Strain-hardening and suppression of shear-banding in rejuvenated bulk metallic glass.

Strain-hardening (the increase of flow stress with plastic strain) is the most important phenomenon in the mechanical behaviour of engineering alloys because it ensures that flow is delocalized, enhances tensile ductility and inhibits catastrophic mechanical failure1,2. Metallic glasses (MGs) lack the crystallinity of conventional engineering alloys, and some of their properties-such as higher yield stress and elastic strain limit3-are greatly improved relative to their crystalline counterparts. MGs can have high fracture toughness and have the highest known 'damage tolerance' (defined as the product of yield stress and fracture toughness)4 among all structural materials. However, the use of MGs in structural applications is largely limited by the fact that they show strain-softening instead of strain-hardening; this leads to extreme localization of plastic flow in shear bands, and is associated with early catastrophic failure in tension. Although rejuvenation of an MG (raising its energy to values that are typical of glass formation at a higher cooling rate) lowers its yield stress, which might enable strain-hardening5, it is unclear whether sufficient rejuvenation can be achieved in bulk samples while retaining their glassy structure. Here we show that plastic deformation under triaxial compression at room temperature can rejuvenate bulk MG samples sufficiently to enable strain-hardening through a mechanism that has not been previously observed in the metallic state. This transformed behaviour suppresses shear-banding in bulk samples in normal uniaxial (tensile or compressive) tests, prevents catastrophic failure and leads to higher ultimate flow stress. The rejuvenated MGs are stable at room temperature and show exceptionally efficient strain-hardening, greatly increasing their potential use in structural applications.

Viral Suppression Trajectories Destabilized After Coronavirus Disease 2019 Among US People With Human Immunodeficiency Virus: An Interrupted Time Series Analysis.

We examined changes in the proportion of people with human immunodeficiency virus (PWH) with virologic suppression (VS) in a multisite US cohort before and since the coronavirus disease 2019 (COVID-19) pandemic. Overall, prior gains in VS slowed during COVID-19, with disproportionate impacts on Black PWH and PWH who inject drugs.

Hierarchical Surface Pattern on Ni-Free Ti-Based Bulk Metallic Glass to Control Cell Interactions.

Ni-free Ti-based bulk metallic glasses (BMGs) are exciting materials for biomedical applications because of their outstanding biocompatibility and advantageous mechanical properties. The glassy nature of BMGs allows them to be shaped and patterned via thermoplastic forming (TPF). This work demonstrates the versatility of the TPF technique to create micro- and nano-patterns and hierarchical structures on Ti40Zr10Cu34Pd14Sn2 BMG. Particularly, a hierarchical structure fabricated by a two-step TPF process integrates 400 nm hexagonal close-packed protrusions on 2.5 µm square protuberances while preserving the advantageous mechanical properties from the as-cast material state. The correlations between thermal history, structure, and mechanical properties are explored. Regarding biocompatibility, Ti40Zr10Cu34Pd14Sn2 BMGs with four surface topographies (flat, micro-patterned, nano-patterned, and hierarchical-structured surfaces) are investigated using Saos-2 cell lines. Alamar Blue assay and live/dead analysis show that all tested surfaces have good cell proliferation and viability. Patterned surfaces are observed to promote the formation of longer filopodia on the edge of the cytoskeleton, leading to star-shaped and dendritic cell morphologies compared with the flat surface. In addition to potential implant applications, TPF-patterned Ti-BMGs enable a high level of order and design flexibility on the surface topography, expanding the available toolbox for studying cell behavior on rigid and ordered surfaces.

Behavioural response to gastrointestinal parasites of yearling dairy calves at pasture.

