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The data-generating process underlying productivity includes both trend and business cycle shocks, generating counterfactuals for prices under full information. In practice, agents' inability to immediately distinguish between the two shocks creates "rational confusion": each shock inherits properties of its counterpart. This confusion magnifies the perceived share of permanent shocks and implies that, contrary to canonical frameworks, transitory shocks are the main driver of long-run risk through trendy business cycles. With learning, the equity premium turns positive, while investment and valuation ratios become procyclical, as in the data. Consequently, rational confusion is key for reconciling disciplined macro-dynamics with equilibrium Authors have furnished an Internet Appendix , which is available on the Oxford University Press Web site next to the link to the final published paper online. [ABSTRACT FROM AUTHOR]

Discovering transiting exoplanets with relatively long orbital periods (>10 d) is crucial to facilitate the study of cool exoplanet atmospheres (T eq < 700 K) and to understand exoplanet formation and inward migration further out than typical transiting exoplanets. In order to discover these longer period transiting exoplanets, long-term photometric, and radial velocity campaigns are required. We report the discovery of TOI-2447 b (=NGTS-29 b), a Saturn-mass transiting exoplanet orbiting a bright (T = 10.0) Solar-type star (Teff = 5730 K). TOI-2447 b was identified as a transiting exoplanet candidate from a single transit event of 1.3 per cent depth and 7.29 h duration in TESS Sector 31 and a prior transit event from 2017 in NGTS data. Four further transit events were observed with NGTS photometry which revealed an orbital period of P = 69.34 d. The transit events establish a radius for TOI-2447 b of |$0.865 \pm 0.010\, \rm R_{\rm J}$|⁠ , while radial velocity measurements give a mass of |$0.386 \pm 0.025\, \rm M_{\rm J}$|⁠. The equilibrium temperature of the planet is 414 K, making it much cooler than the majority of TESS planet discoveries. We also detect a transit signal in NGTS data not caused by TOI-2447 b, along with transit timing variations and evidence for a ∼150 d signal in radial velocity measurements. It is likely that the system hosts additional planets, but further photometry and radial velocity campaigns will be needed to determine their parameters with confidence. TOI-2447 b/NGTS-29 b joins a small but growing population of cool giants that will provide crucial insights into giant planet composition and formation mechanisms. [ABSTRACT FROM AUTHOR]

The hibiscus bud weevil (HBW), Anthonomus testaceosquamosus Linell (Coleoptera: Curculionidae), is a significant threat to tropical hibiscus (Hibiscus rosa-sinensis) in Florida, USA, since its invasion in 2017. As a regulated pest in the state, early detection is crucial. Based on the success of pheromone-based monitoring programs for other weevil pests, such as the boll weevil, cranberry weevil, and pepper weevil, this study explores the potential use of these pheromone lures for early detection of HBW. To account for differences in efficacy based on trap color, height, and design, different pheromone lure sizes (4 mm, 10 mm, full-size), trap types (Yellow sticky trap, Japanese beetle trap, Boll weevil trap), and heights (0 m, 1.1 m) were also tested in this study. In laboratory assays, males and females exhibited higher attraction to full-size cranberry weevil lure discs than other lure size-type combinations. In semi-field trials, yellow sticky traps baited with cranberry weevil lures captured more weevils than Japanese beetle or boll weevil traps baited with cranberry weevil lures, while trap height did not influence HBW capture. In semi-field, 4-choice bioassays, yellow sticky traps baited with cranberry weevil lures captured more HBW compared to yellow sticky traps baited with pepper weevil, boll weevil, or unbaited traps. Further research is required to thoroughly evaluate the cranberry weevil lure's efficacy in capturing HBW. Our study suggests the potential for utilizing yellow sticky traps baited with lures for early HBW detection and highlights the importance of selecting the appropriate lure, trap type, and height for optimal efficacy. [ABSTRACT FROM AUTHOR]

With the increased provision of services by health authorities and community organizations allowing supervised inhalation of illicit substances comes concerns about the potential for secondhand exposure to the substances being used, whether in the adjacent community or to workers at the sites. In order to address community concerns surrounding secondhand illicit substance exposure and better protect harm reduction workers, a validated sampling and LC–MS/MS analysis method was developed for 6 illicit drugs: fentanyl, heroin, methamphetamine, cocaine, etizolam, and bromazolam. It was found that the filter used needed to be silanized to be made more inert and avoid loss of analyte due to degradation. Using the silanized filters, recoveries were good (>90%) and the collected samples were found to be stable at room temperature for 2 wk. The sampling volume validated was up to 960 L. The sensitivity and range of the method make it appropriate for short-term (15 min), full shift (8 h), or environmental sampling. [ABSTRACT FROM AUTHOR]

Background Asthma is one of the most frequent reasons children visit a general practitioner (GP). The diagnosis of childhood asthma is challenging, and a variety of diagnostic tests for asthma exist. GPs may refer to clinical practice guidelines when deciding which tests, if any, are appropriate, but the quality of these guidelines is unknown. Objectives To determine (i) the methodological quality and reporting of paediatric guidelines for the diagnosis of childhood asthma in primary care, and (ii) the strength of evidence supporting diagnostic test recommendations. Design Meta-epidemiological study of English-language guidelines from the United Kingdom and other high-income countries with comparable primary care systems including diagnostic testing recommendations for childhood asthma in primary care. The AGREE-II tool was used to assess the quality and reporting of the guidelines. The quality of the evidence was assessed using GRADE. Results Eleven guidelines met the eligibility criteria. The methodology and reporting quality varied across the AGREE II domains (median score 4.5 out of 7, range 2–6). The quality of evidence supporting diagnostic recommendations was generally of very low quality. All guidelines recommended the use of spirometry and reversibility testing for children aged ≥5 years, however, the recommended spirometry thresholds for diagnosis differed across guidelines. There were disagreements in testing recommendations for 3 of the 7 included tests. Conclusions The variable quality of guidelines, lack of good quality evidence, and inconsistent recommendations for diagnostic tests may contribute to poor clinician adherence to guidelines and variation in testing for diagnosing childhood asthma. [ABSTRACT FROM AUTHOR]

