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Background: Rural residents are more impacted by obesity and related comorbidities than their urban counterparts. Digital weight management interventions may produce meaningful weight loss among rural residents., Objectives: The iREACH Rural Study aims to identify "high-touch" component(s) that contribute to meaningful weight loss (≥1.5 kg) at 6-months, over and above what the 24-week core online program produces. Three treatment components are assessed: group video sessions (yes/no); self-monitoring feedback (counselor-crafted/pre-scripted, modular); and individual coaching calls (yes/no)., Design: The iREACH Rural Study is a factorial experiment (n = 616)., Methods: Participants receive up to 3 "high-touch" components (weekly synchronous facilitated group video sessions, weekly counselor-crafted self-monitoring feedback, and individual coaching calls) to determine which contribute meaningfully to 6-month weight loss. Participants complete assessments at baseline, 2 months, 6 months, and 12 months. Weight loss at 6 months (primary outcome) and 12 months (secondary outcome) is measured by Bluetooth-enabled scales. The study seeks to identify the weight loss approach for underserved rural residents which optimizes weight change outcomes and also examines costs associated with delivering different treatment constellations., Summary: The iREACH Rural Study is the first of its kind to isolate digital weight loss intervention components to determine which meaningfully contribute to long-term weight loss among rural residing individuals. The results may be used to refine digital weight loss programs by enhancing their effectiveness to allow broad dissemination., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention., Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial., Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications., Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER)., Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults., Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention., Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.

Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management., Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity., Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included., Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52)., Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed., Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups., Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice., Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.

The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13-17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3-4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg ( p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3-4 correlated with greater weight loss at week-4 (r = -0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs.

Background: The curriculum for our generalist masters in nursing program required a heavy credit load of science courses shared with the nurse practitioner programs. The bundle of required courses far exceeded the masters in nursing program completion outcomes, increasing tuition costs and prolonging the program of study for students who were not seeking advanced practice credentials., Purpose: The purpose of this project was to streamline the curriculum and better align course content with MS program expected learning outcomes, student learning needs, and recent accreditation requirements., Process: Course expected learning outcomes were drafted and mapped to program expected learning outcomes and AACN The Essentials: Core Competencies for Professional Nursing Education (2021) concepts and sub-competencies. A two-course series totaling 5 credits was developed to integrate the 4Ps (pathophysiology, pharmacology, physical/health assessment, and health promotion) into an online master's level nursing curriculum while decreasing the total number of credits., Outcomes: A total of 67 students successfully completed the online courses during the first semester. Minor revisions based on student feedback were made after the first implementation., Conclusions: Integrating the 4Ps into a series of two courses is a feasible option for streamlining a generalist masters in nursing curriculum., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Saccharomyces boulardii ( Sb ) is an emerging probiotic chassis for delivering biomolecules to the mammalian gut, offering unique advantages as the only eukaryotic probiotic. However, precise control over gene expression and gut residence time in Sb have remained challenging. To address this, we developed five ligand-responsive gene expression systems and repaired galactose metabolism in Sb , enabling inducible gene expression in this strain. Engineering these systems allowed us to construct AND logic gates, control the surface display of proteins, and turn on protein production in the mouse gut in response to dietary sugar. Additionally, repairing galactose metabolism expanded Sb 's habitat within the intestines and resulted in galactose-responsive control over gut residence time. This work opens new avenues for precise dosing of therapeutics by Sb via control over its in vivo gene expression levels and localization within the gastrointestinal tract.

A genomic understanding of the oncogenic processes and individual variability of human cancer has steadily fueled improvement in patient outcomes over the past 20 years. Mutations within tumour tissues are routinely assessed through clinical genomic diagnostic assays by academic and commercial laboratories to facilitate diagnosis, prognosis and effective treatment stratification. The application of genomics has unveiled a wealth of mutation-based biomarkers in canine cancers, suggesting that the transformative principles that have revolutionized human cancer medicine can be brought to bear in veterinary oncology. To advance clinical genomics and genomics-guided medicine in canine oncology, we have developed and validated a canine cancer next-generation sequencing gene panel for the identification of multiple mutation types in clinical specimens. With this panel, we examined the genomic landscapes of 828 tumours from 813 dogs, spanning 53 cancer types. We identified 7856 alterations, encompassing copy number variants, single nucleotide variants, indels and internal tandem duplications. Additionally, we evaluated the clinical utility of these alterations by incorporating a biomarker framework from comprehensive curation of primary canine literature and inferences from human cancer genomic biomarker literature and clinical diagnostics. Remarkably, nearly 90% of the cases exhibited mutations with diagnostic, prognostic or therapeutic implications. Our work represents a thorough assessment of genomic landscapes in a large cohort of canine cancers, the first of its kind for its comprehensive inclusion of multiple mutation types and structured annotation of biomarkers, demonstrating the clinical potential of leveraging mutation-based biomarkers in veterinary oncology., (© 2023 Vidium Animal Health and The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

As the first stage of substantive theory building, this study explored the behavioral responses of people with long-term weight concerns using mHealth to increase their physical activity within a New Zealand context. A constructivist grounded theory method was adopted. Twenty-two participants with long-term weight concerns and personal experience using mobile health to increase physical activity participated in in-depth interviews. Four themes and eight categories were conceptualized: motivation, physical activity behavioral responses, mobile health evaluation, and social interaction. The role of mobile health in increasing physical activity and improving overall wellness is broadly acknowledged and facilitates, to some extent, the social interactions among family, friends and the wider community.

