A new approach to high resolution, high contrast electron microscopy of macromolecular block copolymer assemblies

Determining the structure of macromolecular samples is vital for understanding and adapting their function. Transmission electron microscopy (TEM) is widely used to achieve this, but, owing to the weak electron scattering cross-section of carbon, TEM images of macromolecular samples are generally low contrast and low resolution. Here we implement a fast and practically simple routine to achieve high-contrast imaging of macromolecular samples using exit wave reconstruction (EWR), revealing a new level of structural detail. This is only possible using ultra-low contrast supports such as the graphene oxide (GO) used here and as such represents a novel application of these substrates. We apply EWR on GO membranes to study self-assembled block copolymer structures, distinguishing not only the general morphology or nanostructure, but also evidence for the substructure (i.e. the polymer chains) which gives insight into their formation mechanisms and functional properties

Child-focused state cash transfers and adolescent risk of HIV infection in South Africa: A propensity-score-matched case-control study

Background: Effective and scalable HIV prevention for adolescents in sub-Saharan Africa is needed. Cash transfers can reduce HIV incidence through reducing risk behaviours. However, questions remain about their effectiveness within national poverty-alleviation programmes, and their effects on different behaviours in boys and girls.Methods: In this case-control study, we interviewed South African adolescents (aged 10–18 years) between 2009 and 2012. We randomly selected census areas in two urban and two rural districts in two provinces in South Africa, including all homes with a resident adolescent. We assessed household receipt of state-provided child-focused cash transfers, incidence in the past year and prevalence of transactional sex, age-disparate sex, unprotected sex, multiple partners, and sex while drunk or after taking drugs. We used logistic regression after propensity score matching to assess the effect of cash transfers on these risky sexual behaviours.We interviewed 3515 participants (one per household) at baseline, and interviewed 3401 at follow-up. For adolescent girls (n=1926), receipt of a cash transfer was associated with reduced incidence of transactional sex (odds ratio [OR] 0.49, 95% CI 0.26–0.93; p=0•028), and age-disparate sex (OR 0.29, 95% CI 0.13–0.67; p=0.004), with similar associations for prevalence (for transactional sex, OR 0.47, 95% CI 0.26–0.86; p=0.015; for age-disparate sex, OR 0.37, 95% CI 0.18–0.77; p=0.003). No significant effects were shown for other risk behaviours. For boys (n=1475), no consistent effects were shown for any of the behaviours.Interpretation: National, child-focused cash transfers to alleviate poverty for households in sub-Saharan Africa can substantially reduce unsafe partner selection by adolescent girls. Child-focused cash transfers are of potential importance for effective combination strategies for prevention of HIV

Multiple forms of discrimination and internalized stigma compromise retention in HIV care among adolescents: findings from a South African cohort

Introduction Efficacious antiretroviral treatment (ART) enables people to live long and healthy lives with HIV but young people are dying from AIDS‐related causes more than ever before. Qualitative evidence suggest that various forms of HIV‐related discrimination and resulting shame act as profound barriers to young people’s engagement with HIV services. However, the impact of these risks on adolescent retention in HIV care has not been quantified. This study has two aims: (1) to examine whether and how different types of discrimination compromise retention in care among adolescents living with HIV in South Africa; and (2) to test whether internalized stigma mediates these relationships. Methods Between 2014 and 2017, adolescents living with HIV (aged 10 to 19) from 53 health facilities in the Eastern Cape, South Africa, were interviewed at baseline (n = 1059) and 18‐month follow‐up (n = 979, 92.4%), with responses linked to medical records. Data were analysed through multiple regression and mediation models. Results About 37.9% of adolescents reported full retention in care over the 2‐year period, which was associated with reduced odds of viral failure (OR: 0.371; 95% CI: .224, .614). At baseline, 6.9% of adolescents reported discrimination due to their HIV status; 14.9% reported discrimination due to HIV in their families and 19.1% reported discrimination in healthcare settings. Healthcare discrimination was associated with reduced retention in care both directly (effect: −0.120; CI: −0.190, −0.049) and indirectly through heightened internalized stigma (effect: 0.329; 95% CI: 0.129, 0.531). Discrimination due to family HIV was associated with reduced retention in care both directly (effect: −0.074, CI: −0.146, −0.002) and indirectly through heightened internalized stigma (effect: 0.816, CI: 0.494, 1.140). Discrimination due to adolescent HIV was associated with reduced retention in care only indirectly, through increased internalized stigma (effect: 0.408; CI: 0.102, 0.715). Conclusions Less than half of adolescents reported 2‐year retention in HIV care. Multiple forms of discrimination and the resultant internalized stigma contributed to this problem. More intervention research is urgently needed to design and test adolescent‐centred interventions so that young people living with HIV can live long and healthy lives in the era of efficacious anti‐retroviral treatment

