Support needs of Australians bereaved during the COVID-19 pandemic: A cross-sectional survey study.

BACKGROUND: COVID-19 disrupted access to bereavement support. The objective of this study was to identify the bereavement supports used by Australians during the COVID-19 pandemic, perceived helpfulness of supports used, prevalence and areas of unmet support need, and characteristics of those with unmet support needs. METHODS: A convenience sample of bereaved adults completed an online questionnaire (April 2021-April 2022) about their bereavement experiences including support use and perceived helpfulness, unmet support needs and mental health. Multiple logistic regression was conducted to determine sociodemographic correlates of unmet needs. Open-ended responses were examined using content analysis to determine key themes. RESULTS: 1,878 bereaved Australians completed the questionnaire. Participants were mostly women (94.9%) living in major cities (68%) and reported the death of a parent (45%), with an average age of 55.1 years (SD = 12.2). The five most used supports were family and friends, self-help resources, general practitioners, psychologists, and internet/online community groups. Notably, each was nominated as most helpful and most unhelpful by participants. Two-thirds (66%) reported specific unmet support needs. Those with unmet needs scored lower on mental health measures. Correlates of unmet needs included being of younger age, being a spouse or parent to the deceased; reporting more impacts from public health measures, and not reporting family and friends as supports. The most frequent unmet need was for social support after the death and during lockdown. CONCLUSIONS: This study demonstrates the complexity of bereavement support needs during a pandemic. Specialised grief therapy needs to be more readily available to the minority of grievers who would benefit from it. A clear recommendation for a bereavement support action plan is to bolster the ability of social networks to provide support in times of loss. The fostering of social support in the wake of bereavement is a major gap that needs to be addressed in practice, policy, and research.

Palliative Care in Early Dementia: A Scoping Review.

BACKGROUND: Palliative care is recommended for all people with dementia from diagnosis through end-of-life. However, palliative care needs and effective elements of palliative care are not well-defined for the earlier stages of dementia. OBJECTIVE: To systematically map current research on palliative care early in the disease trajectory of dementia. DESIGN: Scoping review of scientific literature. DATA SOURCES: PubMed, CINAHL, EMBASE, Cochrane, PsycINFO, Web of Science REVIEW METHODS: We included studies published in English over the last decade (through March 2022) that focused on palliative care in early stages of dementia and targeted outcomes in palliative care domains. Two authors independently screened abstracts and full texts and scored the quality of included studies using tools by the Joanna Briggs Institute. RESULTS: Among the 77 papers reviewed, few addressed early stages of dementia specifically. We found that: 1) While "early" palliative care was not well-defined in the literature, evidence indicated that palliative care needs were present at or before diagnosis and across the trajectory. Notable opportunities for palliative care arise at 'tipping points' (i.e., when symptoms, functional status, or caregiving needs change). 2) Palliative care needs in early dementia include advocacy for goal-aligned care in the future, reassurance against the threat of negligence and abandonment by caregivers, planning for future scenarios of care (practical, individual, and relational needs), and establishing of long-term relationships with providers entrusted for care later in disease. 3) Elements of effective palliative care in early dementia could include dementia-specific ACP and goals of care discussions, navigation for building a network of support, provision of tools and resources for family, tailored care and knowledge of the person, and well-prepared dementia-care providers. The scarcity of palliative care studies aimed at early disease indicates a gap in the evidence in dementia care. CONCLUSION: The literature on palliative care in early dementia is sparse. Future studies should focus on assessment tools for optimizing timing of palliative care in early dementia, gaining better understanding of patient and family needs during early phases of disease, and providing training for providers and families in long-term relationships and communication around goals of care and future planning.

The association between neighborhood disadvantage and frailty: A retrospective case series.

