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The purpose of this study was to investigate the social determinants of health for keratoconus.In this retrospective cohort study of patients with keratoconus, the electronic health record was reviewed for keratometry, treatments received, clinical comorbidities, and social characteristics. Outcomes included severe keratoconus at presentation (steep keratometry ≥52 diopters), disease progression (≥0.75 diopters increase from the first to the most recent clinical visit), and corneal transplantation. Logistic regression was used to evaluate factors associated with severity at presentation and corneal transplantation. Cox proportional hazards modeling was used to evaluate progression.A total of 1038 patients with keratoconus were identified, 725 (70%) of whom had baseline imaging. Compared with commercially insured patients, Medicaid recipients were more likely to have severe keratoconus, independent of social and clinical confounders [odds ratio (OR) 1.94, 95% confidence interval (CI), 1.12-3.35, P = 0.017]. Male sex was independently associated with progression (hazard ratio = 1.38, 95% CI, 1.03-1.84, P = 0.030). Medicare and Medicaid recipients were more likely to require transplantation compared with commercially insured patients (OR 2.71, 95% CI, 1.65-4.46, P0.001 and OR 1.74, 95% CI, 1.08-2.80, P = 0.022, respectively). Other social determinants of health, including non-White race/ethnicity, limited English proficiency, and unemployment, were associated with the outcomes only in univariate analysis. Obstructive sleep apnea, atopy, body mass index, and tobacco use were not associated with any outcome.Socioeconomic factors were more consistent predictors of keratoconus severity and corneal transplantation compared with clinical factors that have received relatively greater attention in the keratoconus literature.

The present study examined data from a randomized controlled trial exploring whether behavioral weight loss treatment was associated with changes in internalized weight bias. The relationship between internalized weight bias and psychological functioning was also assessed. Participants were 106 men and women with overweight or obesity enrolled in a treatment outcome study using the Lifestyle Balance Program. Participants completed measures of internalized weight bias, anti-fat attitudes, self-esteem, body image concern, depressive symptoms, anxiety, and stress. Variables were assessed at baseline, post-treatment, and six-month follow-up. Weight bias internalization significantly decreased over the course of treatment. Baseline and follow-up internalized weight bias scores predicted change in body weight. Participants reporting the lowest levels of internalized weight bias at baseline lost nearly twice as much weight as participants reporting the highest levels of internalized weight bias. Significant associations were found between internalized weight bias, body image concern, and self-esteem. Findings indicate a relationship between internalized weight bias and weight change during behavioral weight loss treatment, highlighting the importance of assessing baseline levels of internalized weight bias in weight loss treatment studies. Higher internalized weight bias predicted poorer weight loss outcomes, indicating a need for tailored treatment approaches.

Infant undernutrition is thought to contribute to growth failure and mortality. We evaluated the patterns in underweight in a population-based sample of children aged 1–11 months in rural northwestern Burkina Faso. Data were collected during the baseline assessment of a community-randomized trial evaluating mass azithromycin distribution in Nouna District, Burkina Faso. A door-to-door census was undertaken for all households in all communities. Infants aged 1–11 months were weighed for weight-based dosing in the trial and their weights were used to calculate weight-for-age Z-scores (WAZ). Underweight was defined as WAZ ≤ 2. We evaluated the age patterns in WAZ and underweight by demographic, seasonal, and geographic characteristics. Of 7,109 infants, 6,077 had accurate weight and global positioning system (GPS) coordinate data (85.5%). Infants were a median of 6 months old (interquartile range [IQR] 3–8) and 48.4% were female. Mean WAZ was −0.68 (SD 1.6) and 19.0% were underweight. The WAZ decreased with increasing age, and the prevalence of underweight increased from 2.5% among 1-month-olds to 27.6% among 11-month-olds. Underweight was more common among boys than girls (22.1% among boys versus 15.6% among girls). Improved latrine use by the household was associated with increased WAZ, and this effect was stronger in male compared with female infants. Given the large burden of underweight among infants, interventions addressing undernutrition should specifically include infants.

Glaucoma drainage devices (GDD) are increasingly utilized in the management of childhood glaucoma. This systematic review and meta-analysis assesses the efficacy of first-time Ahmed or Baerveldt implantation in children. PubMed, Embase, and Cochrane Library were searched for relevant English-language, peer-reviewed literature. Postoperative outcomes were pooled using random effects regression models with restricted maximum likelihood estimation. Thirty-two studies (1221 eyes, 885 children) were included. Mean ± standard deviation preoperative IOP was 31.8±3.4 mmHg. Pooled mean IOP at 12 and 24 months postoperatively were 16.5 mmHg (95% CI 15.5–17.6) and 17.6 mmHg (95% CI 16.4–18.7), respectively. Pooled proportions of success were 0.87 (95% CI 0.83–0.91) at 12 months, 0.77 (95% CI 0.71–0.83) at 24 months, 0.54 (95% CI 0.44–0.65) at 48 months, 0.60 (95% CI 0.48–0.71) at 60 months, and 0.37 (95% CI 0.32–0.42) at 120 months. There were no differences in proportion of success at 12 and 24 months among eyes that received Ahmed and Baerveldt tube shunts, nor between eyes with primary glaucoma, glaucoma following cataract surgery or other secondary glaucoma. Our findings show that Ahmed and Baerveldt shunts substantially reduced IOP for at least 24 months in childhood glaucoma, with similar findings among device types and glaucoma etiologies.

