Moderation Effects of Daily Behavior on Associations between Symptoms and Social Participation Outcomes after Burn Injury: A 6-month Digital Phenotyping Study.

OBJECTIVE: To examine the moderation effects of daily behavior on the associations between symptoms and social participation outcomes after burn injury DESIGN: A 6-month prospective cohort study SETTING: Community PARTICIPANTS: 24 adult burn survivors INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Symptoms and social participation outcomes were assessed weekly using smartphone surveys, including symptoms of pain (Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity and Pain Interference), anxiety (PROMIS Anxiety), and depression (Patient Health Questionnaire (PHQ-8)), as well as outcomes of social interactions and social activities (Life Impact Burn Recovery Evaluation (LIBRE) Social Interactions and Social Activities). Daily behaviors were automatically recorded by a smartphone application and smartphone logs, including physical activity (steps, travel miles, and activity minutes), sleep (sleep hours), and social contact (number of phone call and message contacts). RESULTS: Multilevel models controlling for demographic and burn injury variables examined the associations between symptoms and social participation outcomes, and the moderation effects of daily behaviors. Lower (worse) LIBRE Social Interactions and LIBRE Social Activities scores were significantly associated with higher (worse) PROMIS Pain Intensity, PROMIS Pain Interference, PROMIS Anxiety, and PHQ-8 scores (p<0.05). Additionally, daily steps and activity minutes were associated with LIBRE Social Interactions and LIBRE Social Activities (p<0.05), and significantly moderated the association between PROMIS Anxiety and LIBRE Social Activities (p<0.001). CONCLUSIONS: Social participation outcomes are associated with pain, anxiety, and depression symptoms after burn injury, and are buffered by daily physical activity. Future interventions studies should examine physical activity promotion on improving social recovery after burns.

Accuracy of Antenatal Ultrasound in Predicting Large for Gestational Age Babies: Population Based Cohort Study.

BACKGROUND: Pregnancies with large for gestational age fetuses are at increased risk of adverse maternal and neonatal outcomes. There is uncertainty about how to manage birth in such pregnancies. Current guidelines recommend a discussion with women of the pros and cons of options including expectant management, induction of labour and caesarean birth. For women to be able to make an informed decision about birth, antenatal detection of large for gestational age is essential. OBJECTIVE: To investigate the ability of antenatal ultrasound scans to predict large for gestational age at birth. STUDY DESIGN: In this retrospective cohort study, we analysed data from a routinely collected database from the West Midlands, United Kingdom. We included pregnancies that had an antenatal ultrasound estimated fetal weight between 35+0 and 38+0 weeks gestation for any indication, as well as a subgroup where the reason for scan was that the fetus was suspected to be big. Large for gestational age was defined as >90th customized GROW centile, for estimated fetal weight as well as for neonatal weight. We also tested performance of an uncustomized standard, with Hadlock fetal weight >90th centile and neonatal weight >4kg. We calculated diagnostic characteristics for the whole population as well as groups with different maternal body mass indices. RESULTS: The study cohort consisted of 26,527 pregnancies which on average had a scan at 256 days gestation and delivered 20 days later at a median of 276 days (interquartile range 15). In total 2241 (8.4%) of neonates were large for gestational age by customized centiles, of which 1459 (65.1%) had a scan estimated fetal weight >90th centile, with a false positive rate of 8.6% and a positive predictive value of 41.0%. In the subgroup of 912 (3.4%) pregnancies scanned for a suspected large fetus, 293 (32.1%) babies were large for gestational age at birth, giving a positive predictive value of 50.3%, with sensitivity of 77.1% and false positive rate 36.0%. When comparing subgroups from low (<18.5kg/m2) to high body mass index (>30kg/m2), sensitivity increased from 55.6 to 67.8%, false positive rate from 5.2 to 11.5% and positive predictive value from 32.1 to 42.3%. A total of 2585 (9.7%) babies were macrosomic (birthweight >4kg), and of these 1058 (40.9%) were large for gestational age (>90th centile) antenatally by Hadlock's growth standard, with a false positive rate of 4.9% and a positive predictive value 41.0%. Analysis within subgroups showed better performance by customized compared to uncustomized standards for low body mass index (<18.5; diagnostic odds ratio 23.0 vs 6.4) and high body mass index (>30; diagnostic odds ration 16.2 vs 8.8). CONCLUSION: Late third trimester ultrasound estimation of fetal weight for any indication has good ability to identify and predict large for gestational age at birth, and improves with the use of a customised standard. Detection rate is better when ultrasound is performed for a suspected large fetus, however at the risk of higher false positive diagnosis. Our results provide information for women and clinicians to aid antenatal decision making about birth of a fetus suspected of being large for gestational age.