Background: Frailty predicts poorer outcomes in surgical patients. Recent studies have found socioeconomic status to be an important characteristic for surgical outcomes. We evaluated the association of Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), two geospatial atlases that provide a multidimensional evaluation of neighborhood deprivation, with frailty in a surgery population. Design & methods: A retrospective study of patients undergoing routine frailty screening was conducted 12/2020-8/2022. Frailty was measured using Fried's Frailty Phenotype (FFP) and the five-item Modified Frailty Index (mFI-5). ADI and SVI quartiles were determined using patient residence. Logistic regression models were used to evaluated associations of FFP (frail only vs not frail) and mFI-5 (≥2 vs 0-1) with ADI and SVI (α = 0.05). Results: Of 372 screened patients, 41% (154) were women, median age was 68% (63-74), and 46% (170) identified as non-White. Across ADI and SVI quartiles, higher number of comorbidities, decreasing median income, and frailty were associated with increasing deprivation (p < 0.01). When controlling for age, sex, comorbidities, and BMI category, frailty by FFP was associated with the most deprived two quartiles of ADI (OR 2.61, CI: [1.35-5.03], p < 0.01) and the most deprived quartile of SVI (OR 2.33, [1.10-4.95], p < 0.05). These trends were also seen with mFI-5 scores ≥2 (ADI: OR 1.64, [1.02-2.63], p < 0.05; SVI: OR 1.71, [1.01-2.91], p < 0.05). Conclusions: Surgical patients living in socioeconomically deprived neighborhoods are more likely to be frail. Interventions may include screening of disadvantaged populations and resource allocation to vulnerable neighborhoods.

Experiences of Deployed Physicians in Support of Operation Allies Refuge/Operation Allies Welcome: Lessons to Inform Improvements in Training.

INTRODUCTION: Stability operations, including humanitarian assistance and disaster relief missions, are key functions of U.S. Military medicine and the Military Medical Humanitarian Assistance Course (MMHAC) is a 2-day course widely used to prepare military medical personnel for such missions. It focuses on caring for those most vulnerable in the wake of disasters, particularly children. The large-scale humanitarian deployment of military medical providers in support of Operation Allies Welcome/Operation Allies Refuge (OAW/OAR) presents an opportunity to evaluate the preparedness of these providers to care for the needs of the Afghan travelers, so we explored the experiences of military medical providers deployed in support of OAW/OAR to inform improvements in the MMHAC. MATERIALS AND METHODS: We conducted a qualitative study of military medical providers who were deployed in support of OAW/OAR using a series of three virtual focus groups. Focus group questions were structured around the main topics covered in the MMHAC (patient care, ethical considerations, logistical concerns, and preventive and public health) and explicitly asked about adaptive leadership challenges faced and strategies used to overcome them. We analyzed transcripts using inductive thematic analysis within a constructivist paradigm, with adaptive leadership as a sensitizing concept. The study was approved by the Institutional Review Board of Uniformed Services University. RESULTS: We constructed 4 themes from participant responses, each addressing challenges that medical providers faced during their mission: (1) Medical providers navigated tension between medical and public health priorities and military mission priorities; (2) Chronic and complex care needs posed unique challenges for medical personnel; (3) Challenges in patient care were compounded by logistical and system-based barriers; and (4) Cultural barriers led to ethical dilemmas that physicians felt inadequately prepared to handle, most notably with respect to gender-related concerns. Within each theme, participants described which aspects of MMHAC training were most helpful and which areas were inadequate. CONCLUSIONS: Physicians found the OAR/OAW mission meaningful but also identified challenges related to medical care provision, public health, logistics, and ethical dilemmas that hindered their ability to carry out their medical mission. Lessons learned from OAW/OAR highlight several areas in which the MMHAC training could be augmented and improved to further mitigate these challenges.

Prolonged Grief Disorder, but Not Death From COVID-19, Elicits Public Stigma: A Vignette-Based Experiment.

We investigated the effects of cause of death (COVID-19 with an underlying medical condition vs. without) and prolonged grief disorder status (PGD present or absent) on participants' reported public stigma towards the bereaved. Participants (N = 304, 66% women; Mage = 39.39 years) were randomly assigned to read one of four vignettes describing a bereaved man. Participants completed stigma measures assessing negative attributions, desired social distance, and emotional reactions. Participants reported significantly stronger stigmatizing responses towards an individual with PGD (vs. without PGD) across all stigma measures. There was no significant difference in stigma based on cause of death; however, stigma was reported regardless of cause of death. There was no significant interaction between cause of death and PGD on stigma. This study supports the robust finding of public stigma being reported toward an individual with PGD, suggesting these individuals are at risk of public stigma and not receiving adequate bereavement support.