Research from the social sciences suggests an association between higher temperatures and increases in antisocial behaviours, including aggressive, violent, or sabotaging behaviours, and represents a heat-facilitates-aggression perspective. More recently, studies have shown that higher temperature experiences may also be linked to increases in prosocial behaviours, such as altruistic, sharing, or cooperative behaviours, representing a warmth-primes-prosociality view. However, across both literatures, there have been inconsistent findings and failures to replicate key theoretical predictions, leaving the status of temperature-behaviour links unclear. Here we review the literature and conduct meta-analyses of available empirical studies that have either prosocial (e.g., monetary reward, gift giving, helping behaviour) or antisocial (self-rewarding, retaliation, sabotaging behaviour) behavioural outcome variables, with temperature as an independent variable. In an omnibus multivariate analysis (total N = 4577) with 80 effect sizes, we found that there was no reliable effect of temperature on the behavioural outcomes measured. Further, we find little support for either the warmth-primes-prosociality view or the heat- facilitates-aggression view. There were no reliable effects if we consider separately the type of behavioural outcome (prosocial or antisocial), different types of temperature experience (haptic or ambient), or potential interactions with the experimental social context (positive, neutral or negative). We discuss how these findings affect the status of existing theoretical perspectives, and provide specific suggestions advancing research in this area.

Background and aims Homelessness is one of the most significant harms associated with gambling and appears to affect older adults disproportionately, but the relationship has received little research attention. This exploratory study investigated how gambling and homelessness is linked in older adults. Methods Using qualitative research methods, we undertook in-depth semi structured face-to-face individual and group interviews to gather data from a purposive sample (n=48) of key informants working in service provision for older adults (aged 50+ years) experiencing gambling related harm and/or homelessness in Victoria, Australia. Thematic analysis of data focused on evaluating mechanisms and identifying contextual conditions that activate pathways between gambling and homelessness. Results The relationship between gambling and homelessness in older adults is often indirect and non-linear, and can represent a reflexive cycle. Experiencing periods of homelessness into older age can contribute to gambling, often because the adverse impacts of homelessness on older adult's mental and material wellbeing increase the appeal of gambling. Additionally, comorbidities (e.g. substance use, mental illness, past trauma) and structural conditions (e.g. gambling accessibility, poverty, housing insecurity) can activate gambling. Furthermore, because gambling in the older homeless adult population is frequently hidden, and regularly overlooked by service providers, it often continues unabated. Gambling in older adults can also contribute to the onset of first-time homelessness. Large and rapid losses from high-intensity gambling frequently characterise this route to homelessness. Such gambling is often triggered by major life events and changes (e.g. bereavement, job loss, relationship difficulties), and the outcomes are often worsened by the conduct of gambling operators and creditors. Conclusions The link between gambling and homelessness in older adults is complex, with connecting mechanisms often contingent on individual, interpersonal and structural conditions and contexts. There is potential for preventative and ameliorative action given many of the underlying conditions appear modifiable through policy intervention.

Piezo1 is a stretch-gated ion channel required for mechanosensation in many organ systems. Recent findings point to a new role for Piezo1 in the gut, suggesting that it is a sensor of microbial single-stranded RNA (ssRNA) rather than mechanical force. If true, this would redefine the scope of Piezo biology. Here, we sought to replicate the central finding that fecal ssRNA is a natural agonist of Piezo1. While we observe that fecal extracts and ssRNA can stimulate calcium influx in certain cell lines, this response is independent of Piezo1. Additionally, sterilized dietary extracts devoid of gut biome RNA show similar cell line-specific stimulatory activity to fecal extracts. Together, our data highlight potential confounds inherent to gut-derived extracts, exclude Piezo1 as a receptor for ssRNA in the gut, and support a dedicated role for Piezo channels in mechanosensing.

PurposeTo determine whether exposure to unclean cooking fuels was associated with subsequent cataract progression as reported in previous cross-sectional studies.DesignProspective cohort study.MethodsThis is a secondary observational analysis of the community-based Antioxidants in Prevention of Cataracts trial (ClinicalTrials.gov ID NCT01664819). The exposure of interest was cooking fuel type, measured at baseline. Main outcome measures were baseline cataract severity and self-reported cataract surgery at a 15-year visit.ResultsBaseline and 15-year follow-up data were available for 798 and 579 participants, respectively. Wood or kerosene was used by 711 of 798 (89.1%) baseline participants, including 539 of 579 (93.1%) participants with complete follow-up. Cooking fuel type was not associated with cataract severity at baseline (P=.443). Of 8334 person-years of follow-up, 90 cataract surgeries were observed over 15 years (1.08 surgeries per 100 person-years; 95% CI=0.87-1.32). Use of wood or kerosene was not associated with 15-year incidence of cataract surgery relative to use of propane (adjusted P=.154). Cataract surgery was more common in older individuals (HR=1.1 per year, 95% CI=1.1-1.2, P < .001), those with baseline myopia (HR=2.1, 95% CI=1.2-3.5, P=.009), and women (HR=3.5, 95% CI=1.2-10.1, P=.019).ConclusionsThis study found no association between unclean cooking fuels and cataract progression over a 15-year period. No other modifiable risk factors were associated with incident self-reported cataract surgery.

Participation in sport and physical activity (PA) is declining, and the psychosocial factors underpinning avoidance of these activities are not understood. This study developed and tested a new measure assessing the tendency to avoid PA and sport because of weight stigma and appearance-related concerns. University students (n = 581, mean age = 19.8 years) completed an online survey at two time points. Demographic details and measures of weight stigmatization, appearance evaluations, and enjoyment and participation in PA or sport were taken. In addition, we developed and tested a new measure of the tendency to avoid physical activity and sport (TAPAS). Psychometric testing of the scale was conducted, and correlates of TAPAS were examined. The ten-item TAPAS provided a single factor solution, and the final scale score was predictive of lower levels of enjoyment of, and participation in, physical activity and sport (p < 0.001). The scale also displayed good internal and test-retest reliability. This study provides a new measure for assessing people’s tendency to avoid PA and sport because of weight stigma or appearance-related concerns. The results suggest that initiatives seeking to increase participation in PA and sport may need to address weight stigma and associated appearance related concerns.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6–59 months by age and sex. We categorised children into younger (6–23 months) and older (24–59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < −2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Autistic adults commonly experience sensory reactivity differences. Sensory hyperreactivity is frequently researched, whilst hyporeactivity and seeking, and experiences across domains, e.g., vision, are often neglected. Therefore, we aimed to understand more about the sensory experiences of autistic adults. We conducted a mixed-methods study, co-produced with stakeholders; recruiting 49 autistic adults who completed an online survey. Firstly, quantitative results and content analysis enhanced our understanding of sensory input/contexts associated with sensory hyperreactivity, hyporeactivity, and seeking across modalities. Secondly, thematic analysis developed themes relating to ‘Outcomes’, ‘Control’, ‘Tolerance and management’, and ‘The role of other people’, informing a theoretical model of sensory reactivity differences in autistic adults. These findings have implications for support services and improving quality of life for autistic adults.