Ultrasound in Cardiopulmonary Arrest and Resuscitation: Constructing Comprehensive Implementation Frameworks in High-Risk Settings.

OBJECTIVES: Information obtained from point-of-care ultrasound during cardiopulmonary arrest and resuscitation (POCUS-CA) can be used to identify underlying pathophysiology and provide life-sustaining interventions. However, integration of POCUS-CA into resuscitation care is inconsistent. We used expert consensus building methodology to help identify discrete barriers to clinical integration. We subsequently applied implementation science frameworks to generate generalizable strategies to overcome these barriers. MEASURES AND MAIN RESULTS: Two multidisciplinary expert working groups used KJ Reverse-Merlin consensus building method to identify and characterize barriers contributing to failed POCUS-CA utilization in a hypothetical future state. Identified barriers were organized into affinity groups. The Center for Implementation Research (CFIR) framework and Expert Recommendations for Implementing Change (CFIR-ERIC) tool were used to identify strategies to guide POCUS-US implementation. RESULTS: Sixteen multidisciplinary resuscitation content experts participated in the working groups and identified individual barriers, consolidated into 19 unique affinity groups that mapped 12 separate CFIR constructs, representing all 5 CFIR domains. The CFIR-ERIC tool identified the following strategies as most impactful to address barriers described in the affinity groups: identify and prepare champions, conduct local needs assessment, conduct local consensus discussions, and conduct educational meetings. CONCLUSIONS: KJ Reverse-Merlin consensus building identified multiple barriers to implementing POCUS-CA. Implementation science methodologies identified and prioritized strategies to overcome barriers and guide POCUS-CA implementation across diverse clinical settings.

Optimization of alert notifications in electronic patient-reported outcome (ePRO) remote symptom monitoring systems (AFT-39).

PURPOSE: Clinical benefits result from electronic patient-reported outcome (ePRO) systems that enable remote symptom monitoring. Although clinically useful, real-time alert notifications for severe or worsening symptoms can overburden nurses. Thus, we aimed to algorithmically identify likely non-urgent alerts that could be suppressed. METHODS: We evaluated alerts from the PRO-TECT trial (Alliance AFT-39) in which oncology practices implemented remote symptom monitoring. Patients completed weekly at-home ePRO symptom surveys, and nurses received real-time alert notifications for severe or worsening symptoms. During parts of the trial, patients and nurses each indicated whether alerts were urgent or could wait until the next visit. We developed an algorithm for suppressing alerts based on patient assessment of urgency and model-based predictions of nurse assessment of urgency. RESULTS: 593 patients participated (median age = 64 years, 61% female, 80% white, 10% reported never using computers/tablets/smartphones). Patients completed 91% of expected weekly surveys. 34% of surveys generated an alert, and 59% of alerts prompted immediate nurse actions. Patients considered 10% of alerts urgent. Of the remaining cases, nurses considered alerts urgent more often when patients reported any worsening symptom compared to the prior week (33% of alerts with versus 26% without any worsening symptom, p = 0.009). The algorithm identified 38% of alerts as likely non-urgent that could be suppressed with acceptable discrimination (sensitivity = 80%, 95% CI [76%, 84%]; specificity = 52%, 95% CI [49%, 55%]). CONCLUSION: An algorithm can identify remote symptom monitoring alerts likely to be considered non-urgent by nurses, and may assist in fostering nurse acceptance and implementation feasibility of ePRO systems.

Sequence reliance of the Drosophila context-dependent transcription factor CLAMP.

Despite binding similar cis elements in multiple locations, a single transcription factor (TF) often performs context-dependent functions at different loci. How factors integrate cis sequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. The Drosophila context-dependent TF chromatin-linked adaptor for male-specific lethal proteins (CLAMP) targets similar GA-rich cis elements on the X-chromosome and at the histone gene locus but recruits very different, locus-specific factors. We discover that CLAMP leverages information from both cis element and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.

Cytomegalovirus drives Vδ1+ γδ T cell expansion and clonality in common variable immunodeficiency.

The function and phenotype of γδ T cells in the context of common variable immunodeficiency (CVID) has not been explored. CVID is a primary immunodeficiency disorder characterized by impaired antibody responses resulting in increased susceptibility to infections. γδ T cells are a subset of unconventional T cells that play crucial roles in host defence against infections. In this study, we aim to determine the roles and functions of γδ T cells in CVID. We observe a higher frequency of Vδ1+ γδ T cells compared to healthy controls, particularly in older patients. We also find a higher proportion of effector-memory Vδ1+ γδ T cells and a more clonal T cell receptor (TCR) repertoire in CVID. The most significant driver of the Vδ1+ γδ T cell expansion and phenotype in CVID patients is persistent cytomegalovirus (CMV) viremia. These findings provide valuable insights into γδ T cell biology and their contribution to immune defence in CVID.

Social ageing can protect against infectious disease in a group-living primate.

The benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost-benefit ratio of sociality is expected to change across individuals' lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity, and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of 'social ageing' depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence evolutionary dynamics of social ageing in natural populations.

Performance of fluorescence in situ hybridization in biliary brushings with equivocal cytology: an institutional experience.

INTRODUCTION: Biliary brushing (BB) cytology has a sensitivity of 15%-65% and specificity approaching 100% for detecting malignancy. Fluorescence in-situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of malignancies with reported sensitivity of 43%-84%. We sought to evaluate the performance of FISH in BB with equivocal cytology at our institution. MATERIALS AND METHODS: Patients with atypical and suspicious BB with concurrent diagnostic FISH performed at our institution from 2014 to 2021 were identified through a query of our pathology database. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed for pathology results and outcomes. Patients were classified malignant if they had positive pathology or documented clinical impression of malignancy and benign if they had negative pathology and/or documented benign clinical course for at least 12 months. RESULTS: We identified 254 equivocal BB (238 atypical/16 suspicious) with concurrent FISH results from 191 patients (105 benign, 86 malignant). 12% (22/191) of patients were FISH positive. Twenty-four percent (21/86) of patients with malignancy had positive FISH but were nonspecific for pancreaticobiliary/ampullary adenocarcinomas. Almost all positive FISH were associated with malignancy (21/22; 95%). There was 1 positive FISH in a patient with primary sclerosing cholangitis who had a benign outcome. CONCLUSIONS: The small number of positive FISH results in BB with equivocal cytology raises the question of the optimal criteria for malignancy. Using only polysomy could result in lower sensitivity.

Socioecological drivers of injuries in female and male rhesus macaques (Macaca mulatta).

Competition over access to resources, such as food and mates, is believed to be one of the major costs associated with group living. Two socioecological factors suggested to predict the intensity of competition are group size and the relative abundance of sexually active individuals. However, empirical evidence linking these factors to injuries and survival costs is scarce. Here, we leveraged 10 years of data from free-ranging rhesus macaques where injuries inflicted by conspecifics are associated with a high mortality risk. We tested if group size and adult sex ratio predicted the occurrence of injuries and used data on physical aggression to contextualise these results. We found that males were less likely to be injured when living in larger groups, potentially due to advantages in intergroup encounters. Females, instead, had higher injury risk when living in larger groups but this was not explained by within-group aggression among females. Further, male-biased sex ratios predicted a weak increase in injury risk in females and were positively related to male-female aggression, indicating that male coercion during mating competition may be a cause of injuries in females. Overall, our results provide insights into sex differences in the fitness-related costs of competition and empirical evidence for long-standing predictions on the evolution of group living.

Cross-domain Fiber Cluster Shape Analysis for Language Performance Cognitive Score Prediction.

Shape plays an important role in computer graphics, offering informative features to convey an object's morphology and functionality. Shape analysis in brain imaging can help interpret structural and functionality correlations of the human brain. In this work, we investigate the shape of the brain's 3D white matter connections and its potential predictive relationship to human cognitive function. We reconstruct brain connections as sequences of 3D points using diffusion magnetic resonance imaging (dMRI) tractography. To describe each connection, we extract 12 shape descriptors in addition to traditional dMRI connectivity and tissue microstructure features. We introduce a novel framework, Shape--fused Fiber Cluster Transformer (SFFormer), that leverages a multi-head cross-attention feature fusion module to predict subject-specific language performance based on dMRI tractography. We assess the performance of the method on a large dataset including 1065 healthy young adults. The results demonstrate that both the transformer-based SFFormer model and its inter/intra feature fusion with shape, microstructure, and connectivity are informative, and together, they improve the prediction of subject-specific language performance scores. Overall, our results indicate that the shape of the brain's connections is predictive of human language function.

"More support, less distress?": Examining the role of social norms in alleviating practitioners' psychological distress in the context of assisted dying services.

This study explores how providing assisted dying services affects the psychological distress of practitioners. It investigates the influence of professional norms that endorse such services within their field. Study 1 included veterinarians (N = 137, 75.2% female, Mage = 43.1 years, SDage = 12.7 years), and Study 2 health practitioner students (N = 386, 71.0% female, Mage = 21.0 years, SDage = 14.4 years). In both studies, participants indicated their degree of psychological distress following exposure to scenarios depicting assisted dying services that were relevant to their respective situations. In Study 1, we found that higher willingness to perform animal euthanasia was associated with lower distress, as were supportive norms. In Study 2, a negative association between a greater willingness to perform euthanasia and lower psychological distress occurred only when the provision of such services was supported by professional norms. In conclusion, psychological distress is buffered by supportive professional norms.

Identifying potential cases of eating disorders in an acute medical hospital.

OBJECTIVE: To identify patients presenting to an acute medical hospital with common signs and symptoms that occur in people with eating disorders (EDs), and determine by retrospective file audit if these are diagnosed cases of an ED. METHOD: The investigators screened electronic medical records of people 16 years and older for common signs and symptoms of an ED such as hypokalemia, in patients presenting to an acute hospital in Sydney, Australia from 2018 to 2020. Cases where the clinical finding was unexplained had their file audited. Cases with a known ED diagnosis or coded with an ED were also retrieved to audit. RESULTS: Investigators identified 192 definite ED cases with a total of 598 episodes of care from 2018 to 2020 presenting to the hospital. Eighty-three cases were identified as possible EDs due to unexplained clinical signs consistent with an ED, but were not confirmed cases due to lack of clinical history in the file. Only 19.1% of presentations were diagnostically coded with an ED in the electronic medical record. DISCUSSION: Our study revealed a large number of definite ED cases presenting to an acute medical hospital via the emergency department, who were not recognized as having an ED. Greater awareness of clinical signs and symptoms of an ED, such as unexplained low body mass index and hypokalemia, is necessary among acute care clinicians. Correctly identifying EDs in those seeking somatic care should be a public health priority, to facilitate timely and equitable access to diagnostic assessment and evidence based treatment. PUBLIC SIGNIFICANCE: People with eating disorders (EDs) present to acute care settings and have a relatively high utilization of generalist health services with nonspecific problems such as abdominal pain. An enhanced understanding of healthcare utilization by people with EDs, who may not disclose their symptoms, is crucial for improving access to treatment.

Further development and validation of the Multimorbidity Treatment Burden Questionnaire (MTBQ).

OBJECTIVES: To undertake further psychometric testing of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and examine whether reversing the scale reduced floor effects. DESIGN: Survey. SETTING: UK primary care. PARTICIPANTS: Adults (≥18 years) with three or more long-term conditions randomly selected from four general practices and invited by post. MEASURES: Baseline survey: sociodemographics, MTBQ (original or version with scale reversed), Treatment Burden Questionnaire (TBQ), four questions (from QQ-10) on ease of completing the questionnaires. Follow-up survey (1-4 weeks after baseline): MTBQ, TBQ and QQ-10. Anonymous data collected from electronic GP records: consultations (preceding 12 months) and long-term conditions. The proportion of missing data and distribution of responses were examined for the original and reversed versions of the MTBQ and the TBQ. Intraclass correlation coefficient (ICC) and Spearman's rank correlation (Rs) assessed test-retest reliability and construct validity, respectively. Ease of completing the MTBQ and TBQ was compared. Interpretability was assessed by grouping global MTBQ scores into 0 and tertiles (>0). RESULTS: 244 adults completed the baseline survey (consent rate 31%, mean age 70 years) and 225 completed the follow-up survey. Reversing the scale did not reduce floor effects or data skewness. The global MTBQ scores had good test-retest reliability (ICC for agreement at baseline and follow-up 0.765, 95% CI 0.702 to 0.816). Global MTBQ score was correlated with global TBQ score (Rs 0.77, p<0.001), weakly correlated with number of consultations (Rs 0.17, p=0.010), and number of different general practitioners consulted (Rs 0.23, p<0.001), but not correlated with number of long-term conditions (Rs -0.063, p=0.330). Most participants agreed that both the MTBQ and TBQ were easy to complete and included aspects they were concerned about. CONCLUSION: This study demonstrates test-retest reliability and ease of completion of the MTBQ and builds on a previous study demonstrating good content validity, construct validity and internal consistency reliability of the questionnaire.

Generation of human alveolar epithelial type I cells from pluripotent stem cells.

Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs. The resulting cells express a molecular, morphologic, and functional phenotype reminiscent of human AT1 cells, including the capacity to form a flat epithelial barrier producing characteristic extracellular matrix molecules and secreted ligands. Our results provide an in vitro model of human alveolar epithelial differentiation and a potential source of human AT1s.

Gut microbiome composition and metabolic activity in women with diverticulitis.

