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Background: Approximately 22-30% of undergraduate college students have experienced the loss of a loved one within the last year, and almost 50% within the last two years. A College of Nursing located in the Southeastern United States saw an increase in students experiencing an immediate family member loss. The demanding curricula and clinical experiences encountered by these students further heighten grief symptoms and social isolation. Aim: This study aimed to develop a tailored program to provide resources and a support system to nursing students who have experienced loss and grief. Methods: This study employed a quasi-experimental design with two data collection points. Relationships, self-esteem, purpose, and optimism relating to grief symptoms were assessed pre-and-post program using the Flourishing Scale. Due to the limited sample size, the Mann-Whitney U nonparametric test was used to assess differences in Flourishing scores. Results: The results indicated no significant differences between the pre-and-post Flourishing Scale scores. However, participant feedback towards the support group was positive. Conclusion: Grief groups tailored to nursing students provide an important community of support that maintains positive student health and well-being.

Abstract Background A better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls. Methods Blood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests. Results Treatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p

Introduction Epilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive models exist to determine who has a higher risk of recurrence to guide treatment. Emerging evidence suggests alterations in cognition, mood and brain connectivity exist in the population with UFS. Baseline evaluations of these factors following a UFS will enable the development of the first multimodal biomarker-based predictive model of seizure recurrence in adults with UFS.Methods and analysis 200 patients and 75 matched healthy controls (aged 18–65) from the Kingston and Halifax First Seizure Clinics will undergo neuropsychological assessments, structural and functional MRI, and electroencephalography. Seizure recurrence will be assessed prospectively. Regular follow-ups will occur at 3, 6, 9 and 12 months to monitor recurrence. Comparisons will be made between patients with UFS and healthy control groups, as well as between patients with and without seizure recurrence at follow-up. A multimodal machine-learning model will be trained to predict seizure recurrence at 12 months.Ethics and dissemination This study was approved by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board at Queen’s University (DMED-2681-22) and the Nova Scotia Research Ethics Board (1028519). It is supported by the Canadian Institutes of Health Research (PJT-183906). Findings will be presented at national and international conferences, published in peer-reviewed journals and presented to the public via patient support organisation newsletters and talks.Trial registration number NCT05724719.

Objective: The objective of this pilot study was to examine the feasibility of a remote physical activity monitoring program, quantify baseline activity levels, and examine predictors of activity among rurally residing adults with Parkinson disease (PD) or stroke. Design: Thirty-day observational study. Participants completed standardized assessments, connected a wearable device, and synced daily step counts via a remote monitoring platform. Setting: Community-based remote monitoring. Participants: Rurally residing adults with PD or stroke enrolled in the Veterans Health Administration. Intervention: N/A. Main Outcome Measures: Feasibility was evaluated using recruitment data (response rates), study completion (completed assessments and connected the wearable device), and device adherence (days recording ≥100 steps). Daily step counts were examined descriptively. Predictors of daily steps were explored across the full sample, then by diagnosis, using linear mixed-effects regression analyses. Results: Forty participants (n=20 PD; n=20 stroke) were included in the analysis with a mean (SD) age of 72.9 (7.6) years. Participants resided 252.6 (105.6) miles from the coordinating site. Recruitment response rates were 11% (PD) and 6% (stroke). Study completion rates were 71% (PD) and 80% (stroke). Device adherence rates were 97.0% (PD) and 95.2% (stroke). Participants with PD achieved a median [interquartile range] of 2618 [3896] steps per day and participants with stroke achieved 4832 [7383] steps. Age was the only significant predictor of daily steps for the full sample (-265 steps, 95% confidence interval [-407, -123]) and by diagnosis (PD, -175 steps, [-335, -15]; stroke, -357 steps [-603, -112]). Conclusions: A remote physical activity monitoring program for rurally residing individuals with PD or stroke was feasible. This study establishes a model for a scalable physical activity program for rural, older populations with neurologic conditions from a central coordinating site.

