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There is widespread misuse of statistics in research, particularly in the life sciences, which is one of the contributing factors to reproducibility concerns in research. However, the formal quantitative training that life sciences research trainees receive is often quite limited. Our survey of statistics requirements in undergraduate life sciences programmes offered by the top research-intensive universities in Canada, the U15 Group of Canadian Research Universities, confirmed that training in statistics tends to be limited and more general in nature. To help raise awareness and address these limitations, this paper shares findings of this statistics requirements survey and describes the evidence-based framework for a second-year undergraduate course at the University of Toronto, which was introduced to integrate statistics instruction with the life sciences research process. We hope these insights will inform future quantitative course offerings, and ultimately, better prepare students to effectively engage with statistics in life sciences research.

Educators and researchers have been fighting the reading wars for the last century, with battles see-sawing literacy instruction in American schools from phonics to whole language and, most recently, back to phonics again. Over the last decade, 32 states and the District of Columbia have adopted new "science of reading" laws that require schools to use curricula and instructional techniques that are deemed "evidence-based." Such reading programs include direct instruction in phonics and reading comprehension skills, such as finding the main idea of a paragraph, and efforts to accelerate learning tend to double down on more of the same skill-building practice. The authors conduct the first-ever experimental study of this topic, based on randomized kindergarten-enrollment lotteries in nine Colorado charter schools that use an interdisciplinary knowledge-based curriculum called Core Knowledge.

Abstract Background Somalia has over 2.6 million internally displaced people (IDP) that depend on daily wages and humanitarian assistance for their livelihoods. This study investigated the impact of COVID-19 on livelihoods, food security and mental health of Somalia’s IDPs. Methods A questionnaire was conducted with “breadwinners” (n = 585) residing in 15 randomly selected IDP camps. Mental health was assessed using the 5-item World Health Organization Wellbeing Index (WHO-5) and the Patient Health Questionnaire-9 (PHQ-9). Multivariable regression was used to explore the effect of depressive symptoms on soap use and ability to pay for food/medicine/rent. Results Knowledge of COVID-19 symptoms, transmission and prevention was relatively high, however only 55% reported using soap for hand washing. Around one third perceived that prohibition of public gatherings had negatively impacted weekly earnings. Participants reported difficulty buying food (85%), medicine (82%) and paying rent (51%) because of COVID-19. The majority were assessed as having low wellbeing and high depressive symptoms (mean WHO-5 = 44.2/100; mean PHQ-9 = 18.6/27), with most (74%) indicating that they felt worse than before the pandemic. Compared to people with low depressive symptoms, people with high depressive symptoms were less likely to use soap (aOR = 0.3, 95% CI = 0.2, 0.7; P

Abstract Early trials of novel vaccines against tuberculosis (TB) in adults have suggested substantial protection against TB. However, little is known about the feasibility and affordability of rolling out such vaccines in practice. We conducted expert interviews to identify plausible vaccination implementation strategies for the novel M72/AS01E vaccine candidate. The strategies were defined in terms of target population, coverage, vaccination schedule and delivery mode. We modelled these strategies to estimate long-term resource requirements and health benefits arising from vaccination over 2025–2050. We presented these to experts who excluded strategies that were deemed infeasible, and estimated cost-effectiveness and budget impact for each remaining strategy. The four strategies modelled combined target populations: either everyone aged 18–50, or all adults living with HIV, with delivery strategies: either a mass campaign followed by routine vaccination of 18-year olds, or two mass campaigns 10 years apart. Delivering two mass campaigns to all 18–50-year olds was found to be the most cost-effective strategy conferring the greatest net health benefit of 1.2 million DALYs averted having a probability of being cost-effective of 65–70%. This strategy required 38 million vaccine courses to be delivered at a cost of USD 507 million, reducing TB-related costs by USD 184 million while increasing ART costs by USD 79 million. A suitably designed adult TB vaccination programme built around novel TB vaccines is likely to be cost-effective and affordable given the resource and budget constraints in South Africa.

Abstract Background Cytokinins are a class of phytohormone that play a crucial role in the development of plants. They are involved in the regulation of nearly every aspect of plant growth, from germination to senescence. The role of cytokinins in many developmental programs is complex and varies both spatially and temporally. Current techniques used to investigate the functions of cytokinins in plant development lack this spatial and temporal resolution required to observe cell-type specific effects. Results To this end, we present a method of activating a caged cytokinin in single cells. A caged benzyladenine was synthesized, along with caged adenine as a negative control. In vitro testing confirmed ultraviolet light-mediated uncaging, and subsequent root growth assays demonstrated that uncaging produced a cytokinin phenotype. This uncaging was confined to single cells using multiphoton confocal microscopy. Using an Arabidopsis thaliana cytokinin reporter line expressing TCSn::GFP, the resulting GFP expression was confined to the uncaging region, including in single cells. This study presents a novel cell-targeted method of cytokinin delivery, which has the potential to elucidate a broad range of processes in plant development. Conclusions We combined multiphoton confocal microscopy and a caged cytokinin treatment, allowing cell type-specific uncaging of a cytokinin in Arabidopsis roots.

Data on social contact patterns are widely used to parameterize age-mixing matrices in mathematical models of infectious diseases. Most studies focus on close contacts only (i.e., persons spoken with face-to-face). This focus may be appropriate for studies of droplet and short-range aerosol transmission but neglects casual or shared air contacts, who may be at risk from airborne transmission. Using data from 2 provinces in South Africa, we estimated age mixing patterns relevant for droplet transmission, nonsaturating airborne transmission, and Mycobacterium tuberculosis transmission, an airborne infection where saturation of household contacts occurs. Estimated contact patterns by age did not vary greatly between the infection types, indicating that widespread use of close contact data may not be resulting in major inaccuracies. However, contact in persons >50 years of age was lower when we considered casual contacts, and therefore the contribution of older age groups to airborne transmission may be overestimated.