The etiopathogenesis of diverticulitis, among the most common gastrointestinal diagnoses, remains largely unknown. By leveraging stool collected within a large prospective cohort, we performed shotgun metagenomic sequencing and untargeted metabolomics profiling among 121 women diagnosed with diverticulitis requiring antibiotics or hospitalizations (cases), matched to 121 women without diverticulitis (controls) according to age and race. Overall microbial community structure and metabolomic profiles differed in diverticulitis cases compared to controls, including enrichment of pro-inflammatory Ruminococcus gnavus, 1,7-dimethyluric acid, and histidine-related metabolites, and depletion of butyrate-producing bacteria and anti-inflammatory ceramides. Through integrated multi-omic analysis, we detected covarying microbial and metabolic features, such as Bilophila wadsworthia and bile acids, specific to diverticulitis. Additionally, we observed that microbial composition modulated the protective association between a prudent fiber-rich diet and diverticulitis. Our findings offer insights into the perturbations in inflammation-related microbial and metabolic signatures associated with diverticulitis, supporting the potential of microbial-based diagnostics and therapeutic targets.

Experiences of delay-causing obstacles and mental health at the time of abortion seeking.

Objectives: The delays and challenges people encounter when seeking abortion are well-documented, but their psychological implications are understudied. Aiming to fill this gap, we explored the associations between experiences of delay-causing obstacles to abortion care and adverse mental health symptoms among individuals seeking abortion care. Study design: In 2019, we surveyed 784 people (of 1092 approached) ages 15-45 accessing abortion care in four clinics in abortion-supportive states: California, Illinois, and New Mexico. We conducted multivariable Poisson regressions to examine associations between experiencing delay-causing obstacles to abortion care and stress, anxiety, and depression at the abortion appointment. We also used Poisson regression to examine whether some individuals are more likely to experience delay-causing obstacles than others. Results: Three in five participants (58%) experienced delay-causing obstacles when accessing abortion care. The most prevalent obstacles were cost-related (45%), followed by access-related (43%), and travel time-related (35%) delays. In adjusted analyses, experiencing any type of delay-causing obstacle to abortion care was significantly associated with more symptoms of stress, anxiety, and depression and higher risk of anxiety and depressive disorders. Participants were more likely to experience delay-causing obstacles if they traveled from another state or over 100 miles to reach the clinic, sought abortion beyond 13 weeks gestation, lacked money for unexpected expenses, and found it difficult to pay for the abortion. Conclusion: Abortion is a time-sensitive healthcare, but most individuals are forced to delay care due to various obstacles that may have a negative impact on their psychological well-being. Implications: Obstacles causing delays in accessing abortion care may contribute to elevated symptoms of stress, anxiety, and depression and higher risk of anxiety and depressive disorders for abortion patients. As restrictive policies increase, delays are likely to worsen, potentially leading to psychological harm for people seeking abortion.

TractGeoNet: A geometric deep learning framework for pointwise analysis of tract microstructure to predict language assessment performance.

We propose a geometric deep-learning-based framework, TractGeoNet, for performing regression using diffusion magnetic resonance imaging (dMRI) tractography and associated pointwise tissue microstructure measurements. By employing a point cloud representation, TractGeoNet can directly utilize tissue microstructure and positional information from all points within a fiber tract without the need to average or bin data along the streamline as traditionally required by dMRI tractometry methods. To improve regression performance, we propose a novel loss function, the Paired-Siamese Regression loss, which encourages the model to focus on accurately predicting the relative differences between regression label scores rather than just their absolute values. In addition, to gain insight into the brain regions that contribute most strongly to the prediction results, we propose a Critical Region Localization algorithm. This algorithm identifies highly predictive anatomical regions within the white matter fiber tracts for the regression task. We evaluate the effectiveness of the proposed method by predicting individual performance on two neuropsychological assessments of language using a dataset of 20 association white matter fiber tracts from 806 subjects from the Human Connectome Project Young Adult dataset. The results demonstrate superior prediction performance of TractGeoNet compared to several popular regression models that have been applied to predict individual cognitive performance based on neuroimaging features. Of the twenty tracts studied, we find that the left arcuate fasciculus tract is the most highly predictive of the two studied language performance assessments. Within each tract, we localize critical regions whose microstructure and point information are highly and consistently predictive of language performance across different subjects and across multiple independently trained models. These critical regions are widespread and distributed across both hemispheres and all cerebral lobes, including areas of the brain considered important for language function such as superior and anterior temporal regions, pars opercularis, and precentral gyrus. Overall, TractGeoNet demonstrates the potential of geometric deep learning to enhance the study of the brain's white matter fiber tracts and to relate their structure to human traits such as language performance.