Atherogenic potential of microgravity hemodynamics in the carotid bifurcation: a numerical investigation

Long-duration spaceflight poses multiple hazards to human health, including physiological changes associated with microgravity. The hemodynamic adaptations occurring upon entry into weightlessness have been associated with retrograde stagnant flow conditions and thromboembolic events in the venous vasculature but the impact of microgravity on cerebral arterial hemodynamics and function remains poorly understood. The objective of this study was to quantify the effects of microgravity on hemodynamics and wall shear stress (WSS) characteristics in 16 carotid bifurcation geometries reconstructed from ultrasonography images using computational fluid dynamics modeling. Microgravity resulted in a significant 21% increase in flow stasis index, a 22–23% decrease in WSS magnitude and a 16–26% increase in relative residence time in all bifurcation branches, while preserving WSS unidirectionality. In two anatomies, however, microgravity not only promoted flow stasis but also subjected the convex region of the external carotid arterial wall to a moderate increase in WSS bidirectionality, which contrasted with the population average trend. This study suggests that long-term exposure to microgravity has the potential to subject the vasculature to atheroprone hemodynamics and this effect is modulated by subject-specific anatomical features. The exploration of the biological impact of those microgravity-induced WSS aberrations is needed to better define the risk posed by long spaceflights on cardiovascular health

Effect of Bout Length on Gait Measures in People with and without Parkinson’s Disease during Daily Life

Although the use of wearable technology to characterize gait disorders in daily life is increasing, there is no consensus on which specific gait bout length should be used to characterize gait. Clinical trialists using daily life gait quality as study outcomes need to understand how gait bout length affects the sensitivity and specificity of measures to discriminate pathological gait as well as the reliability of gait measures across gait bout lengths. We investigated whether Parkinson’s disease (PD) affects how gait characteristics change as bout length changes, and how gait bout length affects the reliability and discriminative ability of gait measures to identify gait impairments in people with PD compared to neurotypical Old Adults (OA). We recruited 29 people with PD and 20 neurotypical OA of similar age for this study. Subjects wore 3 inertial sensors, one on each foot and one over the lumbar spine all day, for 7 days. To investigate which gait bout lengths should be included to extract gait measures, we determined the range of gait bout lengths available across all subjects. To investigate if the effect of bout length on each gait measure is similar or not between subjects with PD and OA, we used a growth curve analysis. For reliability and discriminative ability of each gait measure as a function of gait bout length, we used the intraclass correlation coefficient (ICC) and area under the curve (AUC), respectively. Ninety percent of subjects walked with a bout length of less than 53 strides during the week, and the majority (\u3e50%) of gait bouts consisted of less than 12 strides. Although bout length affected all gait measures, the effects depended on the specific measure and sometimes differed for PD versus OA. Specifically, people with PD did not increase/decrease cadence and swing duration with bout length in the same way as OA. ICC and AUC characteristics tended to be larger for shorter than longer gait bouts. Our findings suggest that PD interferes with the scaling of cadence and swing duration with gait bout length. Whereas control subjects gradually increased cadence and decreased swing duration as bout length increased, participants with PD started with higher than normal cadence and shorter than normal stride duration for the smallest bouts, and cadence and stride duration changed little as bout length increased, so differences between PD and OA disappeared for the longer bout lengths. Gait measures extracted from shorter bouts are more common, more reliable, and more discriminative, suggesting that shorter gait bouts should be used to extract potential digital biomarkers for people with PD

Parameterizing the impact of seawater temperature and irradiance on dimethylsulfide (DMS) in the Great Barrier Reef and the contribution of coral reefs to the global sulfur cycle