International audience; HARMONI is the first light, adaptive optics assisted, integral field spectrograph for the European Southern Observatory’s Extremely Large Telescope (ELT). A work-horse instrument, it provides the ELT’s diffraction limited spectroscopic capability across the near-infrared wavelength range. HARMONI will exploit the ELT’s unique combination of exquisite spatial resolution and enormous collecting area, enabling transformational science. The design of the instrument is being finalized, and the plans for assembly, integration and testing are being detailed. We present an overview of the instrument’s capabilities from a user perspective, and provide a summary of the instrument’s design. We also include recent changes to the project, both technical and programmatic, that have resulted from red-flag actions. Finally, we outline some of the simulated HARMONI observations currently being analyzed.

Background Weight-related stigma has negative physiological and psychological impacts on individuals’ quality of life. Stigmatized individuals may experience higher psychological distress and therefore increase the potential risk to develop obesity and/or food addiction. The present study examined the associations and mediated effect between perceived weight stigma, weight-related self-stigma, and psychological distress in explaining food addiction among Taiwanese university students. Methods All participants (n = 968) completed an online survey which included the Perceived Weight Stigma Questionnaire, Weight Self-Stigma Questionnaire, Depression, Anxiety, Stress Scale-21, and Yale Food Addiction Scale Version 2. Results After controlling for demographic variables, significant associations were found in the paths from (1) perceived weight stigma to weight-related self-stigma ($$\beta$$ β = 0.23), psychological distress ($$\beta$$ β = 0.35), and food addiction ($$\beta$$ β = 0.23); (2) weight-related self-stigma to psychological distress ($$\beta$$ β = 0.52) and food addiction ($$\beta$$ β = 0.59); and (3) psychological distress to food addiction ($$\beta$$ β = 0.59) (all p-values Conclusions The results provide novel insights that weight-related self-stigma and psychological distress sequentially mediated the relationship between perceived weight stigma and food addiction among Taiwanese university students. The findings of the present study could be implemented into interventions that aim to reduce food addiction derived from weight-related stigma. Future studies should consider group analysis to consider confounding factors or other populations to provide more evidence regarding the mechanism of weight-related stigma.

Because transmission of ocular strains of Chlamydia trachomatis is greatest among preschool-aged children, limiting azithromycin distributions to this age group may conserve resources and result in less antimicrobial resistance, which is a potential advantage in areas with hypoendemic trachoma and limited resources.To determine the efficacy of mass azithromycin distributions to preschool-aged children as a strategy for trachoma elimination in areas with hypoendemic disease.In this cluster randomized clinical trial performed from November 23, 2014, until July 31, 2017, thirty rural communities in Niger were randomized at a 1:1 ratio to biannual mass distributions of either azithromycin or placebo to children aged 1 to 59 months. Participants and study personnel were masked to treatment allocation. Data analyses for trachoma outcomes were performed from October 19, 2021, through June 10, 2022.Every 6 months, a single dose of either oral azithromycin (20 mg/kg using height-based approximation for children who could stand or weight calculation for small children) or oral placebo was provided to all children aged 1 to 59 months.Trachoma was a prespecified outcome of the trial, assessed as the community-level prevalence of trachomatous inflammation-follicular and trachomatous inflammation-intense through masked grading of conjunctival photographs from a random sample of 40 children per community each year during the 2-year study period. A secondary outcome was the seroprevalence of antibodies to C trachomatis antigens.At baseline, 4726 children in 30 communities were included; 1695 children were enrolled in 15 azithromycin communities and 3031 children were enrolled in 15 placebo communities (mean [SD] proportions of boys, 51.8% [4.7%] vs 52.0% [4.2%]; mean [SD] age, 30.8 [2.8] vs 30.6 [2.6] months). The mean coverage of study drug for the 4 treatments was 79% (95% CI, 75%-83%) in the azithromycin group and 82% (95% CI, 79%-85%) in the placebo group. The mean prevalence of trachomatous inflammation-follicular at baseline was 1.9% (95% CI, 0.5%-3.5%) in the azithromycin group and 0.9% (95% CI, 0-1.9%) in the placebo group. At 24 months, trachomatous inflammation-follicular prevalence was 0.2% (95% CI, 0-0.5%) in the azithromycin group and 0.8% (95% CI, 0.2%-1.6%) in the placebo group (incidence rate ratio adjusted for baseline: 0.18 [95% CI, 0.01-1.20]; permutation P = .07).The findings of this trial do not show that biannual mass azithromycin distributions to preschool-aged children were more effective than placebo, although the underlying prevalence of trachoma was low. The sustained absence of trachoma even in the placebo group suggests that trachoma may have been eliminated as a public health problem in this part of Niger.ClinicalTrials.gov Identifier: NCT02048007.