Introduction: Health system disruptions, caused by unexpected emergencies such as disease outbreaks, natural disasters, and cybercrimes, impact the delivery of routine preventative care. As comprehensive care providers, family physicians (FPs) devote significant time to prevention. However, without emergency and pandemic plans in place in primary care, FPs face added barriers to prioritizing and sustaining preventative care when health systems are strained, which was evident during the COVID-19 pandemic. This study aims to describe FPs' experiences providing preventative care during the COVID-19 pandemic and their perceptions of the impacts of disrupted preventative care in primary care settings.Methods: Using a qualitative descriptive approach, we conducted semistructured interviews with FPs across 4 provinces in Canada (i.e. Newfoundland and Labrador, Nova Scotia, Ontario, British Columbia) between October 2020 and June 2021 as part of a larger multiple case study. These interviews broadly explored the roles and responsibilities of FPs during the COVID-19 pandemic. Interviews were coded thematically and codes from the larger study were analysed further using an iterative, phased process of thematic analysis.Results: Interviews averaged 58 min in length (range 17-97 min) and FPs had a mean of 16.9 years of experience. We identified 4 major themes from interviews with FPs (n = 68): (i) lack of capacity and coordination across health systems, (ii) patient fear, (iii) impacts on patient care, and (iv) negative impacts on FPs. Physicians voiced concerns with managing patients' prevention needs when testing availability and coordination of services was limited. Early in the pandemic, patients were also missing or postponing their own primary care appointments. Change in the provision and coordination of routine preventative care had negative impacts on both patients and physicians, affecting disease incidence/progression, physician workload, and psychological wellbeing.Conclusion: During the COVID-19 pandemic, upstream care efforts were impacted, and FPs were forced to reduce their provision of preventative care. FPs contribute direct insight to primary care delivery that can support pandemic planning to ensure preventative care is sustained during future emergencies. [ABSTRACT FROM AUTHOR]

Background Cognitive decline may be an early indicator of major health issues in older adults, though research using population-based data is lacking. Researchers objective was to assess the relationships between distinct cognitive trajectories and subsequent health outcomes, including health status, depressive symptoms, and mortality, using a nationally representative cohort. Methods Data were drawn from the National Health and Aging Trends Study. Global cognition was assessed annually between 2011 and 2018. The health status of 4 413 people, depressive symptoms in 4 342 individuals, and deaths among 5 955 living respondents were measured in 2019. Distinct cognitive trajectory groups were identified using an innovative Bayesian group-based trajectory model. Ordinal logistic, Poisson, and logistic regression models were used to examine the associations between cognitive trajectories and subsequent health outcomes. Results Researchers identified five cognitive trajectory groups with distinct baseline values and subsequent changes in cognitive function. Compared with the group with stably high cognitive function, worse cognitive trajectories (ie, lower baseline values and sharper declines) were associated with higher risks of poor health status, depressive symptoms, and mortality, even after adjusting for relevant covariates. Conclusions Among older adults, worse cognitive trajectories are strongly associated with subsequent poor health status, high depressive symptoms, and high mortality risks. Regular screening of cognitive function may help to facilitate early identification and interventions for older adults susceptible to adverse health outcomes. [ABSTRACT FROM AUTHOR]

Background Diagnosis-code-based algorithms to identify fall injuries in Medicare data are useful for ascertaining outcomes in interventional and observational studies. However, these algorithms have not been validated against a fully external reference standard, in ICD-10-CM, or in Medicare Advantage (MA) data. Methods We linked self-reported fall injuries leading to medical attention (FIMA) from the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial (reference standard) to Medicare fee-for-service (FFS) and MA data from 2015–19. We measured the area under the receiver operating characteristic curve (AUC) based on sensitivity and specificity of a diagnosis-code-based algorithm against the reference standard for presence or absence of ≥1 FIMA within a specified window of dates, varying the window size to obtain points on the curve. We stratified results by source (FFS vs MA), trial arm (intervention vs control), and STRIDE's 10 participating health care systems. Results Both reference standard data and Medicare data were available for 4 941 (of 5 451) participants. The reference standard and algorithm identified 2 054 and 2 067 FIMA, respectively. The algorithm had 45% sensitivity (95% confidence interval [CI]: 43%–47%) and 99% specificity (95% CI: 99%–99%) to identify reference standard FIMA within the same calendar month. The AUC was 0.79 (95% CI: 0.78–0.81) and was similar by FFS or MA data source and by trial arm but showed variation among STRIDE health care systems (AUC range by health care system, 0.71 to 0.84). Conclusions An ICD-10-CM algorithm to identify fall injuries demonstrated acceptable performance against an external reference standard, in both MA and FFS data. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC. Methods We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR–Egger, Contamination Mixture). We used multivariable MR for the mediation analyses. Results Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08–1.24, P -value = 1.4 × 10−5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2–13%) of the association], smoking (31%, 4–57%) and PA (7%, 2–11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA. Conclusions The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI–CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation. [ABSTRACT FROM AUTHOR]

The "Food as Medicine" (FAM) movement encourages public health and medical professionals to recognize the importance of dietary patterns and food access. The purpose of this work was to describe patient and physician engagement with a produce prescription (PRx) program to improve access to fresh vegetables in a healthcare setting. A Federally Qualified Health Center, regenerative farm, and academic institution partnered for the PRx program (2017–21). During harvest seasons, patients redeemed "prescriptions" for initial and "refill" produce boxes. Baseline food insecurity surveys were embedded in electronic medical records. Refill surveys assessed satisfaction and confidence. Electronic surveys to prescribing physicians assessed program knowledge, expectations, and motivations. Across 8 biannual harvests generating 9986 produce boxes, 8046 patients received prescriptions, 6227 redeemed prescriptions for ≥1 box, and 720 redeemed for ≥2 boxes. Seasonally, initial redemption rates ranged from 64.5% to 82.7%; refill rates ranged from 6.8% to 16.7%. Among participants, 70.8% sometimes/often worried food would run out and 66.7% sometimes/often ran out of food. Among those with refills, there was high satisfaction with food quality (95.8%) and variety (97.2%), and 94.2% were confident preparing meals from produce. Among physicians (n = 22), 100% self-reported adequate knowledge about PRx for patient recommendations, and 100% believed PRx had benefit for patients. Chronic conditions (77%), low socioeconomic status (64%), and food insecurity (59%) were common motivating factors for prescriptions. We demonstrated the feasibility of implementing a cross-sector, seasonal PRx program within a multisite healthcare system. More research is needed to refine implementation toward greater patient refill rates. [ABSTRACT FROM AUTHOR]

We study the relation between trade credit, asset prices, and production-network linkages. Empirically, firms extending more trade credit earn 7.6 |$\%$| p.a. lower risk premiums and maintain longer relationships with customers. Using a production-based model, we quantitatively explain these novel facts. Trade credit reduces the departure probability of high-quality customers, thereby reducing firms' exposures to systematic costs incurred in finding new customers. The mechanism predicts that the aggregate amount of trade credit proxies for customer-search costs and that suppliers with shorter-duration links to customers command higher expected returns. We confirm these and other novel predictions in the data. [ABSTRACT FROM AUTHOR]

Terrestrial particle accelerators collide charged particles, then watch the trajectory of outgoing debris – but they cannot manipulate dark matter. Fortunately, dark matter is the main component of galaxy clusters, which are continuously pulled together by gravity. We show that galaxy cluster mergers can be exploited as enormous, natural dark matter colliders. We analyse hydrodynamical simulations of a universe containing self-interacting dark matter (SIDM) in which all particles interact via gravity, and dark matter particles can also scatter off each other via a massive mediator. During cluster collisions, SIDM spreads out and lags behind cluster member galaxies. Individual systems can have quirky dynamics that makes them difficult to interpret. Statistically, however, we find that the mean or median of dark matter's spatial offset in many collisions can be robustly modelled, and is independent of our viewing angle and halo mass even in collisions between unequal-mass systems. If the SIDM cross-section were σ/ m  = 0.1 cm2 g−1 = 0.18 barn GeV−1, the 'bulleticity' lag would be ∼5 per cent that of gas due to ram pressure, and could be detected at 95 per cent confidence level in weak lensing observations of ∼100 well-chosen clusters. [ABSTRACT FROM AUTHOR]