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Jackson, R. L., Gabric, A. J., Matrai, P. A., Woodhouse, M. T., Cropp, R., Jones, G. B., Deschaseaux, E. S. M., Omori, Y., McParland, E. L., Swan, H. B., & Tanimoto, H. Parameterizing the impact of seawater temperature and irradiance on dimethylsulfide (DMS) in the Great Barrier Reef and the contribution of coral reefs to the global sulfur cycle. Journal of Geophysical Research:Oceans, 126(3), (2021): e2020JC016783, https://doi.org/10.1029/2020JC016783.Biogenic emissions of dimethylsulfide (DMS) are an important source of sulfur to the atmosphere, with implications for aerosol formation and cloud albedo over the ocean. Natural aerosol sources constitute the largest uncertainty in estimates of aerosol radiative forcing and climate and thus, an improved understanding of DMS sources is needed. Coral reefs are strong point sources of DMS; however, this coral source of biogenic sulfur is not explicitly included in climatologies or in model simulations. Consequently, the role of coral reefs in local and regional climate remains uncertain. We aim to improve the representation of tropical coral reefs in DMS databases by calculating a climatology of seawater DMS concentration (DMSw) and sea-air flux in the Great Barrier Reef (GBR), Australia. DMSw is calculated from remotely sensed observations of sea surface temperature and photosynthetically active radiation using a multiple linear regression model derived from field observations of DMSw in the GBR. We estimate that coral reefs and lagoon waters in the GBR (∼347,000 km2) release 0.03–0.05 Tg yr−1 of DMS (0.02 Tg yr−1 of sulfur). Based on this estimate, global tropical coral reefs (∼600,000 km2) could emit 0.08 Tg yr−1 of DMS (0.04 Tg yr−1 of sulfur), with the potential to influence the local radiative balance.Australian Research Council. Grant Number: DP150101649 National Science Foundation (NSF). Grant Number: 1543450 Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research. Grant Number: 23310016,16H02967,24241010,15H01732 Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Young Scientists. Grant Number: 17K1281

The Formation and Survival of Discs in a Lambda-CDM Universe

We study the formation of galaxies in a Lambda-CDM Universe using high resolution hydrodynamical simulations with a multiphase treatment of gas, cooling and feedback, focusing on the formation of discs. Our simulations follow eight haloes similar in mass to the Milky Way and extracted from a large cosmological simulation without restriction on spin parameter or merger history. This allows us to investigate how the final properties of the simulated galaxies correlate with the formation histories of their haloes. We find that, at z = 0, none of our galaxies contain a disc with more than 20 per cent of its total stellar mass. Four of the eight galaxies nevertheless have well-formed disc components, three have dominant spheroids and very small discs, and one is a spheroidal galaxy with no disc at all. The z = 0 spheroids are made of old stars, while discs are younger and formed from the inside-out. Neither the existence of a disc at z = 0 nor the final disc-to-total mass ratio seems to depend on the spin parameter of the halo. Discs are formed in haloes with spin parameters as low as 0.01 and as high as 0.05; galaxies with little or no disc component span the same range in spin parameter. Except for one of the simulated galaxies, all have significant discs at z > ~2, regardless of their z = 0 morphologies. Major mergers and instabilities which arise when accreting cold gas is misaligned with the stellar disc trigger a transfer of mass from the discs to the spheroids. In some cases, discs are destroyed, while in others, they survive or reform. This suggests that the survival probability of discs depends on the particular formation history of each galaxy. A realistic Lambda-CDM model will clearly require weaker star formation at high redshift and later disc assembly than occurs in our models.Comment: 14 pages, 10 figures, mn2e.cls. MNRAS in press, updated to match published versio

Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation

Stem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects

Effectiveness of the Mobility Rehab System for Mobility Training in Older Adults: A Pragmatic Clinical Trial

Introduction: Mobility impairments are among the main causes of falls in older adults and patients with neurological diseases, leading to functional dependence and substantial health care costs. Feedback-based interventions applied in controlled, laboratory environments have shown promising results for mobility rehabilitation, enhancing the benefits of standard therapy. However, the effectiveness of sensor-based feedback to improve gait in actual outpatient physical therapy settings is unknown. The proposed trial examines the effectiveness of a physical therapist-assisted, visual feedback system using wearable inertial sensors, Mobility Rehab, for mobility training in older adults with gait disturbances in an outpatient clinic. Methods: The study is a single site, pragmatic clinical trial in older adults with gait disturbances. Two hundred patients undergoing their outpatient rehabilitation program are assigned, by an independent assistant, for screening by one of four therapists, and assigned to either a standard physical therapy or therapist-assisted feedback therapy. Both groups train twice a week for 6 weeks. Four physical therapists were randomized and stratified by years of experience to deliver standard therapy or therapist-assisted feedback rehabilitation. Each session is 45 min long. Gait is trained for 30 min. The additional 15 min include exercises for endurance, strength, and static and dynamic balance in functional tasks. Mobility Rehab uses unobtrusive, inertial sensors on the feet and belt with real-time algorithms to provide real-time feedback on gait metrics (i.e., gait speed, double support time, foot clearance, angle at foot strike, and arm swing), which are displayed on a hand-held monitor. Blinded assessments are carried out before and after the intervention. The primary outcome measure is subjects' perception of balance as measured by the Activities-specific Balance Confidence scale. Gait speed, as measured with wearable inertial sensors during walking, is the secondary outcome measure. Discussion: We hypothesize that therapist-assisted feedback rehabilitation will be more effective than standard rehabilitation for gait. Feedback of motor performance plays a crucial role in rehabilitation and objective characterization of gait impairments by Mobility Rehab has the potential to improve the accuracy of patient-specific gait feedback. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03869879