AIMS: To investigate the association between gastrointestinal parasites (GIP) and animal behaviour in dairy calves under New Zealand pastoral conditions, using animal-mounted, accelerometer-based sensors. METHODS: Thirty-six, 5-6-month-old, Friesian-Jersey, heifer calves fitted with animal activity sensors to track behaviour were randomly allocated to one of two treatment groups. Half the animals were challenged with an oral dose of 20,000 larvae of Ostertagia ostertagi and Cooperia oncophera once a week for 3 weeks and half were unchallenged. Five weeks after the last dose, seven infected and nine uninfected animals were treated with an oral anthelmintic (AHC) and data collected for a further week. Accelerometer data were classified into minutes per day eating, ruminating, in moderate-high activity or in low activity. Live weight and faecal egg counts (FEC) were recorded weekly over the study period. All animals co-grazed a newly sown pasture not previously grazed by ruminants and were moved every week to fresh grazing. Treatment status was blinded to those managing the animals which were otherwise treated identically. RESULTS: Complete behavioural records were available from 30/36 calves, (13 challenged and 17 unchallenged). Before treatment with AHC, FEC increased in infected and un-treated calves over the study, while uninfected animals maintained a near zero FEC. There was no difference in live weight gain between the two groups over the study period. Bayesian, multinomial regression predicted differences in animal behaviour between infected and uninfected animals that were not treated with AHC over the 7 weeks following initial infection. Parasitised calves not treated with AHC were less active and spent up to 6 (95% highest density interval (HDI) = 1-11) minutes/day less in low level activity and up to 15 (95% HDI = 7-20) minutes/day less in moderate to high level activity. They ruminated up to 9 (95% HDI = 2-15) minutes/day more and ate up to 10 (95% HDI = 2-19) minutes/day more than control calves that were not treated with AHC. The effect of AHC on time spent in each behaviour differed between infected and uninfected calves and increased the coefficient of dispersion of the behavioural data. CONCLUSIONS AND CLINICAL RELEVANCE: Small differences in animal behaviour can be measured in calves with GIP. However, to use this to target treatment, further validation studies are required to confirm the accuracy of behavioural classification and understand the complex drivers of animal behaviour in a dynamic and variable pasture-parasite-host environment.

The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Identification of a novel polyomavirus in wild Sonoran Desert rodents of the family Heteromyidae.

Rodents are the largest and most diverse group of mammals. Covering a wide range of structural and functional adaptations, rodents successfully occupy virtually every terrestrial habitat, and they are often found in close association with humans, domestic animals, and wildlife. Although a significant amount of research has focused on rodents' prominence as known reservoirs of zoonotic viruses, there has been less emphasis on the viral ecology of rodents in general. Here, we utilized a viral metagenomics approach to investigate polyomaviruses in wild rodents from the Baja California peninsula, Mexico, using fecal samples. We identified a novel polyomavirus in fecal samples from two rodent species, a spiny pocket mouse (Chaetodipus spinatus) and a Dulzura kangaroo rat (Dipodomys simulans). These two polyomaviruses represent a new species in the genus Betapolyomavirus. Sequences of this polyomavirus cluster phylogenetically with those of other rodent polyomaviruses and two other non-rodent polyomaviruses (WU and KI) that have been identified in the human respiratory tract. Through our continued work on seven species of rodents, we endeavor to explore the viral diversity associated with wild rodents on the Baja California peninsula and expand on current knowledge of rodent viral ecology and evolution.

Optimizing PMTCT Adherence by Treating Depression in Perinatal Women with HIV in South Africa: A Pilot Randomized Controlled Trial.