Abstract Drug-induced parkinsonism (DIP) can be clinically indistinguishable from degenerative parkinsonism, and bedside assessments are needed to differentiate between these conditions. We examined 34 U.S. Veterans with DIP using 123I-FP-CIT (DAT-SPECT) to identify underlying nigrostriatal degeneration. Participants were 94% male with mean age of 64.5 ± 7.1 years. DAT-SPECT was abnormal in 12/34 (35%). Comparing normal and abnormal imaging groups, there were no differences in age, sex, race/ethnicity, psychiatric diagnosis, motor severity, or RBD Screening Questionnaire scores. Those with underlying neurodegeneration reported significantly more non-motor symptoms (NMS), worse olfactory function on the University of Pennsylvania Smell Identification Test, and greater turning duration/steps on the instrumented Timed Up and Go. Area under the curve (AUC) combining poor olfaction and total NMS burden was 0.84 (CI 0.71–0.97), while AUC for turn steps was 0.91 (CI 0.81–1.00). Gait impairment, hyposmia, and NMS may be useful alone and in combination to identify DIP patients with underlying dopaminergic degeneration.

Providing brief interventions by certified peer recovery support specialists (CPRSS) in the emergency department (ED) following a drug related visit is a promising method of service engagement and has garnered national attention. This study examines CPRSS's perceptions of the qualities that enable them to deliver interventions in the ED. We conducted qualitative interviews with 14 CPRSSs working in EDs. Interview topics included how the participants became involved with CPRSS work, experiences working in the ED, how the ED differs from other settings, and what interactions with patients look like. Interviews were digitally recorded, transcribed, and analyzed for emerging categories. Three categories were identified relating to CPRSS work: (1) how they approach peer work, (2) inherent qualities required to do the work, regardless of the setting, and (3) context-specific skills required to do the work in the ED. When describing their approach to this work, participants talked about CPRSS work as their life calling and their passion. Participants also identified certain qualities that all CPRSS workers possess, regardless of the setting, including the ability to build rapport, strong listening skills, and a shared lived experience. Lastly, participants identified how specific hard and soft skills help them to navigate organizational and structural challenges in the ED. The unique conditions of the ED and the required qualities of a CPRSS should be considered when implementing an ED-based intervention.

Schistosome helminths infect over 200 million people across 78 countries and are responsible for nearly 300,000 deaths annually. However, our understanding of basic genetic pathways crucial for schistosome development is limited. The sex determining region Y-box 2 (Sox2) protein is a Sox B type transcriptional activator that is expressed prior to blastulation in mammals and is necessary for embryogenesis. Sox expression is associated with pluripotency and stem cells, neuronal differentiation, gut development, and cancer. Schistosomes express a Sox-like gene expressed in the schistosomula after infecting a mammalian host when schistosomes have about 900 cells. Here, we characterized and named this Sox-like gene SmSOXS1. SmSoxS1 protein is a developmentally regulated activator that localizes to the anterior and posterior ends of the schistosomula and binds to Sox-specific DNA elements. In addition to SmSoxS1, we have also identified an additional six Sox genes in schistosomes, two Sox B, one SoxC, and three Sox genes that may establish a flatworm-specific class of Sox genes with planarians. These data identify novel Sox genes in schistosomes to expand the potential functional roles for Sox2 and may provide interesting insights into early multicellular development of flatworms.

Academic and community interactions are often conducted with good intentions. However, there is exploitation risk for populations engaging in illegal activities. Collaborations with injection drug users (IDUs) can highlight their expertise and support progressive research. The objective of our research was to use community-based participatory research principles to give voice to IDUs, define community, and recommend authentic engagement strategies. In Phase 1, 10 focus groups (n=33, ages 25–64) helped define community and collaborative partnerships. In Phase 2, community forums with 13 additional IDUs provided feedback on focus group themes. Results: (1) primary themes defining community—geography and social networks; (2) community qualities—respectful, accepting, outcasts, and welcoming; (3) engagement recommendations—incentives, recognizing potential for contributions, treating IDUs respectfully, using research results for positive benefit. Conclusions: Providing voice to marginalized communities allows for self-definition, description of needs, and authentic engagement recommendations. This information is crucial for developing effective programs and creating sustainable collaborations between IDUs and academics.

An undergraduate teacher education behavioral principles course focused on pre-service teachers’ accuracy of data collection using simple technology during a field-based experience is described. Pre-teachers, mostly special education majors, completed questionnaires at the beginning and end of the semester regarding whether simple technology (i.e., stopwatch, tally counter, interval timer) impacted data recording and perceived effectiveness. Interrater reliability was randomly assessed across two K-5 locations in which the pre-teachers tutored elementaryaged students in an after-school program. On-campus and on-site data collection interrater reliability results were promising, demonstrating pre-teacher ability to collect data accurately. Conclusions and recommendations for future practices are provided.

