Validation of a laboratory method for evaluating dynamic properties of reconstructed equine racetrack surfaces.

BackgroundRacetrack surface is a risk factor for racehorse injuries and fatalities. Current research indicates that race surface mechanical properties may be influenced by material composition, moisture content, temperature, and maintenance. Race surface mechanical testing in a controlled laboratory setting would allow for objective evaluation of dynamic properties of surface and factors that affect surface behavior.ObjectiveTo develop a method for reconstruction of race surfaces in the laboratory and validate the method by comparison with racetrack measurements of dynamic surface properties.MethodsTrack-testing device (TTD) impact tests were conducted to simulate equine hoof impact on dirt and synthetic race surfaces; tests were performed both in situ (racetrack) and using laboratory reconstructions of harvested surface materials. Clegg Hammer in situ measurements were used to guide surface reconstruction in the laboratory. Dynamic surface properties were compared between in situ and laboratory settings. Relationships between racetrack TTD and Clegg Hammer measurements were analyzed using stepwise multiple linear regression.ResultsMost dynamic surface property setting differences (racetrack-laboratory) were small relative to surface material type differences (dirt-synthetic). Clegg Hammer measurements were more strongly correlated with TTD measurements on the synthetic surface than the dirt surface. On the dirt surface, Clegg Hammer decelerations were negatively correlated with TTD forces.ConclusionsLaboratory reconstruction of racetrack surfaces guided by Clegg Hammer measurements yielded TTD impact measurements similar to in situ values. The negative correlation between TTD and Clegg Hammer measurements confirms the importance of instrument mass when drawing conclusions from testing results. Lighter impact devices may be less appropriate for assessing dynamic surface properties compared to testing equipment designed to simulate hoof impact (TTD).Potential relevanceDynamic impact properties of race surfaces can be evaluated in a laboratory setting, allowing for further study of factors affecting surface behavior under controlled conditions

Placental abnormalities in type 1 and type 2 diabetes mellitus : a systematic review and metaanalysis of shear wave elastography

OBJECTIVE: This study aimed to describe the placental changes occurring in women with preexisting diabetes mellitus and to determine if elastography can detect placental changes in vivo. DATA SOURCES: PubMed, Embase, Medline, and Cochrane were searched to identify English language studies published until July 2020. STUDY ELIGIBILITY CRITERIA: 1) For key question 1, studies that described histopathologic changes in placentas from women with known diabetes mellitus and 2) for key question 2, those that described structural–placental changes detectable by elastography in high-risk pregnancies (eg, those complicated by preeclampsia and/or fetal growth restriction), were included. METHODS: For key question 1, we grouped placental pathologies using the Amsterdam International Consensus Group definitions. For key question 2, we conducted a metaanalysis including all data from studies reporting placental stiffness in meters per second (m/s) or kilopascals (kPa). The mean difference (95% confidence interval) was calculated using a random effects model. RESULTS: Data were extracted from 14 studies of placental histopathology in women with known diabetes. In this group, a wide variety of placental histopathologic changes are described, though none are considered pathognomonic. The histopathologic changes including maternal vascular malperfusion, fetal vascular malperfusion, and/or infectious/inflammatory/other changes were divided into 3 broad categories on the basis of presumed etiology. A total of 15 studies reported the placental stiffness scores in women with a high-risk pregnancy vs those with a normal pregnancy. Only 1 reported stiffness scores for placentas in women with preexisting diabetes mellitus (N<10 women). Pooled analysis of 14 studies with available data included 478 “high-risk pregnancies” and 828 control or healthy pregnancies. Maternal-derived pathologies resulted in higher placental stiffness (mean difference 4.5 kPa [95% confidence interval, 3.16–5.87]) compared with control or healthy pregnancies. Fetal-derived pathologies also resulted in higher placental stiffness (mean difference of 6.5 kPa [95% confidence interval, 1.08–11.86]) compared with control or healthy pregnancies. CONCLUSION: Shear wave elastography may provide an in vivo approximation of placental histopathology in women with certain kinds of high-risk pregnancies. A high-risk pregnancy may involve maternal- and fetal-derived pathologies. Further studies, particularly in women with preexisting diabetes, are needed to confirm this observation

Correction: Validation of a Laboratory Method for Evaluating Dynamic Properties of Reconstructed Equine Racetrack Surfaces.

[This corrects the article DOI: 10.1371/journal.pone.0050534.]

Precis of Vaulting Ambition: Sociobiology and the Quest for Human Nature

The debate about the credentials of sociobiology has persisted because scholars have failed to distinguish the varieties of sociobiology and because too little attention has been paid to the details of the arguments that are supposed to support the provocative claims about human social behavior. I seek to remedy both dcfieieneies. After analysis of the relationships among different kinds of sociobiology and contemporary evolutionary theory, I attempt to show how some of the studies of the behavior of nonhuman animals meet the methodological standards appropriate to evolutionary research. I contend that the efforts of E. O. Wilson, Richard Alexander, Charles Lumsden, and others to generate conclusions about human nature are flawed, both because they apply evolutionary ideas in an unrigorous fashion and because they use dubious assumptions to connect their evolutionary analyses with their conclusions. This contention rests on analyses of many of the major sociobiological proposals about human social behavior, including: differences in sex roles, racial hostility, homosexuality, conflict between parents and adolescent offspring, incest avoidance, the avunculate, alliances in combat, female infanticide, and gene-culture coevolution. Vaulting Ambition thus seeks to identify what is good in sociobiology, to expose the errors of premature speculations about human nature, and to prepare the way for serious study of the evolution of human social behavior

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

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

Validation of a laboratory method for evaluating dynamic properties of reconstructed equine racetrack surfaces.

BackgroundRacetrack surface is a risk factor for racehorse injuries and fatalities. Current research indicates that race surface mechanical properties may be influenced by material composition, moisture content, temperature, and maintenance. Race surface mechanical testing in a controlled laboratory setting would allow for objective evaluation of dynamic properties of surface and factors that affect surface behavior.ObjectiveTo develop a method for reconstruction of race surfaces in the laboratory and validate the method by comparison with racetrack measurements of dynamic surface properties.MethodsTrack-testing device (TTD) impact tests were conducted to simulate equine hoof impact on dirt and synthetic race surfaces; tests were performed both in situ (racetrack) and using laboratory reconstructions of harvested surface materials. Clegg Hammer in situ measurements were used to guide surface reconstruction in the laboratory. Dynamic surface properties were compared between in situ and laboratory settings. Relationships between racetrack TTD and Clegg Hammer measurements were analyzed using stepwise multiple linear regression.ResultsMost dynamic surface property setting differences (racetrack-laboratory) were small relative to surface material type differences (dirt-synthetic). Clegg Hammer measurements were more strongly correlated with TTD measurements on the synthetic surface than the dirt surface. On the dirt surface, Clegg Hammer decelerations were negatively correlated with TTD forces.ConclusionsLaboratory reconstruction of racetrack surfaces guided by Clegg Hammer measurements yielded TTD impact measurements similar to in situ values. The negative correlation between TTD and Clegg Hammer measurements confirms the importance of instrument mass when drawing conclusions from testing results. Lighter impact devices may be less appropriate for assessing dynamic surface properties compared to testing equipment designed to simulate hoof impact (TTD).Potential relevanceDynamic impact properties of race surfaces can be evaluated in a laboratory setting, allowing for further study of factors affecting surface behavior under controlled conditions

Correction: Validation of a Laboratory Method for Evaluating Dynamic Properties of Reconstructed Equine Racetrack Surfaces.

[This corrects the article DOI: 10.1371/journal.pone.0050534.]