BACKGROUND: South Africa (SA) has the greatest HIV prevalence in the world, with rates as high as 40% among pregnant women. Depression is a robust predictor of nonadherence to antiretroviral therapy (ART) and engagement in HIV care; perinatal depression may affect upwards of 47% of women in SA. Evidence-based, scalable approaches for depression treatment and ART adherence in this setting are lacking. METHOD: Twenty-three pregnant women with HIV (WWH), ages 18-45 and receiving ART, were randomized to a psychosocial depression and adherence intervention or treatment as usual (TAU) to evaluate intervention feasibility, acceptability, and preliminary effect on depressive symptoms and ART adherence. Assessments were conducted pre-, immediately post-, and 3 months post-treatment, and included a qualitative exit interview. RESULTS: Most (67.6%) eligible individuals enrolled; 71% completed at least 75% of sessions. Compared to TAU, intervention participants had significantly greater improvements in depressive symptoms at post-treatment, ß = - 11.1, t(24) = - 3.1, p < 0.005, 95% CI [- 18.41, - 3.83], and 3 months, ß = - 13.8, t(24) = - 3.3, p < 0.005, 95% CI [- 22.50, - 5.17]. No significant differences in ART adherence, social support, or stigma were found. Qualitatively, perceived improvements in social support, self-esteem, and problem-solving adherence barriers emerged as key benefits of the intervention; additional sessions were desired. CONCLUSION: A combined depression and ART adherence intervention appears feasible and acceptable, and demonstrated preliminary evidence of efficacy in a high-need population. Additional research is needed to confirm efficacy and identify dissemination strategies to optimize the health of WWH and their children. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03069417. Protocol available at https://clinicaltrials.gov/ct2/show/NCT03069417.

Current Antiretroviral Treatment Among People With Human Immunodeficiency Virus in the United States: Findings from the Centers for AIDS Research Network of Integrated Clinic Systems Cohort.

Among 14 049 people with human immunodeficiency virus in care in 2019-2020, 96% were treated with antiretroviral therapy (ART). Current antiretroviral treatment patterns highlight high uptake of guideline-recommended ART regimens including second-generation integrase strand transfer inhibitors (dolutegravir and bictegravir) and tenofovir alafenamide, especially in antiretroviral-naive individuals initiating ART.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis.

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts. METHODS: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD. RESULTS: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean log10viral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD. CONCLUSIONS: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.

COVID Community-Engaged Testing in Alabama: Reaching Underserved Rural Populations Through Collaboration.

Rural communities are often underserved by public health testing initiatives in Alabama. As part of the National Institutes of Health's Rapid Acceleration of Diagnostics‒Underserved Populations initiative, the University of Alabama at Birmingham, along with community partners, sought to address this inequity in COVID-19 testing. We describe the participatory assessment, selection, and implementation phases of this project, which administered more than 23 000 COVID-19 tests throughout the state, including nearly 4000 tests among incarcerated populations. (Am J Public Health. 2022;112(10):1399-1403. https://doi.org/10.2105/AJPH.2022.306985).

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Towards a unified framework to study causality in Earth-life systems.

There is considerable interest in better understanding how earth processes shape the generation and distribution of life on Earth. This question, at its heart, is one of causation. In this article I propose that at a regional level, earth processes can be thought of as behaving somewhat deterministically and may have an organized effect on the diversification and distribution of species. However, the study of how landscape features shape biology is challenged by pseudocongruent or collinear variables. I demonstrate that causal structures can be used to depict the cause-effect relationships between earth processes and biological patterns using recent examples from the literature about speciation and species richness in montane settings. This application shows that causal diagrams can be used to better decipher the details of causal relationships by motivating new hypotheses. Additionally, the abstraction of this knowledge into structural equation metamodels can be used to formulate theory about relationships within Earth-life systems more broadly. Causal structures are a natural point of collaboration between biologists and Earth scientists, and their use can mitigate against the risk of misassigning causality within studies. My goal is that by applying causal theory through application of causal structures, we can build a systems-level understanding of what landscape features or earth processes most shape the distribution and diversification of species, what types of organisms are most affected, and why.

The hidden landscape: Evidence that sea-level change shaped the present population genomic patterns of marginal marine species.