This study evaluated the implementation process of an email-based walking program from the perspectives of program deliverers. Twenty-four Extension Educators participated in the process evaluation. We used an online survey to examine the perceptions of the implementation process of Get WalkIN’, a twelve-week email-based walking program. Educators agreed that the provided program training and recruitment materials were sufficient for successful program delivery. Program implementation involved sending emails to program participants at least weekly. Educators also agreed that the program was easy to deliver and took twenty minutes or less to implement each week. Strengths and areas for program improvement are discussed. Suggestions included training on evaluation measures, inclusion of a process to send emails via tablets instead of only desktops, and ideas for engaging participants during program delivery. While the outcomes of this email-based program show positive behavior changes without face-to-face interaction between participants and Extension Educators, the face-to-face interactions familiar to Extension staff were still desired. Results will be used to improve implementation. Findings from this study can facilitate the development and implementation of other email-based Extension programs.

The social model of disability—which is grounded in the lived realities of disabled people, as well as their activism, research, and theoretical work—has enabled a historic turn in the understanding of disability. This model also facilitates the transition to the rights-based approach that is at the core of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). However, the social model of disability does not straightforwardly translate to the lives of people who end up being detained and forcibly treated in psychiatric facilities. This paper examines the implications of the lack of an equivalent theoretical framework to counteract the hegemony of the biomedical model of “mental illness” and to underpin and guide the implementation of the CRPD for people with psychiatric diagnoses. Critically engaging with some recent attempts to make the CRPD provisions integral to psychiatry, we expose fundamental contradictions inherent in such projects. Our discussion seeks to extend the task of implementation of the CRPD beyond reforming psychiatry, suggesting a much broader agenda for change. We argue for the indispensability of first-person knowledge in developing and owning this agenda and point to the dangers of merely remaking former treatment objects into objects of human rights.

Introduction: Get WalkIN’ is a 12-week, e-mail-based walking promotion program. The purpose of this study was to (1) compare sociodemographics of participants who enrolled versus completed the program; and (2) evaluate program feasibility/acceptability from perspectives of program participants and county-based Extension Educators who implemented the program. Methods: Participants (N = 875), recruited by county-based Extension Educators, were asked Likert-scale questions (eg, ease of reading the e-mails and frequency of e-mails) to assess program acceptability and open-ended questions regarding improvements. Educators (N = 55) were asked Likert-scale and open-ended questions regarding program training, recruitment, strengths, and areas for improvement. Descriptive statistics summarized participant characteristics, acceptability, and feasibility data. Open-ended responses were analyzed using thematic analysis. Results: There were no significant sociodemographic differences between participants (N = 875) who started the program and completed the program (n = 438). Participants reported intervention e-mails were easy to read (mean = 4.5 ± 0.7), understand (mean = 4.5 ± 0.7), and encouraged more walking (mean = 4.1 ± 0.9). Participants would like to connect/interact with other participants/Educators, have more monitoring tools for accountability, and more visuals/videos embedded within e-mails. Educators reported program training was adequate, e-mail messages were helpful and easy to use, and requested more visuals (eg, videos) to help with recruitment. Educators thought adding a social component (eg, kick-off walk or walking group) would be helpful. Conclusions: This Extension-delivered walking program is acceptable to participants and feasible to deliver. However, participants and Educators reported they would like more interaction, even if virtual. Future e-mail-based programs should consider ways to incorporate social interaction among users as well as provide a wide variety of recruitment resources.

Abstract We document the development of the first version of the U.K. Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane, and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land, and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall, the model performs well, with a stable pre‐industrial state and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealized simulations show a high climate sensitivity relative to previous generations of models: Equilibrium climate sensitivity is 5.4 K, transient climate response ranges from 2.68 to 2.85 K, and transient climate response to cumulative emissions is 2.49 to 2.66 K TtC−1.