BackgroundMost individuals developing tuberculosis (TB) are working age adults living in low- and middle-income countries (LMICs). The resulting disability and death impact economic productivity and burden health systems. New TB vaccine products may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on gross domestic product (GDP) growth in 105 LMICs.Methods and findingsWe adapted an existing macroeconomic model to simulate country-level GDP trends between 2020 and 2080, comparing scenarios for introduction of hypothetical infant and adolescent/adult vaccines to a no-new-vaccine counterfactual. We parameterized each scenario using estimates of TB-related mortality, morbidity, and healthcare spending from linked epidemiological and costing models. We assumed vaccines would be introduced between 2028 and 2047 and estimated incremental changes in GDP within each country from introduction to 2080, in 2020 US dollars. We tested the robustness of results to alternative analytic specifications. Both vaccine scenarios produced greater cumulative GDP in the modeled countries over the study period, equivalent to $1.6 (95% uncertainty interval: $0.8, 3.0) trillion for the adolescent/adult vaccine and $0.2 ($0.1, 0.4) trillion for the infant vaccine. These GDP gains were substantially lagged relative to the time of vaccine introduction, particularly for the infant vaccine. GDP gains resulting from vaccine introduction were concentrated in countries with higher current TB incidence and earlier vaccine introduction. Results were sensitive to secular trends in GDP growth but relatively robust to other analytic assumptions. Uncertain projections of GDP could alter these projections and affect the conclusions drawn by this analysis.ConclusionsUnder a range of assumptions, introducing novel TB vaccines would increase economic growth in LMICs.

Abstract Background Ventilation rates are a key determinant of the transmission rate of Mycobacterium tuberculosis and other airborne infections. Targeting infection prevention and control (IPC) interventions at locations where ventilation rates are low and occupancy high could be a highly effective intervention strategy. Despite this, few data are available on ventilation rates and occupancy in congregate locations in high tuberculosis burden settings. Methods We collected carbon dioxide concentration and occupancy data in congregate locations and public transport on 88 occasions, in Cape Town, South Africa. For each location, we estimated ventilation rates and the relative rate of infection, accounting for ventilation rates and occupancy. Results We show that the estimated potential transmission rate in congregate settings and public transport varies greatly between different settings. Overall, in the community we studied, estimated infection risk was higher in minibus taxis and trains than in salons, bars, and shops. Despite good levels of ventilation, infection risk could be high in the clinic due to high occupancy levels. Conclusion Public transport in particular may be promising targets for infection prevention and control interventions in this setting, both to reduce Mtb transmission, but also to reduce the transmission of other airborne pathogens such as measles and SARS-CoV-2.

Abstract Background Mental health support is often scarce in low- and middle-income countries (LMIC), with mental health stigmatised. Older adults are some of the most vulnerable members of society and may require specific types of mental health support. The aim of this mixed-methods systematic review and meta-analysis was to explore the types, components, and efficacy of psychosocial community-based mental health interventions for older adults (aged 60 + years) residing in LMIC. Methods Six databases were searched in August 2021. Studies published since 2000 were included if they collected primary quantitative or qualitative data on community-based interventions for improving mental health for older adults residing in LMICs, focusing on improving mental health and well-being outcomes. Full texts were screened by two researchers. Results From 24,378 citations identified, 40 studies met eligibility criteria. Across 12 countries, interventions were categorised into those focusing on (1) Established forms of psychological therapy; (2) Exercise; (3) Education; (4) Social engagement; (5) Multi-component. Most interventions were effective in reducing levels of depression, anxiety, and improving well-being, including reminiscence therapy, different types of socialising, and breathing and laughter exercises. Some interventions reported no benefits and those that did at times failed to report continued benefits at follow-up. Given the variations in intervention type and delivery, cultures, and outcome measures used, underpinning factors of intervention success or failure were difficult to establish. Conclusions Psychosocial interventions for older adults in LMIC need to be adapted to local contexts depending on culture and population needs. Existing interventions and their components can be used as a foundation to produce adapted and multi-component interventions, to tackle growing and inadequate mental health care provision in LMIC. Trial registration The review protocol was registered on PROSPERO [CRD42021271404].

High-resolution inelastic X-ray scattering is an established technique in the synchrotron community, used to investigate collective low-frequency responses of materials. When fielded at hard X-ray free-electron lasers (XFELs) and combined with high-intensity laser drivers, it becomes a promising technique for investigating matter at high temperatures and high pressures. This technique gives access to important thermodynamic properties of matter at extreme conditions, such as temperature, material sound speed, and viscosity. The successful realization of this method requires the acquisition of many identical laser-pump/X-ray-probe shots, allowing the collection of a sufficient number of photons necessary to perform quantitative analyses. Here, a 2.5-fold improvement in the energy resolution of the instrument relative to previous works at the Matter in Extreme Conditions (MEC) endstation, Linac Coherent Light Source (LCLS), and the High Energy Density (HED) instrument, European XFEL, is presented. Some aspects of the experimental design that are essential for improving the number of photons detected in each X-ray shot, making such measurements feasible, are discussed. A careful choice of the energy resolution, the X-ray beam mode provided by the XFEL, and the position of the analysers used in such experiments can provide a more than ten-fold improvement in the photometrics. The discussion is supported by experimental data on 10 µm-thick iron and 50 nm-thick gold samples collected at the MEC endstation at the LCLS, and by complementary ray-tracing simulations coupled with thermal diffuse scattering calculations.

Abstract Background Forcibly displaced people are at elevated risk of experiencing circumstances that can adversely impact on mental health. Culturally and contextually relevant tools to assess their mental health and psychosocial needs are essential to inform the development of appropriate interventions and investigate the effectiveness of such interventions. Methods We conducted two related studies: (1) to translate and contextually adapt the Patient Health Questionnaire (PHQ-9), a measure of depressive symptomatology, along with assessment instruments measuring levels of daily stress (Checklist for Daily & Environmental Stressors; CDES), social capital (Shortened and Adapted Social Capital Assessment Tool; SASCAT) and perceived social support (Multidimensional Scale of Perceived Social Support; MSPSS) for use with Congolese refugees; (2) to conduct pilot testing of the assessment instruments (including cognitive interviewing about participants’ views of completing them) and a validation of the adapted PHQ-9 using a ‘known group’ approach by recruiting Congolese refugees from refugee settings in Rwanda (n = 100) and Uganda (n = 100). Results Study 1 resulted in the translation and adaptation of the assessment instruments. No substantive adaptations were made to the SASCAT or MSPSS, while notable linguistic and contextual adaptations were made in both sites to the CDES and the PHQ-9. The cognitive interviewing conducted in Study 2 indicated that the adapted assessment instruments were generally well received by members of the refugee communities. Participants recruited on the basis that local informants adjudged them to have high levels of depressive symptoms had significantly higher PHQ-9 scores (M = 11.02; SD = 5.84) compared to those in the group adjudged to have low levels of depressive symptoms (M = 5.66; SD = 5.04). In both sites, the adapted versions of the PHQ-9 demonstrated concurrent validity via significant positive correlations with levels of daily stressors. Each of the four adapted assessment instruments demonstrated at least adequate levels of internal consistency in both sites. Conclusions The adapted versions of the PHQ-9, CDES, SASCAT and MSPSS are appropriate for use amongst Congolese refugees in Rwanda and Uganda. We recommend further application of the approaches used in the current studies for contextually adapting other assessment instruments in humanitarian settings.