The association between COVID-19 related income loss and diet quality: The mediating role of distress.

The COVID-19 lockdowns saw many individuals lose income, experience distress and increase intake of foods that would typically be considered less 'healthy' (more processed and less fresh produce). Establishing whether there are direct and indirect links between these variables would be of benefit in preparing for similar future events but also has implications for the current global financial climate, where many are experiencing relative decreases in income. Adults in two locations (UK and Australia) (N = 917) completed online questionnaires to explore the impact of the first COVID-19 lockdown on their change in income, emotional wellbeing (depression, anxiety, stress, loneliness), resilience and diet quality. A structural equation model revealed that income loss was indirectly associated with diet quality via distress. As such, the greater the loss of income experienced, the more distress reported; distress was then directly associated with a less nutritious diet. This pattern of results existed when data from both countries were combined but also when they were modelled individually. Our findings indicate that where individuals experience a sudden reduction of income there are likely to be negative consequences for both mental and physical health. It is plausible that these findings would extend to other circumstances in which sudden loss of income may be experienced such as reductions in state social care, rising inflation and interest rates and sudden increases to the general cost of living.

Comparison of No-Test Telehealth and In-Person Medication Abortion.

Importance: In the US, access to medication abortion using history-based (no-test) eligibility assessment, including through telehealth and mailing of mifepristone, has grown rapidly. Additional evidence on the effectiveness and safety of these models is needed. Objective: To evaluate whether medication abortion with no-test eligibility assessment and mailing of medications is as effective as in-person care with ultrasonography and safe overall. Design, Setting, and Participants: Prospective, observational study with noninferiority analysis. Sites included 4 abortion-providing organizations in Colorado, Illinois, Maryland, Minnesota, Virginia, and Washington from May 2021 to March 2023. Eligible patients were seeking medication abortion up to and including 70 days' gestation, spoke English or Spanish, and were aged 15 years or older. Exposure: Study groups reflected the model of care selected by the patient and clinicians and included: (1) no-test (telehealth) eligibility assessment and mailing of medications (no-test + mail) (n = 228); (2) no-test eligibility assessment and pickup of medications (no-test + pickup) (n = 119); or (3) in-person with ultrasonography (n = 238). Main Outcomes and Measures: Effectiveness, defined as a complete abortion without the need for repeating the mifepristone and misoprostol regimen or a follow-up procedure, and safety, defined as an abortion-related serious adverse event, including overnight hospital admission, surgery, or blood transfusion. Outcomes were derived from patient surveys and medical records. Primary analysis focused on the comparison of the no-test + mail group with the in-person with ultrasonography group. Results: The mean age of the participants (N = 585) was 27.3 years; most identified as non-Hispanic White (48.6%) or non-Hispanic Black (28.1%). Median (IQR) gestational duration was 45 days (39-53) and comparable between study groups (P = .30). Outcome data were available for 91.8% of participants. Overall effectiveness was 94.4% (95% CI, 90.7%-99.2%) in the no-test + mail group and 93.3% (95% CI, 88.3%-98.2%) in the in-person with ultrasonography group in adjusted models (adjusted risk difference, 1.2 [95% CI, -4.1 to 6.4]), meeting the prespecified 5% noninferiority margin. Serious adverse events included overnight hospitalization (n = 4), blood transfusion (n = 2), and emergency surgery (n = 1) and were reported by 1.1% (95% CI, 0.4%-2.4%) of participants, with 3 in the no-test + mail group, 3 in the in-person with ultrasonography group, and none in the no-test + pickup group. Conclusions and Relevance: This prospective, observational study found that medication abortion obtained following no-test telehealth screening and mailing of medications was associated with similar rates of complete abortion compared with in-person care with ultrasonography and met prespecified criteria for noninferiority, with a low prevalence of adverse events.

Validation of assessments to accurately analyze the body composition of highly trained sitting volleyball players: A pilot study.

