by 10.9°, p; = 0.005 walk and by 8.1°, p; = 0.005 jog); increased midfoot plantarflexion during midstance (by 5.0°, p; = 0.037 jog) and propulsion (by 6.7°, p; = 0.044 walk and by 5.4°, p;= 0.020 jog); increased midfoot inversion during contact (by 3.8°, p;= 0.042 jog) and reduced hallux dorsiflexion during walking 10% prior to heel strike (by 6.5°, p; = 0.005) at heel strike (by 4.9°, p; = 0.031) and 10% post toe-off (by 10.7°, p; = 0.001). CONCLUSIONS: Ankle dorsiflexion during the contact phase of walking and jogging, combined with reduced hallux dorsiflexion during walking, suggests a mechanism to retain the thong during weight acceptance. Greater midfoot plantarflexion throughout midstance while walking and throughout midstance and propulsion while jogging may indicate a gripping action to sustain the thong during stance. While these compensations exist, the overall findings suggest that foot motion whilst wearing thongs may be more replicable of barefoot motion than originally thought

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types.

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK [C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC]. Funding for the Collaborative Oncological Gene-environment Study (COGS) infrastructure came from: the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the US National Institutes of Health (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the US Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented under Supplementary Financial Support.This is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/2159-8290.CD-15-122

Association between intensity of statin therapy and mortality in persons with chronic kidney disease

Background: The 2013 American College of Cardiology/American Heart Association lipid guideline recommends statin dosing based on intensity, rather than targeting specific low-density lipoprotein cholesterol (LDL-C) concentrations, among general populations. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) lipid guideline recommends statins for most adults with chronic kidney disease (CKD), but dose-dependent statin effects in CKD are unclear.Methods: We performed a retrospective cohort study of US veterans with CKD Stages G3a, G3b or G4, and new, persistent statin use, from 2005 to 2015. We tested the association of intensity of statin therapy [categorized as low (expected LDL-C reduction \u3c30%), medium (30 to \u3c50%) or high (≥50%)] during the initial 1-year exposure period, with all-cause mortality over the subsequent 4 years. We used Cox proportional hazard models to evaluate the association between statin intensity and all-cause mortality, adjusting for demographics, comorbidities and laboratory measurements.Results: Our cohort included 65 292 persons, of whom 40 124 (61.5%) had CKD G3a, 20 183 (30.9%) G3b and 4985 (7.6%) G4. Overall, 4878 (7.5%) used high-intensity, 39 070 (59.8%) used moderate-intensity and 21 344 (32.7%) used low-intensity statins. High-intensity statins were used more in recent years, and among persons diagnosed with atherosclerotic cardiovascular disease. There was no association between statin intensity and mortality in unadjusted or multivariable-adjusted analyses.Conclusions: There were no significant associations between statin intensity over 1 year of exposure and subsequent mortality among US veterans with CKD. This supports the current KDIGO guideline recommendations to use statins and dosages that have been studied specifically in CKD populations, rather than intensity-based dosing

Kidney Function Trajectories and Right Heart Failure Following LVAD Implantation

Background Preoperative kidney dysfunction is a risk factor for right heart failure (RHF) after implantation of a left ventricular assist device (LVAD). However, characteristic kidney function trajectories before and after post‐LVAD RHF are uncertain, so we investigated this. Methods and Results We identified individuals who received primary continuous‐flow LVAD implantation from July 1, 2014 to December 31, 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data set. Incident RHF was ascertained using the INTERMACS definition at 1 and 3 months and classified as transient or persistent. Kidney function trajectories before and after RHF onset, and relationships of baseline kidney function with RHF risk at the different time points, were assessed. We identified 8076 LVAD recipients who met inclusion criteria. Incident RHF was present at 1 month in 26.4%. There were 4850 individuals with follow‐up at 3 months, with incident RHF in 4.2%. Kidney function trajectories differed from pre‐LVAD implantation to 1‐month follow‐up by RHF category, with those developing persistent RHF having no improvement in baseline kidney function. For trajectories before the 3‐month RHF ascertainment time, the shape was similar for those with and without RHF, with lower estimated glomerular filtration rate levels among those who developed RHF. Baseline estimated glomerular filtration rate levels below the normal range were associated with higher risk of RHF at 1 and 3 months. Conclusions In LVAD recipients, preimplantation kidney function and subsequent kidney function trajectories differed substantially by RHF at 1 and 3 months postimplantation, even after adjustment for several confounders. This may demonstrate bidirectional associations between kidney function and right ventricular function in LVAD recipients

Renin-angiotensin system blocker discontinuation and adverse outcomes in chronic kidney disease

Background: Treatment with renin-angiotensin system inhibitors (RASIs), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is the standard of care for those with chronic kidney disease (CKD) and albuminuria. However, ACEI/ARB treatment is often discontinued for various reasons. We investigated the association of ACEI/ARB discontinuation with outcomes among US veterans with non-dialysis-dependent CKD.Methods: We performed a retrospective cohort study of patients in the Veterans Affairs healthcare system with non-dialysis-dependent CKD who subsequently were started on ACEI/ARB therapy (new user design). Discontinuation events were defined as a gap in ACEI/ARB therapy of ≥14 days and were classified further based on duration (14-30, 31-60, 61-90, 91-180 and \u3e180 days). This was treated as a time-varying risk factor in adjusted Cox proportional hazards models for the outcomes of death and incident end-stage kidney disease (ESKD), which also adjusted for relevant confounders.Results: We identified 141 252 people with CKD and incident ACEI/ARB use who met the inclusion criteria; these were followed for a mean 4.87 years. There were 135 356 discontinuation events, 68 699 deaths and 6152 incident ESKD events. Discontinuation of ACEI/ARB was associated with a higher risk of death [hazard ratio (HR) 2.3, 2.0, 1.99, 1.92 and 1.74 for those discontinued for 14-30, 31-60, 61-90, 91-180 and \u3e180 days, respectively]. Similar associations were noted between ACEI and ARB discontinuation and ESKD (HR 1.64, 1.47, 1.54, 1.65 and 1.59 for those discontinued for 14-30, 31-60, 61-90, 91-180 and \u3e180 days, respectively).Conclusions: In a cohort of predominantly male veterans with CKD Stages 3 and 4, ACEI/ARB discontinuation was independently associated with an increased risk of subsequent death and ESKD. This may be due to the severity of illness factors that drive the decision to discontinue therapy. Further investigations to determine the causes of discontinuations and to provide an evidence base for discontinuation decisions are needed