Competition shapes the landscape of X-chromosome-linked genetic diversity.

X chromosome inactivation (XCI) generates clonal heterogeneity within XX individuals. Combined with sequence variation between human X chromosomes, XCI gives rise to intra-individual clonal diversity, whereby two sets of clones express mutually exclusive sequence variants present on one or the other X chromosome. Here we ask whether such clones merely co-exist or potentially interact with each other to modulate the contribution of X-linked diversity to organismal development. Focusing on X-linked coding variation in the human STAG2 gene, we show that Stag2variant clones contribute to most tissues at the expected frequencies but fail to form lymphocytes in Stag2WT Stag2variant mouse models. Unexpectedly, the absence of Stag2variant clones from the lymphoid compartment is due not solely to cell-intrinsic defects but requires continuous competition by Stag2WT clones. These findings show that interactions between epigenetically diverse clones can operate in an XX individual to shape the contribution of X-linked genetic diversity in a cell-type-specific manner.

Greater hepatic lipid saturation is associated with impaired glycaemic regulation in men with metabolic dysfunction-associated steatotic liver disease but is not altered by 6 weeks of exercise training.

AIMS: To examine the impact of impaired glycaemic regulation (IGR) and exercise training on hepatic lipid composition in men with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: In Part A (cross-sectional design), 40 men with MASLD (liver proton density fat fraction [PDFF] ≥5.56%) were recruited to one of two groups: (1) normal glycaemic regulation (NGR) group (glycated haemoglobin [HbA1c] < 42 mmol∙mol-1 [<6.0%]; n = 14) or (2) IGR group (HbA1c ≥ 42 mmol∙mol-1 [≥6.0%]; n = 26). In Part B (randomized controlled trial design), participants in the IGR group were randomized to one of two 6-week interventions: (1) exercise training (EX; 70%-75% maximum heart rate; four sessions/week; n = 13) or (2) non-exercise control (CON; n = 13). Saturated (SI; primary outcome), unsaturated (UI) and polyunsaturated (PUI) hepatic lipid indices were determined using proton magnetic resonance spectroscopy. Additional secondary outcomes included liver PDFF, HbA1c, fasting plasma glucose (FPG), homeostatic model assessment of insulin resistance (HOMA-IR), peak oxygen uptake (VO2 peak), and plasma cytokeratin-18 (CK18) M65, among others. RESULTS: In Part A, hepatic SI was higher and hepatic UI was lower in the IGR versus the NGR group (p = 0.038), and this hepatic lipid profile was associated with higher HbA1c levels, FPG levels, HOMA-IR and plasma CK18 M65 levels (rs ≥0.320). In Part B, hepatic lipid composition and liver PDFF were unchanged after EX versus CON (p ≥ 0.257), while FPG was reduced and VO2 peak was increased (p ≤ 0.030). ΔVO2 peak was inversely associated with Δhepatic SI (r = -0.433) and positively associated with Δhepatic UI and Δhepatic PUI (r ≥ 0.433). CONCLUSIONS: Impaired glycaemic regulation in MASLD is characterized by greater hepatic lipid saturation; however, this composition is not altered by 6 weeks of moderate-intensity exercise training.