Aim Increasing numbers of tracheostomy patients are discharged from the Intensive Care Unit (ICU) to general hospital wards. There is evidence that a Multidisciplinary Tracheostomy Team (MTT) can have a positive impact on the care of tracheostomy patients discharged from the ICU. We compared tracheostomy management and patient outcome in two time periods, at the start of our MTT practice in 2009-2011 and again in 2017. Methods In a retrospective audit, we compared tracheostomy management and patient outcome in 117 patients who had a tracheostomy in 2009-2011 with 81 patients who had a tracheostomy in 2017. Results The duration of tracheostomy cannulation was significantly shorter (21 vs 31 days, p=0.0005) in 2017 compared to 2009-2011. A Mini-Trach was used after tracheostomy decannulation in 56 of the 81 (69%) tracheostomy patients in 2017. Conclusions The continued development of our MTT service over 8 years was associated with a significantly shorter duration of tracheostomy cannulation and the introduction of Mini-Trach use after tracheostomy decannulation. These results support the importance of maintaining an active MTT service to manage tracheostomy patients after discharge from the ICU.

Background: The COVID-19 pandemic exploits existing inequalities in the social determinants of health (SDOH) that influence disease burden and access to healthcare. The role of health behaviours and socioeconomic status in genitourinary (GU) malignancy has also been highlighted. Our aim was to evaluate predictors of patient-level and neighbourhood-level factors contributing to disparities in COVID-19 outcomes in GU cancer patients. Methods: Demographic information and co-morbidities for patients screened for COVID-19 across the Mount Sinai Health System (MSHS) up to 10 June 2020 were included. Descriptive analyses and ensemble feature selection were performed to describe the relationships between these predictors and the outcomes of positive SARS-CoV-2 RT-PCR test, COVID-19-related hospitalisation, intubation and death. Results: Out of 47,379 tested individuals, 1094 had a history of GU cancer diagnosis; of these, 192 tested positive for SARS-CoV-2. Ensemble feature selection identified social determinants including zip code, race/ethnicity, age, smoking status and English as the preferred first language—being the majority of significant predictors for each of this study’s four COVID-19-related outcomes: a positive test, hospitalisation, intubation and death. Patient and neighbourhood level SDOH including zip code/ NYC borough, age, race/ethnicity, smoking status, and English as preferred language are amongst the most significant predictors of these clinically relevant outcomes for COVID-19 patients. Conclusion: Our results highlight the importance of these SDOH and the need to integrate SDOH in patient electronic medical records (EMR) with the goal to identify at-risk groups. This study’s results have implications for COVID-19 research priorities, public health goals, and policy implementations.

Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus that is asymptomatic in healthy individuals but can cause serious disease in immunocompromised patients. HCMV is also the leading cause of virus-mediated birth defects. Many of these defects manifest within the central nervous system and include microcephaly, sensorineural hearing loss, and cognitive developmental delays. Nitric oxide is a critical effector molecule produced as a component of the innate immune response during infection. Congenitally infected fetal brains show regions of brain damage, including necrotic foci with infiltrating macrophages and microglia, cell types that produce nitric oxide during infection. Using a 3-dimensional cortical organoid model, we demonstrate that nitric oxide inhibits HCMV spread and simultaneously disrupts neural rosette structures, resulting in tissue disorganization. Nitric oxide also attenuates HCMV replication in 2-dimensional cultures of neural progenitor cells (NPCs), a prominent cell type in cortical organoids that differentiate into neurons and glial cells. The multipotency factor SOX2 was decreased during nitric oxide exposure, suggesting that early neural differentiation is affected. Nitric oxide also reduced maximal mitochondrial respiration in both uninfected and infected NPCs. We determined that this reduction likely influences neural differentiation, as neurons (Tuj1(+) GFAP(−) Nestin(−)) and glial populations (Tuj1(−) GFAP(+) Nestin(−)) were reduced following differentiation. Our studies indicate a prominent, immunopathogenic role of nitric oxide in promoting developmental defects within the brain despite its antiviral activity during congenital HCMV infection. IMPORTANCE Human cytomegalovirus (HCMV) is the leading cause of virus-mediated congenital birth defects. Congenitally infected infants can have a variety of symptoms manifesting within the central nervous system. The use of 3-dimensional (3-D) cortical organoids to model infection of the fetal brain has advanced the current understanding of development and allowed broader investigation of the mechanisms behind disease. However, the impact of the innate immune molecule nitric oxide during HCMV infection has not been explored in neural cells or cortical 3-D models. Here, we investigated the effect of nitric oxide on cortical development during HCMV infection. We demonstrate that nitric oxide plays an antiviral role during infection yet results in disorganized cortical tissue. Nitric oxide contributes to differentiation defects of neuron and glial cells from neural progenitor cells despite inhibiting viral replication. Our results indicate that immunopathogenic consequences of nitric oxide during congenital infection promote developmental defects that undermine its antiviral activity.

Antibiotics are routinely used as part of the management of severe acute malnutrition and are known to reduce gut microbial diversity in non-malnourished children. We evaluated gut microbiomes in children participating in a randomized controlled trial (RCT) of azithromycin versus amoxicillin for severe acute malnutrition. Three hundred one children aged 6 to 59 months with uncomplicated severe acute malnutrition (mid-upper arm circumference < 11.5 cm and/or weight-for-height Z-score < −3 without clinical complications) were enrolled in a 1:1 RCT of single-dose azithromycin versus a 7-day course of amoxicillin (standard of care). Of these, 109 children were randomly selected for microbiome evaluation at baseline and 8 weeks. Rectal swabs were processed with metagenomic DNA sequencing. We compared alpha diversity (inverse Simpson’s index) at 8 weeks and evaluated relative abundance of microbial taxa using DESeq2. Of 109 children enrolled in the microbiome study, 95 were followed at 8 weeks. We found no evidence of a difference in alpha diversity between the azithromycin and amoxicillin groups at 8 weeks controlling for baseline diversity (mean difference −0.6, 95% CI −1.8 to 0.6, P = 0.30). Gut microbiomes did not diversify during the study. Differentially abundant genera at the P < 0.01 level included Salmonella spp. and Shigella spp., both of which were overabundant in the azithromycin compared with amoxicillin groups. We found no evidence to support an overall difference in gut microbiome diversity between azithromycin and amoxicillin among children with uncomplicated severe acute malnutrition, but potentially pathogenic bacteria that can cause invasive diarrhea were more common in the azithromycin group. Trial Registration: ClinicalTrials.gov NCT03568643.