Barriers to healthcare access and experiences of stigma: Findings from a coproduced Long Covid case-finding study

Background and Aim Long Covid is often stigmatised, particularly in people who are disadvantaged within society. This may prevent them from seeking help and could lead to widening health inequalities. This coproduced study with a Community Advisory Board (CAB) of people with Long Covid aimed to understand healthcare and wider barriers and stigma experienced by people with probable Long Covid. Methods An active case finding approach was employed to find adults with probable, but not yet clinically diagnosed, Long Covid in two localities in London (Camden and Merton) and Derbyshire, England. Interviews explored the barriers to care and the stigma faced by participants and were analysed thematically. This study forms part of the STIMULATE-ICP Collaboration. Findings Twenty-three interviews were completed. Participants reported limited awareness of what Long Covid is and the available pathways to management. There was considerable self-doubt among participants, sometimes reinforced by interactions with healthcare professionals (HCPs). Participants questioned their deservedness in seeking healthcare support for their symptoms. Hesitancy to engage with healthcare services was motivated by fear of needing more investigation and concerns regarding judgement about the ability to carry out caregiving responsibilities. It was also motivated by the complexity of the clinical presentation and fear of all symptoms being attributed to poor mental health. Participants also reported trying to avoid overburdening the health system. These difficulties were compounded by experiences of stigma and discrimination. The emerging themes reaffirmed a framework of epistemic injustice in relation to Long Covid, where creating, interpreting and conveying knowledge has varied credibility based on the teller's identity characteristics and/or the level of their interpretive resources. Conclusion We have codeveloped recommendations based on the findings. These include early signposting to services, dedicating protected time to listening to people with Long Covid, providing a holistic approach in care pathways, and working to mitigate stigma. Regardless of the diagnosis, people experiencing new symptoms must be encouraged to seek timely medical help. Clear public health messaging is needed among communities already disadvantaged by epistemic injustice to raise awareness of Long Covid, and to share stories that encourage seeking care and to illustrate the adverse effects of stigma

Comparison of the environmental, energy, and thermal comfort performance of air and radiant cooling systems in a zero-energy office building in Singapore

In an experimental study set in Singapore's tropical climate, we evaluated the thermal environmental performance, energy consumption, and thermal comfort of air and radiant cooling systems, operating at an operative and air temperature of 26 °C. 78 participants across five groups answered thermal comfort surveys in a crossover study design. Environmental performance metrics indicated that both systems produced similar conditions, with a noticeable difference in air velocity. The mean radiant temperature to air temperature difference was less than 0.5 °C in both systems. The radiant system exhibited a 33 % higher heat flux extraction than the air system and required less electrical power for the transportation of the cooling medium and ventilation air. Overall, the radiant system used 4 % less energy than the air system when controlled at 26 °C and 34 % when operated at 23 °C. Results show that radiant and air systems provided equal thermal comfort in cooling, with over 60 % of participants expressing satisfaction and ∼ 20 % voted neutral thermal satisfaction. ∼ 40 % of participants preferred cooler conditions, and ∼ 30 % desired increased air movement

Characterizing Sensitive Cardiac Substructure Excursion Due to Respiration

PURPOSE: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design. METHODS AND MATERIALS: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts. RESULTS: Paired t tests revealed reasonable maintenance of geometric and anatomic properties (P \u3c .05 for 4/39 volume comparisons). Maximum displacements \u3e5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery D(mean) varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations \u3c0.5 Gy). CONCLUSIONS: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality

STACKing the odds for adolescent survival: health service factors associated with full retention in care and adherence amongst adolescents living with HIV in South Africa