Background: Health information technology (HIT) is increasingly used to enable health service/system transformation. Most HIT implementations fail to some degree; very few demonstrate sustainable success. No guidelines exist for health service leaders to leverage factors associated with success. The purpose of this paper is to present an evidence-based guideline for leaders to test and leverage in practice., Methods: This guideline was developed from a literature review and refined by a set of eight interviews with people in senior HIT roles, which were thematically analysed. It was refined in the consultancy work of the first author and confirmed after minor refinements., Results: Five key actions were identified: relationships, vision, HIT system attributes, constant evaluation and learning culture., Conclusions: This guideline presents a significant opportunity for health system leaders to systematically check relevant success factors during the implementation process of single projects and regional/national programmes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: This study aimed to describe pneumococcal polysaccharide vaccine-23 (PPSV23) vaccination use in high-risk pediatric patients with chronic heart disease (CHD)., Method: This was a single-center retrospective cohort study. Patients were included if they were aged 2-18 years and were diagnosed with CHD. The primary outcome was PPSV23 vaccination. Secondary outcomes included missed opportunities and the incidence of infections., Results: Three hundred ninety-two patients were included; the mean age was 8.8 years. Only 40 patients (10.2%) had documentation of PPSV23 vaccination. Patients had a median number of three clinic visits in 2019. There were 114 cases of pneumonia documented in patients before receiving PPSV23 and one case reported after PPSV23 vaccination., Discussion: PPSV23 vaccination in high-risk pediatric patients with CHD was low, with many documented missed opportunities for vaccination. This may be attributed to the PPSV23 not being a routine vaccination on the pediatric schedule., (Copyright © 2023 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Contamination from acid mine drainage affects ecosystems and usability of groundwater for domestic and municipal purposes. The Captain Jack Superfund Site outside of Ward, Boulder County, Colorado, USA, hosts a draining mine adit that was remediated through emplacement of a hydraulic bulkhead to preclude acid mine drainage from entering nearby Lefthand Creek. During impoundment of water within the mine workings in 2020, a diverse and novel dataset of stable isotopes of water, sulfate, and carbon ( δ 2 H , δ 18 O H 2 O , δ 18 O SO 4 , δ 34 S , δ 13 C DIC ), rare earth elements, and environmental tracers (noble gases and tritium) were collected to understand groundwater recharge and mixing, mechanisms of sulfide oxidation and water-rock interaction, and the influence of remediation on the hydrologic and geochemical system. Water isotopes indicate that groundwater distal from the mine workings has seasonally variable recharge sources whereas water within the workings has a distinctive composition with minimal temporal variability. Sulfate isotopes indicate that sulfide oxidation occurs both within the mine workings and in adjacent igneous dikes, and that sulfide oxidation may occur under suboxic conditions with ferric iron as the oxidant. Carbon isotopes track the neutralization of acidic waters and the carbon mass budget of the system. Rare earth elements corroborate stable isotopes in indicating groundwater compartmentalization, and additionally illustrate enhanced mineral weathering in the mine workings. Environmental tracers indicate mixing of modern and pre-modern groundwater and inform timelines that active remediation may be needed. Together these datasets provide a useful template for similar investigations of abandoned mine sites where physical mixing processes, sources of solute loading, or remediation timeframes are of importance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: All Long QT syndrome (LQTS) patients are at elevated risk for channelopathy-induced delayed myocardial repolarization and consequently potentially life-threatening cardiac events with 90% of initial cardiac events occurring between preteen and 40 years old. Utilizing ECG and derived vectorcardiographic parameters, including T wave Vector Magnitude (TwVM) measurement data, this study attempts to determine whether TwVM from baseline ECGs is effectively predictive of future cardiac events for genotype-positive LQTS patients., Methods: Verified carriers of established LQTS disease-causing genotypes were selected from University of Minnesota patient encounters between 2010 and 2020 for inclusion in this retrospective study. Baseline and predictive ECG and derived vectorcardiographic parameter evaluation, clinical data, and statistical analysis were compared between patients with and patients without cardiac events. First recorded ECG was at presentation to our hospital and final ECG is defined as ECG just prior to cardiac event (event defined below in Methods) or the most final documented ECG before cut-off year of 2020 for the event-free group., Results: Of 41 participants, 15 experienced cardiac events and 26 did not. While many baseline electrocardiographic parameter measurements did not show significant differences between patient groups, vectorcardiographic parameters at baseline, specifically the QRS vector magnitude (QRSVM) and azimuth of the spatial ventricular gradient, showed significance. Additionally, final vectorcardiographic parameters, particularly the QRSVM, TwVM, and azimuth of the spatial ventricular gradient showed significant differences between patient groups. Final T-wave frontal axis was significantly larger in those without cardiac events. Significant Kaplan-Meier curve separation between patient groups was noted based on a QRSVM of 1.43 mV or lower, with additional consideration to patient age, genotype, and beta blocker use., Conclusion: This study shows evidence of ECG and derived vectorcardiographic parameters, including TwVM, being effective in early prediction of cardiac events in genotype-positive LQTS patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Obstructive sleep apnoea (OSA) and obesity share a complex bi-directional relationship as location of body fat and changes in regional body composition may be more important for OSA improvement than changes in total body weight only. The aim of this study was to evaluate the impact of a 6-month weight loss intervention for adults newly diagnosed with moderate-severe OSA and obesity on regional body composition. The secondary aims evaluated the relationship between changes in OSA symptoms and severity and anthropometry and regional body composition during the first 12-months after commencing CPAP and explored differences in outcomes between males and females., Methods: Participants (n = 59) received CPAP overnight at home alongside a 6-month modified fasting intervention with 12-months follow up. Regional body composition was measured by Dual X-ray absorptiometry, (DXA) and anthropometry before and after the lifestyle intervention. OSA severity was measured using the apnoea hypopnea index via overnight polysomnography and OSA symptoms were measured using the Epworth Sleepiness scale., Results: Forty-seven adults (74% male) had complete measures available with a mean age of 50.0 y (SD 11.0) and BMI 34.1 kg/m 2 (SD 5.0). Following the intervention average fat mass changed by -5.27 kg (5.36), p < 0.001) and visceral adipose tissue (-0.63 kg (0.67), p < 0.001) significantly decreased in males only with a maintenance of fat-free mass (mean -0.41 kg (1.80), p = 0.18). Females (n = 12) had significant decreases in waist circumference (mean -3.36 cm (3.18) p < 0.01), android lean (-0.12 kg (0.04), p < 0.05) and android total mass (-0.28 kg (0.39), p < 0.05) only. Regional body composition changes in males were positively associated with improvements in OSA severity (p < 0.01) but not OSA symptoms., Conclusion: Improvements in regional body composition were seen in males only which were related to improvements in OSA severity but not OSA symptoms. Females may exhibit different OSA pathophysiology and may require different treatment approaches., Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369975&isReview=trueAACTRN12616000203459 ACTRN12616000203459., Competing Interests: Conflict of interest This trial was an investigator-initiated trial. Air Liquide provided CPAP machines and support to participants at no cost and had no role in the trial design and protocol development. By contractual agreement, researchers at Monash University have responsibility and independence regarding data management, analysis and publication. GSH has received equipment to support research from Resmed, Philips Respironics and Air Liquide Healthcare. All other authors declare no other competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Social media platforms are being increasingly used to support participant recruitment into paediatric health-related research. This study aimed to develop a multi-phase approach for using social media as a recruitment strategy for paediatric research studies., Methods: The process was informed by the authors' prior experiences recruiting for paediatric obesity-related research studies, expertise in social media marketing and digital participant/ patient recruitment. Reflection on these experiences resulted in the iterative creation of a draft process which was further refined. A narrative literature review using a structured search was conducted to refine and augment the content and finalise the process., Results: A six-phase recruitment approach was developed that includes: (i) plan for social media use as a recruitment strategy, (ii) explore relevant ethical considerations to protect the wellbeing of potentially vulnerable groups and create an ethical management plan, (iii) identify and understand the different target audiences and develop the advertising strategy, (iv) develop and design campaign content, (v) implement, monitor and iteratively refine the recruitment campaign, (vi) evaluate the campaign success. Potential activities and key considerations relevant for paediatric research are presented within each phase., Conclusion: Due to the widespread use and diverse characteristics of social media users, social media has the potential to disseminate details of research opportunities to community members who may otherwise not hear about, engage with, and potentially benefit from research participation. Researchers should collaborate with communication experts and target audiences to generate relevant and effective recruitment campaigns. Researchers should implement processes to protect vulnerable audiences' wellbeing at each stage of the process. Recruitment via social media may support wider community participation in research studies designed to improve young people's health., (© 2023 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.)

Once considered a rare disease, eosinophilic oesophagitis (EoE) is becoming increasingly prevalent, yet many healthcare professionals (HCPs) remain unfamiliar with the underlying pathophysiology and optimal management approaches. For this study, we developed a faculty-led, online, continuing medical education activity on EoE. The effectiveness of this activity was evaluated according to Moore's framework, with changes in knowledge and competence (Moore's Levels 3 and 4) assessed for a cohort of gastroenterologists, dietitians, allergists and immunologists ( N  = 300), using questionnaires completed before and after participation. Changes in HCP confidence in treating EoE were also reported and remaining educational gaps were identified. The activity was viewed by a global audience of 5,330 participants within 6 months, and significant improvements in knowledge and competence were reported following participation in the activity across all specialities, regions and experience (mean [standard deviation] score pre- versus post-activity: 4.32 [1.38] versus 5.46 [0.82]; p  < 0.001). Confidence in treating EoE also increased from pre- to post-activity, with the proportion of participants reporting that they felt moderately or extremely confident increasing from 53% to 82%. Several educational unmet needs were identified, which can be used to inform the design of future educational activities in EoE., Competing Interests: KB, KD, AN, and AMN are employees of Touch Independent Medical Education Ltd and have no financial interests/relationships or affiliations in relation to this activity. AJB received research funding from Nutricia, Norgine, DrFalkPharma, Thelial, and SST, and received speaker and/or consulting fees from Laborie, Medtronic, Dr. Falk Pharma, Alimentiv, Sanofi/Regeneron and AstraZeneca. JS received consultancy fees from Allakos, Novartis, Regeneron Pharmaceuticals, Inc. and Sanofi; grant/research support from Celgene, Novartis, Regeneron Pharmaceuticals, Inc. and Sanofi; and other financial or material support (royalties, patent, etc.) from UpToDate. IS received speaker’s bureau fee from Thermo Fisher Scientific (2021) (relationship terminated)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Two synoptic sampling campaigns were conducted to quantify metal loading to Illinois Gulch, a small stream affected by historical mining activities. The first campaign was designed to determine the degree to which Illinois Gulch loses water to the underlying mine workings and to determine the effect of these losses on observed metal loads. The second campaign was designed to evaluate metal loading within Iron Springs, a subwatershed that was responsible for the majority of the metal loading observed during the first campaign. A continuous, constant-rate injection of a conservative tracer was initiated prior to both sampling campaigns and maintained throughout the duration of each study. Tracer concentrations were subsequently used to determine streamflow in gaining stream reaches using the tracer-dilution method, and as an indicator of hydrologic connections between Illinois Gulch and subsurface mine workings. Streamflow losses to the mine workings were quantified during the first campaign using a series of slug additions in which specific conductivity readings were used as a surrogate for tracer concentration. Data from the continuous injections and slug additions were combined to develop spatial streamflow profiles along each study reach. Streamflow estimates were multiplied by observed metal concentrations to yield spatial profiles of metal load that were in turn used to quantify and rank metal sources. Study results indicate that Illinois Gulch loses water to subsurface mine workings and that remedial measures that reduce flow loss (e.g. channel lining) could lessen metal loading from the Iron Springs area. The primary sources of metals to Illinois Gulch include diffuse springs and groundwater, and a draining mine adit. Diffuse sources were determined to have a much larger effect on water quality than other sources that had been the subject of previous investigations due to their visual appearance, supporting the idea that "the truth is in the stream." The overall approach of combining spatially intensive sampling with a rigorous hydrological characterization is applicable to non-mining constituents such as nutrients and pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Background: Over the past years, homelessness has become a substantial issue around the globe. The largest social services organization in Thunder Bay, Ontario, Canada, has observed that a majority of the people experiencing homelessness in the city were from outside of the city or province. Thus, to improve programming and resource allocation for people experiencing homelessness in the city, including shelter use, it was important to investigate the trends associated with homelessness and migration., Objective: This study aimed to address 3 research questions related to homelessness and migration in Thunder Bay: What factors predict whether a person who migrated to the city and is experiencing homelessness stays or leaves shelters? If an individual stays, how long are they likely to stay? What factors predict stay duration?, Methods: We collected the required data from 2 sources: a survey conducted with people experiencing homelessness at 3 homeless shelters in Thunder Bay and the database of a homeless information management system. The records of 110 migrants were used for the analysis. Two feature selection techniques were used to address the first and third research questions, and 8 machine learning models were used to address the second research question. In addition, data augmentation was performed to improve the size of the data set and to resolve the class imbalance problem. The area under the receiver operating characteristic curve value and cross-validation accuracy were used to measure the models' performances while avoiding possible model overfitting., Results: Factors predicting an individual's stay duration included home or previous district, highest educational qualification, recent receipt of mental health support, migrating to visit family or friends, and finding employment upon arrival. For research question 2, among the classification models developed for predicting the stay duration of migrants, the random forest and gradient boosting tree models presented better results with area under the receiver operating characteristic curve values of 0.91 and 0.93, respectively. Finally, home district, band membership, status card, previous district, and recent support for drug and/or alcohol use were recognized as the factors predicting stay duration., Conclusions: Applying machine learning enables researchers to make predictions related to migrants' homelessness and investigate how various factors become determinants of the predictions. We hope that the findings of this study will aid future policy making and resource allocation to better serve people experiencing homelessness. However, further improvements in the data set size and interpretation of the identified factors in decision-making are required., (©Chandreen Ravihari Liyanage, Vijay Mago, Rebecca Schiff, Ken Ranta, Aaron Park, Kristyn Lovato-Day, Elise Agnor, Ravi Gokani. Originally published in JMIR Formative Research (https://formative.jmir.org), 02.05.2023.)

Introduction: Wound cleansing is integral during early-stage wound management and affords the transition to modalities promoting granulation tissue formation and reepithelialization, or preparation for wound coverage/closure. NPWTi-d includes periodic instillation of topical wound cleansing solutions and negative pressure for infectious material removal., Materials and Methods: This was a retrospective study of 5 patients who were admitted to an acute care hospital and treated for PI. After initial wound debridement, NPWTi-d instilled normal saline or HOCl solution (40 mL-80 mL) onto the wound for a dwell time of 20 minutes followed by 2 hours of subatmospheric pressure (-125 mm Hg). NPWTi-d duration was 3 to 6 days with 48-hour dressing changes., Results: NPWTi-d helped cleanse 10 PIs in 5 patients (age, 39-89 years) with comorbidities to facilitate primary closure using rotation flaps. In 4 patients, rotation flap closures were performed without immediate postoperative complications, followed by hospital discharge within 72 hours. In one patient, closure was preempted due to an unrelated medical issue. A stoma was created to prevent further contamination. The patient returned for flap coverage post colostomy., Conclusion: The findings herein support the use of NPWTi-d in the cleansing of complex wounds and suggest that it may facilitate an expedited transition to rotation flap closure for this wound type.

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called "neo-shamanic" ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Perkins, Ruffell, Day, Pinzon Rubiano and Sarris.)

Objective: To decrease the percentage of patients undergoing an abdominal radiograph for evaluation of constipation within 24 hours of their initial gastroenterology visit., Study Design: In January 2015, we implemented a quality improvement, evidence-based guideline (EBG) aimed at standardizing the initial assessment of patients presenting for a new outpatient gastroenterology visit with a primary complaint of constipation. Over the subsequent 5 years, we followed the clinical impact of this guideline initiation with the goal of decreasing unnecessary abdominal radiograph use by 10% within 1 year of EBG launch. Patients older than 6 months and younger than 19 years were included., Results: In total, 6723 patients completed new patient gastroenterology visits for a primary diagnosis of constipation between 2013 and 2019. Of these, 993 (14.8%) patients had abdominal radiographs taken within 24 hours of their initial visit. Over the 7 years of this project, a mean frequency of abdominal radiograph use decreased from 24% to less than 11%. In addition, a 57% decrease in hospital charges related to decreased radiograph use for constipation was found. No increases in subsequent emergency department visits or hospitalization for constipation within 30 days of patients' initial visits were seen., Conclusions: Through local adoption of an EBG, routine use of abdominal radiographs taken during a patient's initial outpatient gastroenterology visit for constipation decreased by more than 50%. This reduction was maintained over a subsequent 5-year period without any detrimental side effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/objectives: Continuous positive airway pressure (CPAP) concomitant with weight loss is a recommended treatment approach for adults with moderate-severe obstructive sleep apnoea (OSA) and obesity. This requires multiple synchronous behaviour changes. The aim of this study was to examine the effectiveness of a 6-month lifestyle intervention and to determine whether the timing of starting a weight loss attempt affects weight change and trajectory after 12 months in adults newly diagnosed with moderate-severe OSA and treated at home with overnight CPAP., Methods: Using a stepped-wedge design, participants were randomised to commence a six-month lifestyle intervention between one and six-months post-enrolment, with a 12-month overall follow-up. Adults (n = 60, 75% males, mean age 49.4 SD 10.74 years) newly diagnosed with moderate-severe OSA and above a healthy weight (mean BMI 34.1 SD 4.8) were recruited., Results: After 12 months, exposure to the intervention (CPAP and lifestyle) resulted in a 3.7 (95% CI: 2.6 to 4.8, p < 0.001) kg loss of weight compared to the control condition (CPAP alone). Timing of the weight loss attempt made no difference to outcomes at 12 months. When exposed to CPAP only (control period) there was no change in body weight (Coef, [95% CI] 0.03, [-0.3 to 0.36], p = 0.86)., Conclusions: The lifestyle intervention resulted in a modest reduction in body weight, while timing of commencement did not impact the degree of weight loss at 12 months. These findings support the recommendation of adjunctive weight-loss interventions within six-months of starting CPAP., (© 2022. The Author(s).)

Background: Excessive gestational weight gain has increased over time and is resistant to intervention, especially in women living with overweight or obesity. This study described the process evaluation methods and findings from a behavioral lifestyle intervention for African American and white women living with overweight and obesity that spanned pregnancy (≤ 16 weeks gestation) through 6 months postpartum., Methods: The Health in Pregnancy and Postpartum (HIPP) study tested a theory-based behavioral intervention (vs. standard care) to help women (N = 219; 44% African American, 29.1 ± 4.8 years) living with overweight or obesity meet weight gain guidelines in pregnancy and lose weight in postpartum. Participants completed process evaluation surveys at 32 weeks gestation (n = 183) and 6 months postpartum (n = 168) regarding their perceptions of most and least helpful aspects of the intervention. A database tracked delivery and receipt of intervention components (in-depth counseling session, telephone calls, podcasts). Descriptive statistics are used to report fidelity, dose, and participants' perceptions. We also tested whether dose of behavioral intervention components was associated with gestational weight gain and 6-month postpartum weight retention with linear regression models controlling for baseline age and gestational weeks, receipt of Medicaid, race, parity, and marital status. A content analysis was used to code and analyze responses to open-ended survey questions., Results: Over 90% of participants (both groups) would recommend the program to a friend. Implementation fidelity was moderately high and greater in pregnancy than postpartum for all intervention components. Dose received and participants' ratings of the in-depth counseling session and telephone calls were more favorable than podcasts. The Facebook group was not perceived to be very helpful, likely because of low participant interaction. Although podcasts were created to reinforce call topics, this redundancy was viewed negatively by some. More calls completed and more podcasts downloaded related to lower gestational weight gain (p < .05)., Conclusion: Study findings underscore challenges in engaging this important but busy population, especially during the postpartum period., Trial Registration: The study was registered at clinicaltrials.gov (NCT02260518) on 10/09/2014. https://clinicaltrials.gov/ct2/show/NCT02260518 ., (© 2022. The Author(s).)

Managing wildlife populations in the face of global change requires regular data on the abundance and distribution of wild animals, but acquiring these over appropriate spatial scales in a sustainable way has proven challenging. Here we present the data from Snapshot USA 2020, a second annual national mammal survey of the USA. This project involved 152 scientists setting camera traps in a standardized protocol at 1485 locations across 103 arrays in 43 states for a total of 52,710 trap-nights of survey effort. Most (58) of these arrays were also sampled during the same months (September and October) in 2019, providing a direct comparison of animal populations in 2 years that includes data from both during and before the COVID-19 pandemic. All data were managed by the eMammal system, with all species identifications checked by at least two reviewers. In total, we recorded 117,415 detections of 78 species of wild mammals, 9236 detections of at least 43 species of birds, 15,851 detections of six domestic animals and 23,825 detections of humans or their vehicles. Spatial differences across arrays explained more variation in the relative abundance than temporal variation across years for all 38 species modeled, although there are examples of significant site-level differences among years for many species. Temporal results show how species allocate their time and can be used to study species interactions, including between humans and wildlife. These data provide a snapshot of the mammal community of the USA for 2020 and will be useful for exploring the drivers of spatial and temporal changes in relative abundance and distribution, and the impacts of species interactions on daily activity patterns. There are no copyright restrictions, and please cite this paper when using these data, or a subset of these data, for publication., (© 2022 The Authors. Ecology © 2022 The Ecological Society of America.)

This case reports peripheral blood mononuclear cell (PBMC) transcriptomic changes in a pair of male monozygotic pediatric twins with metabolic syndrome (MetS) undertaking assisted weight loss. These 14-year-old boys presented with similar baseline biochemistry and body composition. After a 16-week weight-loss intervention, percent body weight loss was similar (Twin A 12%, and Twin B 13%). MetS resolved in Twin A but Twin B maintained elevated triglycerides after weight loss. Analysis of the PBMC transcriptome before and after weight loss revealed very different changes in gene expression including differences in the direction of expression of genes related to immune cell activation. 48.7% of genes that were downregulated in Twin A were upregulated in Twin B. This case highlights a novel approach to report the influence of chronic low-grade inflammation and metabolic dysfunction on the PBMC transcriptome. It explores whether expression of genes related to immune functions may underlie the differences in response to weight loss or whether transcriptomic alterations in immune cells may precede more traditional biomarkers of chronic pro-inflammation. These monozygotic twins present an example of divergence of phenotypic outcomes despite identical genetic background and similar treatment response.

BACKGROUND: Patients with migraine, particularly with multiple prior preventive treatment failures, often have high rates of acute headache medication use and are at risk for overuse (acute or symptomatic headache medication use between 10 and 15 days per month [depending on the medication] for > 3 months). Furthermore, these patients have greater health care resource utilization (HCRU). OBJECTIVE: To examine acute headache medication use and HCRU with galcanezumab compared with placebo in a population with multiple prior migraine preventive treatment failures. METHODS: In the 3-month double-blind phase, patients with episodic or chronic migraine and treatment failures to 2 to 4 standard-of-care migraine preventive categories (lack of effectiveness or safety/tolerability) received galcanezumab 120 mg/month (following a 240-mg loading dose) or placebo; an optional 3 month open-label phase followed. Acute headache medication use (monthly days with acute headache medication utilization) was self-reported daily. The change from baseline in monthly days with acute headache medication used a mixed-model repeated measures analysis. HCRU was reported at baseline (for the previous 6 months) and at monthly visits. Migraine-related HCRU rates were evaluated in the total population per 100 patient-years. RESULTS: Of the 462 patients (galcanezumab n=232, placebo n=230), baseline mean days/month of acute headache medication was 12.3; 44.8% had acute headache medication overuse. Across months 1-3, least squares (LS) mean reductions in acute headache medication use were greater for the galcanezumab group (4.2) compared with placebo (0.9); the LS mean difference was 3.4 (95% CI = 2.7-4.1; P < 0.0001). Greater reductions in the galcanezumab group were observed as early as month 1; statistical separation continued at months 2 and 3 (all P < 0.0001). During the open-label phase, reductions from baseline ranged from 4.7 to 5.3 days and were similar in patients who transitioned from placebo to patients continuing galcanezumab. Reductions from baseline of migraine-specific health care visits (double-blind phase) were numerically greater with galcanezumab than placebo (215.5 vs 155.3). Patients switching to galcanezumab had reductions (212.9 days) similar to patients continuing galcanezumab (222.6 days). Migraine-specific emergency department visits decreased by two-thirds at month 3 in the galcanezumab group compared with nearly no reduction in the placebo group that experienced a similar reduction during the open-label phase. For both groups, migraine-specific hospitalizations were less than 2 per 100 patient-years. CONCLUSIONS: These results demonstrate that galcanezumab has the potential to reduce acute headache medication use and overuse and HCRU in patients with prior migraine preventive treatment failures. DISCLOSURES: Data were presented in part as a poster presentation at the 14th European Headache Congress (European Headache Federation), Virtual Meeting, July 3-5, 2020. Dr Ambrosini is on the advisory board for Eli Lilly and Company and received honorarium from Teva, Novartis, and Eli Lilly and Company. Dr Estemalik is on the advisory boards for Eli Lilly and Company, Lundbeck, and Allergan and the speakers' bureau for Teva, Lundbeck, Eli Lilly and Company, Allergan, and Biohaven. He received consulting fees from Eli Lilly and Company, Teva, Lundbeck, and Allergan and support for attending meetings and/or travel from Eli Lilly and Company, Allergan, Biohaven, Teva, and Lundbeck. Dr Pascual received research support from Instituto de Salud Carlos III, Ministry of Economy, Spain. He was also on advisory boards for Allergan, Amgen-Novartis, Eli Lilly and Company, and Stendhal and received consulting fees or honoraria from Allegan, Eli Lilly and Company, Novartis-Amgen, and Teva. Dr Rettiganti is an employee of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. She is also a minor stock and restricted stockholder of Eli Lilly and Company. Mr. Stroud and Ms. Day are employees of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. Dr Ford is an employee of and holds stock of Eli Lilly and Company and/or one of its subsidiaries, Indianapolis, IN. She also received support for attending meetings and/or travel from Eli Lilly and Company.

High-throughput analysis of low-volume samples for detection of subvisible particles (SVPs) in biologic formulations remains an unmet need in the pharmaceutical industry. Some commonly used methods, such as light obscuration and microflow imaging, for SVP analysis are not high throughput and require significant amounts of sample volume, which may impede the collection of SVP data when therapeutic protein amounts are limited, typically during early stages of formulation development. We evaluated backgrounded membrane imaging (BMI) as an orthogonal method for SVP analysis and identified critical experimental parameters. Protein concentration, sample viscosity, and membrane coverage area had to be adjusted for each sample, especially those with high protein concentrations. A comparative analysis of particle counts obtained from BMI, light obscuration, and microflow imaging for five protein samples revealed that particle counts obtained with BMI were significantly higher than those acquired with the other two techniques for all particle size categories. BMI could not accurately count particles in protein-containing samples, as the image analysis software could not accurately trace the boundaries of translucent particles. Based on our results, BMI could be used as an orthogonal method for particle characterization when sample material is limited, such as during the early stages of formulation development or screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The epigenetic patterns that are established during early thymic development might determine mature T cell physiology and function, but the molecular basis and topography of the genetic elements involved are not fully known. Here we show, using the Cd4 locus as a paradigm for early developmental programming, that DNA demethylation during thymic development licenses a novel stimulus-responsive element that is critical for the maintenance of Cd4 gene expression in effector T cells. We document the importance of maintaining high CD4 expression during parasitic infection and show that by driving transcription, this stimulus-responsive element allows for the maintenance of histone H3K4me3 levels during T cell replication, which is critical for preventing de novo DNA methylation at the Cd4 promoter. A failure to undergo epigenetic programming during development leads to gene silencing during effector T cell replication. Our study thus provides evidence of early developmental events shaping the functional fitness of mature effector T cells., (© 2022. The Author(s).)