Association Between Time to Treatment With Endovascular Thrombectomy and Home-Time After Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Home-time is a patient-prioritized stroke outcome that can be derived from administrative data linkages. The effect of faster time-to-treatment with endovascular thrombectomy (EVT) on home-time after acute stroke is unknown. METHODS: We used the Quality Improvement and Clinical Research registry to identify a cohort of patients who received EVT for acute ischemic stroke between 2015 and 2022 in Alberta, Canada. We calculated days at home in the first 90 days after stroke. We used ordinal regression across 6 ordered categories of home-time to evaluate the association between onset-to-arterial puncture and higher home-time, adjusting for age, sex, rural residence, NIH Stroke Scale, comorbidities, intravenous thrombolysis, and year of treatment. We used restricted cubic splines to assess the nonlinear relationship between continuous variation in time metrics and higher home-time, and also reported the adjusted odds ratios within time categories. We additionally evaluated door-to-puncture and reperfusion times. Finally, we analyzed home-time with zero-inflated models to determine the minutes of earlier treatment required to gain 1 day of home-time. RESULTS: We had 1,885 individuals in our final analytic sample. There was a nonlinear increase in home-time with faster treatment when EVT was within 4 hours of stroke onset or 2 hours of hospital arrival. There was a higher odds of achieving more days at home when onset-to-puncture time was <2 hours (adjusted odds ratio 2.36, 95% CI 1.77-3.16) and 2 to <4 hours (1.37, 95% CI 1.11-1.71) compared with ≥6 hours, and when door-to-puncture time was <1 hour (aOR 2.25, 95% CI 1.74-2.90), 1 to <1.5 hours (aOR 1.89, 95% CI 1.47-2.41), and 1.5 to <2 hours (1.35, 95% CI 1.04-1.76) compared with ≥2 hours. Results were consistent for reperfusion times. For every hour of faster treatment within 6 hours of stroke onset, there was an estimated increase in home-time of 4.7 days, meaning that approximately 1 day of home-time was gained for each 12.8 minutes of faster treatment. DISCUSSION: Faster time-to-treatment with EVT for acute stroke was associated with greater home-time, particularly within 4 hours of onset-to-puncture and 2 hours of door-to-puncture time. Within 6 hours of stroke onset, each 13 minutes of faster treatment is associated with a gain of 1 day of home-time.

Development of a new class of stable and adaptable free-standing fibre mats with high room-temperature hydroxide-ion conductivity.

For alkaline anion-exchange membrane electrolysers and fuel cells to become a technological reality, hydroxide-ion (OH-) conducting membranes that are flexible, robust, affording high OH- conductivity, and synthesised in a low-cost and scalable way must be developed. In this paper, we engineer a stable, self-supporting, and flexible fibre mat using a low-cost ZIF-8 metal-organic framework composited with ionic liquid tetrabutylammonium hydroxide and widely used polyacrylonitrile as polymeric backbone. We obtain mats with a high intrinsic OH- conductivity for a metal-organic framework-based material already at room temperature, without added ion-conductor polymers. This approach will contribute to the development of low-cost and tuneable ion-conducting membranes.

The association of smoking with different eating and dietary behaviours: A cross-sectional analysis of 80 296 United Kingdom adults.

BACKGROUND AND AIMS: Smokers typically have a lower body mass index (BMI) than non-smokers, while smoking cessation is associated with weight gain. In pre-clinical research, nicotine in tobacco smoking suppresses appetite and influences subsequent eating behaviour; however, this relationship is unclear in humans. This study measured the associations of smoking with different eating and dietary behaviours. DESIGN: A cross-sectional analysis of data from health assessments conducted between 2004 and 2022. SETTING: An independent healthcare-based charity within the United Kingdom. PARTICIPANTS: A total of 80 296 men and women (mean ± standard deviation [SD]: age, 43.0 ± 10.4 years; BMI, 25.7 ± 4.2 kg/m2; 62.5% male) stratified into two groups based on their status as a smoker (n = 6042; 7.5%) or non-smoker (n = 74 254; 92.5%). MEASUREMENTS: Smoking status (self-report) was the main exposure, while the primary outcomes were selected eating and dietary behaviours. Age, sex and socioeconomic status (index of multiple deprivation [IMD]) were included as covariates and interaction terms, while moderate-to-vigorous exercise and sleep quality were included as covariates only. FINDINGS: Smokers had lower odds of snacking between meals and eating food as a reward or out of boredom versus non-smokers (all odds ratio [OR] ≤ 0.82; P < 0.001). Furthermore, smokers had higher odds of skipping meals, going more than 3 h without food, adding salt and sugar to their food, overeating and finding it hard to leave something on their plate versus non-smokers (all OR ≥ 1.06; P ≤ 0.030). Additionally, compared with non-smokers, smoking was associated with eating fried food more times per week (rate ratio [RR] = 1.08; P < 0.001), eating fewer meals per day, eating sweet foods between meals and eating dessert on fewer days per week (all RR ≤ 0.93; P < 0.001). Several of these relationships were modified by age, sex and IMD. CONCLUSIONS: Smoking appears to be associated with eating and dietary behaviours consistent with inhibited food intake, low diet quality and altered food preference. Several of these relationships are moderated by age, sex and socioeconomic status.

Supporting Emergency Medical Services Clinicians Through Acute and Sustained Crises With Informal Peer Support and Intentional Acts of Kindness: The Emergency Medical Services Code Lavender Program.

OBJECTIVE: Given the recommendations against the use of critical incident stress debriefing, the emergency medical services (EMS) Code Lavender program was created as a mechanism to consistently recognize and reach out to EMS clinicians after acute crisis events, offer nonintrusive informal peer support and acts of kindness, and provide stepwise support via mental health professionals as needed. The study aimed to assess program utilization and evaluate the program's impact on EMS clinicians' perceptions of support and resources available to them after an acute crisis event. METHODS: Anonymous surveys were distributed before program implementation and 18 months later. Program utilization was tracked using REDCap (Vanderbilt University, Nashville, TN). Fisher exact tests and logistic regression were used to analyze the survey results. RESULTS: Within 30 months, 87 referrals were made. Seventy-seven preprogram (59% response rate) and 104 intraprogram (88% response rate) surveys were collected. There were no differences between respondents by sex or role. There were significant improvements in knowing where to go for help (from 40% to 85%, P < .001) and willingness to seek help if needed (from 40% to 59%, P = .02). CONCLUSION: The implementation of an EMS Code Lavender program led to significant increases in EMS clinician self-reported knowledge of where to go and willingness to seek help after acute crisis events.

A systematic review and qualitative synthesis of weight management interventions for people with spinal cord injury.

People with spinal cord injury (SCI) are at greater risk of developing obesity and related co-morbidities than those without SCI. The objectives of this systematic review were to examine the effectiveness of weight management interventions for people with SCI and to synthesize the experiences of people involved with SCI weight management (e.g., SCI healthcare professionals and caregivers). Five databases were searched (up to July 31, 2023) and 5,491 potentially eligible articles were identified. Following screening, 22 articles were included, comprising 562 adults. There was considerable heterogeneity in study design and weight loss interventions included behavioral nutritional and exercise education sessions, recalling food diaries, exercise interventions, and pharmaceuticals. The mean percentage change of the pooled body mass data equated to -4.0 ± 2.3%, with a range from -0.5 to -7.6%. In addition, 38% of the individuals with SCI who completed a weight loss intervention (N = 262) had a ≥5% reduction in body weight. Collectively, although on average the included interventions led to moderate weight loss, the finding that just over a third of individuals achieved clinically meaningful 5% weight loss suggests that available interventions for this population may need to be improved.

Three-dimensional chromatin mapping of sensory neurons reveals that cohesin-dependent genomic domains are required for axonal regeneration.

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration.

Characterizing Longitudinal Patterns in Cognition, Mood, And Activity in Depression With 6-Week High-Frequency Wearable Assessment: Observational Study.

BACKGROUND: Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal methodology to implement and synthesize these techniques. OBJECTIVE: The objective of this study was to examine (1) longitudinal changes in mood, cognition, activity levels, and heart rate over 6 weeks; (2) diurnal and weekday-related changes; and (3) co-occurrence of fluctuations between mood, cognitive function, and activity. METHODS: A total of 30 adults with current mild-moderate depression stabilized on antidepressant monotherapy responded to testing delivered through an Apple Watch (Apple Inc) for 6 weeks. Outcome measures included cognitive function, assessed with 3 brief n-back tasks daily; self-reported depressed mood, assessed once daily; daily total step count; and average heart rate. Change over a 6-week duration, diurnal and day-of-week variations, and covariation between outcome measures were examined using nonlinear and multilevel models. RESULTS: Participants showed initial improvement in the Cognition Kit N-Back performance, followed by a learning plateau. Performance reached 90% of individual learning levels on average 10 days after study onset. N-back performance was typically better earlier and later in the day, and step counts were lower at the beginning and end of each week. Higher step counts overall were associated with faster n-back learning, and an increased daily step count was associated with better mood on the same (P<.001) and following day (P=.02). Daily n-back performance covaried with self-reported mood after participants reached their learning plateau (P=.01). CONCLUSIONS: The current results support the feasibility and sensitivity of high-frequency cognitive assessments for disease and treatment monitoring in patients with depression. Methods to model the individual plateau in task learning can be used as a sensitive approach to better characterize changes in behavior and improve the clinical relevance of cognitive data. Wearable technology allows assessment of activity levels, which may influence both cognition and mood.

Th17-to-Tfh plasticity during periodontitis limits disease pathology.

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.

Increased prevalence of germline pathogenic CHEK2 variants in individuals with pituitary adenomas.

CONTEXT: CHEK2 is a cell cycle checkpoint regulator gene with a long-established role as a clinically relevant, moderate risk breast cancer predisposition gene, with greater risk ascribed to truncating variants than missense variants. METHODS: We assessed 165 individuals with pituitary adenomas for CHEK2 variants. The study consisted of a primary cohort of 29 individuals who underwent germline and tumour whole exome sequencing, and a second, independent cohort of 136 individuals who had a targeted next-generation sequencing panel performed on both germline and tumour DNA (n=52) or germline DNA alone (n=84). RESULTS: We identified rare, coding, non-synonymous germline CHEK2 variants amongst 3/29 (10.3%) patients in our primary cohort and 5/165 (3.0%) patients overall, with affected patients having a range of hormone secretion types (prolactinoma, thyrotrophinoma, somatotrophinoma and non-functioning pituitary adenoma). No somatic variants were identified. Two variants were definitive null variants (c.1100delC, c.444+1G>A), classified as pathogenic. Two variants were missense variants (p.Asn186His, p.Thr476Met), classified as likely pathogenic. Even when considering the null variants only, the rate of CHEK2 variants was higher in our cohort compared to national control data (1.8% vs. 0.5%, P=0.049). CONCLUSIONS: This is the first study to suggest a role for the breast cancer predisposition gene, CHEK2, in pituitary tumorigenesis, with pathogenic/likely pathogenic variants found in 3% of patients with pituitary adenomas. As pituitary adenomas are relatively common and typically lack classical autosomal dominant family histories, risk alleles - such as these variants found in CHEK2 - might be a significant contributor to pituitary adenoma risk in the general population.

Effects of Exercise Training on Muscle Mass and Physical Function in Patients with Hepatocellular Carcinoma After Diagnosis: A Systematic Review.

BACKGROUND AND AIMS: Decreased muscle mass and physical function are common complications in hepatocellular carcinoma (HCC) patients who are associated with increased morbidity and mortality. Thus, there have been targeted efforts to prevent and/or improve both by enrolling these patients in exercise training programs. We performed a systematic review to evaluate the effects of exercise training on muscle mass and physical function in people with HCC after diagnosis. METHODS: A systematic literature search was conducted using the Medline, Base, PubMed, Cochrane and Scopus, and trial registries, through April 2023 for studies that assessed the effects of an exercise training program in adults with HCC. The primary outcomes were muscle mass and physical function. To assess the risk of bias, we used the Quality Assessment Tool for Quantitative Studies from the Effective Public Health Practice Project. RESULTS: Eight studies met inclusion criteria, comprising a total of 809 participants. Interventions included aerobic exercise training, resistance exercise training, balance and flexibility training, or home-based exercise training. Four studies showed statistically significant improvements in at least one muscular outcome. Three studies showed a maintenance of muscular outcomes, and one study showed a decrease in muscle mass. Four articles showed statistically improvements in at least one physical fitness variable, and two showed a maintenance of physical function variable. CONCLUSION: Together, the results suggest that patients may benefit from physical exercise training after treatment to improve muscle mass and physical function.