In atomic solids, substitutional doping of atoms into the lattice of a material to form solid solutions is one of the most powerful approaches to modulating its properties and has led to the discovery of various metal alloys and semiconductors. Herein we have prepared solid solutions in hierarchical solids that are built from atomically precise clusters. Two geometrically similar metal chalcogenide clusters, Co6Se8(PEt3)6 and Cr6Te8(PEt3)6, were combined as random substitutional mixture, in three different ratios, in a crystal lattice together with fullerenes. This does not alter the underlying crystalline structure of the [cluster][C60]2 material, but it influences its electronic and magnetic properties. All three solid solutions showed increased electrical conductivities compared with either the Co- or Cr-based parent material, substantially so for two of the Co:Cr ratios (up to 100-fold), and lowered activation barriers for electron transport. We attribute this to the existence of additional energy states arising from the materials' structural heterogeneity, which effectively narrow transport gaps.

Diffraction imaging is the process of separating diffraction events from the seismic wavefield and imaging them independently, highlighting subsurface discontinuities. While there are many analytic‐based methods for diffraction imaging which use kinematic, dynamic or both, properties of the diffracted wavefield, they can be slow and require parameterization. Here, we propose an image‐to‐image generative adversarial network to automatically separate diffraction events on pre‐migrated seismic data in a fraction of the time of conventional methods. To train the generative adversarial network, plane‐wave destruction was applied to a range of synthetic and real images from field data to create training data. These training data were screened and any areas where the plane‐wave destruction did not perform well, such as synclines and areas of complex dip, were removed to prevent bias in the neural network. A total of 14,132 screened images were used to train the final generative adversarial network. The trained network has been applied across several geologically distinct field datasets, including a 3D example. Here, generative adversarial network separation is shown to be comparable to a benchmark separation created with plane‐wave destruction, and up to 12 times faster. This demonstrates the clear potential in generative adversarial networks for fast and accurate diffraction separation.

Background Extremity weakness, fatigue, and postural instability often contribute to mobility deficits in persons after stroke. Wearable technologies are increasingly being utilized to track many health-related parameters across different patient populations. The purpose of this systematic review was to identify how wearable technologies have been used over the past decade to assess gait and mobility in persons with stroke. Methods We performed a systematic search of Ovid MEDLINE, CINAHL, and Cochrane databases using select keywords. We identified a total of 354 articles, and 13 met inclusion/exclusion criteria. Included studies were quality assessed and data extracted included participant demographics, type of wearable technology utilized, gait parameters assessed, and reliability and validity metrics. Results The majority of studies were performed in either hospital-based or inpatient settings. Accelerometers, activity monitors, and pressure sensors were the most commonly used wearable technologies to assess gait and mobility post-stroke. Among these devices, spatiotemporal parameters of gait that were most widely assessed were gait speed and cadence, and the most common mobility measures included step count and duration of activity. Only 4 studies reported on wearable technology validity and reliability metrics, with mixed results. Conclusion The use of various wearable technologies has enabled researchers and clinicians to monitor patients’ activity in a multitude of settings post-stroke. Using data from wearables may provide clinicians with insights into their patients’ lived-experiences and enrich their evaluations and plans of care. However, more studies are needed to examine the impact of stroke on community mobility and to improve the accuracy of these devices for gait and mobility assessments amongst persons with altered gait post-stroke.

Background Biannual distribution of azithromycin to children 1–59 months old reduced mortality by 14% in a cluster-randomized trial. The World Health Organization has proposed targeting this intervention to the subgroup of children 1–11 months old to reduce selection for antimicrobial resistance. Here, we describe a trial designed to determine the impact of age-based targeting of biannual azithromycin on mortality and antimicrobial resistance. Methods AVENIR is a cluster-randomized, placebo-controlled, double-masked, response-adaptive large simple trial in Niger. During the 2.5-year study period, 3350 communities are targeted for enrollment. In the first year, communities in the Dosso region will be randomized 1:1:1 to 1) azithromycin 1–11: biannual azithromycin to children 1–11 months old with placebo to children 12–59 months old, 2) azithromycin 1–59: biannual azithromycin to children 1–59 months old, or 3) placebo: biannual placebo to children 1–59 months old. Regions enrolled after the first year will be randomized with an updated allocation based on the probability of mortality in children 1–59 months in each arm during the preceding study period. A biannual door-to-door census will be conducted to enumerate the population, distribute azithromycin and placebo, and monitor vital status. Primary mortality outcomes are defined as all-cause mortality rate (deaths per 1000 person-years) after 2.5 years from the first enrollment in 1) children 1–59 months old comparing the azithromycin 1–59 and placebo arms, 2) children 1–11 months old comparing the azithromycin 1–11 and placebo arm, and 3) children 12–59 months in the azithromycin 1–11 and azithromycin 1–59 arms. In the Dosso region, 50 communities from each arm will be followed to monitor antimicrobial resistance. Primary resistance outcomes will be assessed after 2 years of distributions and include 1) prevalence of genetic determinants of macrolide resistance in nasopharyngeal samples from children 1–59 months old, and 2) load of genetic determinants of macrolide resistance in rectal samples from children 1–59 months old. Discussion As high-mortality settings consider this intervention, the results of this trial will provide evidence to support programmatic and policy decision-making on age-based strategies for azithromycin distribution to promote child survival. Trial registration This trial was registered on January 13, 2020 (clinicaltrials.gov: NCT04224987).

BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) pandemic has generated negative effects on psychological well-being worldwide, including in schoolchildren. Government requirements to stay at home and avoid social and school settings may impact psychological well-being by modifying various behaviors such as problematic phone and Internet use, yet there is a paucity of research on this issue. This study examined whether the COVID-19 outbreak may have impacted problematic smartphone use (PSU), problematic gaming (PG), and psychological distress, specifically the pattern of relationships between PSU, PG, and psychological distress in schoolchildren. METHODS: Longitudinal data on psychological distress, PSU, and PG were collected from 575 children in primary schools in 3 waves: Waves 1 and 2 were conducted before the COVID-19 outbreak and Wave 3 during the outbreak. Cross-lagged panel models were used to examine relationships between factors across the 3 waves. RESULTS: Cross-lagged models found that higher levels of PSU were not significantly related prospectively to greater psychological distress before the COVID-19 outbreak, but this prospective relationship became significant during the COVID-19 outbreak. Whereas PG was associated prospectively with psychological distress before the COVID-19 outbreak (ie, between Waves 1 and 2), this association became nonsignificant during the COVID-19 lockdown (ie, between Waves 2 and 3). CONCLUSIONS: The COVID-19 outbreak has seemed to change prospective relationships between PSU and psychological distress and PG and psychological distress in schoolchildren. Future research should examine whether restrictions on or information provided to schoolchildren may exacerbate PSUs effects on psychological distress.

Objective To determine the relationship between visual impairment and other disabilities in a developing country. Methods In this cross-sectional ancillary study, all individuals 50 years and older in 18 communities in the Chitwan region of Nepal were administered visual acuity screening and the Washington Group Short Set (WGSS) of questions on disability. The WGSS elicits a 4-level response for six disability domains: vision, hearing, walking/climbing, memory/concentration, washing/dressing, and communication. The association between visual impairment and disability was assessed with age- and sex-adjusted logistic regression models. Results Overall, 4719 of 4726 individuals successfully completed visual acuity and disability screening. Median age of participants was 61 years (interquartile range: 55-69 years), and 2449 (51.9%) were female. Participants with vision worse than 6/60 in the better-seeing eye were significantly more likely to be classified as having a disability in vision (OR 18.4, 95% CI 9.9-33.5), walking (OR 5.3, 95% CI 2.9-9.1), washing (OR 9.4, 95% CI 4.0-21.1), and communication (OR 5.0, 95% CI 1.7-13.0), but not in hearing (OR 0.6, 95% CI 0.006-2.2) or memory (OR 2.2, 95% CI 0.7-5.1). Conclusions Visually impaired participants were more likely to self-report disabilities, though causality could not be ascertained. Public health programs designed to reduce visual impairment could use the WGSS to determine unintended benefits of their interventions.

Background: Most patients with early stage oestrogen receptor positive (ER+) and HER2 negative breast cancer will be cured of their cancer. However, up to 20% of patients may experience disease recurrence in the first 10 years. Molecular relapse of ER+ breast cancer can be detected with circulating tumour DNA (ctDNA) before clinical relapse occurs. Palbociclib, a CDK4/6 inhibitor, plus fulvestrant, a selective oestrogen receptor degrader, is a standard first line therapy for patients with ER+ breast cancer who have relapsed on standard endocrine therapy. We designed TRAK-ER to establish a surveillance system for ctDNA detection and then to assess whether treating patients, who have ctDNA detected molecular relapse, with palbociclib and fulvestrant may defer or prevent relapse. Design: TRAK-ER is a phase 2 multi-centre, randomised, open-label parallel superiority trial in patients with ER+ early breast cancer, recruiting at centres in the UK and France. In the surveillance phase patients will be monitored for molecular recurrence with ctDNA testing. To be eligible for the surveillance phase patients must be aged 18 or over, have ER+ (≥10% or Allred score 6/8 or greater) and HER2 negative breast cancer and have completed their primary surgery, chemotherapy and radiotherapy. Standard endocrine therapy (GnRH analogues, aromatase inhibitors and tamoxifen) must have been received for a minimum of 6 months and a maximum of 7 years and be planned to continue for at least another 3 years. Inclusion criteria in patients who did not receive neoadjuvant chemotherapy are at least one of: (a) four or more involved axillary or positive supraclavicular lymph node; (b) tumour size >5cm; (c) one to three involved axillary lymph nodes together with at least one of: tumour size >3cm, grade 3 or a high genomic risk score. Patients who received neoadjuvant chemotherapy require at least one lymph node positive or a tumour size >3cm after chemotherapy. Invitae Personalized Cancer Monitoring (PCM TM) will be used for ctDNA analysis, a pan-cancer, tumour-informed liquid biopsy test that uses next-generation sequencing to detect minimal or molecular residual disease (MRD) in solid tumours. ctDNA analysis will be every 3 months for up to 3 years. Detection of ctDNA will trigger staging imaging. If no overt metastatic disease is identified, patients will be able to enter the treatment phase of the study, and be 1:1 randomised using minimisation to either remain on standard endocrine therapy or switch to palbociclib plus fulvestrant. Those who are allocated to remain on endocrine therapy are allowed to continue on the same therapy or change standard endocrine therapy. Duration of palbociclib and fulvestrant will be 2 years, or until relapse. Up to 1300 patients will enrol for tissue screening to allow 1100 patients to enter into ctDNA surveillance. 132 patients will enter the treatment part of the study. The primary endpoint of the surveillance phase is ctDNA detection rate. The primary endpoint of the treatment phase is relapse free survival (RFS). RFS will be calculated in the intention to treat population using Kaplan Meier methods from the date of randomisation to the date of recurrence or death from any cause. Secondary endpoints include relapse free interval, invasive disease free survival, distant recurrence free survival, overall survival and ctDNA clearance. (NCT04985266) Citation Format: Nicholas Turner, Edward R. Phillips, Catey Bunce, Marie Robert, Caroline Bailleux, Isaac Garcia-Murillas, Komel Khabra, Iain Macpherson, Ciara S. O’Brien, Alicia F. Okines, Carlo Palmieri, Peter Schmid, Claire Swift, Sabrina Yara, Simon Connolly, Jérôme Lemonnier, Dymphna Lee, Fabrice Andre. A randomised phase II trial of palbociclib and fulvestrant vs standard endocrine therapy in patients with ER positive HER2 negative breast cancer and ctDNA detected molecular relapse during adjuvant endocrine therapy (TRAK-ER) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-01-01.

