Resonance in Human Walking Economy: How Natural Is It?

Locomotion and movement economy are cornerstone topics in movement science. Modeling the leg as a hybrid mass-spring pendulum shows walking economy should be optimized when stride frequency matches the resonant frequency of the limb. Human walking is described as self-optimizing because mean preferred (PSF) and modeled resonant (RSF) stride frequencies usually are statistically equivalent, but this depiction may not be fully justified. Purpose: To more thoroughly examine the self-optimization characterization and the consequences of obligating use of the RSF. Methods: Forty-seven individuals of diverse statures completed 3 consecutive days of preferred walking trials on a treadmill where stride rate, stride length, walking speed, heart rate and walking economy measures were made under steady state heart rate conditions. Anthropometric measures were taken to build a hybrid model of the leg and model the RSF. Reliability across days was evaluated via repeated measures analysis of variance (ANOVA) and intra-class correlation (á=.05) and correlations were calculated for PSF and RSF. A separate sample of 20 participants walked under 3 conditions, (1) completely preferred; (2) at the original preferred speed using the RSF; and (3) with the option to establish a new preferred speed while using the RSF. Results: Gait characteristics were fundamentally reliable across days and the correlation between PSF and RSF was weak (8% explained variance). Walking economy improved 14% when using the RSF and allowed to self-select the speed / stride length used at that cadence. Conclusions: The results raised slight questions about current self-optimization presumptions and further emphasized the role of resonance in walking economyFaculty Sponsor: Dr. Philip K. Scho

Why do some coronaviruses become pandemic threats when others do not?

Despite multiple spillover events and short chains of transmission on at least 4 continents, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has never triggered a pandemic. By contrast, its relative, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has, despite apparently little, if any, previous circulation in humans. Resolving the unsolved mystery of the failure of MERS-CoV to trigger a pandemic could help inform how we understand the pandemic potential of pathogens, and probing it underscores a need for a more holistic understanding of the ways in which viral genetic changes scale up to population-level transmission

Coagulation factor VIII, white matter hyperintensities and cognitive function: Results from the Cardiovascular Health Study

Objective: To investigate the relationship between high FVIII clotting activity (FVIII:C), MRI-defined white matter hyperintensities (WMH) and cognitive function over time. Methods: Data from the population-based Cardiovascular Health Study (n = 5,888, aged ≥ 65) were used. FVIII:C was measured in blood samples taken at baseline. WMH burden was assessed on two cranial MRI scans taken roughly 5 years apart. Cognitive function was assessed annually using the Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST). We used ordinal logistic regression models adjusted for demographic and cardiovascular factors in cross-sectional and longitudinal WMH analyses, and adjusted linear regression and linear mixed models in the analyses of cognitive function. Results: After adjustment for confounding, higher levels of FVIII:C were not strongly associated with the burden of WMH on the initial MRI scan (OR>p75 = 1.20, 95% CI 0.99-1.45; N = 2,735) nor with WMH burden worsening over time (OR>p75 = 1.18, 95% CI 0.87-1.59; N = 1,527). High FVIII:C showed no strong association with cognitive scores cross-sectionally (3MSE>p75 β = -0.06, 95%CI -0.45 to 0.32, N = 4,005; DSST>p75 β = -0.69, 95%CI -1.52 to 0.13, N = 3,954) or over time (3MSE>p75 β = -0.07,95% CI -0.58 to 0.44, N = 2,764; DSST>p75 β = -0.22, 95% CI -0.97 to 0.53, N = 2,306) after confounding adjustment. Interpretation: The results from this cohort study of older adult participants indicate no strong relationships between higher FVIII:C levels and WMH burden or cognitive function in cross-sectional and longitudinal analyses

Fresolimumab Treatment Decreases Biomarkers and Improves Clinical Symptoms in Systemic Sclerosis Patients

BACKGROUND. TGF-β has potent profibrotic activity in vitro and has long been implicated in systemic sclerosis (SSc), as expression of TGF-β–regulated genes is increased in the skin and lungs of patients with SSc. Therefore, inhibition of TGF-β may benefit these patients. METHODS. Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab, a high-affinity neutralizing antibody that targets all 3 TGF-β isoforms. Seven patients received two 1 mg/kg doses of fresolimumab, and eight patients received one 5 mg/kg dose of fresolimumab. Serial mid-forearm skin biopsies, performed before and after treatment, were analyzed for expression of the TGF-β–regulated biomarker genes thrombospondin-1 (THBS1) and cartilage oligomeric protein (COMP) and stained for myofibroblasts. Clinical skin disease was assessed using the modified Rodnan skin score (MRSS). RESULTS. In patient skin, THBS1 expression rapidly declined after fresolimumab treatment in both groups (P = 0.0313 at 7 weeks and P = 0.0156 at 3 weeks), and skin expression of COMP exhibited a strong downward trend in both groups. Clinical skin disease dramatically and rapidly decreased (P \u3c 0.001 at all time points). Expression levels of other TGF-β–regulated genes, including SERPINE1 and CTGF, declined (P = 0.049 and P = 0.012, respectively), and a 2-gene, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment (P = 0.0067). Dermal myofibroblast infiltration also declined in patient skin after fresolimumab (P \u3c 0.05). Baseline levels of THBS1 were predictive of reduced THBS1 expression and improved MRSS after fresolimumab treatment. CONCLUSION. The rapid inhibition of TGF-β–regulated gene expression in response to fresolimumab strongly implicates TGF-β in the pathogenesis of fibrosis in SSc. Parallel improvement in the MRSS indicates that fresolimumab rapidly reverses markers of skin fibrosis