Voluntary exercise fails to prevent metabolic dysfunction-associated steatotic liver disease progression in male rats fed a high-fat high-cholesterol diet.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health issue with a worldwide prevalence of 30%-32%. In animal models, voluntary exercise may be an alternative to forced physical activity, avoiding stress, potential injuries, and being logistically simpler. Here, we assessed voluntary exercise (Vex) in Sprague-Dawley rats fed a high-fat, high-cholesterol diet for 18 weeks to induce MASLD. We quantified workload (speed and distance) using exercise wheels and evaluated energy expenditure using calorimetric cages. MASLD progression was assessed using circulating and hepatic biochemical and gene markers of steatosis, inflammation, and fibrosis. The animals ran an average of 301 km during the study period, with the average daily distance peaking at 4937 m/day during Weeks 3-4 before decreasing to 757 m/day by the end of the study. Rats exposed to Vex showed no improvement in any of the MASLD-associated features, such as steatosis, inflammation, or fibrosis. Rats exposed to Vex exhibited a higher total energy expenditure during the night phase (+0.35 kcal/h; p = 0.003) without resulting in any effect on body composition. We conclude that, in our experimental conditions, Vex failed to prevent MASLD progression in male Sprague-Dawley rats exposed to a high-fat high-cholesterol diet for 18 weeks.

The COVID-19 ambulance response assessment (CARA) study: a national survey of ambulance service healthcare professionals' preparedness and response to the COVID-19 pandemic.

Background: The COVID-19 pandemic placed significant demand on the NHS, including ambulance services, but it is unclear how this affected ambulance service staff and paramedics in other clinical settings (e.g. urgent and primary care, armed services, prisons). This study aimed to measure the self-perceived preparedness and impact of the first wave of the pandemic on paramedics' psychological stress and perceived ability to deliver care. Methods: Ambulance clinicians and paramedics working in other healthcare settings were invited to participate in a three-phase sequential online survey during the acceleration (April 2020), peak (May 2020) and deceleration (September/October 2020) phases of the first wave of COVID-19 in the United Kingdom. Recruitment used social media, Trust internal bulletins and the College of Paramedics' communication channels, employing a convenience sampling strategy. Data were collected using purposively developed open- and closed-ended questions and the validated general health questionnaire-12 (GHQ-12). Data were analysed using multi-level linear and logistic regression models. Results: Phase 1 recruited 3717 participants, reducing to 2709 (73%) by phase 2 and 2159 (58%) by phase 3. Participants were mostly male (58%, n = 2148) and registered paramedics (n = 1992, 54%). Mean (standard deviation) GHQ-12 scores were 16.5 (5.2) during phase 1, reducing to 15.2 (6.7) by phase 3. A total of 84% of participants (n = 3112) had a GHQ-12 score ≥ 12 during the first phase, indicating psychological distress. Participants that had higher GHQ-12 scores were feeling unprepared for the pandemic, and reported a lack of confidence in using personal protective equipment and managing cardiac arrests in confirmed or suspected COVID-19 patients. Conclusions: Most participants reported psychological distress, the reasons for which are multi-factorial. Ambulance managers need to be aware of the risks to staff mental health and take action to mitigate these, to support staff in the delivery of unscheduled, emergency and urgent care under these additional pressures.

Age-Specific Association of Co-Morbidity With Home-Time After Acute Stroke.