Background Understanding and addressing the needs of frail patients has been identified as an important strategy by the Nova Scotia Health Authority (NSHA). Primary care (PC) providers are in a key position to aid in the identification of, and response to frailty as part of routine care. Unlike singular chronic conditions such as diabetes and hypertension which garner a disease-based approach and identification as part of standard practice, frailty is only just emerging as a concept for PC. The web-based Frailty Portal was developed to aid in the identification of, assessment and care planning for frail patients in PC practice. In this study we assess the implementation feasibility and impact of the Frailty Portal by: (1) identifying factors influencing the Frailty Portal’s use in community PC practice, and (2) examination of the immediate impact of the ‘Frailty Portal’ on frail patients, their caregivers and PC providers. Methods A convergent mixed method approach was implemented among PC providers in community-based practice in the NSHA, Central Zone. Quantitative and qualitative data were collected concurrently over a 9-month period. A sample of patients who underwent assessment and/or their caregiver were approached for survey participation. Results Fourteen community PC providers (10 family physicians, 4 nurse practitioners) completed 48 patient assessments and completed or begun 41 care plans; semi-structured interviews were conducted among 9 providers. Nine patients and 5 caregivers participated in the survey. PC providers viewed frailty as an important concept but implementation challenges were met, primarily with respect to the time required for use and lack of fit with traditional practice routines. Additional barriers included tool usability and accessibility, training and care planning steps, and privacy. Impacts of the tools use with respect to confidence and knowledge showed early promise. Conclusion This feasibility study highlights the need for added health system supports, resources and financial incentives for successful implementation of the Frailty Portal in community PC practice. We suggest future implementation integrate the Frailty Portal to practice electronic medical records (EMRs) and target providers with largely geriatric practice populations and those practicing within interdisciplinary, collaborative primary healthcare (PHC) teams.

Unilateral abdominal wall clonic seizures are a rare manifestation of epilepsy. We report three cases of focal aware seizures manifesting as unilateral abdominal clonic motor movements. Standard EEG for patients with focal motor abdominal seizures is often unrevealing, which can make the diagnosis difficult. We report the first case of intracranial EEG in the diagnosis of a patients with this type of semiology during a focal seizure. In the absence of an electroclinical seizure verified by video-EEG monitoring, caution should be made with the diagnosis. A careful history should be obtained to help differentiate between unilateral abdominal clonic jerking and other abdominal complaints.

Fluidic soft robots bring a high degree of dexterity and adaptability to robotics problems requiring safe interactions with complex structures. While they are low cost and easy to manufacture, they are difficult to control due to their typical reliance on external pressure sources that become bulky as more degrees of freedom are introduced to the robot. Various techniques from microfluidics and fluid logic are used to introduce valves into soft robots to increase their autonomy, although this has frequently introduced unwanted rigidity. Herein, a magnetorheological (MR) fluid valve that uses magnetic fields to control the pressure within a continuous‐flow fluidic actuator is introduced. A predictive model for the pressure drop in such a flow is presented and validated experimentally. Guidelines for the design of single‐ and multiactuator systems with a single inlet and outlet are presented. The introduction of actuation methods that simplify fluidic control via the application of magnetic fields leads to robots capable of increased autonomy in a scalable and compliant format.

Using the RE-AIM framework, this study evaluates the statewide dissemination of an evidenced-based, email-delivered physical activity intervention implemented through Cooperative Extension. The Get WalkIN' program is comprised of 16 email messages sent over 12 weeks. Email messages target social cognitive theory constructs of self-efficacy, goal-setting, self-monitoring, and social support. Program reach, effectiveness, adoption, implementation, and maintenance were assessed with quantitative measures in a pre-post design. Findings indicate that within the Extension system, program adoption was high and program maintenance was moderate. Program effectiveness was demonstrated with an increase of 77.1 ± 49.9 min in weekly walking post-program. This increase in walking was maintained 3 months post-program. Capturing data on the implementation process was challenging. Overall, the results indicate success in program adoption and maintenance with further efforts needed to improve follow-up data collection from participants.