Background In vitro–in vivo discordance in β-lactams' activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance is attributed to the supra-physiologic zinc concentration in in vitro testing media. Methods A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam + aztreonam) were documented. The patients' isolates were used to induce septicemia in mice, and survival upon meropenem treatment was recorded. Meropenem minimum inhibitory concentrations (MICs) were determined in standard media and in the presence of physiological zinc concentrations. Results Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration, 4 days) were compared with 29 receiving MBL-active β-lactams. The 14-day mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality (P <.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower vs MICs in zinc-unadjusted broth (≥64 mg/L). Conclusions Our data provide foundational support to establish pharmacokinetic/pharmacodynamic relationships using MICs derived in physiologic zinc concentration, which may better predict β-lactam therapy outcome. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What are the clinical pregnancy and live birth rates in women who underwent up to two more euploid blastocyst transfers after three failures in the absence of another known factor that affects implantation? SUMMARY ANSWER The fourth and fifth euploid blastocyst transfers resulted in similar live birth rates of 40% and 53.3%, respectively, culminating in a cumulative live birth rate of 98.1% (95% CI = 96.5–99.6%) after five euploid blastocyst transfers. WHAT IS KNOWN ALREADY The first three euploid blastocysts have similar implantation and live birth rates and provide a cumulative live birth rate of 92.6%. STUDY DESIGN, SIZE, DURATION An international multi-center retrospective study was conducted at 25 individual clinics. The study period spanned between January 2012 and December 2022. A total of 123 987 patients with a total of 64 572 euploid blastocyst transfers were screened for inclusion. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients with a history of any embryo transfer at another clinic, history of any unscreened embryo transfer at participating clinics, parental karyotype abnormalities, the use of donor oocytes or a gestational carrier, untreated intracavitary uterine pathology (e.g. polyp, leiomyoma), congenital uterine anomalies, adenomyosis, communicating hydrosalpinx, endometrial thickness <6 mm prior to initiating of progesterone, use of testicular sperm due to non-obstructive azoospermia in the male partner, transfer of an embryo with a reported intermediate chromosome copy number (i.e. mosaic), preimplantation genetic testing cycles for monogenic disorders, or structural chromosome rearrangements were excluded. Ovarian stimulation protocols and embryology laboratory procedures including trophectoderm biopsy followed the usual practice of each center. The ploidy status of blastocysts was determined with comprehensive chromosome screening. Endometrial preparation protocols followed the usual practice of participating centers and included programmed cycles, natural or modified natural cycles. MAIN RESULTS AND THE ROLE OF CHANCE A total of 105 (0.085% of the total population) patients met the criteria and underwent at least one additional euploid blastocyst transfer after failing to achieve a positive pregnancy test with three consecutive euploid blastocyst transfers. Outcomes of the fourth and fifth euploid blastocyst transfers were similar across participating centers. Overall, the live birth rate was similar with the fourth and fifth euploid blastocysts (40% vs 53.3%, relative risk = 1.33, 95% CI = 0.93–1.9, P value = 0.14). Sensitivity analyses excluding blastocysts biopsied on Day 7 postfertilization, women with a BMI >30 kg/m2, cycles using non-ejaculate or donor sperm, double-embryo transfer cycles, and cycles in which the day of embryo transfer was modified due to endometrial receptivity assay test result yielded similar results. Where data were available, the fourth euploid blastocyst had similar live birth rate with the first one (relative risk = 0.84, 95% CI = 0.58–1.21, P  = 0.29). The cumulative live birth rate after five euploid blastocyst transfers was 98.1% (95% CI = 96.5–99.6%). LIMITATIONS, REASONS FOR CAUTION Retrospective design has its own inherent limitations. Patients continuing with a further euploid embryo transfer and patients dropping out from treatment after three failed euploid transfers can be systematically different, perhaps with regard to ovarian reserve or economic status. WIDER IMPLICATION OF THE FINDINGS Implantation failure seems to be mainly due to embryonic factors. Given the stable and high live birth rates up to five euploid blastocysts, unexplained recurrent implantation failure should have a prevalence of <2%. Proceeding with another embryo transfer can be the best next step once a known etiology for implantation failure is ruled out. STUDY FUNDING/COMPETING INTEREST(s) None. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The competitive success of ferns has been foundational to hypotheses about terrestrial recolonization following biotic upheaval, from wildfires to the Cretaceous–Paleogene asteroid impact (66 million years ago). Rapid fern recolonization in primary successional environments has been hypothesized to be driven by ferns' high spore production and wind dispersal, with an emphasis on their competitive advantages as so-called disaster taxa. We propose that a competition-based view of ferns is outdated and in need of reexamination in light of growing research documenting the importance of positive interactions (i.e. facilitation) between ferns and other species. Here, we integrate fossil and modern perspectives on fern ecology to propose that ferns act as facilitators of community assemblage following biotic upheaval by stabilizing substrates, enhancing soil properties, and mediating competition. Our reframing of ferns as facilitators has broad implications for both community ecology and ecosystem recovery dynamics, because of ferns' global distribution and habitat diversity. [ABSTRACT FROM AUTHOR]

Background Despite significant support system disruptions during the coronavirus 2019 (COVID-19) pandemic, little is known about the relationship between social support and symptom burden among older adults following COVID-19 hospitalization. Methods From a prospective cohort of 341 community-living persons aged ≥60 years hospitalized with COVID-19 between June 2020 and June 2021 who underwent follow-up at 1, 3, and 6 months after discharge, we identified 311 participants with ≥1 follow-up assessment. Social support prehospitalization was ascertained using a 5-item version of the Medical Outcomes Study Social Support Survey (range, 5–25), with low social support defined as a score ≤15. At hospitalization and each follow-up assessment, 14 physical symptoms were assessed using a modified Edmonton Symptom Assessment System inclusive of COVID-19-relevant symptoms. Mental health symptoms were assessed using Patient Health Questionnaire-4. Longitudinal associations between social support and physical and mental health symptoms, respectively, were evaluated through multivariable regression. Results Participants' mean age was 71.3 years (standard deviation, 8.5), 52.4% were female, and 34.2% were of Black race or Hispanic ethnicity. 11.8% reported low social support. Over the 6-month follow-up period, low social support was independently associated with higher burden of physical symptoms (adjusted rate ratio [aRR], 1.26; 95% confidence interval [CI], 1.05–1.52), but not mental health symptoms (aRR, 1.14; 95% CI, 0.85–1.53). Conclusions Low social support is associated with greater physical, but not mental health, symptom burden among older survivors of COVID-19 hospitalization. Our findings suggest a potential need for social support screening and interventions to improve post-COVID-19 symptom management in this vulnerable group. [ABSTRACT FROM AUTHOR]