Oftentimes, to understand the genetic relatedness and diversity of today's populations requires considering the ancient landscape on which those populations evolved. Nowhere is this clearer than along Earth's coastline, which has been in its present-day configuration for only about 6.5% of the past 800,000 years (Dolby et al., 2020; Miller et al., 2005). During ice ages when glaciers expanded in the Northern Hemisphere, they stored enough of the planet's water to drop global sea level by ~120 m below present levels ("lowstand", Figure 1a), and there have been at least eight of these 100,000-year cycles preceding today. When glaciers melted, ocean water reflooded shorelines, shifting and re-forming marginal marine habitats globally and shaping the relatedness of populations (Dolby et al., 2016). In a From the Cover article in this issue of Molecular Ecology, Stiller et al. (2020) integrate population genomic analysis of leafy seadragons in southern Australia with estimates of available seabed area to reveal that the expansion of habitat that accompanied this reflooding led to strong demographic expansions. With statistical models, they also show that western populations were eliminated and then recolonized because the continental shelf there is narrow, leaving little available habitat when sea level was low (Figure 1b). Their results document the dynamic and interrelated nature of a hidden, changing landscape and the evolution of species inhabiting it.

Rejuvenation of metallic glasses by non-affine thermal strain.

When a spatially uniform temperature change is imposed on a solid with more than one phase, or on a polycrystal of a single, non-cubic phase (showing anisotropic expansion-contraction), the resulting thermal strain is inhomogeneous (non-affine). Thermal cycling induces internal stresses, leading to structural and property changes that are usually deleterious. Glasses are the solids that form on cooling a liquid if crystallization is avoided--they might be considered the ultimate, uniform solids, without the microstructural features and defects associated with polycrystals. Here we explore the effects of cryogenic thermal cycling on glasses, specifically metallic glasses. We show that, contrary to the null effect expected from uniformity, thermal cycling induces rejuvenation, reaching less relaxed states of higher energy. We interpret these findings in the context that the dynamics in liquids become heterogeneous on cooling towards the glass transition, and that there may be consequent heterogeneities in the resulting glasses. For example, the vibrational dynamics of glassy silica at long wavelengths are those of an elastic continuum, but at wavelengths less than approximately three nanometres the vibrational dynamics are similar to those of a polycrystal with anisotropic grains. Thermal cycling of metallic glasses is easily applied, and gives improvements in compressive plasticity. The fact that such effects can be achieved is attributed to intrinsic non-uniformity of the glass structure, giving a non-uniform coefficient of thermal expansion. While metallic glasses may be particularly suitable for thermal cycling, the non-affine nature of strains in glasses in general deserves further study, whether they are induced by applied stresses or by temperature change.

Human papillomavirus sequencing reveals its usefulness for the management of HIV-infected women at risk for developing cervical cancer.

AIM: Next-generation sequencing (NGS) is able to describe the composition of human papillomaviruses (HPVs) as percent (%) reads rather than positive/negative results. Therefore, we used this unique approach to assess the prevalence of cervical HPVs of HIV infected (HIV+) in order to understand the determinants of being infected with higher % reads of high risk (HR)-HPVs and cervical abnormalities of atypical squamous cells of unknown significance or higher (ASCUS+). METHODS: Study included 66 women characterized for relevant risk factors/cytology. Receiver-operating curve curve was used to derive the optimal % read cut point to identify ASCUS+ in relation to any HR-HPV genotype or other specific HPV genotypes. The determinants of ASCUS+ and HR-HPVs were tested using logistic regression. RESULTS: Women with >20% reads of any HR-HPV or >12% any HR-HPV other than HPV 16/18 were 5.7 and 12.6 times more likely to be diagnosed with ASCUS+, respectively. Lower CD4 count was a significant determinant of >20% reads of HR-HPV (odds ratio [OR] = 4.1) or >12% any HR-HPV other than HPV 16/18 (OR = 4.5). CONCLUSION: We envision that the NGS-based HPV detection will be more accurate for screening and management of HIV+ at risk for developing cervical cancer (CC). We raise concerns regarding the limitations of 16/18-based HPV testing for triage and the efficacy of current HPV vaccines for preventing CC in HIV+.

Organizational support for frontline harm reduction and systems navigation work among workers with living and lived experience: qualitative findings from British Columbia, Canada.