OBJECTIVE: To examine the association of co-morbidity with home-time after acute stroke and whether the association is influenced by age. METHODS: We conducted a province-wide study using linked administrative databases to identify all admissions for first acute ischemic stroke or intracerebral hemorrhage between 2007 and 2018 in Alberta, Canada. We used ischemic stroke-weighted Charlson Co-morbidity Index of 3 or more to identify those with severe co-morbidity. We used zero-inflated negative binomial models to determine the association of severe co-morbidity with 90-day and 1-year home-time, and logistic models for achieving ≥ 80 out of 90 days of home-time, assessing for effect modification by age and adjusting for sex, stroke type, comprehensive stroke center care, hypertension, atrial fibrillation, year of study, and separately adjusting for estimated stroke severity. We also evaluated individual co-morbidities. RESULTS: Among 28,672 patients in our final cohort, severe co-morbidity was present in 27.7% and was associated with lower home-time, with a greater number of days lost at younger age (-13 days at age < 60 compared to -7 days at age 80+ years for 90-day home-time; -69 days at age < 60 compared to -51 days at age 80+ years for 1-year home-time). The reduction in probability of achieving ≥ 80 days of home-time was also greater at younger age (-22.7% at age < 60 years compared to -9.0% at age 80+ years). Results were attenuated but remained significant after adjusting for estimated stroke severity and excluding those who died. Myocardial infarction, diabetes, and cancer/metastases had a greater association with lower home-time at younger age, and those with dementia had the greatest reduction in home time. CONCLUSION: Severe co-morbidity in acute stroke is associated with lower home-time, more strongly at younger age.

Amygdala enlargement in temporal lobe epilepsy: Histopathology and surgical outcomes.

OBJECTIVES: Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. METHODS: This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. RESULTS: Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). SIGNIFICANCE: The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.

Chemistry-albedo feedbacks offset up to a third of forestation's CO2 removal benefits.

Forestation is widely proposed for carbon dioxide (CO2) removal, but its impact on climate through changes to atmospheric composition and surface albedo remains relatively unexplored. We assessed these responses using two Earth system models by comparing a scenario with extensive global forest expansion in suitable regions to other plausible futures. We found that forestation increased aerosol scattering and the greenhouse gases methane and ozone following increased biogenic organic emissions. Additionally, forestation decreased surface albedo, which yielded a positive radiative forcing (i.e., warming). This offset up to a third of the negative forcing from the additional CO2 removal under a 4°C warming scenario. However, when forestation was pursued alongside other strategies that achieve the 2°C Paris Agreement target, the offsetting positive forcing was smaller, highlighting the urgency for simultaneous emission reductions.

Diagnostic strategies in postpartum individuals with suspected venous thromboembolism: A scoping review.

BACKGROUND: The risk of venous thromboembolism (VTE) is increased postpartum and contributes to important morbidity and mortality. While there have been advances in evaluating diagnostic algorithms for suspected VTE during pregnancy, there is limited data for postpartum individuals. OBJECTIVE: We conducted a scoping review to describe and evaluate diagnostic strategies used to investigate suspected VTE in postpartum individuals. METHODS: A comprehensive search strategy was conducted in Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (January 1, 2000-September 30, 2022) to identify original articles that reported on diagnostic strategies in postpartum individuals with suspected VTE. We extracted demographics, clinical decision rules used, D-dimer and imaging completed, including test performance and VTE outcomes. RESULTS: A total of 13 studies conducted across 11 countries with separate postpartum data were included for 759 individuals with suspected PE (n = 634) or DVT (n = 125), including unpublished data (n = 251). Among those with suspected PE, computed tomography pulmonary angiography was conducted more commonly (n = 522) than ventilation-perfusion scans (n = 69), with PE positivity rates that ranged from 4 %-27.6 % and 0-50 % across studies, respectively. Among 131 postpartum individuals with suspected PE who had a D-dimer measured, only 4.6 % (6/131) had a negative D-dimer test. For postpartum individuals with suspected DVT, the most common diagnostic test was compression ultrasonography (positivity rate 12.2 %-18.6 %). There were limited retrospective data evaluating the clinical decision rules. CONCLUSIONS: There are heterogeneous approaches globally in the diagnosis of suspected postpartum VTE. Limited high-quality data available underscores the need for more robust evidence to inform clinical practice.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.