The UK Biobank study contains several sources of diagnostic data, including hospital inpatient data and data on self-reported conditions for approximately 500,000 participants and primary-care data for approximately 177,000 participants (35%). Epidemiologic investigations require a primary disease definition, but whether to combine data sources to maximize statistical power or focus on only 1 source to ensure a consistent outcome is not clear. The consistency of disease definitions was investigated for venous thromboembolism (VTE) by evaluating overlap when defining cases from 3 sources: hospital inpatient data, primary-care reports, and self-reported questionnaires. VTE cases showed little overlap between data sources, with only 6% of reported events for persons with primary-care data being identified by all 3 sources (hospital, primary-care, and self-reports), while 71% appeared in only 1 source. Deep vein thrombosis–only events represented 68% of self-reported VTE cases and 36% of hospital-reported VTE cases, while pulmonary embolism–only events represented 20% of self-reported VTE cases and 50% of hospital-reported VTE cases. Additionally, different distributions of sociodemographic characteristics were observed; for example, patients in 46% of hospital-reported VTE cases were female, compared with 58% of self-reported VTE cases. These results illustrate how seemingly neutral decisions taken to improve data quality can affect the representativeness of a data set. [ABSTRACT FROM AUTHOR]

Introduction Fall prevention is a global health priority. Strength and balance exercise programmes are effective at reducing falls. Emerging literature suggests dance is an enjoyable and sociable form of exercise. However, there is little evidence that dance reduces fall incidence. Methods Systematic review and meta-analysis examining effectiveness and cost-effectiveness of dance for falls prevention in older adults. Five databases were searched with no restrictions on publication date or intervention settings. Risk of bias was assessed using variants of Cochrane Risk of bias tools, Mixed-Methods Appraisal and Drummond checklist as appropriate. Certainty of evidence was assessed using GRADE. Results Forty-one studies were included (19 RCTs, 13 quasi-experimental, two mixed-method, seven observational studies, 2,451 participants). Five types of dance interventions were identified: ballroom and Latin dance, dance exercise, cultural dance, dance therapy, and low-impact dance. Meta-analysis was only possible for functional outcome measures: Timed-Up-and-Go (dance versus usual care, mean difference (MD) = 1.36; 95% CI −3.57 to 0.85), Sit-to-Stand (dance versus exercise MD = −0.85; 95% CI −2.64 to 0.93: dance versus education MD = −1.64; 95% CI −4.12 to 0.85), Berg Balance Scale (dance versus usual care MD = 0.61; 95% CI −4.26 to 5.47). There was unexplained variance in effects and no significant differences between intervention and control groups. Overall, certainty of evidence was very low; we are uncertain about the effect of dance interventions in reducing falls. Conclusions There is very low certainty evidence for dance as an alternative to strength and balance training if the aim is to prevent falls. No robust evidence on the cost-effectiveness of dance interventions for the prevention of falls was found. PROSPERO registration CRD42022382908. [ABSTRACT FROM AUTHOR]

Background Patients infected with difficult-to-treat Pseudomonas aeruginosa are likely to receive meropenem (MEM) empirically before escalation to ceftolozane/tazobactam (C/T). We assessed whether pre-exposure to MEM affected C/T resistance development on C/T exposure. Materials and methods Nine clinical P. aeruginosa isolates were exposed to MEM 16 mg/L for 72 h. Then, isolates were serially passaged in the presence of C/T (concentration of 10 mg/L) for 72 h as two groups: an MEM-exposed group inoculated with MEM pre-exposed isolates and a non-MEM control group. At 24 h intervals, samples were plated on drug-free and drug-containing agar (C/T concentration 16/8 mg/L) and incubated to quantify bacterial densities (log10 cfu/mL). Growth on C/T agar indicated resistance development, and resistant population was calculated by dividing the cfu/mL on C/T plates by the cfu/mL on drug-free agar. Results At 72 h, resistant populations were detected in 6/9 isolates. In five isolates, MEM exposure significantly increased the prevalence of ceftolozane/tazobactam-resistance development; the percentages of resistance population were 100%, 100%, 53.5%, 31% and 3% for the MEM-exposed versus 0%, 0%, 2%, 0.35% and ≤0.0003% in the unexposed groups. One isolate had a similar resistant population at 72 h between the two groups. The remaining isolates showed no development of resistance, regardless of previous MEM exposure. Conclusions MEM exposure may pre-dispose to C/T resistance development and thus limit the therapeutic utility of this β-lactam/β-lactamase inhibitor. Resistance may be a result of stress exposure or molecular-level mutations conferring cross-resistance. Further in vivo studies are needed to assess clinical implications of these findings. [ABSTRACT FROM AUTHOR]

Baseline information about declining North American shorebird populations is essential to determine the effects of global warming at low-lying coastal areas of the Arctic and subarctic, where numerous taxa breed, and to assess population recovery throughout their range. We estimated population sizes on the Yukon–Kuskokwim Delta (YKD) in western Alaska on the eastern edge of the Bering Sea. We conducted ground-based surveys during 2015 and 2016 at 589 randomly selected plots from an area of 35,769 km2. We used stratified random sampling in 8 physiographic strata and corrected population estimates using detection ratios derived from double sampling on a subset of plots. We detected 11,110 breeding individuals of 21 taxa. Western Sandpiper (Calidris mauri), Red-necked Phalarope (Phalaropus lobatus), Dunlin (subspecies C. alpina pacifica), and Wilson's Snipe (Gallinago delicata) were the most abundant taxa. We estimated that ~7 million individual shorebirds were breeding on the entire YKD in 2015 and 2016. Our surveys of this region provided robust population estimates (coefficient of variations ≤ 0.35) for 14 species. Our results indicate that the YKD supports a large proportion of North America's breeding populations of the Pacific Golden-Plover (Pluvialis fulva), the western population of a Whimbrel subspecies (Numenius phaeopus hudsonicus), a Bar-tailed Godwit subspecies (Limosa lapponica baueri), Black Turnstone (Arenaria melanocephala), a Dunlin subspecies (C. alpina pacifica), and Western Sandpiper. Our study highlights the importance of breeding shorebirds of this relatively pristine but climatically sensitive deltaic system. Estuaries and deltaic systems worldwide are rapidly being degraded by anthropogenic activities. Our population estimates can be used to refine prior North American population estimates, determine the effects of global warming, and evaluate conservation success by measuring population change over time. [ABSTRACT FROM AUTHOR]

Background The cascade of care, commonly used to assess HIV and hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals' engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people with HIV and HCV. Methods We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers biannually. Markov multistate models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) reengaged (reentry into cohort after being LTFU); (3) withdrawn from the study (ie, moved); (4) death; otherwise remained (5) engaged-in-care. Results A total of 1809 participants met the eligibility criteria and contributed 12 591 person-years from 2003 to 2022. LTFU was common, with 46% experiencing at least 1 episode, of whom only 57% reengaged. One in 5 (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (adjusted hazards ratio [aHR], 1.37; 95% confidence interval [CI], 1.13–1.67), evidence of HCV treatment but no sustained virologic response result (aHR, 1.99; 95% CI, 1.56–2.53), and recent incarceration (aHR, 1.94; 95% CI, 1.58–2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Interpretation Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies. [ABSTRACT FROM AUTHOR]

Aims Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed. Methods and results To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38–0.51, P = 2.6e−28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39–0.76, P = 4.2e−04) but not with bleeding (OR = 1.13, 95% CI = 0.93–1.36, P = 2.2e−01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58–0.64, P = 4.1e−85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69–0.86, P = 4.1e−06) but not with bleeding (OR = 1.01, 95% CI = 0.95–1.08, P = 7.5e−01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses. Conclusion These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk. [ABSTRACT FROM AUTHOR]

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood–brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5–17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of −20 600, 95% confidence interval (CI): −35 868 to −5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (−431 streamlines placebo versus −37 streamlines BMMNC; mean difference of −394, 95% CI: −803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics. [ABSTRACT FROM AUTHOR]

Human populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here, we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 yr ago, which distinctly shares a deep ancestral connection with Native Americans. Second, we provide plausible historical models tracing genetic changes in West Baikal and Yakutia in fine resolution. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history. [ABSTRACT FROM AUTHOR]

We present a study of the detection efficiency for the TESS mission, focusing on the yield of longer period transiting exoplanets (P > 25 d). We created the Transit Investigation and Recoverability Application (TIaRA) pipeline to use real TESS data with injected transits to create sensitivity maps which we combine with occurrence rates derived from Kepler. This allows us to predict longer period exoplanet yields, which will help design follow-up photometric and spectroscopic programs, such as the NGTS (Next Generation Transit Survey) Monotransit Program. For the TESS Years 1 and 3 SPOC (Science Processing Operations Centre) FFI (Full Frame Image) light curves, we find |$2271^{+241}_{-138}$| exoplanets should be detectable around AFGKM dwarf host stars. We find |$215^{+37}_{-23}$| exoplanets should be detected from single-transit events or 'monotransits'. An additional |$113^{+22}_{-13}$| detections should result from 'biennial duotransit' events with one transit in Year 1 and a second in Year 3. We also find that K dwarf stars yield the most detections by TESS per star observed. When comparing our results to the TOI (TESS objects of interest) catalogue, we find our predictions agree within 1σ of the number of discovered systems with periods between 0.78 and 6.25 d and agree to 2σ for periods between 6.25 and 25 d. Beyond periods of 25 d, we predict |$403^{+64}_{-38}$| detections, which is three times as many detections as there are in the TOI catalogue with >3σ confidence. This indicates a significant number of long-period planets yet to be discovered from TESS data as monotransits or biennial duotransits. [ABSTRACT FROM AUTHOR]

Observations of low-mass stars have frequently shown a disagreement between observed stellar radii and radii predicted by theoretical stellar structure models. This 'radius inflation' problem could have an impact on both stellar and exoplanetary science. We present the final results of our observation programme with the CHaracterising ExOPlanet Satellite (CHEOPS) to obtain high-precision light curves of eclipsing binaries with low-mass stellar companions (EBLMs). Combined with the spectroscopic orbits of the solar-type companions, we can derive the masses, radii, and effective temperatures of 23 M-dwarf stars. We use the pycheops data analysis software to analyse their primary and secondary occultations. For all but one target, we also perform analyses with Transiting Exoplanet Survey Satellite (TESS) light curves for comparison. We have assessed the impact of starspot-induced variation on our derived parameters and account for this in our radius and effective temperature uncertainties using simulated light curves. We observe trends in inflation with both metallicity and orbital separation. We also observe a strong trend in the difference between theoretical and observational effective temperatures with metallicity. There is no such trend with orbital separation. These results are not consistent with the idea that the observed inflation in stellar radius combines with lower effective temperature to preserve the luminosity predicted by low-mass stellar models. Our EBLM systems provide high-quality and homogeneous measurements that can be used in further studies of radius inflation. [ABSTRACT FROM AUTHOR]

Mammals (or properly, mammaliaforms) originated in the Late Triassic and the first 50 Myr of their evolution through Late Triassic and Early Jurassic are best documented by rich faunas from numerous localities around Bristol in south-west England and in South Wales. The mode of preservation of the fossils, in sediment washed into karst features such as caves, is unusual but has led to a demand for specialized processing methods to extract the exquisitely preserved tiny teeth and bones from huge volumes of sediment. This rich documentation of the oldest mammals has made them especially important for mammalian palaeobiology on a global scale. The first specimens were found in the 1860s, and collection and study has been sporadic, with especially fruitful times in the 1860s, and then from 1938–1979. Throughout, the field collecting, processing, and interpretation of the fossils has been fraught, with heated debates between leading protagonists during the second half of the past century. Here, we track the substantial contributions made by Charles Moore, Walter Kühne, Rex Parrington, Kenneth Kermack, Pamela Robinson, and others, using published sources, unpublished letters and notebooks, and interviews, to establish some of the facts about the most heated public disputes. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the efficacy of human-simulated regimens (HSRs) of ceftazidime, ceftazidime/avibactam, imipenem, imipenem/relebactam, meropenem and meropenem/vaborbactam in a murine thigh infection model against serine carbapenemase-producing Pseudomonas aeruginosa. Methods Nine P. aeruginosa clinical isolates harbouring GES-5 (n = 1), GES-20 (n = 1), GES-5/20 (n = 1), GES-19, GES-20 (n = 3) and KPC (n = 3) were evaluated. Six mice were administered HSRs of ceftazidime 2 g q8h (2 h infusion), ceftazidime/avibactam 2.5 g q8h (2 h infusion), meropenem 2 g q8h (3 h infusion), imipenem 0.5 g q6h (0.5 h infusion), imipenem/relebactam 1.25 g q6h (0.5 h infusion) and meropenem/vaborbactam 4 g q8h (3 h infusion). Change in bacterial burden relative to baseline and the percent of isolates meeting the 1 log10 kill endpoint were assessed. Results The addition of avibactam to ceftazidime increased the percentage of isolates meeting 1 log10 kill from 33% to 100% of GES- or KPC-harbouring isolates. Imipenem/relebactam HSR produced ≥1 log10 of kill against 83% and 100% of GES- and KPC-harbouring isolates, respectively, while imipenem alone failed to reach 1 log10 kill for any isolates. Vaborbactam resulted in variable restoration of meropenem activity as 1 log10 kill was achieved in only 33% and 66% of GES- and KPC-harbouring isolates, respectively, compared with no isolates for meropenem alone. Conclusions Ceftazidime/avibactam and imipenem/relebactam were active against 100% and 89% of KPC- or GES-harbouring isolates tested in vivo. The activity of meropenem/vaborbactam was variable, suggesting this may be an inferior treatment option in this setting. Further studies to evaluate clinical outcomes in GES- and KPC-producing P. aeruginosa are warranted given their increasing prevalence worldwide. [ABSTRACT FROM AUTHOR]

In early 2021, the term BAME (Black, Asian, and Minority Ethnic) was commonly used by the government, public bodies, and the mass media to describe minority ethnic groups in Britain. However, this usage faced fierce criticism, particularly due to complex tensions surrounding racial and ethnic identity, solidarity, and history. This article critically evaluates these tensions and the meaning behind BAME through 10 interviews with activists working in the field of British race relations. My principle focus amid this debate revisits the foundations of the term BAME, which, I argue, is rooted in the rise and fall of Political Blackness. Additionally, I examine the broader strategic purposes of BAME as well as emphasize the importance of colorism within our discussions of racialization in Britain. Ultimately, this discussion seeks a richer account of our current climate around ethnic identification that considers both the potential and the limits of the term BAME. [ABSTRACT FROM AUTHOR]

Background Coexisting long-term conditions (LTCs) in psoriasis and their potential causal associations with the disease are not well -established. Objectives To determine distinct clusters of LTCs in people with psoriasis and the potential bidirectional causal association between these LTCs and psoriasis. Methods Using latent class analysis, cross-sectional data from people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related comorbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTCs. Two-sample bidirectional Mendelian randomization (MR) analysis assessed the potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10–8). Results Five comorbidity clusters were identified in a population of 10 873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure [genetic correlation (rg) = 0.23, P = 8.8 × 10−8], depression (rg = 0.12, P = 2.7 × 10−5), coronary artery disease (CAD; rg = 0.15, P = 2 × 10−4) and type 2 diabetes (rg = 0.19, P = 3 × 10−3). Genetic liability to CAD was associated with an increased risk of psoriasis [inverse variance weighted (IVW) odds ratio (ORIVW) 1.159, 95% confidence interval (CI) 1.055–1.274; P = 2 × 10−3]. The MR pleiotropy residual sum and outlier (MR-PRESSO; ORMR-PRESSO 1.13, 95% CI 1.042–1.228; P = 6 × 10−3) and the MR-robust adjusted profile score (RAPS) (ORMR-RAPS 1.149, 95% CI 1.062–1.242; P = 5 × 10−4) approaches corroborate the IVW findings. The weighted median (WM) generated similar and consistent effect estimates but was not statistically significant (ORWM 1.076, 95% CI 0.949–1.221; P = 0.25). Evidence for a suggestive increased risk was detected for CAD (ORIVW 1.031, 95% CI 1.003–1.059; P = 0.03) and heart failure (ORIVW 1.019, 95% CI 1.005–1.033; P = 9 × 10−3) in those with a genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance. Conclusions Five distinct clusters of psoriasis comorbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Coexisting LTCs share with psoriasis common genetic and nongenetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted CAD is possibly associated with an increased risk of psoriasis, altering our prior knowledge. [ABSTRACT FROM AUTHOR]

Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5–20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [ P = 0.361, 95% confidence interval (CI) (−0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [ P < 0.001, 95% CI (−4.378, −2.323)] and HRQoL [ P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (−2.847, −0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted. [ABSTRACT FROM AUTHOR]

Discovering transiting exoplanets with long orbital periods allows us to study warm and cool planetary systems with temperatures similar to the planets in our own Solar system. The Transiting Exoplanet Survey Satellite (TESS) mission has photometrically surveyed the entire Southern Ecliptic Hemisphere in Cycle 1 (2018 August–2019 July), Cycle 3 (2020 July–2021 June), and Cycle 5 (2022 September–2023 September). We use the observations from Cycle 1 and Cycle 3 to search for exoplanet systems that show a single transit event in each year, which we call duotransits. The periods of these planet candidates are typically in excess of 20 d, with the lower limit determined by the duration of individual TESS observations. We find 85 duotransit candidates, which span a range of host star brightnesses: 8 <  T mag < 14, transit depths between 0.1 per cent and 1.8 per cent, and transit durations between 2 and 10 h with the upper limit determined by our normalization function. Of these candidates, 25 are already known, and 60 are new. We present these candidates along with the status of photometric and spectroscopic follow-up. [ABSTRACT FROM AUTHOR]

Time-resolved linear polarization (Π) measurements of the prompt gamma-ray burst emission can reveal its dominant radiation mechanism. A widely considered mechanism is synchrotron radiation, for which linear polarization can be used to probe the jet's magnetic-field structure, and in turn its composition. In axisymmetric jet models, the polarization angle (PA) can only change by 90°, as Π temporarily vanishes. However, some time-resolved measurements find a continuously changing PA, which requires the flow to be non-axisymmetric in at least one out of its emissivity, bulk Lorentz factor, or magnetic field. Here, we consider synchrotron emission in non-axisymmetric jets, from an ultrarelativistic thin shell, comprising multiple radially expanding mini-jets (MJs) or emissivity patches within the global jet, that yield a continuously changing PA. We explore a wide variety of possibilities with emission consisting of a single pulse or multiple overlapping pulses, presenting time-resolved and integrated polarization from different magnetic field configurations and jet angular structures. We find that emission from multiple incoherent MJs/patches reduces the net polarization due to partial cancellation in the Stokes plane. When these contain a large-scale ordered field in the plane transverse to the radial direction, Π always starts near maximal and then declines over the single pulse or shows multiple highly polarized peaks due to multiple pulses. Observing |$\Pi \lesssim 40~{{\ \rm per\ cent}}$| (15  per cent) integrated over one (several) pulse(s) will instead favour a shock-produced small-scale field either ordered in the radial direction or tangled in the plane transverse to it. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are multifactorial and include environmental as well as genetic drivers. Although much progress has been made in understanding the nature of genetic underpinnings of autoimmune disease, by comparison much less is understood regarding how environmental factors interact with genetics in the development of autoimmunity and autoimmune disease. In this report, we utilize the (New Zealand black × New Zealand white [NZB × NZW]) F1 mouse model of systemic lupus erythematosus (SLE). Mercury is a xenobiotic that is environmentally ubiquitous and is epidemiologically linked with the development of autoimmunity. Among other attributes of human SLE, (NZB × NZW) F1 mice spontaneously develop autoimmune-mediated kidney disease. It has been previously shown that if (NZB × NZW) F1 mice are exposed to inorganic mercury (Hg2+), the development of autoimmunity, including autoimmune kidney pathology, is accelerated. We now show that in these mice, the development of kidney disease is correlated with a decreased percentage of marginal zone (MZ) B-cells in the spleen. In Hg2+-intoxicated mice, kidney disease is significantly augmented, and matched by a greater decrease in MZ B-cell splenic percentages than found in control mice. In Hg2+- intoxicated mice, the decrease in MZ B-cells appears to be linked to aberrant B-cell receptor signal strength in transitory 2 (T2) B-cells, developmental precursors of MZ B-cells. [ABSTRACT FROM AUTHOR]

Children are consistently not achieving recommended levels of physical activity (PA) despite it being a compulsory requirement of the national curriculum in England. Fruit and vegetable consumption also falls below recommended levels for both adults and children. With school PA increasingly being outsourced, football foundations (linked to professional football clubs) are now prominent providers of children's PA. However, research exploring coach-led interventions in schools is limited with a particular gap in knowledge surrounding the qualitative experiences of children and parents/carers. The current study therefore aimed to explore the experiences of children and parents engaged in a 6-week family football programme. Family football is a free after-school programme engaging parents/carers and their children, to enhance their engagement in PA and healthy nutritional habits. A purposive sample of parents/carers and their children (N  = 36) took part in qualitative focus groups to discuss their experiences of participating in family football. Reflexive thematic analysis revealed two themes: (i) healthy lifestyle facilitators and challenges and (ii) added value of programme participation. Children discussed programme content around nutritional practices and parents/carers discussed examples of where nutritional practices had improved at home, though some parents/carers and children highlighted persistent barriers to health improvement. Both parents/carers and children reflected on how the programme had enabled them to spend dedicated time with one another. The findings emphasize the significance of direct parent/carer involvement in school-based health interventions as well as the value of coach-led interventions in the enhancement of PA enjoyment, nutritional knowledge and connectedness of families within schools. [ABSTRACT FROM AUTHOR]

Objectives To determine the in vitro activity of cefiderocol in a global collection of carbapenem-resistant Pseudomonas aeruginosa including >200 carbapenemase-producing isolates. Methods Isolates (n  = 806) from the ERACE-PA Surveillance Program were assessed. Broth microdilution MICs were determined for cefiderocol (iron-depleted CAMHB) and comparators (CAMHB). Susceptibility was interpreted by CLSI and EUCAST breakpoints and reported as percent of isolates. The MIC distribution of cefiderocol in the entire cohort and by carbapenemase status was assessed. Results In the entire cohort, cefiderocol was the most active agent (CLSI 98% susceptible; EUCAST 95% susceptible; MIC50/90, 0.25/2 mg/L). Amikacin (urinary only breakpoint) was the second most active, with 70% of isolates testing as susceptible. The percentage of isolates susceptible to all other agents was low (<50%) including meropenem/vaborbactam, imipenem/relebactam, piperacillin/tazobactam and levofloxacin. Cefiderocol maintained significant activity against the most commonly encountered carbapenemases including VIM- (CLSI 97% susceptible; EUCAST 92% susceptible) and GES (CLSI 100% susceptible; EUCAST 97% susceptible)-harbouring isolates. The cefiderocol MIC distribution was similar regardless of carbapenemase status, with MIC50/90 values of 0.5/4 mg/L, 0.5/2 mg/L and 0.25/1 mg/L for MBL, serine carbapenemase and molecular carbapenemase-negative isolates, respectively. Conclusions Cefiderocol displayed potent in vitro activity in this global cohort of carbapenem-resistant P. aeruginosa including >200 carbapenemase-harbouring isolates. Cefiderocol was highly active against MBL-producing isolates, where treatment options are limited. These data can help guide empirical therapy guidelines based on local prevalence of carbapenemase-producing P. aeruginosa or in response to rapid molecular diagnostics. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to coproduce a smart-phone application for digital falls reporting in people with Parkinson disease (PD) and to determine usability using an explanatory mixed-methods approach. Methods This study was undertaken in 3 phases. Phase 1 was the development phase, in which people with PD were recruited as co-researchers to the project. The researchers, alongside a project advisory group, coproduced the app over 6 months. Phase 2 was the implementation phase, in which 15 people with PD were invited to test the usability of the app. Phase 3 was the evaluation phase, in which usability was assessed using the systems usability scale by 2 focus groups with 10 people with PD from phase 2. Results A prototype was successfully developed by researchers and the project advisory group. The usability of the app was determined as good (75.8%) by people with PD when rating using the systems usability scale. Two focus groups (n = 5 per group) identified themes of 1) usability, 2) enhancing and understanding management of falls, and 3) recommendations and future developments. Conclusions A successful prototype of the iFall app was developed and deemed easy to use by people with PD. The iFall app has potential use as a self-management tool for people with PD alongside integration into clinical care and research studies. Impact This is the first digital outcome tool to offer reporting of falls and near-miss fall events. The app may benefit people with PD by supporting self-management, aiding clinical decisions in practice, and providing an accurate and reliable outcome measure for future research. Lay Summary A smartphone application designed in collaboration with people who have PD to record their falls was acceptable and easy to use by people with PD. [ABSTRACT FROM AUTHOR]

We study the monopole (⁠|$\bar{B}^0_0$|⁠) and quadrupole (⁠|$\bar{B}^0_2$|⁠) moments of the 21-cm bispectrum (BS) from EoR simulations and present results for squeezed and stretched triangles. Both |$\bar{B}^0_0$| and |$\bar{B}^0_2$| are positive at the early stage of EoR where the mean neutral hydrogen (⁠|${\rm H\, {\small I}}$|⁠) density fraction |$\bar{x}_{\rm {\rm H\, {\small I}}}\approx 0.99$|⁠. The subsequent evolution of |$\bar{B}^0_0$| and |$\bar{B}^0_2$| at large and intermediate scales (k  = 0.29 and |$0.56 \, {\rm Mpc}^{-1}$|⁠ , respectively) is punctuated by two sign changes which mark transitions in the |${\rm H\, {\small I}}$| distribution. The first sign flip where |$\bar{B}^0_0$| becomes negative occurs in the intermediate stages of EoR |$(\bar{x}_{\rm {\rm H\, {\small I}}}\gt 0.5)$|⁠ , at large scale first followed by the intermediate scale. This marks the emergence of distinct ionized bubbles in the neutral background. |$\bar{B}^0_2$| is relatively less affected by this transition, and it mostly remains positive even when |$\bar{B}^0_0$| becomes negative. The second sign flip, which affects both |$\bar{B}^0_0$| and |$\bar{B}^0_2$|⁠ , occurs at the late stage of EoR |$(\bar{x}_{\rm {\rm H\, {\small I}}}\lt 0.5)$|⁠. This marks a transition in the topology of the |${\rm H\, {\small I}}$| distribution, after which we have distinct |${\rm H\, {\small I}}$| islands in an ionized background. This causes |$\bar{B}^0_0$| to become positive. The negative |$\bar{B}^0_2$| is a definite indication that the |${\rm H\, {\small I}}$| islands survive only in underdense regions. [ABSTRACT FROM AUTHOR]

Background It is currently unclear whether (and when) physical function exhibits a terminal decline phase, that is, a substantial acceleration of decline in the very last years before death. Methods 702 deceased adults aged 70 years and older from the Yale PEP Study provided 4 133 measurements of physical function (Short Physical Performance Battery, SPPB) up to 20 years before death. In addition, continuous gait and chair rise subtest scores (in seconds) were assessed. Generalized mixed regression models with random change points were used to estimate the onset and the steepness of terminal decline in physical function. Results Decline accelerated in the last years of life in all 3 measures of physical function. The onset of terminal decline occurred 1 year before death for the SPPB, and at 2.5 and 2.6 years before death for chair rise and gait speed test scores, respectively. Terminal declines in physical function were 6–8 times steeper than pre-terminal declines. Relative to those whose condition leading to death was frailty, participants who died from dementia and cancer had an up to 6 months earlier and 3 months later onset of terminal decline in SPPB, respectively. Conclusions Terminal decline in physical function among older adults is comparable to the more established terminal decline phenomenon in cognition. Our results provide additional evidence of late-life rapid decline in physical function due to impending death. [ABSTRACT FROM AUTHOR]