BACKGROUND: The inclusion of people with lived and living experience of substance use is essential to effective and client-centered harm reduction services and strategies. The aim of this study is to critically examine and characterize peer worker roles and the definition, recognition, and support for these roles within harm reduction organizations. METHODS: Fifteen interviews were conducted with peer workers-people with lived and living experience of substance use engaged in harm reduction service delivery-in British Columbia, Canada. An interpretive descriptive approach to data analysis was used to generate themes that best illustrated the roles of peer workers. FINDINGS: Two interrelated and overarching themes are presented: (1) peer work in practice; (2) organizational support. Our findings illustrate that peer work is incredibly complex and demanding, requiring peers to be at the forefront of support within their communities while simultaneously navigating the oppressive structures within which they work. While peer workers found a high degree of purpose and meaning in their day-to-day work, their roles lacked definition within organizations, which produced feelings of ineffectiveness and being undervalued. A lack of organizational understanding and recognition of their roles was evident from unclear "peer" role titles, a lack of role communication and expectations, the representation of experiential knowledge, and a lack of role support and training. CONCLUSIONS: These findings may help harm reduction organizations understand peer work and worker roles which may inform and promote equity in future harm reduction initiatives that include people with living and lived experience of substance use.

Healthcare is a Team Sport: Stress, Resilience, and Correlates of Well-Being Among Health System Employees in a Crisis.

EXECUTIVE SUMMARY: While the COVID-19 pandemic has added stressors to the lives of healthcare workers, it is unclear which factors represent the most useful targets for interventions to mitigate employee distress across the entire healthcare team. A survey was distributed to employees of a large healthcare system in the Southeastern United States, and 1,130 respondents participated. The survey measured overall distress using the 9-item Well-Being Index (WBI), work-related factors, moral distress, resilience, and organizational-level factors. Respondents were also asked to identify major work, clinical, and nonwork stressors. Multivariate regression was used to evaluate associations between employee characteristics and WBI distress score. Overall, 82% of employees reported high distress (WBI ≥ 2), with nurses, clinical support staff, and advanced practice providers reporting the highest average scores. Factors associated with higher distress included increased job demands or responsibilities, heavy workload or long hours, higher frequency of moral distress, and loneliness or social isolation. Factors associated with lower distress were perceived organizational support, work control, perceived fairness of salary cuts, and resilience. Most factors significantly associated with distress-heavy workloads and long hours, increased job demands, and moral distress, in particular-were work-related, indicating that efforts can be made to mitigate them. Resilience explained a small portion of the variance in distress relative to other work-related factors. Ensuring appropriate staffing levels may represent the single largest opportunity to significantly move the needle on distress. However, the financial impact of the COVID-19 pandemic on the healthcare system may represent a barrier to addressing these stressors.

Author Correction: Poisson's ratio and modern materials.

In the version of this Review Article originally published, parentheses were misplaced and the longitudinal and transverse speeds were inverted in two expressions for Poisson's ratio in Box 2; the expressions should have read, respectively, ν = (3B/G - 2)/(6B/G + 2) and ν = [½(Vl/Vt)2 - 1]/[(Vl/Vt)2 - 1].

Metallic Glass Films with Nanostructured Periodic Density Fluctuations Supported on Si/SiO2 as an Efficient Hydrogen Sorber.

Nanostructured metallic glass films (NMGF) can exhibit surface and intrinsic effects that give rise to unique physical and chemical properties. Here, a facile synthesis and electrochemical, structural, and morphologic characterization of Pd-Au-Si based MGs of approximately 50 nm thickness supported on Si/SiO2 is reported. Impressively, the maximum total hydrogen charge stored in the Pd-Au-Si nanofilm is equal to that in polycrystalline Pd films with 1 µm thickness in 0.1 m H2 SO4 electrolyte. The same NMGF has a volumetric desorption charge that is more than eight times and 25 % higher than that of polycrystalline PdNF and Pd-Cu-Si NMGF with the same thickness supported on Si/SiO2 , respectively. A significant number of nanovoids originating from PdHx crystals, and an increase in the average interatomic spacing is detected in Pd-Au-Si NMGF by high-resolution TEM. Such a high amount of hydrogen sorption is linked to the unique density fluctuations without any chemical segregation exclusively observed for this NMGF.