Body composition is a fundamental component of physical fitness related to the performance of Sitting volleyball (SV) players. Also, establishing the best method for evaluating the body composition of these para-athletes would be highly necessary for this field. The purpose of this study was (1) to describe the body composition of male and female highly trained SV players, (2) to compare the values obtained from this population by two different methods and (3) to establish validity on one of these methods. Thirteen Brazilian SV national team players (five males and eight females) participated in this study. The air-displacement plethysmography (ADP) method as the criterion assessment and the skinfolds (SF) method were conducted for each player. Results showed that there were no significant differences between the values of all players, which ADP and SF measured for body fat percentage (BF%) and body density (BD) (p > 0.05). We found significantly different values between male and female players for BF% by SF (p = 0.04) and BD by SF (p = 0.04). A high degree of reliability was found between ADP and SF measures for BF% and BD. There were statistically significant positive correlations between BF% and BD in all values for both methods (p < 0.01). This pilot study suggests that considering the magnitude of space, expense, and other limitations related to the ADP method against the SF method, we recommend using the SF method, which is a valid, viable and reliable method for measuring body composition in elite SV players.

Psychosocial distress among spouses of persons with dementia before and after their partner's death.

BACKGROUND: Spouses of persons living with dementia may face heightened psychosocial distress in the years immediately before and after their partner's death. We compared the psychosocial needs of spouses of partners with dementia with spouses of partners with non-impaired cognition nearing and after the end of life, focusing on loneliness, depression, life satisfaction, and social isolation. METHODS: We used nationally representative Health and Retirement Study married couples data (2006-2018), restricting to spouses 50+ years old. We included 2098 spouses with data on loneliness and depressive symptoms 2 years before and after the partner's death. We additionally examined a subset of spouses (N = 1113) with available data on life satisfaction and social isolation 2 years before their partner's death. Cognitive status of partners was classified as non-impaired cognition, cognitive impairment not dementia (cognitive impairment), and dementia. We used multivariable logistic regression to determine: 1) the change in loneliness and depression for spouses pre- and post-partner's death, and 2) life satisfaction and social isolation 2 years before the partner's death. RESULTS: Spouses were on average 73 years old (SD: 10), 66% women, 7% Black, 7% Hispanic non-White, 24% married to persons with cognitive impairment, and 19% married to partners with dementia. Before their partner's death, spouses married to partners with dementia experienced more loneliness (non-impaired cognition: 8%, cognitive impairment: 16%, dementia: 21%, p-value = 0.002) and depressive symptoms (non-impaired cognition: 20%, cognitive impairment: 27%, dementia: 31%, p-value < 0.001), and after death a similar prevalence of loneliness and depression across cognitive status. Before their partner's death, spouses of partners with dementia reported less life satisfaction (non-impaired cognition: 74%, cognitive impairment: 68%; dementia: 64%, p-value = 0.02) but were not more socially isolated. CONCLUSION: Results emphasize a need for clinical and policy approaches to expand support for the psychosocial needs of spouses of partners with dementia in the years before their partner's death rather than only bereavement.

Transferring Learned Behaviors between Similar and Different Radios.

Transfer learning (TL) techniques have proven useful in a wide variety of applications traditionally dominated by machine learning (ML), such as natural language processing, computer vision, and computer-aided design. Recent extrapolations of TL to the radio frequency (RF) domain are being used to increase the potential applicability of RFML algorithms, seeking to improve the portability of models for spectrum situational awareness and transmission source identification. Unlike most of the computer vision and natural language processing applications of TL, applications within the RF modality must contend with inherent hardware distortions and channel condition variations. This paper seeks to evaluate the feasibility and performance trade-offs when transferring learned behaviors from functional RFML classification algorithms, specifically those designed for automatic modulation classification (AMC) and specific emitter identification (SEI), between homogeneous radios of similar construction and quality and heterogeneous radios of different construction and quality. Results derived from both synthetic data and over-the-air experimental collection show promising performance benefits from the application of TL to the RFML algorithms of SEI and AMC.

Among-population variation in drought responses is consistent across life stages but not between native and non-native ranges.