Status loss due to COVID-19, traditional masculinity, and their association with recent suicide attempts and suicidal ideation

The COVID-19 pandemic is causing extensive job loss leading to a loss of social status in many men. Endorsement of traditional masculinity ideology may render some men particularly sensitive to status loss and thereby to an increased risk for suicidality. In this anonymous online survey conducted in German-speaking European countries, 490 men completed questionnaires regarding loss of social status due to the COVID-19 pandemic, past-month and lifetime suicide attempt and suicidal ideation. Furthermore, endorsement of traditional masculinity ideology and prototypical and male-typical externalizing depression symptoms were measured. Out of a total of 490 men, 14.7% of men reported experiencing status loss due to the pandemic. These men were more than four times as likely to have attempted suicide in the past month (OR = 4.48, 95% CI [1.72, 11.67]) and more than twice as likely to report suicidal ideation during the past 2 weeks (OR = 2.47, 95% CI [1.42, 4.28]), than men not reporting status loss. Status loss, but not endorsement of traditional masculinity ideology, was associated with suicide outcomes. However, when male-typical externalizing depression symptoms and prototypical depression symptoms were included in the models, they exhibited the only direct associations with suicide outcomes (e.g., for past-month suicide attempt: male-typical externalizing depression symptoms OR = 2.18, 95% CI [1.31, 3.62], prototypical depression symptoms OR = 2.41, 95% CI [1.13, 5.12]). A significant interaction between status loss and endorsement of traditional masculinity ideology further suggests an enhancing moderating effect of traditional masculinity on the relationship between status loss and past-month suicide attempts (OR = 3.27, 95% CI [1.16, 9.27]). Status loss due to the COVID-19 pandemic emerges as risk factor for suicide in men. Men who experience status loss due to the COVID-19 pandemic while concomitantly exhibiting strong endorsement of traditional masculinity ideology have an additional increased risk of suicide

Selective deforestation and exposure of African wildlife to bat-borne viruses

Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017–2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how “upstream” drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk.Peer reviewe

Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

OBJECTIVE: Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder. METHODS: We analyzed 644 bipolar families ascertained by the National Institute of Mental Health Human Genetics Initiative for bipolar disorder. The families have been genotyped with microsatellite loci spaced every approximately 10 cM or less across the genome. Earlier analyses of these pedigrees have been limited to nonparametric (model-free) methods and thus, information from unaffected subjects with genotypes was not considered. In this study, we used parametric analyses assuming dominant and recessive transmission and specifying a maximum penetrance of 70%, so that information from unaffecteds could be weighed in the linkage analyses. As in previous linkage analyses of these pedigrees, we analyzed three diagnostic categories: model 1 included only bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately 4% were schizoaffective, bipolar); model 2 included all individuals in model 1 plus bipolar II patients (1764 total individuals); and model 3 included all individuals in model 2 with the addition of patients with recurrent major depressive disorder (2046 total persons). RESULTS: Assuming dominant inheritance the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with D16S749 using model 2 patients. Multipoint analyses of this region yielded a maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20 markers were positive and multipoint analyses of the area gave a maximum LOD of 3.0 with model 2 cases. CONCLUSION: The chromosome 16p and 20 regions have been implicated by some studies and the data reported herein provide additional suggestive evidence of bipolar susceptibility genes in these regions

Engaging Undergraduates in Science Research: Not Just About Faculty Willingness.

Despite the many benefits of involving undergraduates in research and the growing number of undergraduate research programs, few scholars have investigated the factors that affect faculty members' decisions to involve undergraduates in their research projects. We investigated the individual factors and institutional contexts that predict faculty members' likelihood of engaging undergraduates in their research project(s). Using data from the Higher Education Research Institute's 2007-2008 Faculty Survey, we employ hierarchical generalized linear modeling to analyze data from 4,832 science, technology, engineering, and mathematics (STEM) faculty across 194 institutions to examine how organizational citizenship behavior theory and social exchange theory relate to mentoring students in research. Key findings show that faculty who work in the life sciences and those who receive government funding for their research are more likely to involve undergraduates in their research project(s). In addition, faculty at liberal arts or historically Black colleges are significantly more likely to involve undergraduate students in research. Implications for advancing undergraduate research opportunities are discussed

The Global Task Force for Chronic Pain in People with HIV (PWH):Developing a research agenda in an emerging field

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward