We report that methanol, widely regarded as an inhibitor of clathrate hydrate (CH) formation, can be incorporated into a structure-I CH relevant to interstellar ices, under ultrahigh vacuum (10-10 mbar) and cryogenic (125 K) conditions. In the experiment, layered dimethyl ether (DME)-methanol-water ices were deposited at 10 K and thermally annealed to 125 K. Reflection-absorption infrared spectroscopy (RAIRS) reveals the emergence of a distinct band at 1021 cm-1 that is absent in pure CH3OH and binary CH3OH-H2O ices. Density functional theory (DFT) calculations assign this band to the C-O stretching mode of methanol encapsulated in the 51262 cage of structure-I CH. This clathrate occurs only in sequentially layered ices and requires a clathrate-promoting guest, such as DME. Similar behavior was observed with ethylene oxide, and methanol consistently occupies the 51262 cage independent of the promoter molecule. RAIRS and DFT analyses further indicate that CH3OH···H2O hydrogen-bonded environments are involved in the methanol enclathration. These results identify a specific, morphology-dependent pathway through which methanol, traditionally considered a clathrate inhibitor, can be incorporated into the clathrate cages under nonequilibrium cryogenic conditions, with possible relevance to volatile trapping in thermally processed interstellar and cometary ices.
The photochemical processing of organic ices is a key driver of molecular complexity in planetary atmospheres and surfaces. On Titan, diacetylene (C4H2) has been detected in the atmosphere and is expected to condense at lower altitudes, yet its subsequent solid-phase photochemistry remains poorly understood. This study investigates the vacuum ultraviolet photolysis of C4H2 ices to understand how distinct solid phases influence photoreactivity and product formation under simulated Titan conditions. Thin films of C4H2 ice in amorphous (20 K) and crystalline (20 K and 70 K) phases were irradiated for 48 hours, with chemical evolution monitored via infrared spectroscopy and temperature-programmed desorption mass spectrometry. Photolysis cross-sections were found to be phase and temperature-dependent, with the amorphous ice exhibiting the highest reactivity, while infrared spectroscopy showed evidence of crystalline phase amorphisation only in the ice irradiated at 70 K. The presence of volatile hydrocarbons including C6H2 and C8H6 was detected across all phases, while crystalline ice irradiated at 70 K yielded the most complex suite of products, with ions detected up to m/z 200. Non-volatile refractory residues with saturated and unsaturated spectral signatures remained at 300 K for all ices. The results suggest that VUV photons can drive the formation of larger, more complex organic molecules in C4H2 ices, with the solid-phase structure modulating the reaction pathways and product distribution. This solid-phase chemistry may contribute to the inventory of complex organics on Titan's surface, providing potential targets for future in situ exploration by missions such as Dragonfly.
Boranes are prototypical electron-deficient species central to boron chemistry and chemical vapor deposition. Despite extensive studies of diborane (B2H6), key reactive intermediates-particularly the monobridged and dibridged diboranyl (B2H5) radicals-have remained incompletely characterized because of their high reactivity. Here, we report the experimental identification of the hitherto elusive dibridged diboranyl radical together with its monobridged isomer in low-temperature diborane ices exposed to energetic electron irradiation. The radicals were identified in irradiated diborane and fully deuterated diborane-d 6 ices at 40 K via Fourier transform infrared spectroscopy, revealing the formation of the monobridged radical through B-H bond cleavage, followed by isomerization to the dibridged isomer. Additionally, utilizing vacuum ultraviolet photoionization reflectron time-of-flight mass spectrometry combined with isotopic labeling experiments, complex boranes ranging from B6H10 to B12H26 were detected in the gas phase during temperature-programmed desorption. The formation of these increasingly complex boranes is proposed to proceed through sequential boron-insertion reactions involving BH and BH3 addition coupled with hydrogenation pathways. These findings highlight the critical role of non-equilibrium chemistry in the synthesis of reactive diboranyl radicals and complex boranes in low-temperature ices, providing fundamental insight into boron chemistry under extreme conditions.
Geminal dithiols─organic molecules bearing two thiol groups on the same carbon atom─are versatile synthons in organic and atmospheric chemistry, exhibiting significantly greater stability than their oxygen analogues. Here, we report the first formation of the smallest geminal dithiol, methanedithiol (CH2(SH)2), and its structural isomer, methyl hydrodisulfide (CH3SSH), in low-temperature model interstellar ices composed of methane and hydrogen sulfide via energetic electron irradiation, simulating secondary electrons generated by galactic cosmic rays. Both isomers were identified in the gas phase using isomer-selective vacuum ultraviolet (VUV) photoionization reflectron time-of-flight mass spectrometry (PI-ReToF-MS), guided by quantum chemically computed adiabatic ionization energies, and confirmed through isotopic labeling and ultraviolet photolysis studies. These results not only demonstrate that methanedithiol and methyl hydrodisulfide can form on ice-coated interstellar nanoparticles and represent promising candidates for future astronomical detection, but they also provide fundamental insights into the nonequilibrium synthesis of geminal dithiols in extraterrestrial environments.
Nanoporous ices, also referred to as water oxygen-lattice frameworks (WOFs) due to their structural characteristics, exhibit promising potential for applications in gas storage, purification, and separation owing to their high surface-to-volume ratio. This prospect has attracted significant interest from both experimental and computational researchers. To identify nanoporous ice structures with small pores, we conducted a comprehensive computational search using molecular dynamics simulations at 270 K, employing polymers as structural templates. Notably, by systematically varying the unit-cell angle γ and the spacings between polymers, we observed the spontaneous formation of ∼40 novel WOFs. Furthermore, our analysis revealed that the liquid-to-WOF phase transitions are the first-order phase transitions, with freezing temperatures near ambient conditions under atmospheric pressure. A key finding is that successful WOF formation requires interpolymer spacings between 5.0 and 10.0 Å, which accommodate confined water as a monolayer, bilayer, or trilayer. Overall, this work demonstrates the effectiveness of the host-guest approach in fabricating WOFs and underscores their rich phase behavior. These novel nanoporous ice frameworks hold considerable promise for future technological applications.
Integrative and conjugative elements (ICEs) are widespread autonomous mobile DNA within bacterial chromosomes. ICEs contain the genes necessary for excision from the chromosome, conjugative transfer to a new recipient cell, and chromosomal reintegration. They can also carry accessory genes that, while not essential for transfer, confer adaptive phenotypes to the host, contributing to host survival under stressful or changing conditions. Genome studies have indicated that Pseudomonas aeruginosa clinical isolates carry a wide range of related ICEs with adaptive genes enriched for heavy metal resistance and efflux systems; however, their mobility has remained understudied. Here, we studied the activation and transfer mechanisms of a representative subset of ICEclc-type elements. We found that ICE excision could be induced in P. aeruginosa by ectopic expression of BisDC, the known master regulator of ICEclc activation, pointing to a similar regulatory cascade. A number of elements could be transferred to P. putida, where they conferred increased tolerance to specific heavy metals. We also assessed ICE excision rates in response to different classes of stressors using qPCR-based quantification. Sub-lethal copper exposure significantly increased ICE excision rates in several P. aeruginosa strains, although this response was strongly strain-dependent and absent in isolates with enhanced copper tolerance, highlighting the importance of host background. Despite elevated excision, copper did not stimulate ICE transfer or induce conjugation gene expression, indicating that ICE excision and conjugation can be uncoupled processes. Transcriptomic analyses revealed strain-specific regulatory responses to copper stress, including differential activation of metal-responsive regulators, oxidative stress pathways, and virulence-associated systems.IMPORTANCEIntegrative and conjugative elements (ICEs) play a major role in bacterial adaptation by mediating horizontal gene transfer; however, the environmental cues governing their activation remain poorly understood. Here, we demonstrate that ICEclc-type elements in Pseudomonas aeruginosa are transferable at low frequencies and that their excision rates can be selectively increased by specific stress conditions, notably copper exposure and hypoosmotic stress. Our findings reveal that ICE excision and conjugative transfer can be uncoupled and are strongly influenced by host genetic background, underscoring the complexity of ICE regulation. This work aimed to explore whether clinical conditions or antimicrobial treatment could inadvertently promote ICE-mediated gene transfer, with implications for understanding the evolution of antibiotic resistance and virulence.
Data on preventive care visits and long-term healthcare use patterns among children with prenatal opioid exposure remain limited. From a life course perspective, early impacts on health care engagement may shape patterns of health service use across childhood. To characterise early and long-term healthcare service visits among children with prenatal opioid exposure using linked population-based health administrative databases from Ontario, Canada. We conducted a population-based retrospective cohort study of live-born infants born between April 1, 2007, and March 31, 2018, who were born to mothers aged 15-50 years and who were eligible for provincial health insurance for at least 3 months before conception. Prenatal opioid use identified during routine prenatal care was extracted from clinical and perinatal health records. The primary outcome was the uptake of well-child visits until 24 months of age, an important early life preventive care period. Rates of all-cause inpatient, outpatient, and emergency department visits were examined and compared across the follow-up period and within specific time intervals up to 13 years of age. The final cohort totalled 1,343,653 live births, of whom 13,290 children (0.99%) had documented prenatal exposure to opioids. Prenatal opioid exposure was associated with reduced incidence of well-child visits (adjusted incidence rate ratio: 0.82 (95% CI: 0.81, 0.83)) from birth to 2 years. Exposed children were less likely to receive an enhanced 18-month well-child visit (adjusted risk ratio: 0.89 (95% CI: 0.88, 0.90)). Prenatal exposure was associated with increased rates of emergency department visits, specialist visits, hospitalisations and same-day surgery visits over the follow-up period. Differences in rates of health care visits were most pronounced in early childhood and attenuated for some services at older ages. Prenatal opioid exposure was associated with reduced uptake of preventive health services and greater use of ambulatory care. This finding is consistent with a life course model, in which early gaps in preventive care may influence later-life care use patterns, and highlights the need for effective strategies to promote access to and engagement with preventive care services for opioid-exposed children.
Curative-intent surgical treatment for hepatocellular carcinoma (HCC) varies in complexity and resource requirements, potentially leading to regional disparities in access. We sought to assess the incidence of HCC and geographic variation in access to treatment (liver transplantation or resection) and outcomes across Ontario. We conducted a retrospective, population-based cohort study using ICES administrative data of patients who received a first HCC diagnosis in Ontario between 2004 and 2021. We stratified patients by Local Health Integration Network (LHIN) to evaluate regional differences in treatment and outcomes. Descriptive statistics summarized demographics, treatment patterns, and survival outcomes. We included 18 494 patients with a mean age of 63.4 (standard deviation 5.3) years, of whom 37.2% were female and 10.6% lived in rural areas. The age- and sex-standardized incidence rate of HCC was 16.8 per 100 000 people, with metabolic-associated steatotic liver disease as the leading cause (55.1%). Treatment varied by region, with most surgeries performed in urban areas. Survival differed significantly, with the top 3 LHINs located in central Ontario and the poorest outcomes in remote regions. Geographic differences in surgical treatment and survival observed across Ontario are likely multifactorial and may reflect differences in clinical presentation, patient demographics, and system-level factors influencing care pathways. These differences highlight opportunities to strengthen HCC care delivery and coordination across the province. Les traitements chirurgicaux à visée curative contre le carcinome hépatocellulaire (CHC) se présentent avec des degrés de complexité et des besoins en ressources divers, menant potentiellement à des disparités régionales en matière d'accès. Nous cherchons à évaluer l'incidence du CHC et les variations géographiques de l'accès aux traitements (transplantation ou résection hépatique) et leurs résultats en Ontario. MÉTHODES : Nous avons réalisé une étude de cohorte rétrospective de population fondée sur des données administratives de l'Institut de recherche en services de santé (IRSS) provenant de patients ayant obtenu un premier diagnostic de CHC entre 2004 et 2021, en Ontario. Nous avons regroupé les patients selon leur Réseau local d'intégration des services de santé (RLISS) afin d'évaluer les différences régionales au niveau des traitements et des résultats. Les statistiques descriptives récapitulent les données démographiques, les modalités thérapeutiques et les chances de survie. RÉSULTATS : Nous avons inclus 18 494 malades ayant un âge moyen de 63,4 (écarttype de 5,3) ans, dont 37,2 % étaient de sexe féminin et 10,6 % résidaient en milieu rural. Les taux d'incidence normalisés selon l'âge et le sexe du CHC étaient de 16,8 par 100 000 habitants, avec comme cause principale la stéatose hépatique associée à un dysfonctionnement métabolique (55,1 %). Les avenues thérapeutiques variaient selon les régions, avec la grande majorité des interventions chirurgicales réalisées en zones urbaines. Les taux de survie variaient grandement, les 3 meilleurs RLISS se situant dans le centre de l'Ontario et ceux présentant les moins bons résultats étant situés en régions éloignées. Les différences géographiques en matière de traitements chirurgicaux et de taux de survie observées à travers l'Ontario sont probablement multifactorielles et peuvent être le reflet de différences dans le tableau clinique et les caractéristiques démographiques des patients ainsi que d'autres facteurs systémiques influençant les trajectoires de soins. Ces différences mettent en lumière des occasions de renforcer la prestation des soins contre le CHC, de même que la coordination à l'échelle de la province.
This study investigated the impact of the COVID-19 pandemic on homecare service use among individuals with physical disabilities, stratified by age, sex, and mental health conditions. Monthly utilization of personal support and nursing services was assessed using linked health administrative databases from ICES in Ontario, Canada, over two periods: pre-pandemic (March 2015 to February 2020) and during the pandemic (March 2020 to June 2022). Predictive Autoregressive Integrated Moving Average (ARIMA) models were used to estimate changes in service use. During the pandemic, personal support service use declined significantly across multiple subgroups with some groups experiencing greater impacts. Significant decreases were observed in 78.5% of months for males, 14.3% for females, 78.5% for individuals aged 65 years and younger, 17.9% for those older than 65 years, and 78.5% for individuals with mental health conditions. In contrast, nursing service use increased significantly, with significant increases observed in 85.7% of months for males, 60.7% for females, 60.7% for those aged 65 years and younger, 17.9% for those older than 65 years, 85.7% for individuals with mental health conditions, and 28.6% for those without mental health conditions. The findings highlight substantial variation in the pandemic's impact across subpopulations, with certain groups disproportionately affected. Targeted strategies are needed to mitigate these disparities and ensure equitable access to homecare services. Further research is warranted to explore the long-term implications and the underlying factors contributing to these differences.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections and hospitalizations among infants in Canada. New long-acting monoclonal antibodies (mAbs) and vaccines administered during pregnancy have expanded prevention options, yet the most cost-effective immunization program remains uncertain. We updated a Canadian cost-utility model to evaluate seven seasonal RSV prevention strategies over one year (with a lifetime horizon for mortality impacts), from health system and societal perspectives. Strategies included RSVpreF vaccination in late pregnancy; targeted or universal infant mAb programs using nirsevimab or clesrovimab; and combination programs in which infants could receive protection from either RSVpreF or mAbs. Sequential incremental cost-effectiveness ratios (ICERs) were estimated in 2024 Canadian dollars per quality-adjusted life year (QALY), using a $50,000/QALY threshold. The primary analysis used immunization product list prices. The most cost-effective strategy was a seasonal combination program: RSVpreF vaccination for pregnancies due during the RSV season, with mAb for infants at high risk (<32 weeks' gestation), including catch-up for infants at high risk born before the season. This strategy had an ICER of $35,408/QALY compared to seasonal mAb for infants at moderate risk (320/7 to 366/7 weeks' gestation) or high-risk with catch-up. Expanding mAb to unimmunized non-high-risk infants born in-season increased the ICER to $132,131/QALY. Universal infant protection, with mAb alone or combined with RSVpreF in pregnancy, was not cost-effective across analyses. RSVpreF alone was dominated. Results were most sensitive to product prices, target populations, age at administration, and RSV burden. A seasonal combination program with RSVpreF for in-season deliveries and mAb for infants at high risk of RSV offers the best value for money for protecting Canadian infants from RSV disease. Broader infant immunization programs may be cost-effective with substantial price reductions or in regions with higher disease burden and healthcare costs.
This research protocol outlines a systematic approach to updating the Consolidated Standards of Reporting Trials (CONSORT) extension for Pragmatic trials, originally published in 2008. Pragmatic trials, whose intention is to provide evidence for real-world decision makers choosing between alternative interventions, differ in design from explanatory trials, whose intention is to test hypotheses on mechanism of action often under tightly controlled conditions, which are often contrived in comparison with usual care conditions for that condition and intervention. As the understanding of trials with explanatory and pragmatic intentions has evolved, there is a need to revise the reporting guidelines to better align with current best practices and emerging challenges. This protocol is an update to the previous CONSORT statement extension for pragmatic trials and involves five key steps; conducting a scoping review to identify relevant literature, engaging an international panel including trialists, trial methodologists, clinicians and policy decision-makers, biostatisticians, regulatory representatives, research funders, journal editors, and patient partners in a Delphi process to achieve consensus on necessary updates, to finalize the revised guidelines, develop and pilot test the product. The updated CONSORT extension for randomized trials (RCTs) with declared pragmatic or explanatory intention designed using the PRECIS tool (CONSORT-PRECIS) will emphasize the clear reporting of trial intention, design choices, settings, delivery, and outcomes and analysis, to enhance the understanding and applicability of findings to clinical practice and decision-making or, alternatively to testing mechanistic hypotheses. By improving the transparency and completeness of reporting for both pragmatic and explanatory trials, this updated CONSORT extension aims to support informed healthcare decisions, promote trust in trial results, and advance scientific knowledge.
Although intermediate clinical endpoints (ICEs) may expedite completion of randomized controlled trials (RCTs) evaluating perioperative systemic treatments for localized muscle-invasive bladder cancer (MIBC), no validated surrogate for overall survival (OS) has been established. We aimed to assess the surrogacy of pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS) for OS. We analyzed 4,828 patients with MIBC (cT2-T4N0M0) who underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) across 29 European centers (2001-2024). The inverse probability of treatment weighting (IPTW) approach was used to adjust for confounding between NAC and RC-only groups. Surrogacy was evaluated using: (1) adapted Prentice criteria to test whether each ICE remained a significant predictor of OS while the treatment effect disappeared in IPTW-adjusted multivariable Cox models; (2) the proportion of treatment effect explained (PTE); and (3) an emulated 2-stage meta-analytic framework to estimate the pseudo-trial-level R2 between treatment effects on each ICE and OS across 1,000 replicates of 5 random clusters. The surrogate threshold effect (STE) was calculated for ICEs demonstrating strong surrogacy (R2≥0.7). Overall, 1,288 (26.7%) patients received NAC followed by RC and 3,540 (73.3%) underwent RC alone. In IPTW-adjusted Cox regression analyses including NAC and each ICE separately, pCR (hazard ratio [HR], 0.32; 95% CI, 0.24-0.41; P<.001), pOR (HR, 0.26; 95% CI, 0.21-0.31; P<.001), and DFS (HR, 5.17; 95% CI, 4.56-5.86; P<.001) were independent predictors of OS. The PTE was 0.42 (95% CI, 0.22-0.54), 0.48 (95% CI, 0.24-0.58), and 0.84 (95% CI, 0.66-0.96) for pCR, pOR, and DFS, respectively. At the pseudo-trial level, the R2 was 0.22 (95% CI, 0.20-0.25), 0.33 (95% CI, 0.31-0.36), and 0.83 (95% CI, 0.81-0.84) for the correlation between treatment effects on pCR, pOR, and DFS and OS, respectively. The STE was 0.82 (95% CI, 0.81-0.84) for DFS. We observed uncertainty regarding the surrogacy of pCR and pOR in patients undergoing RC with or without NAC for localized MIBC. Only DFS consistently mediated the treatment effect on OS, supporting its use as a surrogate for RCT dimensioning when a recurrence or death risk reduction of ≥18% is expected.
Long-term benzodiazepine use has been associated with increased risk of morbidity and mortality. Preventing long-term use through safer prescribing practices has received little attention to date. We sought to better understand associations between initial prescription characteristics and duration of benzodiazepine use. This was a retrospective population-based cohort study of 1,820,808 adults in Ontario with incident benzodiazepine prescriptions between January 1, 2013 and December 31, 2020, with follow-up to December 31, 2021. The primary exposure was duration of the index prescription (≤7 days-referent group, 8-14 days, 15-30 days, or >30 days). Secondary exposures were: (a) duration of action of index benzodiazepine(s) prescription (short-acting, long-acting or both); (b) number of benzodiazepine dispensed on index (1 or 2+); and (c) mean daily dose of the index prescription in Diazepam Milligram Equivalents (DMEs). The primary outcome was time to benzodiazepine discontinuation in days. Multivariable models were adjusted for age, sex, anxiety, insomnia, and substance use disorders as well as other important comorbidities and socio-demographic characteristics. The median age at index was 53 years (Interquartile Range (IQR) 38-67), and 62.6% were women. The median time to discontinuation in women was 16 days (IQR: 6-29) while the median time to discontinuation in men was 19 days (IQR: 6-29). Lorazepam was the most commonly prescribed benzodiazepine on index (63.9%), followed by clonazepam (17.3%) and diazepam (5.8%). In multivariable Cox Proportional Hazards Models, longer index prescriptions were associated with a lower likelihood of benzodiazepine discontinuation (adjusted Hazard Ratio (aHR) 0.54 (95% Confidence Interval (CI) [0.54,0.54]) for 8-14 days; aHR 0.26 (95% CI [0.25,0.26] for 15-30 days and aHR 0.14 (95% CI [0.14,0.14]) for >30 days, compared to ≤7 days, respectively). Being prescribed two or more benzodiazepines versus 1 was also associated with a reduced likelihood of discontinuation (aHR 0.59 (95% CI [0.57,0.61])), as was being prescribed long-acting benzodiazepines (aHR 0.80 (95% CI [0.80,0.80])) or a combination of short and long acting benzodiazepine (aHR 0.84 (95% CI [0.80,0.88])) versus short-acting benzodiazepines alone. Mean daily doses of >5 to ≤10 DME and >10 to ≤20 DME were associated with an increased likelihood of discontinuation (aHR 1.03 (95% CI [1.03,1.03]); aHR: 1.03 (95% CI [1.03,1.04])), whereas doses >20 DME were associated with a reduced likelihood of discontinuation (aHR 0.98 (95% CI [0.97,0.98])) compared with ≤5 DME. Findings may be subject to bias from unmeasured confounding. This large population-based cohort study found that prescribing shorter courses of benzodiazepines, use of a single benzodiazepine, use of a short-acting agent, were associated with reduced likelihood of long-term benzodiazepine use. Findings suggest that simple changes to prescribing practices could reduce prolonged benzodiazepine use and the morbidity and mortality associated with long-term use of these medications.
Older adults with low back pain (LBP) experience challenges when seeking rehabilitation; a comprehensive view of structural factors to access is needed to inform rehabilitation delivery. We aimed to systematically map the experiences regarding structural barriers and facilitators to accessing rehabilitation among adults aged 50 years and older with LBP; and explore whether experiences vary by social factors. We conducted a scoping review based on Joanna Briggs Institute methodology. Eligible studies were qualitative and mixed-method studies (qualitative component) on structural barriers or facilitators to rehabilitation access among adults ≥ 50 years with LBP. Structural factors included socioeconomic and political contexts, governance, policies, and cultural/societal values. We searched databases from inception to February 2025. Paired reviewers independently screened citations and extracted data. We conducted a descriptive synthesis to map the structural barriers/facilitators and identify knowledge gaps. An Advisory Committee including people with lived experience, family members, and healthcare practitioners provided critical input across stages. Of the 8550 citations screened, 16 studies were relevant (3 from middle-income countries, 12 from high-income countries, 1 covering both; 12 studies on LBP, 4 studies on lumbar spinal stenosis). Common domains of structural barriers/facilitators to access were mapped for LBP and lumbar spinal stenosis in middle- or high-income countries: (1) finances (e.g., costs, insurance coverage, financial support from family); (2) location, transportation, inaccessibility or service unavailability (e.g., inadequate public transportation, wait-times, close proximity to services and resources); (3) lack of knowledge, perceptions, or stigma with certain rehabilitation approaches (e.g., limited education of treatment options provided to patients). Some older adults described ageism from providers (e.g., advised to accept back pain as part of aging) or stigma with certain rehabilitation approaches (e.g., mobility aids) as barriers. Studies in high-income countries also explored healthcare-related factors (e.g., referrals, collaboration across providers) as structural barriers/facilitators to access. Findings varied by rurality, socioeconomic strata, and disabilities. In middle- and high-income countries, older adults with LBP or lumbar spinal stenosis experience many structural barriers to rehabilitation access that vary across social factors. Structural factors relate to finances, location/transportation, availability of services, healthcare provider-related factors, ageism, and stigma. Findings inform future work towards strategies for equitable rehabilitation delivery in middle- and high-income countries. Research is needed in low-income countries.
Understanding which habitats function as nurseries is essential for assessing population connectivity and managing exploited marine fishes. Early life stages often concentrate in estuarine and coastal environments, yet high larval abundance does not necessarily translate into recruitment to adult stocks. Here, we compared otolith chemistry and field-based abundance data to evaluate the nursery role of major estuarine systems (Guadiana, Odiel-Tinto, Guadalquivir, Cadiz Bay) and adjacent coastal areas for European anchovy (Engraulis encrasicolus) in the Gulf of Cadiz during 2016-2018. Using LA-ICPMS, we obtained elemental fingerprints from postlarvae as young as ∼20 days old, representing the first application of this technique at such an early developmental stage for this species. Despite some interannual variability, otolith elemental signatures differed consistently among locations, allowing accurate classification (80.1%) using Random Forest models. Zn, Ba, Cu, P and Pb were the most important predictors and showed positive relationships with ambient water concentrations. Adult anchovies sampled offshore in 2018 were assigned to their most probable nursery origins, revealing that ∼20% of the adult stock had used estuarine habitats, mainly the Guadiana estuary and Cadiz Bay. Importantly, the estuarine contribution did not correlate with postlarval density, particularly in the Guadalquivir estuary, highlighting the role of hydrodynamic processes in decoupling abundance from recruitment success. The heavily mining-impacted Odiel-Tinto system showed elevated metal concentrations in water and otoliths, negligible contribution to the adult stock, and evidence that Ba-based salinity marker can be confounded by contamination. Overall, this approach improves understanding of anchovy dynamics in ICES Division 9a-South.
Postoperative hypoalbuminemia is a common, persistent, and ominous abnormality following major surgery and has uncertain etiology. The purpose of this study was to investigate the incidence of protein-losing enteropathy as measured by alpha-1-antitrypsin clearance after major surgery. We conducted a prospective cohort study of consecutive patients undergoing cardiac surgery at one hospital (n = 38, mean age = 65 years, male = 79%). Alpha-1-antitrypsin was measured in both blood and stool samples using standard techniques for diagnosing protein-losing enteropathy. Sensitivity, specificity, and predictive indices were calculated taking into account the measured serum albumin concentration. Postoperative hypoalbuminemia was a common finding and occurred in 82% of patients (95% confidence interval: 66 to 91). Paired analyses of blood and stool for alpha-1-antitrypsin clearance showed protein-losing enteropathy in 39% of patients (95% confidence interval: 26 to 55). Stool alpha-1-antitrypsin clearance for detecting postoperative hypoalbuminemia had a sensitivity of 48% (95% confidence interval: 30 to 67) and a specificity of 100% (95% confidence interval: 59 to 100). The positive predictive value was about 100% (95% confidence interval: 59 to 100). We suggest protein-losing enteropathy may partially explain some cases of postoperative hypoalbuminemia after cardiac surgery.
Antimicrobial resistance (AMR) in aquatic ecosystems is an escalating One Health concern. However, viable antibiotic-resistant bacteria (ARB)-particularly pathogenic strains-and their mobility remain poorly characterized at hydrological interfaces such as river confluences. Here, we integrated culture enrichment, high-throughput 16S rRNA gene sequencing, isolate phenotyping and whole-genome analysis to profile ARB and antibiotic-resistant bacterial pathogens (ARBPs) in sediments from the Fenhe River-Yellow River confluence. Non-selective enrichment reduced community complexity yet uniquely recovered dozens of rare taxa absent from direct sequencing. Antibiotic enrichment induced pronounced, drug-specific ARB shifts; antibiotic type explained more variance (19.3%) than hydrological region (11.2%). Pathogen signals were strongly amplified by enrichment, and ARBP communities retained significant regional clustering. Notably, the confluence hydrodynamic region (CHR) consistently exhibited the highest ARBP richness. Of the 121 recovered isolates, 94.2% were phenotypically resistant and 73.5% were multidrug-resistant; 89.3% matched in situ ASVs, bridging community profiles and cultivable strains. We recovered seven high-risk multidrug-resistant pathogens (belonging to Pseudomonas, Acinetobacter, Aeromonas) as viable isolates, even though they were rare or undetected by direct sequencing. Whole-genome sequencing revealed 658 virulence factors and 312 antibiotic-resistance genes (ARGs). Clinically relevant determinants (e.g., AAC(6')-Iaa, OXA-917, OprN) were embedded within mobile genetic elements, including transposons, plasmid-like contigs, and integrative and conjugative elements (ICEs). The edeine acetyltransferase gene edeQ showed 100% nucleotide identity to alleles from clinical sources, indicating overlap between environmental and clinical resistomes. Collectively, our findings highlight river confluences as priority surveillance nodes and demonstrate that culture-enriched sequencing more effectively quantifies viable AMR hazards than sequencing alone.
Canadian healthcare systems face mounting pressures from rising chronic disease prevalence, persistent specialist shortages and escalating healthcare expenditures. Rheumatology exemplifies these challenges, with growing patient demand and a persistently limited rheumatologist workforce caring for patients requiring intensive ongoing specialist care. Population-level data on rheumatology patients demonstrate increasing rheumatic disease prevalence, emergency department utilization, disability and medication expenditures, underscoring the unsustainability of physician-centric care models. Across Canada, there is a broad policy consensus that team-based care is essential to improving access, reducing system pressures and enhancing outcomes for patients with chronic disease. However, team-based models have not been systematically extended to specialty care across jurisdictions. Team-based models of rheumatology care that integrate allied health practitioners in rheumatology practices are essential to improving access, enhancing care quality and optimizing workforce capacity. Leveraging existing interprofessional team funding mechanisms to rheumatology settings represents a pragmatic, evidence-informed policy pathway to modernize specialist care delivery and improve the sustainability of the healthcare system.
Older adults experiencing social marginalization may face inequitable access to publicly funded home care services. In Ontario, Canada, the Ontario Marginalization Index (ON-Marg) provides a multidimensional measure of area-level marginalization. This study examined whether ON-Marg dimensions were associated with access to publicly funded home care among community-dwelling adults aged 75 years and older. We conducted a population-based retrospective cohort study using linked administrative health data from Ontario, Canada, for the year 2019. The cohort included individuals aged 75 + residing in the community (excluding those in long-term care). Home care access was stratified by ON-Marg dimensions: residential instability, material deprivation, dependency, and ethnic concentration. The primary outcomes were receipt of long-stay (≥ 90 days) and short-stay (< 90 days) home care aggregated at the community level (Aggregated Dissemination Areas -ADAs). Multivariable regression models adjusted for age, sex, hospitalization, and health complexity. Among 1,071,899 older adults, 14% received long-stay home care and 9% received short-stay home care. Communities in the highest deprivation and ethnic concentration quintiles had a 1.60 and 2.77 percentage point greater probability, respectively, of receiving long-stay care compared to the least marginalized areas. In contrast, the most dependent communities had a 0.68 percentage point lower probability of long-stay access. For short-stay care, the highest instability quintile was associated with a 0.90 percentage point greater probability of access, while the highest ethnic concentration quintile was associated with a 2.26 percentage point lower probability. Regional analyses revealed considerable variation in these patterns across Ontario. Access to home care in Ontario varies by dimension of marginalization. While some marginalized groups may have greater access-likely reflecting higher underlying need-populations with high dependency may face persistent barriers. Equity-focused reforms should consider how specific forms of marginalization affect not only need but also access and service delivery.
Ionic conductive elastomers (ICEs), as vital components for flexible electronics and human-machine interfaces, face a persistent challenge in reconciling mechanical robustness with ionic conductivity and self-healing capacity. Herein, a high-performance ICE was developed by constructing a coordination-driven supramolecular network utilizing epoxidized natural rubber (ENR) and chitosan hydrochloride (CSCl). In this integrated architecture, LiO coordination bonds and interfacial hydrogen bonds serve as dynamic molecular bridges, coupling the rigid CSCl moieties with the flexible ENR matrix. The rigid CSCl segments function as multifunctional supramolecular junctions, which not only provide robust mechanical reinforcement but also utilize their dense polar groups to trigger the accelerated dissociation of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), thereby elevating the local charge carrier concentration. Complementarily, the flexible ENR matrix, characterized by superior segmental mobility and a loosely coordinated environment, establishes rapid transport pathways for the liberated Li+ while imparting exceptional self-healing capabilities to the system. Benefiting from the synergy of this supramolecular integration, the resulting ICE simultaneously achieves a tensile strength of 9.2 MPa, a toughness of 22 MJ/m3, a conductivity of 3.8 × 10-2 S/m, and a self-healing efficiency of 93%. These properties enable sensitive motion and respiration sensing, demonstrating significant potential for advanced wearable electronics.