Receptor activity-modifying proteins (RAMPs) modulate the activity of many Family B heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs). The glucagon receptor (GCGR), a Family B GPCR responsible for maintenance of proper blood sugar levels, interacts with RAMP2, though the purpose and consequence of this interaction is poorly understood. Using a series of biochemical and cell-based assays, we show that RAMP2 interacts with and broadly inhibits GCGR-induced downstream signaling. Hydrogen-deuterium exchange monitored by mass spectrometry (HDX-MS) demonstrates that RAMP2 enhances local flexibility in select locations in and near the receptor extracellular domain (ECD) as well as at a key region in the 6th transmembrane helix, while single-molecule fluorescence resonance energy transfer (smFRET) experiments show that this RAMP2-induced ECD disorder results in inhibition of active and intermediate states of the intracellular face of the receptor. Using cryo-electron microscopy (cryoEM), we determined the structure of the GCGR-Gs complex at 2.9 Å resolution in the presence of RAMP2. RAMP2 apparently does not interact with GCGR in an ordered manner, yet the ECD of GCGR is indeed largely disordered in the presence of RAMP2. This disorder is accompanied by rearrangements of several key areas of the receptor, resulting in the formation of a likely unproductive complex. Together, our studies suggest that RAMP2 acts as a negative allosteric modulator of GCGR by enhancing conformational sampling of the ECD.

Previous studies have used subjective assessments to implicate darker skin color as a risk factor for glaucoma. This study used objective measurements to determine whether skin melanin is a risk fa...

Penile squamous cell carcinoma (SCC) is a rare malignancy, which is known to invade local inguinal lymph nodes prior to progressing to the pelvis. Dynamic sentinel lymph node biopsy (DSLNB) is a standard for the minimally invasive assessment of lymphadenopathy in patients with subclinical groin metastasis. Hybrid 99mTc Single-Photon Emission Computed Tomography (SPECT-CT) has been shown to increase the accuracy of identifying first draining “sentinel” nodes (SN). Unilateral inguinal visualization on SPECT-CT is a rare presentation, which may increase the likelihood of a false negative SN biopsy. Retrospective analysis from three-penile cancer uro-oncologists in Melbourne, Australia identified 78 groins undergoing DSLNB for intermediate/high risk primary disease. Unilateral SPECT-CT results were observed in four patients suggesting a functional pattern of lymph diversion. Analysis confirmed malignancy (n = 2), sarcoidosis (n = 1), and evidence of local inflammation in SPECT-CT negative groins. Findings re-iterate the role of SPECT-CT a pre-operative adjunct. Experienced multimodal groin assessment using palpation, SPECT-CT, lymphoscintigraphy, and blue dye tracking remains paramount. Unilateral SN on pre-operative SPECT-CT in men with intermediate/high-risk penile SCC should elicit a higher degree of clinical suspicion. We recommend a low threshold for recommending radical inguinal lymph node dissection (ILND) for groins refractory to minimally invasive assessment.

Background: Homophobic language is common in male sport and associated with negative physical and mental health outcomes for athletes. Evidence-based interventions are needed to reduce such language, and foster safer sport settings. Purpose: Evaluate the effectiveness of a short, discussion-based educational intervention delivered by professional rugby union players to teenage rugby union teams. Study design: Two-arm, cluster randomised controlled trial. Methods: Thirteen youth rugby teams from nine clubs (N = 167 players, ages 16 – 20 years) were randomised into treatment or wait-list control groups. Two professional rugby players delivered a social-cognitive educational intervention to treatment teams. Frequency of homophobic language use (eg, fag) was measured two weeks pre and again two weeks post intervention. Factors hypothesized to be associated homophobic language were also measured, including descriptive norms, prescriptive and proscriptive injunctive norms, and attitudes around the acceptability of this behaviour. The study was preregistered prior to analyses (https://osf.io/c7tdm). Results: At baseline, 49.1% of participants self-reported using homophobic language in the past two weeks. Significant relationships were found between this behaviour and all factors targeted by the intervention. However, generalised estimating equations found, relative to controls, the intervention did not significantly change the homophobic language used by athletes or alter the associated norms and attitudes. Conclusion: In this study, using professional rugby union players to deliver a theory-informed, short, educational intervention to reduce homophobic language usage was not effective. Other approaches may be needed, such as peer-to-peer education and monitoring of coaches to ensure they are enforcing existing anti-discrimination policies.

PurposeTo determine whether a community health worker (CHW) program increases referrals to local eye care providers and ultimately reduces the incidence of corneal ulcers.DesignCluster-randomized trial performed from 2014 to 2017 in rural South India.MethodsThis was a community-based study that included all inhabitants of 42 rural South Indian communities. CHWs were trained to diagnose corneal abrasions and assist participants in seeking care at a local vision center. Given the nature of the intervention, the trial was not masked. The main outcome measure was incident corneal ulcer, defined as an active infiltrate or evidence of a new opacity, as assessed by means of penlight examination during an annual door-to-door census.ResultsTwenty-one study clusters were randomized to the CHW intervention and 21 to no intervention. Vision centers diagnosed 195 corneal abrasions from the intervention clusters during the 2-year study (rate, 223 per 100,000 person-years; 95% CI, 28-1743) and 62 from the control clusters (rate, 62 per 100,000 person-years; 95% CI, 8-496; incidence rate ratio, 3.57; 95% CI, 2.01-6.35; P < .001). The estimated incidence of corneal ulceration during the study period was 60 per 100,000 person-years (95% CI, 25-141) in the intervention group and 32 per 100,000 person-years (95% CI, 13-80) in the control group (incidence rate ratio, 1.86; 95% CI, 0.5-6.4; P=.32).ConclusionsA CHW program resulted in 3.5 times more referrals to local eye care providers for corneal abrasions, but no difference could be detected in the incidence of corneal ulceration. CHW programs provide a mechanism for increasing referrals to eye hospitals.Trial registrationClinicalTrials.gov ID: NCT02284698.

We evaluated limb salvage (LS), amputation-free survival (AFS), and target extremity reintervention (TER) after plain old balloon angioplasty (POBA), stenting, and atherectomy for treatment of infrapopliteal disease (IPD) with chronic limb-threatening ischemia (CLTI).All index peripheral vascular interventions for IPD and CLTI were identified from the Vascular Quality Initiative registry. Of the multilevel procedures, the peripheral vascular intervention type was indexed to the infrapopliteal segment. Propensity score matching was used to control for baseline differences between groups. Kaplan-Meier and Cox regression were used to calculate and compare LS and AFS.The 3-year LS for stenting vs POBA was 87.6% vs 81.9% (P = .006) but was not significant on Cox regression analysis (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.56-0.76; P = .08). AFS was superior for stenting vs POBA (78.1% vs 69.5%; P = .001; HR, 0.73; 95% CI, 0.60-0.90; P = .003). LS was similar for POBA and atherectomy (81.9% vs 84.8%; P = .11) and for stenting and atherectomy (87.6% vs 84.8%; P = .23). The LS rate after propensity score matching for POBA vs stenting was 83.4% vs 88.2% (P = .07; HR, 0.71; 95% CI, 0.50-1.017; P = .062). The AFS rate for stenting vs POBA was 78.8% vs 69.4% (P = .005; HR, 0.69; 95% CI, 0.54-0.89; P = .005). No significant differences were found between stenting and atherectomy (P = .21 for atherectomy; and P = .34 for POBA). The need for TER did not differ across the groups but the interval to TER was significantly longer for stenting than for POBA or atherectomy (stenting vs POBA, 12.8 months vs 7.7 months; P = .001; stenting vs atherectomy, 13.5 months vs 6.8 months; P .001).Stenting and atherectomy had comparable LS and AFS for patients with IPD and CLTI. However, stenting conferred significant benefits for AFS compared with POBA but atherectomy did not. Furthermore, the interval to TER was nearly double for stenting compared with POBA or atherectomy. These factors should be considered when determining the treatment strategy for this challenging anatomic segment.

Significance Deep profiling of the plasma proteome at scale has been a challenge for traditional approaches. We achieve superior performance across the dimensions of precision, depth, and throughput using a panel of surface-functionalized superparamagnetic nanoparticles in comparison to conventional workflows for deep proteomics interrogation. Our automated workflow leverages competitive nanoparticle–protein binding equilibria that quantitatively compress the large dynamic range of proteomes to an accessible scale. Using machine learning, we dissect the contribution of individual physicochemical properties of nanoparticles to the composition of protein coronas. Our results suggest that nanoparticle functionalization can be tailored to protein sets. This work demonstrates the feasibility of deep, precise, unbiased plasma proteomics at a scale compatible with large-scale genomics enabling multiomic studies.

Many psychological inclinations, such as maladaptive beliefs, can diminish the capacity of individuals to manage their weight effectively and sustainably. Yet, interventions that purportedly address these psychological inclinations and improve weight management are not always beneficial. To be effective, these interventions should offer participants several choices, should be devoid of features that have not been validated in isolation, and should arrange the various activities in an efficient and effective sequence. Few if any programs fulfill these criteria. The aim of this paper was to construct an intervention that assimilates all the validated features of interventions that overcome the psychological impediments to weight loss. To achieve this goal, we blended a technique called intervention component analysis with thematic analysis. Specifically, we extracted refereed journal articles about weight loss from PsycInfo, distilled the practical recommendations from these articles, excluded recommendations that had not been validated in isolation of other features, integrated overlapping recommendations, and applied several principles to arrange these recommendations into the most effective sequence. This procedure generated an intervention that could comprise up to 43 features and activities, including self-affirmation to foster openness to change, anecdotes about dramatic improvements, ambitious rather than modest targets, an emphasis on strategies rather than targets, rewards for attempts, implementation intentions with partners, self-hypnosis, cognitive reframing, and distancing. If these features are unsuccessful, practices that demand more resources-such as group disclosure, virtual environments, motivational interviewing, and customized programs-were also recommended.

SUMMARYNonlinear wave propagation is an important consideration in several geophysical problems as heterogeneities within the subsurface give rise to nonlinear stress–strain relationships in rocks. To address these problems, where the inclusion of subsurface complexity is accounted for, numerical solutions are required. Here, we outline a discrete particle or lattice numerical method that can simulate dynamic and static deformation in an isotropic viscoelastic nonlinear medium where the nonlinearity includes the fourth-order elastic tensor coefficients. The relationship between the local interaction constants in the lattice method and the macroscopic nonlinear coefficients is derived and the relationships presented. The theoretical dispersion properties of the system is determined from a nonlinear perturbation method and are validated against some numerical results. There is an excellent agreement between the theory and numerical results and the method reproduces the common features of nonlinear wave propagation, for example, harmonics, waveform distortion and spectra shifts. As expected the system is shown to be dependent on the wave amplitudes and an example is presented which shows the complexity that can arise in both dynamic and static deformation in a complex model where nonlinearity is included.