Abstract Background Clinical practice guidelines recommend exercise as the first line of management for hip osteoarthritis, yet high-quality evidence from Cochrane reviews suggest only slight benefits for pain and physical function; and no benefit on quality of life (low-quality evidence). However, the scope of physical impairments identified in people with hip osteoarthritis may not have been adequately addressed with targeted rehabilitation options in previous randomised controlled trials (RCTs). Potential targeted options include gait retraining to address spatio-temporal impairments in walking; motor control training to address deep gluteal (gluteus minimus) dysfunction; and progressive, high-intensity resistance exercises to address atrophy of the gluteal muscles. The aim of this study is to investigate the effect of a targeted gluteal rehabilitation programme that incorporates gait retraining, motor control and progressive, high-intensity resistance-strength training, to address physical activity levels and self-reported physical function in people with mild to moderate disability from hip osteoarthritis. Methods Ninety people diagnosed with mild to moderately disabling hip osteoarthritis will be recruited and randomised to receive one of two exercise programmes (sham or GHOst programme). Interventions will be 12 weeks in duration, with weekly, supervised physiotherapy sessions, and daily home exercises. Both groups will receive standardised education. Outcomes will be assessed at baseline, 7 weeks, 13 weeks (primary time-point) and 25 weeks. The primary outcome will be self-reported physical function measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes include physical activity measured with a tri-axial accelerometer, physical function tests, self-reported physical activity, isometric hip-muscle strength tests, hip-related patient-reported outcome measures, pain thoughts and depressive symptoms, quality of life, global rating of change, gluteal-muscle activity (electromyography (EMG)) and gluteal-muscle size and adiposity (magnetic resonance imaging (MRI)). Discussion This will be the first study to compare a targeted gluteal rehabilitation programme to a sham exercise programme. The targeted GHOst programme includes exercises designed to address gait impairments as well as gluteal-muscle atrophy and dysfunction. Trial registration Australian New Zealand Clinical Trials Registry, ID: ACTRN12617000970347. Registered prospectively on 5 July 2017. Protocol version 3.0.

Abstract Background Frailty is associated with multi-system deterioration, and typically increases susceptibility to adverse events such as falls. Frailty can be better managed with early screening and intervention, ideally conducted in primary health care (PHC) settings. This study used the Consolidated Framework for Implementation Research (CFIR) as an evaluation framework during the second stage piloting of a novel web-based tool called the Frailty Portal, developed to aid in the screening, identification, and care planning of frail patients in community PHC. Methods This qualitative study conducted semi-structured key informant interviews with a purposive sample of PHC providers (family physicians, nurse practitioners) and key PHC stakeholders who were administrators, decision makers and staff. The CFIR was used to guide data collection and analysis. Framework Analysis was used to determine the relevance of the CFIR constructs to implementing the Frailty Portal. Results A total of 17 interviews were conducted. The CFIR-inspired interview questions helped clarify critical aspects of implementation that need to be addressed at multiple levels if the Frailty Portal is to be successfully implemented in PHC. Finding were organized into three themes 1) PHC Practice Context, 2) Intervention attributes affecting implementation, and 3) Targeting providers with frail patients. At the intervention level the Frailty Portal was viewed positively, despite the multi-level challenges to implementing it in PHC practice settings. Provider participants perceived high opportunity costs to using the Frailty Portal due to changes they needed to make to their practice routines. However, those who had older patients, took the time to learn how to use the Frailty Portal, and created processes for sharing tasks with other PHC personnel become proficient at using the Frailty Portal. Conclusions Structuring our evaluation around the CFIR was instrumental in identifying multi-level factors that will affect large-scale adoption of the Frailty Portal in PHC practices. Incorporating CFIR constructs into evaluation instruments can flag factors likely to impede future implementation and impact the effectiveness of innovative practices. Future research is encouraged to identify how best to facilitate changes in PHC practices to address frailty and to use implementation frameworks that honor the complexity of implementing innovations in PHC.

Background Understanding and addressing the needs of frail persons is an emerging health priority for Nova Scotia and internationally. Primary healthcare (PHC) providers regularly encounter frail persons in their daily clinical work. However, routine identification and measurement of frailty is not standard practice and, in general, there is a lack of awareness about how to identify and respond to frailty. A web-based tool called the Frailty Portal was developed to aid in identifying, screening, and providing care for frail patients in PHC settings. In this study, we will assess the implementation feasibility and impact of the Frailty Portal to: (1) support increased awareness of frailty among providers and patients, (2) identify the degree of frailty within individual patients, and (3) develop and deliver actions to respond to frailtyl in community PHC practice. Methods This study will be approached using a convergent mixed method design where quantitative and qualitative data are collected concurrently, in this case, over a 9-month period, analyzed separately, and then merged to summarize, interpret and produce a more comprehensive understanding of the initiative’s feasibility and scalability. Methods will be informed by the ‘Implementing the Frailty Portal in Community Primary Care Practice’ logic model and questions will be guided by domains and constructs from an implementation science framework, the Consolidated Framework for Implementation Research (CFIR). Discussion The ‘Frailty Portal’ aims to improve access to, and coordination of, primary care services for persons experiencing frailty. It also aims to increase primary care providers’ ability to care for patients in the context of their frailty. Our goal is to help optimize care in the community by helping community providers gain the knowledge they may lack about frailty both in general and in their practice, support improved identification of frailty with the use of screening tools, offer evidence based severity-specific care goals and connect providers with local available community supports.