The M72/AS01E tuberculosis vaccine has shown 50% efficacy in preventing pulmonary TB disease in infected 18–50 year olds. Here, the authors demonstrate that, in most scenarios modelled, vaccination of adolescents would also be cost effective in two high incidence settings, South Africa and India.

Abstract Background Tuberculosis (TB) preventive therapy is recommended for all people living with HIV (PLHIV). Despite the elevated risk of TB amongst PLHIV, most of those eligible for preventive therapy would never develop TB. Tests which can identify individuals at greatest risk of disease would allow more efficient targeting of preventive therapy. Methods We used mathematical modelling to estimate the potential impact of using a blood transcriptomic biomarker (RISK11) to target preventive therapy amongst PLHIV. We compared universal treatment to RISK11 targeted treatment and explored the effect of repeat screening of the population with RISK11. Results Annual RISK11 screening, with preventive therapy provided to those testing positive, could avert 26% (95% CI 13–34) more cases over 10 years compared to one round of universal treatment. For the cost per case averted to be lower than universal treatment, the maximum cost of the RISK11 test was approximately 10% of the cost of preventive therapy. The benefit of RISK11 screening may be greatest amongst PLHIV on ART (compared to ART naïve individuals) due to the increased specificity of the test in this group. Conclusions Biomarker targeted preventive therapy may be more effective than universal treatment amongst PLHIV in high incidence settings but would require repeat screening.

Abstract Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn’t been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.

Background: Longitudinal studies examining mental health trajectories in refugees and asylum seekers are scarce. Objectives: To investigate trajectories of psychological symptoms and wellbeing in refugees and asylum seekers, and identify factors associated with these trajectories. Method: 912 asylum seekers and refugees from the control arm of three trials in Europe (n = 229), Turkey (n = 320), and Uganda (n = 363) were included. We described trajectories of psychological symptoms and wellbeing, and used trauma exposure, age, marital status, education, and individual trial as predictors. Then, we assessed the bidirectional interactions between wellbeing and psychological symptoms, and the effect of each predictor on each outcome controlling for baseline values. Results: Symptom improvement was identified in all trials, and for wellbeing in 64.7% of participants in Europe and Turkey, versus 31.5% in Uganda. In Europe and Turkey domestic violence predicted increased symptoms at post-intervention (ß = 1.36, 95% CI 0.17–2.56), whilst murder of family members at 6-month follow-up (ß = 1.23, 95% CI 0.27–2.19). Lower wellbeing was predicted by murder of family member (ß = −1.69, 95% CI −3.06 to −0.32), having been kidnapped (ß = −1.67, 95% CI −3.19 to −0.15), close to death (ß = −1.38, 95% CI −2.70 to −0.06), and being in the host country ≥2 years (ß = −1.60, 95% CI −3.05 to −0.14). In Uganda at post-intervention, having been kidnapped predicted increased symptoms (ß = 2.11, 95% CI 0.58–3.65), and lack of shelter (ß = −2.51, 95% CI −4.44 to −0.58) and domestic violence predicted lower wellbeing (ß = −1.36, 95% CI −2.67 to −0.05). Conclusion: Many participants adapt to adversity, but contextual factors play a critical role in determining mental health trajectories.

Abstract Background South Africa implemented rapid and strict physical distancing regulations to minimize SARS-CoV-2 epidemic spread. Evidence on the impact of such measures on interpersonal contact in rural and lower-income settings is limited. Methods We compared population-representative social contact surveys conducted in the same rural KwaZulu-Natal location once in 2019 and twice in mid-2020. Respondents reported characteristics of physical and conversational (‘close interaction’) contacts over 24 hours. We built age-mixing matrices and estimated the proportional change in the SARS-CoV-2 reproduction number (R0). Respondents also reported counts of others present at locations visited and transport used, from which we evaluated change in potential exposure to airborne infection due to shared indoor space (‘shared air’). Results Respondents in March–December 2019 (n = 1704) reported a mean of 7.4 close interaction contacts and 196 shared air person-hours beyond their homes. Respondents in June-July 2020 (n = 216), as the epidemic peaked locally, reported 4.1 close interaction contacts and 21 shared air person-hours outside their home, with significant declines in others’ homes and public spaces. Adults aged over 50 had fewer close contacts with others over 50, but little change in contact with 15–29 year olds, reflecting ongoing contact within multigenerational households. We estimate potential R0 fell by 42% (95% plausible range 14–59%) between 2019 and June-July 2020. Conclusions Extra-household social contact fell substantially following imposition of Covid-19 distancing regulations in rural South Africa. Ongoing contact within intergenerational households highlighted a potential limitation of social distancing measures in protecting older adults.

**Background:** While prior research has shown that patients with osteoarthritis (OA) who are prescribed opioids have higher rates of falls and fractures following drug initiation, there is a limited body of work establishing a comprehensive model of factors that influence the risk of falls or fractures among these patients. **Objective:** Opioids are associated with negative clinical outcomes, including increased risk of falls and fractures. This study assessed the frequency, treatment characteristics, and risk factors associated with falls or fractures among patients with OA taking opioids. **Methods:** Optum Healthcare Solutions, Inc data (January 2012–March 2017) were used to identify patients over 18 with at least 2 diagnoses of hip and/or knee OA, and at least 90 days’ supply of opioids. Patients with cancer were excluded. Falls or fractures outcomes were assessed in the 36-month follow-up period after the date of the first opioid prescription after first OA diagnosis. Demographic, treatment, and clinical characteristics associated with falls or fractures were assessed using logistic regression. **Results:** Of 16 663 patients meeting inclusion criteria, 3886 (23%) had at least 1 fall or fracture during follow-up. Of these 3886 patients, 1349 (35%) had at least 1 fall with an average of 3 fall claims, and 3299 (85%) patients had at least 1 fracture with an average of 8 claims during follow-up. Spine (15.8%) and hip (12.5%) fractures were most common. Median time to fall or fracture was 18.6 and 13.9 months, respectively. Significant (_P_

It has recently been demonstrated experimentally that a turbulent plasma created by the collision of two inhomogeneous, asymmetric, weakly magnetized, laser-produced plasma jets can generate strong stochastic magnetic fields via the small-scale turbulent dynamo mechanism, provided the magnetic Reynolds number of the plasma is sufficiently large. In this paper, we compare such a plasma with one arising from two pre-magnetized plasma jets whose creation is identical save for the addition of a strong external magnetic field imposed by a pulsed magnetic field generator. We investigate the differences between the two turbulent systems using a Thomson-scattering diagnostic, x-ray self-emission imaging, and proton radiography. The Thomson-scattering spectra and x-ray images suggest that the external magnetic field has a limited effect on the plasma dynamics in the experiment. Although the external magnetic field induces collimation of the flows in the colliding plasma jets and although the initial strengths of the magnetic fields arising from the interaction between the colliding jets are significantly larger as a result of the external field, the energies and morphologies of the stochastic magnetic fields post-amplification are indistinguishable. We conclude that, for turbulent laser-plasmas with supercritical magnetic Reynolds numbers, the dynamo-amplified magnetic fields are determined by the turbulent dynamics rather than the seed fields or modest changes in the initial flow dynamics of the plasma, a finding consistent with theoretical expectations and simulations of turbulent dynamos.

Wave packet molecular dynamics (WPMD) has recently received a lot of attention as a computationally fast tool with which to study dynamical processes in warm dense matter beyond the Born–Oppenheimer approximation. These techniques, typically, employ many approximations to achieve computational efficiency while implementing semi-empirical scaling parameters to retain accuracy. We investigated three of the main approximations ubiquitous to WPMD: a restricted basis set, approximations to exchange, and the lack of correlation. We examined each of these approximations in regard to atomic and molecular hydrogen in addition to a dense hydrogen plasma. We found that the biggest improvement to WPMD comes from combining a two-Gaussian basis with a semi-empirical correction based on the valence-bond wave function. A single parameter scales this correction to match experimental pressures of dense hydrogen. Ultimately, we found that semi-empirical scaling parameters are necessary to correct for the main approximations in WPMD. However, reducing the scaling parameters for more ab-initio terms gives more accurate results and displays the underlying physics more readily.

Abstract Background The formation of infection threads in the symbiotic infection of rhizobacteria in legumes is a unique, fascinating, and poorly understood process. Infection threads are tubes of cell wall material that transport rhizobacteria from root hair cells to developing nodules in host roots. They form in a type of reverse tip-growth from an inversion of the root hair cell wall, but the mechanism driving this growth is unknown, and the composition of the thread wall remains unclear. High resolution, 3-dimensional imaging of infection threads, and cell wall component specific labelling, would greatly aid in our understanding of the nature and development of these structures. To date, such imaging has not been done, with infection threads typically imaged by GFP-tagged rhizobia within them, or histochemically in thin sections. Results We have developed new methods of imaging infection threads using novel and traditional cell wall fluorescent labels, and laser confocal scanning microscopy. We applied a new Periodic Acid Schiff (PAS) stain using rhodamine-123 to the labelling of whole cleared infected roots of Medicago truncatula; which allowed for imaging of infection threads in greater 3D detail than had previously been achieved. By the combination of the above method and a calcofluor-white counter-stain, we also succeeded in labelling infection threads and plant cell walls separately, and have potentially discovered a way in which the infection thread matrix can be visualized. Conclusions Our methods have made the imaging and study of infection threads more effective and informative, and present exciting new opportunities for future research in the area.

Abstract Background Impacts of the Covid-19 pandemic and its public health measures go beyond physical and mental health and incorporate wider well-being impacts in terms of what people are free to do or be. We explored the impacts of the Covid-19 lockdown and relevant vulnerabilities on capability well-being, mental health and social support in Austria. Methods Adult Austrian residents (n = 560) provided responses to a cross-sectional online survey about their experiences during Covid-19 lockdown (15 March-15 April 2020). Instruments measuring capabilities (OxCAP-MH), depression and anxiety (HADS), social support (MSPSS) and mental well-being (WHO-5) were used in association with six pre-defined vulnerabilities using multivariable linear regression. Results 31% of the participants reported low mental well-being and only 30% of those with a history of mental health treatment received treatment during lockdown. Past mental health treatment had a significant negative effect across all outcome measures with an associated capability well-being score reduction of − 6.54 (95%CI, − 9.26, − 3.82). Direct Covid-19 experience and being ‘at risk’ due to age and/or physical health conditions were also associated with significant capability deprivations. When adjusted for vulnerabilities, significant capability reductions were observed in association with increased levels of depression (− 1.77) and anxiety (− 1.50), and significantly higher capability levels (+ 3.75) were associated with higher levels of social support. Compared to the cohort average, individual capability impacts varied between − 9% for those reporting past mental health treatment and + 5% for those reporting one score higher on the social support scale. Conclusions Our study is the first to assess the capability limiting aspects of lockdown and relevant vulnerabilities alongside their impacts on mental health and social support. The negative capability well-being, mental health and social support impacts of the Covid-19 lockdown were strongest for people with a history of mental health treatment. Future public health policies concerning lockdowns should pay special attention to improve social support levels in order to increase public resilience.

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

To address the unmet need for accessible mental health services for refugees and asylum seekers in high-income countries, the PROSPER study is testing implementation of the World Health Organization Problem Management Plus (PM+) intervention. Incorporating task-sharing strategies, the intervention is delivered by Peer Lay Therapists with lived experience of seeking asylum or migration. The PM+ training adopts a cascade apprenticeship model, where Master Trainers train and supervise Wellbeing Mentors; who subsequently train and supervise the Peer Lay Therapists. We describe application of this training and supervision approach in PROSPER, drawing on Master Trainer and Wellbeing Mentor perspectives. We then reflect on our experiences, highlighting logistical challenges when working with refugee and asylum-seeking Peer Lay Therapists, the strategies to promote their ongoing engagement and the opportunities for team and personal growth. A core learning point has been the role of straddling the intervention and research components of the PROSPER study. Based on our experiences, we make recommendations for others adopting a task-sharing approach by training refugees and asylum seekers as Peer Lay Therapists in high-income countries, so that this might inform service programming and/or associated research activity.