Mapping of allelic imbalance (AI) at heterozygous loci has the potential to establish links between genetic risk for disease and biological function. Leveraging multi-omics data for AI analysis and functional annotation, we discovered a novel functional risk variant rs1047643 at 8p23 in association with systemic lupus erythematosus (SLE). This variant displays dynamic AI of chromatin accessibility and allelic expression on FDFT1 gene in B cells with SLE. We further found a B-cell restricted super-enhancer (SE) that physically contacts with this SNP-residing locus, an interaction that also appears specifically in B cells. Quantitative analysis of chromatin accessibility and DNA methylation profiles further demonstrated that the SE exhibits aberrant activity in B cell development with SLE. Functional studies identified that STAT3, a master factor associated with autoimmune diseases, directly regulates both the AI of risk variant and the activity of SE in cultured B cells. Our study reveals that STAT3-mediated SE activity and cis-regulatory effects of SNP rs1047643 at 8p23 locus are associated with B cell deregulation in SLE., Competing Interests: YZ, KD, DA No competing interests declared, (© 2022, Zhang et al.)

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spreads rapidly amongst residents of skilled nursing facilities (SNFs). The rapid transmission dynamics and high morbidity and mortality that occur in SNFs emphasize the need for early detection of cases. We hypothesized that residents of SNFs infected with SARS-CoV-2 would demonstrate an acute change in either temperature or oxygen saturation (SpO 2 ) prior to symptom onset. The Minnesota Department of Health (MDH) conducted a retrospective analysis of both temperature and SpO 2 at two separate SNFs to assess the utility of these quantitative markers to identify SARS-CoV-2 infection prior to the development of symptoms., Methods: A retrospective analysis was conducted of 165 individuals positive for SARS-CoV-2 who were residents of SNFs that experienced coronavirus disease 2019 (COVID-19) outbreaks during April-June 2020 in a metropolitan area of Minnesota. Age, sex, symptomology, temperature and SpO 2 values, date of symptom onset, and date of positive SARS-CoV-2 test were analyzed. Temperature and SpO 2 values for the period 14 days before and after the date of initial positive test were included. Descriptive analyses evaluated changes in temperature and SpO 2 , defined as either exceeding a set threshold or demonstrating an acute change between consecutive measurements., Results: Two (1%) residents had a temperature value ≥100°F, and 30 (18%) had at least one value ≥99°F within 14 days before symptom development. One hundred and sixteen residents (70%) had at least one SpO 2 value ≤94%, while 131 (80%) had an acute decrease in SpO 2 of ≥3% between consecutive values in the 14 days prior to symptom onset., Conclusions: Our results suggest that acute change in SpO 2 might be useful in the identification of SARS-CoV-2 infection prior to the development of symptoms among residents living in SNFs. Facilities may consider adding SpO 2 to daily temperature and symptom screening checklists to improve early detection of residents of SNFs infected with SARS-CoV-2., (© 2021 The American Geriatrics Society.)

Nutrition education through school-based garden programs is a promising intervention to promote youth health and development. Gardeneers is a Chicago-based nonprofit, leading garden programming across area schools. To better understand their impact on youth health, Gardeneers aimed to define their model more clearly. Using a collective case study design, this mixed-method, formative program evaluation focused on describing program implementation variation across schools. General program design included nutrition education through hands-on garden-based learning. Stakeholder engagement was a strength for some schools and a challenge for others. Sustainability was an ongoing challenge for all schools, particularly funding. Priority student outcomes also varied between schools. Adaptability is core to Gardeneers' approach-the challenge lies in replicable program design and manageable growth, but the strength lies in the ability to meet specific school and student needs. Using these findings, Gardeneers refined their program model and identified program improvements opportunities.

Purpose of Review: Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions., Recent Findings: Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood., Summary: Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Nursing and midwifery informatics position statements are important to guide and inform our workforce. Australasian position statements have been developed to establish the place of nursing and midwifery informatics in the health system and progress the development of senior roles.

Gene expression is controlled by multiple regulators and their interactions. Data from genome-wide gene expression assays can be used to estimate molecular activities of regulators within a model organism and extrapolate them to biological processes in humans. This approach is valuable in studies to better understand complex human biological systems which may be involved in diseases and hence, have potential clinical relevance. In order to achieve this, it is necessary to infer gene interactions that are not directly observed (i.e. latent or hidden) by way of structural equation modeling (SEM) on the expression levels or activities of the downstream targets of regulator genes. Here we developed an R Shiny application, termed "Structural Equation Modeling of In silico Perturbations (SEMIPs)" to compute a two-sided t-statistic (T-score) from analysis of gene expression data, as a surrogate to gene activity in a given human specimen. SEMIPs can be used in either correlational studies between outcome variables of interest or subsequent model fitting on multiple variables. This application implements a 3-node SEM model that consists of two upstream regulators as input variables and one downstream reporter as an outcome variable to examine the significance of interactions among these variables. SEMIPs enables scientists to investigate gene interactions among three variables through computational and mathematical modeling (i.e. in silico ). In a case study using SEMIPs, we have shown that putative direct downstream genes of the GATA Binding Protein 2 (GATA2) transcription factor are sufficient to infer its activities in silico for the conserved progesterone receptor (PGR)-GATA2-SRY-box transcription factor 17 (SOX17) genetic network in the human uterine endometrium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Bushel, Lin, Day, Wang, DeMayo, Wu and Li.)

Observational studies indicate that selenium may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Transcriptomic exploration of the aetiology and progression of NAFLD may offer insight into the role selenium plays in this disease. This study compared gene expression levels of known selenoprotein pathways between individuals with a healthy liver to those with NAFLD. Publicly available gene expression databases were searched for studies that measured global gene expression in liver samples from patients with steatosis and non-alcoholic steatohepatitis (NASH) and healthy controls (with [HOC] or without [HC] obesity). A subset of five selenoprotein-related pathways (164 genes) were assessed in the four datasets included in this analysis. The gene TXNRD3 was less expressed in both disease groups when compared with HOC. SCLY and SELENOO were less expressed in NASH when compared with HC. SELENOM, DIO1, GPX2 , and GPX3 were highly expressed in NASH when compared to HOC. Disease groups had lower expression of iron-associated transporters and higher expression of ferritin-encoding sub-units, consistent with dysregulation of iron metabolism often observed in NAFLD. Our bioinformatics analysis suggests that the NAFLD liver may have lower selenium levels than a disease-free liver, which may be associated with a disrupted iron metabolism. Our findings indicate that gene expression variation may be associated with the progressive risk of NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Day, Seale, Graham and Cardoso.)

Background: Chicago has a history of gun violence with some neighborhoods, particularly Black and Brown communities, being disproportionately affected and Black male youth experiencing an even more disparate impact. Too often, violence prevention research is developed and carried out with little or no input from the people living in the most affected communities. The objective of the Community-Academic Collaboration to Prevent Violence in Chicago (CACPVC) was to bring together individuals from impacted communities with academic researchers and other community stakeholders to discuss violence and co-create a research agenda that addresses topics of mutual concern, and recommendations for engaging stakeholders including community members and organizations and funders in violence and violence prevention research., Methods: From 2014 to 2015, community members and organizations from seven defined regions across Chicago were recruited to participate. An organization network gathering was held in each region for researchers, funders, and community organization representatives to discuss violence prevention. Open community forums then took place in each community. Violence data by region was shared followed by facilitated group discussions that were recorded by youth scribes. Notes were thematically coded, grouped, and compiled after which a list of topics was refined by the CACPVC Work Group, allowing for investigator triangulation. A survey was disseminated to community stakeholders to prioritize the topics., Results: Seven network gatherings (127 attendees) and community forums (133 attendees) were held. Topic areas identified during the gatherings and forums included root causes/cycle of violence, racism and bias/structural violence, trajectory of violence, protective factors and nonviolence, geographic pattern change, violence prevention strategies, youth, family factors, community factors, school, police, gangs/street organizations, and media and public perceptions. Recommendations to support community engagement were grouped as role of research in reducing violence, role of community in violence research, relationships and respect, academic-community communication, financial considerations, training, practical considerations, research design, sharing results, communication about and use of data, and recommendations for funders., Conclusions: The violence research agenda will be used to inform community-engaged violence prevention research. The recommendations for community engagement provide a resource for researchers about topics to consider to meaningfully engage community members in future research., (© 2021. The Author(s).)

Objective: "Drunkorexia" or compensatory eating behaviors in response to alcohol consumption, resembles a subclinical eating disorder, and is a current public health concern. Eating disorders and alcohol abuse are associated with dysfunction of the hypothalamic-pituitary-adrenal axis (HPA). One index of HPA function is cortisol. As causes of drunkorexia remain elusive, the present study examined cortisol function as it relates to drunkorexia. Participants: n  = 73 (49 women) college students. Method: Participants provided daytime saliva samples for cortisol analyses prior to completing an online survey measuring alcohol consumption, drunkorexia, and alcohol problems as measured by the Rutgers Alcohol Problem Index (RAPI). Results: Multiple regressions indicated that baseline cortisol significantly positively correlated with drunkorexia behaviors in women but not men. Higher baseline cortisol and aspects of drunkorexia related to alcohol problems. Conclusion: Programs educating about stress management and health risks of drunkorexia may decrease engagement in drunkorexia behaviors among college students.

Background and Objectives: Peripheral blood mononuclear cells (PBMCs) have shown promise as a tissue sensitive to subtle and possibly systemic transcriptomic changes, and as such may be useful in identifying responses to weight loss interventions. The primary aim was to comprehensively evaluate the transcriptomic changes that may occur during weight loss and to determine if there is a consistent response across intervention types in human populations of all ages., Methods: Included studies were randomised control trials or cohort studies that administered an intervention primarily designed to decrease weight in any overweight or obese human population. A systematic search of the literature was conducted to obtain studies and gene expression databases were interrogated to locate corresponding transcriptomic datasets. Datasets were normalised using the ArrayAnalysis online tool and differential gene expression was determined using the limma package in R. Over-represented pathways were explored using the PathVisio software. Heatmaps and hierarchical clustering were utilised to visualise gene expression., Results: Seven papers met the inclusion criteria, five of which had raw gene expression data available. Of these, three could be grouped into high responders (HR, ≥ 5% body weight loss) and low responders (LR). No genes were consistently differentially expressed between high and low responders across studies. Adolescents had the largest transcriptomic response to weight loss followed by adults who underwent bariatric surgery. Seven pathways were altered in two out of four studies following the intervention and the pathway 'cytoplasmic ribosomal proteins' (WikiPathways: WP477) was altered between HR and LR at baseline in the two datasets with both groups. Pathways related to 'toll-like receptor signalling' were altered in HR response to the weight loss intervention in two out of three datasets., Conclusions: Transcriptomic changes in PBMCs do occur in response to weight change. Transparent and standardised data reporting is needed to realise the potential of transcriptomics for investigating phenotypic features., Registration Number: PROSPERO: CRD42019106582., (© 2021. The Author(s).)

Introduction: The underrepresentation of women among senior faculty members in medical education is a longstanding problem. The purpose of this international qualitative investigation was to explore women and men's experiences of attaining full professorship and to investigate why women remain underrepresented among the senior faculty ranks., Methods: Conducted within a social constructionist orientation, our qualitative study employed narrative analysis. Two female and two male participants working in medical education were recruited from five nations: Australia, Canada, the Netherlands, United Kingdom and United States. All participants held an MD or PhD. During telephone interviews, participants narrated the story of their careers. The five faculty members on the research team were also interviewed. Their narratives were included in analysis, rendering their experiences equal to those of the participants., Results: A total of 24 full professors working in medical education were interviewed (n = 15 females and n = 9 males). While some aspects were present across all narratives (ie personal events, career milestones and facilitating and/or impeding factors), participants' experience of those aspects differed by gender. Men did not narrate fatherhood as a role navigated professionally, but women narrated motherhood as intimately connected to their professional roles. Both men and women narrated career success in terms of hard work and overcoming obstacles; however, male participants described promotion as inevitable, whereas women narrated promotion as a tenuous navigation of social structures towards uncertain outcomes. Female and male participants encountered facilitators and inhibitors throughout their careers but described acting on those experiences differently within the cultural contexts they faced., Discussion: Our data suggest that female and male participants had different experiences of the work involved in achieving full professor status. Understanding these gendered experiences and their impact on career progression is an important advancement for better understanding what leads to the underrepresentation of women among senior faculty members in medical education., (© 2020 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Background: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline., Research Question: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation?, Study Design and Methods: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [S acin ]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV 1 , FEV 1 /FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions., Results: S acin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639)., Interpretation: Increased S acin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