Background: To report a patient of choledochoduodenal fistulae (CDF) who presented with melena and review a specific treatment for CDF. Methods: This study was designed as a retrospective chart review using patient’s clinical data, imaging, endoscopic report, treatment review, and literature review for treatment options. Results: A 74-year-old female presented with diffuse, non-tender abdominal pain and associated melena for one week. Physical examination showed mildly icteric sclera and mild epigastric tenderness on deep palpation. Initial diagnoses included cholangitis with anemia and acute kidney injury. Computed tomography of the abdomen revealed dilated common bile duct (CBD) with a likely 1 cm stone at the distal common bile duct. The patient was given intravenous antibiotic and proper fluid administration. An ERCP was performed noting a fistula from the bile duct to the 2nd part of the duodenum with stone impaction. Sphincterotomy was performed from papilla to fistula. Balloon extraction of 1 cm stone from the CBD was done. Conclusion: The clinical presentation of CDF is generally quite nonspecific. In this case report, we present a presentation of a patient with gastrointestinal hemorrhage as an example of the presentation of CDF associated with a CBD stone. This study also discussed recent data concerning proposed treatment of CDF.

The intracellular applications of STED microscopy are limited by the availability of dyes. Here the authors develop a two-colour labelling strategy based on SiR and ATTO590 dyes, and apply their strategy to image various subcellular membrane compartments.

As one of the main drivers for climate change, it is important to understand changes in anthropogenic aerosol emissions and evaluate the climate impact. Anthropogenic aerosols have affected global climate while exerting a much larger influence on regional climate by their short lifetime and heterogeneous spatial distribution. In this study, the effective radiative forcing (ERF), which has been accepted as a useful index for quantifying the effect of climate forcing, was evaluated to understand the effects of aerosol on regional climate over a historical period (1850–2014). Eastern United States (EUS), Western European Union (WEU), and Eastern Central China (ECC), are regions that predominantly emit anthropogenic aerosols and were analyzed using Coupled Model Intercomparison Project 6 (CMIP6) simulations implemented within the framework of the Aerosol Chemistry Model Intercomparison Project (AerChemMIP) in the UK’s Earth System Model (UKESM1). In EUS and WEU, where industrialization occurred relatively earlier, the negative ERF seems to have been recovering in recent decades based on the decreasing trend of aerosol emissions. Conversely, the radiative cooling in ECC seems to be strengthened as aerosol emission continuously increases. These aerosol ERFs have been largely attributed to atmospheric rapid adjustments, driven mainly by aerosol-cloud interactions rather than direct effects of aerosol such as scattering and absorption.

As climate change increases the frequency and intensity of extreme heat events researchers and public health officials must work towards understanding the causes and outcomes of heat-related morbidity and mortality. While there have been many studies on both heat-related illness (HRI), there are fewer on heat-related morbidity than on heat-related mortality.To identify individual and environmental risk factors for hospitalizations and document patterns of household cooling.We performed a pooled cross-sectional analysis of secondary U.S. data, the Nationwide Inpatient Sample. Risk ratios were calculated from multivariable models to identify risk factors for hospitalizations. Hierarchical modeling was also employed to identify relationships between individual and hospital level predictors of hospitalizations. Patterns of air conditioning use were analyzed among the vulnerable populations identified.Hospitalizations due to HRI increased over the study period compared to all other hospitalizations. Populations at elevated risk for HRI hospitalization were blacks, males and all age groups above the age of 40. Those living in zip-codes in the lowest income quartile and the uninsured were also at an increased risk. Hospitalizations for HRI in rural and small urban clusters were elevated, compared to urban areas.Risk factors for HRI include age greater than 40, male gender and hospitalization in rural areas or small urban clusters. Our analysis also revealed an increasing pattern of HRI hospitalizations over time and decreased association between common comorbidities and heat illnesses which may be indicative of underreporting.

The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb). Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and C-terminal segments of gp120 and the disulfide-bonded region (DSR) of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D) with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn¹³⁶ in V1 (T138N mutation) in conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N¹³⁹INN sequence, which ablates the overlapping Asn¹⁴¹-Asn¹⁴²-Ser-Ser potential N-linked glycosylation sequons in V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu⁵⁹³, Trp⁵⁹⁶ and Lys⁶⁰¹. The 136 and/or 142 glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan shield in a setting of NAb selection.