INTRODUCTION: There are two million HIV-positive adolescents in southern Africa, and this group has low retention in care and high mortality. There is almost no evidence to identify which healthcare factors can improve adolescent self-reported retention. This study examines factors associated with retention amongst antiretroviral therapy (ART)-initiated adolescents in South Africa. METHODS: We collected clinical records and detailed standardized interviews (n = 1059) with all 10- to 19 year-olds ever initiated on ART in all 53 government clinics of a health subdistrict, and community traced to include lost-to-follow-up (90.1% of eligible adolescents interviewed). Associations between full self-reported retention in care (no past-year missed appointments and 85% past-week adherence) and health service factors were tested simultaneously in sequential multivariate regression and marginal effects modelling, controlling for covariates of age, gender, urban/rural location, formal/informal housing, maternal and paternal orphanhood, vertical/horizontal HIV infection, overall health, length of time on ART and type of healthcare facility. RESULTS: About 56% of adolescents had self-reported retention in care, validated against lower detectable viral load (AOR: 0.63, CI: 0.45 to 0.87, p = 0.005). Independent of covariates, five factors (STACK) were associated with improved retention: clinics Stocked with medication (OR: 3.0, CI: 1.6 to 5.5); staff with Time for adolescents (OR: 2.7, CI: 1.8 to 4.1); adolescents Accompanied to the clinic (OR: 2.3, CI: 1.5 to 3.6); enough Cash to get to clinic safely (OR: 1.4, CI: 1.1 to 1.9); and staff who are Kind (OR: 2.6, CI: 1.8 to 3.6). With none of these factors, 3.3% of adolescents reported retention. With all five factors, 69.5% reported retention. CONCLUSIONS: This study identifies key intervention points for adolescent retention in HIV care. A basic package of clinic and community services has the potential to STACK the odds for health and survival for HIV-positive adolescents

Predictors of internalised HIV-related stigma: a systematic review of studies in sub-Saharan Africa

This systematic review aims to synthesise evidence on predictors of internalised HIV stigma amongst people living with HIV in sub-Saharan Africa. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Studies were identified through electronic databases, grey literature, reference harvesting and contacts with key researchers. Quality of findings was assessed through an adapted version of the Cambridge Quality Checklists. A total of 590 potentially relevant titles were identified. Seventeen peer-reviewed articles and one draft book chapter were included. Studies investigated socio-demographic, HIV-related, intra-personal and interpersonal correlates of internalised stigma. Eleven articles used cross-sectional data, six articles used prospective cohort data and one used both prospective cohort and cross-sectional data to assess correlates of internalised stigma. Poor HIV-related health weakly predicted increases in internalised HIV stigma in three longitudinal studies. Lower depression scores and improvements in overall mental health predicted reductions in internalised HIV stigma in two longitudinal studies, with moderate and weak effects, respectively. No other consistent predictors were found. Studies utilising analysis of change and accounting for confounding factors are necessary to guide policy and programming but are scarce. High-risk populations, other stigma markers that might layer upon internalised stigma, and structural drivers of internalised stigma need to be examined

Ductal Carcinoma in Situ of the Breast: MR Imaging Findings With Histopathologic Correlation.

Ductal carcinoma in situ (DCIS) is a noninvasive malignancy that is commonly encountered at routine breast imaging. It may be a primary tumor or may be seen in association with other focal higher-grade tumors. Early detection is important because of the large proportion of DCIS that can progress to invasive carcinoma. The extent of DCIS involvement is frequently underestimated at mammography, which can reliably help detect only calcified DCIS; consequently, magnetic resonance (MR) imaging evaluation can alter the course of treatment. Seven biopsy-proved cases of DCIS were evaluated with T2-weighted MR imaging sequences, as well as T1-weighted sequences performed both before and after contrast material administration. The signal intensity and enhancement patterns of the tumors were analyzed, and the findings were correlated with the relevant underlying histopathologic features. Common enhancement patterns of DCIS include clumped linear-ductal enhancement, clumped focal enhancement, and masslike enhancement. The most common enhancement distribution pattern is segmental, followed by focal, diffuse, linear-ductal, and regional patterns. At T2-weighted MR imaging, DCIS is typically isointense relative to breast parenchyma; less commonly, it is hypointense or hyperintense. The use of MR imaging in the evaluation of DCIS is controversial, and many questions remain with regard to treatment and management. However, breast MR imaging can be extremely useful in the preoperative diagnosis and evaluation of DCIS when used in conjunction with other imaging modalities