Tuberculosis (TB) remains a leading infectious cause of death worldwide and the coronavirus disease 2019 pandemic has negatively impacted the global TB burden of disease indicators. If the targets of TB mortality and incidence reduction set by the international community are to be met, new more effective adult and adolescent TB vaccines are urgently needed. There are several new vaccine candidates at different stages of clinical development. Given the limited funding for vaccine development, it is crucial that trial designs are as efficient as possible. Prevention of infection (POI) approaches offer an attractive opportunity to accelerate new candidate vaccines to advance into large and expensive prevention of disease (POD) efficacy trials. However, POI approaches are limited by imperfect current tools to measure Mycobacterium tuberculosis infection end-points. POD trials need to carefully consider the type and number of microbiological tests that define TB disease and, if efficacy against subclinical (asymptomatic) TB disease is to be tested, POD trials need to explore how best to define and measure this form of TB. Prevention of recurrence trials are an alternative approach to generate proof of concept for efficacy, but optimal timing of vaccination relative to treatment must still be explored. Novel and efficient approaches to efficacy trial design, in addition to an increasing number of candidates entering phase 2–3 trials, would accelerate the long-standing quest for a new TB vaccine.

Introduction:. Evidence-based protocols identifying COVID-19 cases in pediatric preoperative settings are lacking. With COVID-19 positioned to remain a threat to children, this study examines effectiveness of preoperative COVID-19 symptom screening in pediatric patients. Methods:. This retrospective cohort study included hospital billing/medical record queries of (1) procedures performed under conscious sedation/general anesthesia and (2) laboratory-confirmed COVID-19 (+) cases from April 6, 2020, to June 15, 2020. Descriptive analyses were performed for demographic, procedural, symptom, and COVID-19 test result data obtained from medical records. Bivariate analyses examined associations between SARS-CoV-2 test results and symptom, demographic, and procedural data. Results:. Among 2900 surgical cases, median (interquartile range) age was 8.1 (12.8) years. The majority were male (n = 1609, 55.5%), white (n = 1614, 55.7%), and not Hispanic/Latino (n = 1658, 57.2%). Additionally, 85.4% (n = 2412) of cases were non-emergent. Fifteen COVID-19 (+) cases were identified, for a 0.5% positivity rate. COVID-19 positivity was not associated with sex, American Society of Anesthesiologists physical status, or preoperative symptom status. Notably, 92.9% (n = 13) of COVID-19 (+) cases were asymptomatic. COVID-19 (+) patients were significantly older (15.6 years) than COVID-19 (−) patients (8.0 years). Patients who were not white, were Hispanic/Latino, or had a relatively lower economic status, were more likely to test positive. Conclusions:. Preoperative symptom screenings insufficiently identified COVID-19 (+) patients. During outbreaks, testing protocols should be implemented to identify COVID-19 (+) patients. Future research should examine if observations are similar for other variants, and how health disparities associate with COVID-19.

Summary: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a global health concern, yearly resulting in 10 million new cases of active TB. Immunologic investigation of lung granulomas is essential for understanding host control of bacterial replication. Here, we identify and compare the pathological, cellular, and functional differences in granulomas at 4, 12, and 20 weeks post-infection in Chinese cynomolgus macaques. Original granulomas differ in transcription-factor expression within adaptive lymphocytes, with those at 12 weeks showing higher frequencies of CD8+T-bet+ T cells, while CD4+T-bet+ T cells increase at 20 weeks post-infection. The appearance of T-bet+ adaptive T cells at 12 and 20 weeks is coincident with a reduction in bacterial burden, suggesting their critical role in Mtb control. This study highlights the evolution of T cell responses within lung granulomas, suggesting that vaccines promoting the development and migration of T-bet+ T cells would enhance mycobacterial control.

The structural evolution of laser-excited systems of gold has previously been measured through ultrafast MeV electron diffraction. However, there has been a long-standing inability of atomistic simulations to provide a consistent picture of the melting process, leading to large discrepancies between the predicted threshold energy density for complete melting, as well as the transition between heterogeneous and homogeneous melting. We make use of two-temperature classical molecular dynamics simulations utilizing three highly successful interatomic potentials and reproduce electron diffraction data presented by Mo et al. [Science 360, 1451–1455 (2018)]. We recreate the experimental electron diffraction data, employing both a constant and temperature-dependent electron–ion equilibration rate. In all cases, we are able to match time-resolved electron diffraction data, and find consistency between atomistic simulations and experiments, only by allowing laser energy to be transported away from the interaction region. This additional energy-loss pathway, which scales strongly with laser fluence, we attribute to hot electrons leaving the target on a timescale commensurate with melting.

Abstract Background Refugees fleeing conflict often experience poor mental health due to experiences in their country of origin, during displacement, and in new host environments. Conditions in refugee camps and settlements, and the wider socio-political and economic context of refugees’ lives, create structural conditions that compound the effects of previous adversity. Mental health and psychosocial support services must address the daily stressors and adversities refugees face by being grounded in the lived reality of refugee’s lives and addressing issues relevant to them. Methods We undertook a rapid qualitative study between March and May 2019 to understand the local prioritisation of problems facing Congolese refugees living in two refugee settings in Uganda and Rwanda. Thirty free list interviews were conducted in each setting, followed by 11 key informant interviews in Uganda and 12 in Rwanda. Results Results from all interviews were thematically analysed following a deductive process by the in-country research teams. Free list interview findings highlight priority problems of basic needs such as food, shelter, and healthcare access; alongside contextual social problems including discrimination/inequity and a lack of gender equality. Priority problems relating to mental and psychosocial health explored in key informant interviews include discrimination and inequity; alcohol and substance abuse; and violence and gender-based violence. Conclusions Our findings strongly resonate with models of mental health and psychosocial wellbeing that emphasise their socially determined and contextually embedded nature. Specifically, findings foreground the structural conditions of refugees’ lives such as the physical organisation of camp spaces or refugee policies that are stigmatising through restricting the right to work or pursue education. This structural environment can lead to disruptions in social relationships at the familial and community levels, giving rise to discrimination/inequity and gender-based violence. Therefore, our findings foreground that one consequence of living in situations of pervasive adversity caused by experiences of discrimination, inequity, and violence is poor mental health and psychosocial wellbeing. This understanding reinforces the relevance of feasible and acceptable intervention approaches that aim to strengthening familial and community-level social relationships, building upon existing community resources to promote positive mental health and psychosocial wellbeing among Congolese refugees in these settings.

Abstract LUX-ZEPLIN (LZ) is a second-generation direct dark matter experiment with spin-independent WIMP-nucleon scattering sensitivity above $${1.4 \times 10^{-48}}\, {\hbox {cm}}^{2}$$ 1.4 × 10 - 48 cm 2 for a WIMP mass of $${40}\, \hbox {GeV}/{\hbox {c}}^{2}$$ 40 GeV / c 2 and a $${1000}\, \hbox {days}$$ 1000 days exposure. LZ achieves this sensitivity through a combination of a large $${5.6}\, \hbox {t}$$ 5.6 t fiducial volume, active inner and outer veto systems, and radio-pure construction using materials with inherently low radioactivity content. The LZ collaboration performed an extensive radioassay campaign over a period of six years to inform material selection for construction and provide an input to the experimental background model against which any possible signal excess may be evaluated. The campaign and its results are described in this paper. We present assays of dust and radon daughters depositing on the surface of components as well as cleanliness controls necessary to maintain background expectations through detector construction and assembly. Finally, examples from the campaign to highlight fixed contaminant radioassays for the LZ photomultiplier tubes, quality control and quality assurance procedures through fabrication, radon emanation measurements of major sub-systems, and bespoke detector systems to assay scintillator are presented.

Cutaneous oomycotic infections are a rare dermatological disease primarily affecting horses and dogs. Response to medical management with antifungal therapies is poor because these organisms are not true fungi. Complete cure is unlikely if the infected tissue is unable to be completely surgically excised. This is a case report of successfully-managed cutaneous paralagenidiosis infection of the perianal tissue in an 11-month-old male intact Labrador retriever utilizing hyperbaric oxygen therapy, corticosteroids, minocycline, mefenoxam, and surgery.

Abstract The stressful experiences that many asylum seekers and refugees (AS&R) are exposed to during forced migration, and during resettlement in host countries, can have a profound impact on their mental health. Comparatively less research attention has been allocated to exploring other indices of quality of life (QoL) in AS&R populations. This review aimed to (i) synthesize the predictors and correlates of QoL of AS&R populations in high-income countries, and (ii) to identify the methodological strengths and weaknesses of this body of research. Fourteen databases were systematically searched (Medline, PsychINFO, CINAHL, Cochrane Library, Health Technology Assessment, National Health Service Economic Evaluation, Educational Resource Index and Abstracts, BiblioMap, Scopus, Social Sciences Citation Index, Evidence Aid, DARE, Web of Science and PubMed). Eligibility criteria included: adults seeking asylum or refuge in a high-income country, primary quantitative data, the use of a measure based on the WHO’s definition of QoL, published in a peer-reviewed journal. A narrative synthesis approach was used, and the quality was assessed using the AXIS tool for cross-sectional studies and the CASP tool for longitudinal studies. Of the 13.656 papers identified, 23 met the eligibility criteria. A wide range of factors were found to have significant associations with QoL. Both positive and negative correlates of QoL were largely dominated by social (e.g. social networks) and mental health factors (e.g. depression). Although all of the cross-sectional studies met over half of the quality criteria, only 12 met 75% or more of these criteria. For the longitudinal studies, for all but one study lacked statistical precision and the results cannot be applied to the local population. Key findings across the various forms of QoL (overall, physical, psychological, social and environmental) were that having established social networks and social integration were associated with higher QoL, whereas having mental disorders (i.e. PTSD or depression) was strongly associated with reduced QoL. More research is needed into physical and environmental predictors and correlates of QoL. The findings of the review can be used to inform policies and interventions aimed at supporting AS&R and promoting the integration and wellbeing of these populations.

Social contact patterns might contribute to excess burden of tuberculosis in men. We conducted a study of social contact surveys to evaluate contact patterns relevant to tuberculosis transmission. Available data describe 21 surveys in 17 countries and show profound differences in sex-based and age-based patterns of contact. Adults reported more adult contacts than children. Children preferentially mixed with women in all surveys (median sex assortativity 58%, interquartile range [IQR] 57%–59% for boys, 61% [IQR 60%–63%] for girls). Men and women reported sex-assortative mixing in 80% and 95% of surveys (median sex assortativity 56% [IQR 54%–58%] for men, 59% [IQR 57%–63%] for women). Sex-specific patterns of contact with adults were similar at home and outside the home for children; adults reported greater sex assortativity outside the home in most surveys. Sex assortativity in adult contacts likely contributes to sex disparities in adult tuberculosis burden by amplifying incidence among men.

Abstract Background Asylum seekers and refugees (AS&Rs) experience impaired mental health and wellbeing, related to stresses in their country of origin, experiences in transit and reception on arrival, including significant barriers to accessing mainstream services. Their contact with health care is often crisis-driven and mediated through non-governmental organisations (NGOs). Problem Management Plus (PM+) is a psychosocial intervention recommended by the World Health Organisation to address distress experienced by adults affected by humanitarian crises. We are investigating its application for the first time in a high-income country. Methods In a pilot randomised controlled trial (RCT), PM+ will be delivered to AS&Rs in contact with NGOs in Liverpool City Region, UK by lay therapists who have lived experience of forced migration. Following systematic review and stakeholder engagement, PM+ has been adapted to the local context, and lay therapists have been trained in its delivery. We will assess the feasibility of conducting a three-arm RCT of five 90-min sessions of PM+, delivered individually or in groups by lay therapists to AS&Rs experiencing emotional distress and functional impairment, compared with each other and with usual support offered by local NGOs. Distress and impairment at baseline will be measured by the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule (WHO-DAS). We aim to recruit 105 participants, 35 per arm. Primary health outcomes are anxiety and depressive symptoms at 3 months, measured by HADS. Secondary outcomes include subjective wellbeing, functional status, progress on identified problems, presence of post-traumatic stress disorder and depressive disorder and service usage. Longer-term impact will be assessed at 6 months post baseline, on the same parameters. We will assess the feasibility of conducting a full RCT in relation to the following elements: recruitment and retention of lay therapists and study participants; fidelity of delivery of PM+; and suitability of the study measures, including any linguistic or cultural barriers. Discussion We will use these findings to specify the parameters for a full RCT to test the effectiveness and cost-effectiveness of PM+ in reducing emotional distress and health inequalities, and improving functional ability and wellbeing, amongst asylum seekers and refugees. Trial registration ISRCTN, ID: ISRCTN15214107 . Registered on 10 September 2019.

Abstract Background The lysosphingolipid, sphingosine-1-phosphate, is a well-described and potent pro-angiogenic factor. Receptors, as well as the sphingosine phosphorylating enzyme sphingosine kinase 1, are expressed in the placentomes of sheep and the decidua of rodents; however, a function for this signaling pathway during pregnancy has not been established. The objective of this study was to investigate whether sphingosine-1-phosphate promoted angiogenesis within the placentomes of pregnant ewes. Ewes were given daily jugular injections of FTY720 (2-amino-2[2-(− 4-octylphenyl)ethyl]propate-1,3-diol hydrochloride), an S1P analog. Results FTY720 infusion from days 30 to 60 of pregnancy did not alter maternal organ weights nor total number or mass of placentomes, but did alter placentome histoarchitecture. Interdigitation of caruncular crypts and cotyledonary villi was decreased, as was the relative area of cotyledonary tissue within placentomes. Also, the percentage of area occupied by cotyledonary villi per unit of placentome was increased, while the thickness of the caruncular capsule was decreased in ewes treated with FTY720. Further, FTY720 infusion decreased the number and density of blood vessels within caruncular tissue near the placentome capsule where the crypts emerge from the capsule. Finally, FTY720 infusion decreased asparagine and glutamine in amniotic fluid and methionine in allantoic fluid, and decreased the crown rump length of day 60 fetuses. Conclusions While members of the sphingosine-1-phosphate signaling pathway have been characterized within the uteri and placentae of sheep and mice, the present study uses FTY720 to address the influence of S1P signaling on placental development. We present evidence that modulation of the S1P signaling pathway results in the alteration of caruncular vasculature, placentome architecture, abundance of amino acids in allantoic and amniotic fluids, and fetal growth during pregnancy in sheep. The marked morphological changes in placentome histoarchitecture, including alteration in the vasculature, may be relevant to fetal growth and survival. It is somewhat surprising that fetal length was reduced as early as day 60, because fetal growth in sheep is greatest after day 60. The subtle changes observed in the fetuses of ewes exposed to FTY720 may indicate an adaptive response of the fetuses to cope with altered placental morphology.

Background Treatment and prognosis of vertebrobasilar atherosclerotic disease differs depending on stroke mechanism, such as artery‐to‐artery embolism, branch atheromatous disease, and hemodynamic ischemia. Our aim was to investigate the relationship between infarction pattern and flow status using quantitative magnetic resonance angiography (QMRA), to determine the validity of using infarction patterns to infer stroke mechanism. Methods and Results This is a retrospective study of patients with ischemic stroke with intra‐ or extracranial vertebrobasilar atherosclerotic stenosis, who underwent magnetic resonance imaging of the brain, neurovascular imaging, and QMRA, between 2009 and 2021. Patients with cerebral infarction predating or following QMRA by ≥1 year, or QMRA studies performed for basilar thrombosis, vertebral dissection, or only postangioplasty/stenting, were excluded. Poststenotic flow (basilar and posterior cerebral arteries) was dichotomized as low‐flow or normal‐flow based on published criteria. Of 1211 consecutive patients who underwent QMRA noninvasive optimal analysis, 69 met inclusion. Mixed patterns were most common (46.4%), followed by perforator (23.2%), borderzone (14.5%), and territorial (15.9%). Patients with low‐flow had a significantly higher rate of borderzone+ patterns (borderzone alone or in mixed pattern) compared with patients with normal‐flow (77.4% low‐flow versus 39.5% normal‐flow, P=0.002). Borderzone+ patterns were associated with 61.5% probability of low‐flow state, while no borderzone (perforator/territorial) patterns were associated with 76.7% probability of normal‐flow state. Conclusions Borderzone infarction pattern (alone or mixed) was associated with low poststenotic posterior circulation flow by QMRA. However, borderzone pattern only moderately predicted low‐flow state, and may be an unreliable flow marker. Therefore, infarct topography may complement, but should not replace hemodynamic studies to establish flow status.

Hunting is a prominent feature of many human societies. Advancements in hunting technologies can challenge the ethics and sustainability of hunting globally. We investigated the efficacy of an electronic acoustic lure ('quail caller'), in attracting the otherwise difficult-to hunt stubble quail Coturnix pectoralis in Victoria, Australia. Using distance sampling, the density and abundance of stubble quail was estimated at 79 sites across a range of habitat types in an agricultural setting, each with an active 'quail caller' station continuously broadcasting for 48 hours, and a control station (no broadcast). Quail detectability at the active stations (62.9%) far exceeded that at control stations (6.3%). Most (57%) detections occurred within 30 m of active 'quail callers'. Stubble quail relative abundance was substantially greater when 'quail callers' were broadcasting. Cameras mounted near 'quail callers' identified the predatory red fox as a non-target predator, although rates of attraction appear similar between active and control sites. 'Quail callers' are highly effective at attracting stubble quail and concentrating them to a known area, raising questions in relation to sustainable hunting practices, indirect effects, and ethical implications. 'Quail callers' do, however, also offer a tool for estimating quail abundance and developing more accurate population size estimates.

Objectives Selected Zambian communities formed part of a cluster randomised trial: the Zambia and South Africa TB and AIDS Reduction study (ZAMSTAR). There was wide variability in the prevalence of Mycobacterium tuberculosis infection and tuberculosis (TB) disease across these communities. We sought to clarify whether specific communities could have been more/less vulnerable to M. tuberculosis transmission as a result of sociological variety relevant to transmission efficiency.Design We conducted a mixed methods secondary analysis using existing data sets. First, we analysed qualitative data to categorise and synthesise patterns of socio-spatial engagement across communities. Second, we compared emergent sociological variables with a measure of transmission efficiency: the ratio of the annual risk of infection to TB prevalence.Setting ZAMSTAR communities in urban and peri-urban Zambia, spanning five provinces.Participants Fifteen communities, each served by a health facility offering TB treatment to a population of at least 25 000. TB notification rates were at least 400 per 100 000 per annum and HIV seroprevalence was estimated to be high.Results Crowding, movement, livelihoods and participation in recreational activity differed across communities. Based on 12 socio-spatial indicators, communities were qualitatively classified as more/less spatially crowded and as more/less socially ‘open’ to contact with others, with implications for the presumptive risk of M. tuberculosis transmission. For example, watching video shows in poorly ventilated structures posed a presumptive risk in more socially open communities, while outdoor farming and/or fishing were particularly widespread in communities with lower transmission measures.Conclusions A dual dynamic of ‘social permeability’ and crowding appeared relevant to disparities in M. tuberculosis transmission efficiency. To reduce transmission, certain socio-spatial aspects could be adjusted (eg, increasing ventilation on transport), while more structural aspects are less malleable (eg, reliance on public transport). We recommend integrating community level typologies with genome sequencing techniques to further explore the significance of ‘social permeability’.Trial registration number ISRCTN36729271.

A system for calibrating single photon detector efficiency that is traceable to the SI through a state-of-the-art classical optical fibre radiometer has been developed and is in the process of being vetted as a calibration service at the National Institute of Standards and Technology (NIST). The method of calibration is direct substitution to power meters relative to NIST's optical fibre cryogenic primary standard and builds on the existing measurement infrastructure for the calibration of optical fibre power meters. Recent improvements to the optical fibre cryogenic radiometer make it more robust and deployable. The traceability of the single photon detector calibration service under development to these classical measurements is discussed, along with a description of the technique used in this calibration service to calibrate the detection efficiency of single photon detectors. Finally, we discuss work on the development of these technologies so that in the future they may be deployable to the point-of- use.

Background Elevated rates of tuberculosis in healthcare workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high-burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees.Methods An individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions—codeveloped with health professionals and policy-makers—were simulated: (1) queue management systems with outdoor waiting areas, (2) ultraviolet germicidal irradiation (UVGI) systems, (3) appointment systems, (4) opening windows and doors, (5) surgical mask wearing by clinic attendees, (6) simple clinic retrofits and (7) increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the Central Chronic Medicine Dispensing and Distribution (CCMDD) service.Results In the model, (1) outdoor waiting areas reduced the transmission to clinic attendees by 83% (IQR 76%–88%), (2) UVGI by 77% (IQR 64%–85%), (3) appointment systems by 62% (IQR 45%–75%), (4) opening windows and doors by 55% (IQR 25%–72%), (5) masks by 47% (IQR 42%–50%), (6) clinic retrofits by 45% (IQR 16%–64%) and (7) increasing the coverage of CCMDD by 22% (IQR 12%–32%).Conclusions The majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.

Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previously been suggested to be potentially useful in this situation. We propose a novel approach for locating optimal vaccine dose based on the non-parametric Continuous Correlated Beta Process model and adaptive trial design. We call this the ‘Correlated Beta’ or ‘CoBe’ dose optimisation approach. We evaluated the CoBe dose optimisation approach compared to other vaccine dose optimisation approaches using a simulation study. Despite using simpler assumptions than other modelling-based methods, we found that the CoBe dose optimisation approach was able to effectively locate the maximum efficacy dose for both single and prime/boost administration vaccines. The CoBe dose optimisation approach was also effective in finding a dose that maximises vaccine efficacy and minimises vaccine-related toxicity. Further, we found that these modelling methods can benefit from the inclusion of expert knowledge, which has been difficult for previous parametric modelling methods. This work further shows that using mathematical modelling and adaptive trial design is likely to be beneficial to locating optimal vaccine dose, ensuring maximum vaccine benefit and disease burden reduction, ultimately saving lives

Plasma accelerators can generate ultra-high-brightness electron beams that open the door to light sources with a smaller physical footprint and properties un-achievable with conventional accelerator technology. In this paper, we show that electron beams from Plasma WakeField Accelerators can generate few-cycle coherent tunable soft x-ray pulses with TW peak power and a duration of tens of attoseconds, an order of magnitude more powerful, shorter, and with better stability than state-of-the-art X-ray Free Electron Lasers (XFELs). Such a light source would significantly enhance the ability to experimentally investigate electron dynamics on ultrafast timescales, having a broad-ranging impact across multiple scientific fields. Rather than starting from noise as in typical XFELs, the x-ray emission in this approach is driven by coherent radiation from a pre-bunched, high peak current electron beam of attosecond duration. This relaxes the restrictive tolerances that have hindered progress toward utilizing plasma accelerators as coherent x-ray drivers thus far, presenting a new paradigm for advanced accelerator light source applications.

Understanding the evolution of the solid electrolyte-electrode interface is currently one of the most challenging obstacles in the development of solid-state batteries (SSBs). Here, we develop an X-ray Photoelectron Spectroscopy (XPS) that allows for operando measurement during cycling. Based on theoretical analysis and the modulated electrode and detector co-grounding mode, the displacement of binding energy can be correlated with the surface electrostatic potential of the material, revealing the charge distribution and composition evolution of the space charge layer between the cathode and the electrolyte. In the investigation of typical LiCoO2 (LCO)/Li6PS5Cl (LPSC)/Li-In batteries, we observed the static potential difference and oxidative decomposition between LPSC and LCO, and the effectiveness of the LiNbO3 coating in reducing potential difference and inhibiting the diffusion of Co and oxidation of S species. Furthermore, our study also revealed that the potential drop between LiNi0·8Co0·1Mn0·1O2 and LPSC is smaller than that of LCO, whilst that between Li3InCl6 and LCO remains near zero. The proposed operando XPS method offers a novel approach for real-time monitoring of interface potential and species formation, providing rational guidance for the interface engineering in SSBs. [ABSTRACT FROM AUTHOR]

Abstract Background Adrenal patients have a lifelong dependency on steroid replacement therapy and are vulnerable to sudden death from undertreated adrenal crisis. Urgent treatment with parenteral steroids is needed, often with IV saline for volume repletion. Episodes of adrenal crisis are, for most patients, relatively infrequent and they may not be well prepared to respond. This study explores how patients recall previous episodes of adrenal crisis and their satisfaction with UK emergency medical treatment. Methods We invited members of the main UK support groups representing steroid-dependent adrenal patients to complete an online questionnaire identifying the number, causes and location of previous adrenal crises (episodes needing injected steroids and/or IV fluids). Respondents were asked to rate the adequacy of their medical treatment in 2 successive questionnaires, conducted 2013 and 2017–18. Results Vomiting was the major factor identified as a cause of adrenal crisis, indicated by 80% of respondents. The most common location, at 70%, was the home. Of the 30% away from home, 1 in 3 were overseas or travelling long-distance. Self-treatment played an increasing role in emergency response: in the 5 year interval between questionnaires an increasing number of patients self-injected. By the time of the 2017–18 survey self-injection was the most common method of initial treatment, with less than two-thirds travelling to hospital for follow-up medical treatment. This finding help to explain the higher rate of adrenal crisis identified in patient surveys than in hospital records. Satisfaction with medical care received stayed constant between the 2 surveys despite growing resourcing pressures across the NHS. Two-thirds were happy with the quality of the medical treatment they received for their most recent adrenal emergency; timeliness was the main factor influencing satisfaction. Conclusions Around one-third of adrenal patients report sub-optimal treatment at emergency medical departments. Medical staff have a low probability of encountering adrenal crisis and may be unfamiliar with either the urgency of adrenal crisis or the specific treatment response it requires. Comprehensive protocols for emergency medical staff with detailed patient education and training are needed in how to respond to this infrequently encountered – but acutely life-threatening – scenario.