The movement system has been adopted as the key identity for the physical therapy profession, and recognition of physical therapists' primary expertise in managing movement dysfunction is an important achievement. However, existing movement system models seem inadequate for guiding education, practice, or research. Lack of a clear, broadly applicable model may hamper progress in physical therapists actually adopting this identity. We propose a model composed of 4 primary elements essential to all movement: motion, force, energy, and control. Although these elements overlap and interact, they can each be examined and tested with some degree of specificity. The proposed 4-element model incorporates specific guidance for visual, qualitative assessment of movement during functional tasks that can be used to develop hypotheses about movement dysfunction and serve as a precursor to more quantitative tests and measures. Human movement always occurs within an environmental context and is affected by personal factors, and these concepts are represented within the model. The proposed scheme is consistent with other widely used models within the profession, such as the International Classification of Functioning, Disability and Health and the Patient Management Model. We demonstrate with multiple examples how the model can be applied to a broad spectrum of patients across the lifespan with musculoskeletal, neurologic, and cardiopulmonary disorders., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Telehealth became the most practical option for general practice consultations in Aotearoa New Zealand (NZ) as a result of the national lockdowns in response to the COVID-19 pandemic. What is the consumer experience of access to telehealth and how do consumers and providers perceive this mode of care delivery going forward?, Methods and Analysis: A national survey of general practice consumers and providers who used telehealth services since the national lockdowns in 2020 will be distributed. It is based on the Unified Theory of Acceptance and Use of Technology framework of technology acceptance and the access to care framework. The data will be statistically analysed to create a foundation for in-depth research on the use of telehealth services in NZ general practice services, with a specific focus on consumer experiences and health outcomes., Ethics and Dissemination: Ethics approval was granted by the Auckland Health Research Ethics Committee on 13/11/2020, reference AH2539. The survey will be disseminated online., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated a significant reduction in monthly migraine headache days compared with placebo. Here, we analyze data from 3 randomized clinical trials (2 episodic trials [EVOLVE-1, EVOLVE-2] and 1 chronic trial [REGAIN]), to examine if galcanezumab also alleviates the severity and symptoms of migraine., Methods: The episodic migraine trials were 6-month, double-blind studies in patients with episodic migraine (4-14 monthly migraine headache days). The chronic migraine trial was a 3-month, double-blind study in patients with chronic migraine (≥ 15 headache days per month, where ≥ 8 met criteria for migraine). Patients (18-65 years) were randomized to placebo or galcanezumab 120 mg with a 240-mg loading dose or 240 mg. Patients recorded headache characteristics, duration, severity, and presence of associated symptoms with each headache. The outcomes analyzed were changes from baseline in number of monthly migraine headache days with nausea and/or vomiting, photophobia and phonophobia, aura, and prodromal symptoms other than aura. Additional outcomes analyzed included the number of moderate-to-severe monthly migraine headache days, number of severe migraine headache days, and mean severity of remaining migraine headache days. Change from baseline in the proportion of days with nausea and/or vomiting and the proportion of days with photophobia and phonophobia among the remaining monthly migraine headache days were also analyzed., Results: Galcanezumab was superior to placebo in reducing the frequency of migraine headache days with associated symptoms of migraine such as nausea and/or vomiting, photophobia and phonophobia, and prodromal symptoms. Galcanezumab reduced the frequency of migraine headache days with aura in the episodic migraine studies. There was a significant reduction in the proportion of remaining migraine headache days with nausea and/or vomiting for the episodic and chronic migraine studies, and with photophobia and phonophobia for the episodic migraine studies. Galcanezumab was superior to placebo in reducing the number of monthly moderate-to-severe migraine headache days and the overall and monthly severe migraine headache days., Conclusions: Galcanezumab reduces the frequency of migraine headache days and can alleviate potentially disabling non-pain symptoms on days when migraine is present in patients with episodic or chronic migraine., Trial Registration: NCT, NCT02614183 (EVOLVE-1), registered 25 November 2015; NCT, NCT02614196 , (EVOLVE-2), registered 25 November 2015; NCT, NCT02614261 (REGAIN), registered 25 November 2015.

Purpose: Approximately 20% of caregivers (CGs) live > 1 hour away from the patient and are considered distance caregivers (DCGs) who often report higher distress and anxiety than local CGs. The purpose of this study was to test the effectiveness of an intervention aimed at reducing anxiety and distress in DCGs of patients with cancer., Methods: This randomized controlled trial enrolled DCGs of patients with all cancer types who were being seen monthly by oncologists in outpatient clinics. There were three arms of the intervention delivered over a 4-month period: arm 1 (a) received 4 monthly videoconference-tailored coaching sessions with an advanced practice nurse or social worker focused on information and support, (b) participated in patient's appointments with the oncologist via videoconference over the 4-month study period, and (c) had access to a website designed for DCGs. Arm 2 did not receive the coaching sessions but received the other two components, and arm 3 received access to the DCG website only., Results: There were 302 DCGs who provided pre- and postintervention data. There were significant anxiety by group ( P = .028 and r = 0.16) and distress by group interactions ( P = .014 and r = 0.17). Arm 1 had the greatest percentage of DCGs who demonstrated improvement in anxiety (18.6%) and distress (25.2%)., Conclusion: Coaching and use of videoconference technology (to join the DCG into the patient-oncologist office visit) were effective in reducing both anxiety and distress for DCGs. These components could be considered for local CGs who-with COVID-19-are unable to accompany the patient to oncologist visits.

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species., Competing Interests: The authors have declared that no competing interests exist.

According to Eviction Lab there were 6877 evictions in Chicago in 2016. The rate was "1.1%" and came out to 18.79 evictions per day in Chicago in 2016. The presence of children in a household (HH) poses a greater risk for eviction than race or gender. Census tract-level data from the Chicago Department of Public Health, the Eviction Lab and American Community Survey was used to assess the relationship between eviction and pediatric health outcomes for 653 census tracts in Chicago. Correlation matrices and linear regression models were used to evaluate the relationship between eviction and health outcomes. Regression models were adjusted for the following: (1) female-led family HH with less than a high school degree and below poverty and (2) race/ethnicity. Compared to White Non-Hispanic HH, predominantly Black and Hispanic HH had higher rates of very low birth weight (VLBW), infant mortality (IM), eviction filings, and evictions. All covariates were found to be significantly correlated (p < 0.01). Eviction filing rates and eviction rates were significant predictors for both VLBW and IM in both unadjusted and adjusted models (p < 0.05). Though we cannot conclude causality, these results suggest that census tracts which experience high rates of eviction also experience high rates of VLBW and IM and this relationship should be further investigated.