Understanding how widespread species adapt to variation in abiotic conditions across their ranges is fundamental to ecology. Insight may come from studying how among-population variation (APV) in the common garden corresponds with the environmental conditions of source populations. However, there are no such studies comparing native vs non-native populations across multiple life stages. We examined APV in the performance and functional traits of 59 Conyza canadensis populations, in response to drought, across large aridity gradients in the native (North America) and non-native (Eurasia) ranges in three experiments. Our treatment (dry vs wet) was applied at the recruitment, juvenile, and adult life stages. We found contrasting patterns of APV in drought responses between the two ranges. In the native range, plant performance was less reduced by drought in populations from xeric than mesic habitats, but such relationship was not apparent for non-native populations. These range-specific patterns were consistent across the life stages. The weak adaptive responses of non-native populations indicate that they can become highly abundant even without complete local adaptation to abiotic environments and suggest that long-established invaders may still be evolving to the abiotic environment. These findings may explain lag times in invasions and raise concern about future expansions.

Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion.

Importance: Sport-related concussion (SRC), a form of mild traumatic brain injury, is a prevalent occurrence in collision sports. There are no well-established approaches for tracking neurobiologic recovery after SRC. Objective: To examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC. Design, Setting, and Participants: A cohort study recruiting from April 10, 2021, to September 17, 2022, was conducted through the Victorian Amateur Football Association, Melbourne, Australia. Participants included adult Australian football players with or without SRC. Data analysis was performed from May 26, 2023, to March 27, 2024. Exposure: Sport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms. Main Outcomes and Measures: Primary outcomes were serum GFAP and NfL levels at 24 hours, and 1, 2, 4, 6, 8, 12, and 26 weeks. Secondary outcomes were symptoms, cognitive performance, and return to training times. Results: Eighty-one individuals with SRC (median age, 22.8 [IQR, 21.3-26.0] years; 89% male) and 56 control individuals (median age, 24.6 [IQR, 22.4-27.3] years; 96% male) completed a total of 945 of 1057 eligible testing sessions. Compared with control participants, those with SRC exhibited higher GFAP levels at 24 hours (mean difference [MD] in natural log, pg/mL, 0.66 [95% CI, 0.50-0.82]) and 4 weeks (MD, 0.17 [95% CI, 0.02-0.32]), and NfL from 1 to 12 weeks (1-week MD, 0.31 [95% CI, 0.12-0.51]; 2-week MD, 0.38 [95% CI, 0.19-0.58]; 4-week MD, 0.31 [95% CI, 0.12-0.51]; 6-week MD, 0.27 [95% CI, 0.07-0.47]; 8-week MD, 0.36 [95% CI, 0.15-0.56]; and 12-week MD, 0.25 [95% CI, 0.04-0.46]). Growth mixture modeling identified 2 GFAP subgroups: extreme prolonged (16%) and moderate transient (84%). For NfL, 3 subgroups were identified: extreme prolonged (7%), moderate prolonged (15%), and minimal or no change (78%). Individuals with SRC who reported loss of consciousness (LOC) (33% of SRC cases) had higher GFAP at 24 hours (MD, 1.01 [95% CI, 0.77-1.24]), 1 week (MD, 0.27 [95% CI, 0.06-0.49]), 2 weeks (MD, 0.21 [95% CI, 0.004-0.42]) and 4 weeks (MD, 0.34 [95% CI, 0.13-0.55]), and higher NfL from 1 week to 12 weeks (1-week MD, 0.73 [95% CI, 0.42-1.03]; 2-week MD, 0.91 [95% CI, 0.61-1.21]; 4-week MD, 0.90 [95% CI, 0.59-1.20]; 6-week MD, 0.81 [95% CI, 0.50-1.13]; 8-week MD, 0.73 [95% CI, 0.42-1.04]; and 12-week MD, 0.54 [95% CI, 0.22-0.85]) compared with SRC participants without LOC. Return to training times were longer in the GFAP extreme compared with moderate subgroup (incident rate ratio [IRR], 1.99 [95% CI, 1.69-2.34]; NfL extreme (IRR, 3.24 [95% CI, 2.63-3.97]) and moderate (IRR, 1.43 [95% CI, 1.18-1.72]) subgroups compared with the minimal subgroup, and for individuals with LOC compared with those without LOC (IRR, 1.65 [95% CI, 1.41-1.93]). Conclusions and Relevance: In this cohort study, a subset of SRC cases, particularly those with LOC, showed heightened and prolonged increases in GFAP and NfL levels, that persisted for at least 4 weeks. These findings suggest that serial biomarker measurement could identify such cases, guiding return to play decisions based on neurobiologic recovery. While further investigation is warranted, the association between prolonged biomarker elevations and LOC may support the use of more conservative return to play timelines for athletes with this clinical feature.