Health System strengthening is high on the agenda of the global health community. We review some of the specific challenges faced by Small Island Developing States in the development of their health systems. We propose a list of action points for aid actors willing to adapt their health programs and interventions. [ABSTRACT FROM AUTHOR]

Objective Falls are a common cause of potentially preventable death, disability and loss of independence with an annual estimated cost of £4.4bn. People living with dementia (PlwD) or mild cognitive impairment (MCI) have an increased fall risk. This overview evaluates evidence for technologies aiming to reduce falls and fall risk for PlwD or MCI. Methods In October 2022, we searched five databases for evidence syntheses. We used standard methods to rapidly screen, extract data, assess risk of bias and overlap, and synthesise the evidence for each technology type. Results We included seven systematic reviews, incorporating 22 relevant primary studies with 1,412 unique participants. All reviews had critical flaws on AMSTAR-2: constituent primary studies were small, heterogeneous, mostly non-randomised and assessed as low or moderate quality. Technologies assessed were: wearable sensors, environmental sensor-based systems, exergaming, virtual reality systems. We found no evidence relating to apps. Review evidence for the direct impact on falls was available only from environmental sensors, and this was inconclusive. For wearables and virtual reality technologies there was evidence that technologies may differentiate PlwD who fell from those who did not; and for exergaming that balance may be improved. Conclusions The evidence for technology to reduce falls and falls risk for PlwD and MCI is methodologically weak, based on small numbers of participants and often indirect. There is a need for higher-quality RCTs to provide robust evidence for effectiveness of fall prevention technologies. Such technologies should be designed with input from users and consideration of the wider implementation context. [ABSTRACT FROM AUTHOR]

Background Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005–2018 among adult PWH in NA-ACCORD. Methods Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort. Results We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/μL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%–22.3%) in 2005 to 16.3% (95% CI, 14.1%–18.5%) in 2018. Absolute annual trends were −0.34% (95% CI, −.48% to −.19%) in unadjusted and −0.19% (95% CI, −.35% to −.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization. Conclusions Readmissions decreased over 2005–2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH. [ABSTRACT FROM AUTHOR]

Background Mortality remains elevated among Black versus White adults receiving human immunodeficiency virus (HIV) care in the United States. We evaluated the effects of hypothetical clinic-based interventions on this mortality gap. Methods We computed 3-year mortality under observed treatment patterns among >40 000 Black and >30 000 White adults entering HIV care in the United States from 1996 to 2019. We then used inverse probability weights to impose hypothetical interventions, including immediate treatment and guideline-based follow-up. We considered 2 scenarios: "universal" delivery of interventions to all patients and "focused" delivery of interventions to Black patients while White patients continued to follow observed treatment patterns. Results Under observed treatment patterns, 3-year mortality was 8% among White patients and 9% among Black patients, for a difference of 1 percentage point (95% confidence interval [CI],.5–1.4). The difference was reduced to 0.5% under universal immediate treatment (95% CI, −.4% to 1.3%) and to 0.2% under universal immediate treatment combined with guideline-based follow-up (95% CI, −1.0% to 1.4%). Under the focused delivery of both interventions to Black patients, the Black–White difference in 3-year mortality was −1.4% (95% CI, −2.3% to −.4%). Conclusions Clinical interventions, particularly those focused on enhancing the care of Black patients, could have significantly reduced the mortality gap between Black and White patients entering HIV care from 1996 to 2019. [ABSTRACT FROM AUTHOR]

Mendelian randomization (MR) is a widely used method to estimate the causal effect of an exposure on an outcome by using genetic variants as instrumental variables. MR analyses that use variants from only a single genetic region (cis‐MR) encoding the protein target of a drug are able to provide supporting evidence for drug target validation. This paper proposes methods for cis‐MR inference that use many correlated variants to make robust inferences even in situations, where those variants have only weak effects on the exposure. In particular, we exploit the highly structured nature of genetic correlations in single gene regions to reduce the dimension of genetic variants using factor analysis. These genetic factors are then used as instrumental variables to construct tests for the causal effect of interest. Since these factors may often be weakly associated with the exposure, size distortions of standard t‐tests can be severe. Therefore, we consider two approaches based on conditional testing. First, we extend results of commonly‐used identification‐robust tests for the setting where estimated factors are used as instruments. Second, we propose a test which appropriately adjusts for first‐stage screening of genetic factors based on their relevance. Our empirical results provide genetic evidence to validate cholesterol‐lowering drug targets aimed at preventing coronary heart disease. [ABSTRACT FROM AUTHOR]

Background Antimicrobial resistance in Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLIs) avibactam, relebactam and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL)/BLI combinations against serine carbapenemase-producing P. aeruginosa is unknown. Objectives To compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam and meropenem against serine β-lactamase-producing P. aeruginosa. Methods Carbapenem-resistant P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. MICs were determined by broth microdilution to each novel BL/BLI and BL alone. Results GES was the most common carbapenemase identified (n  = 59) followed by KPC (n  = 8). Ceftazidime/avibactam had MIC50/MIC90 values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC50/MIC90 of imipenem/relebactam were 16/>16 mg/L and 13% of all isolates were defined as susceptible. Of the KPC-producing isolates, 38% were susceptible to imipenem/relebactam, compared with 0% to imipenem. The meropenem/vaborbactam MIC50/MIC90 were >16/>16 mg/L, and 6% of isolates were susceptible, which was similar to meropenem alone (MIC50/90, >8/>8 mg/L; 3% susceptible) suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms. Conclusions Among the novel BL/BLIs, ceftazidime/avibactam displayed better in vitro activity and thus is a rational treatment option for serine carbapenemase-harbouring P. aeruginosa. While imipenem/relebactam displayed some activity, particularly against isolates with bla KPC, meropenem/vaborbactam exhibited poor activity, with MICs similar to meropenem alone. [ABSTRACT FROM AUTHOR]

Background: There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. Patients and Methods: A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. Results: In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). Conclusion: Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control. Uncertainty remains regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer. This article reports patterns of disease recurrence and outcomes of reoperative surgery in a cohort of consecutively treated patients. [ABSTRACT FROM AUTHOR]

Background Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (<0.8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. Methods Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (<0.8 m/s). Agreement and prevalence estimates were compared using Cohen's Kappa (CK). Results Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR <20.50 kg, area under curve [AUC] = 0.68) and men (GR <31.05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8–1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK <0.2) between EWGSOP2 and SDOC. Conclusions Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently. [ABSTRACT FROM AUTHOR]