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.<p></p> Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.<p></p> Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.<p></p> Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.<p></p> Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

Effect of rAd5-Vector HIV-1 Preventive Vaccines on HIV-1 Acquisition: A Participant- Level Meta-Analysis of Randomized Trial

Background Three phase 2b, double-blind, placebo-controlled, randomized efficacy trials have tested recombinant Adenovirus serotype-5 (rAd5)-vector preventive HIV-1 vaccines: MRKAd5 HIV-1 gag/pol/nef in Step and Phambili, and DNA/rAd5 HIV-1 env/gag/pol in HVTN505. Due to efficacy futility observed at the first interim analysis in Step and HVTN505, participants of all three studies were unblinded to their vaccination assignments during the study but continued follow–up. Rigorous meta-analysis can provide crucial information to advise the future utility of rAd5-vector vaccines. Methods We included participant-level data from all three efficacy trials, and three Phase 1–2 trials evaluating the HVTN505 vaccine regimen. We predefined two co-primary analysis cohorts for assessing the vaccine effect on HIV-1 acquisition. The modified-intention-to-treat (MITT) cohort included all randomly assigned participants HIV-1 uninfected at study entry, who received at least the first vaccine/placebo, and the Ad5 cohort included MITT participants who received at least one dose of rAd5-HIV vaccine or rAd5-placebo. Multivariable Cox regression models were used to estimate hazard ratios (HRs) of HIV-1 infection (vaccine vs. placebo) and evaluate HR variation across vaccine regimens, time since vaccination, and subgroups using interaction tests. Findings Results are similar for the MITT and Ad5 cohorts; we summarize MITT cohort results. Pooled across the efficacy trials, over all follow-up time 403 (n = 224 vaccine; n = 179 placebo) of 6266 MITT participants acquired HIV-1, with a non-significantly higher incidence in vaccine recipients (HR 1.21, 95% CI 0.99–1.48, P = 0.06). The HRs significantly differed by vaccine regimen (interaction P = 0.03; MRKAd5 HR 1.41, 95% CI 1.11–1.78, P = 0.005 vs. DNA/rAd5 HR 0.88, 95% CI 0.61–1.26, P = 0.48). Results were similar when including the Phase 1–2 trials. Exploratory analyses based on the efficacy trials supported that the MRKAd5 vaccine-increased risk was concentrated in Ad5-positive or uncircumcised men early in follow-up, and in Ad5-negative or circumcised men later. Overall, MRKAd5 vaccine-increased risk was evident across subgroups except in circumcised Ad5-negative men (HR 0.97, 95% CI 0.58−1.63, P = 0.91); there was little evidence that the DNA/rAd5 vaccine, that was tested in this subgroup, increased risk (HR 0.88, 95% CI 0.61–1.26, P = 0.48). When restricting the analysis of Step and Phambili to follow-up time before unblinding, 114 (n = 65 vaccine; n = 49 placebo) of 3770 MITT participants acquired HIV-1, with a non-significantly higher incidence in MRKAd5 vaccine recipients (HR 1.30, 95% CI 0.89–1.14, P = 0.18). Interpretation and Significance The data support increased risk of HIV-1 infection by MRKAd5 over all follow-up time, but do not support increased risk of HIV-1 infection by DNA/rAd5. This study provides a rationale for including monitoring plans enabling detection of increased susceptibility to infection in HIV-1 at-risk populations