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: Twenty-four 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), 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 calls 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 Patient Health Questionnaire-8 scores (P<.05). Additionally, daily steps and activity minutes were associated with LIBRE Social Interactions and LIBRE Social Activities (P<.05), and significantly moderated the association between PROMIS Anxiety and LIBRE Social Activities (P<.001). CONCLUSIONS: Social participation outcomes are associated with pain, anxiety, and depression symptoms after burn injury, and are buffered by daily physical activity. Future intervention studies should examine physical activity promotion to improve social recovery after burns.

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.

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.

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.

Counter-gradient variation in gene expression between fish populations facilitates colonization of low-dissolved oxygen environments.

The role of phenotypic plasticity during colonization remains unclear due to the shifting importance of plasticity across timescales. In the early stages of colonization, plasticity can facilitate persistence in a novel environment; but over evolutionary time, processes such as genetic assimilation may reduce variation in plastic traits such that species with a longer evolutionary history in an environment can show lower levels of plasticity than recent invaders. Therefore, comparing species in the early stages of colonization to long-established species provides a powerful approach for uncovering the role of phenotypic plasticity during different stages of colonization. We compared gene expression between low-dissolved oxygen (DO) and high-DO populations of two cyprinid fish: Enteromius apleurogramma, a species that has undergone a recent range expansion, and E. neumayeri, a long-established native species in the same region. We sampled tissue either immediately after capture from the field or after a 2-week acclimation under high-DO conditions, allowing us to test for both evolved and plastic differences in low-DO vs high-DO populations of each species. We found that most genes showing candidate-evolved differences in gene expression did not overlap with those showing plastic differences in gene expression. However, in the genes that did overlap, there was counter-gradient variation such that plastic and evolved gene expression responses were in opposite directions in both species. Additionally, E. apleurogramma had higher levels of plasticity and evolved divergence in gene expression between field populations. We suggest that the higher level of plasticity and counter-gradient variation may have allowed rapid genetic adaptation in E. apleurogramma and facilitated colonization. This study shows how counter-gradient variation may impact the colonization of divergent oxygen environments.

Dysregulated DnaB unwinding induces replisome decoupling and daughter strand gaps that are countered by RecA polymerization.

The replicative helicase, DnaB, is a central component of the replisome and unwinds duplex DNA coupled with immediate template-dependent DNA synthesis by the polymerase, Pol III. The rate of helicase unwinding is dynamically regulated through structural transitions in the DnaB hexamer between dilated and constricted states. Site-specific mutations in DnaB enforce a faster more constricted conformation that dysregulates unwinding dynamics, causing replisome decoupling that generates excess ssDNA and induces severe cellular stress. This surplus ssDNA can stimulate RecA recruitment to initiate recombinational repair, restart, or activation of the transcriptional SOS response. To better understand the consequences of dysregulated unwinding, we combined targeted genomic dnaB mutations with an inducible RecA filament inhibition strategy to examine the dependencies on RecA in mitigating replisome decoupling phenotypes. Without RecA filamentation, dnaB:mut strains had reduced growth rates, decreased mutagenesis, but a greater burden from endogenous damage. Interestingly, disruption of RecA filamentation in these dnaB:mut strains also reduced cellular filamentation but increased markers of double strand breaks and ssDNA gaps as detected by in situ fluorescence microscopy and FACS assays, TUNEL and PLUG, respectively. Overall, RecA plays a critical role in strain survival by protecting and processing ssDNA gaps caused by dysregulated helicase activity in vivo.