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Anterior cruciate ligament reconstruction using quadriceps tendon (QT) autograft has recently gained popularity because newer techniques allow harvest of a robust graft with little soft-tissue dissection or donor-site morbidity. The QT graft can provide a safe, reproducible, and versatile option for primary and revision anterior cruciate ligament reconstruction with equivalent outcomes and failure rates to those of bone–patellar tendon–bone and hamstring tendon grafts. Therefore, continued improvement in surgical technique may help to further improve patient outcomes. This study introduces a modification of current QT techniques using a partial-thickness graft with continuous-loop EndoButton fixation (Smith & Nephew, Andover, MA).

The continuing expansion of seaweed cultivation could assist in ensuring future global food security. The Laminariales species Alaria esculenta and Saccharina latissima are each cultivated for food across their European ranges. The predominant method for cultivating European kelps involves growing juveniles on twine within a hatchery which is then deployed at a farm site. The associated hatchery and deployment cost of this approach are relatively high. A new and innovative methodology—called binder-seeding—can reduce these costs, but, has yet to be validated. We compare the biomass yield and morphology of A. esculenta and S. latissima cultured using either the traditional twine-longline method or binder-seeding onto AlgaeRope and AlgaeRibbon, specially designed textiles. In a controlled growth experiment, A. esculenta had a similar biomass yield on all materials, but fronds were shorter (23 ± 7%) and thinner on the AlgaeRibbon (42 ± 4%) due to a 3–4-fold higher density of developing sporophytes compared to the twine-longline. In contrast, S. latissima gave a 4-fold higher biomass yield on the AlgaeRibbon in June (4.0 kg m−1), but frond morphology was not different between materials, despite a 4-fold higher sporophyte density on the AlgaeRibbon. The stipe length of both species also increased at the higher sporophyte density on the AlgaeRibbon. The AlgaeRope gave an intermediate response or was similar to the twine-longline. These results show that binder-seeding onto the AlgaeRibbon significantly increases the achieved biomass yield in S. latissima. These results can assist cultivators to select the most appropriate method of kelp cultivation depending on morphological/yield requirements of the end use. Further study is needed on the optimisation of the binder-seeding density and its impact on thallus morphology.

Background Few reports are available on the contribution of general and abdominal obesity to the progression of carotid atherosclerosis in late adulthood. This study investigated the impact of four simple anthropometric measures of general and abdominal obesity on the progression of carotid atherosclerosis and the extent to which the association between adiposity and the progression of plaque burden is mediated by cardiometabolic markers. Methods Four thousand three hundred forty-five adults (median age 60) from the population-based Tromsø Study were followed over 7 years from the first carotid ultrasound screening to the next. The progression of carotid atherosclerosis was measured in three ways: incidence of plaques in previously plaque-free participants; change in the number of plaques; and total plaque area (TPA). We used generalised linear models to investigate the association between each adiposity measure – body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) – and each outcome. Models were adjusted for potential confounders (age, sex, smoking, education, physical activity). The pathways through which any associations observed might operate were investigated by further adjusting for cardiometabolic mediators (systolic blood pressure, cholesterol, and HbA1c). Results There was little evidence that adiposity was related to the formation of new plaques during follow-up. However, abdominal adiposity was associated with TPA progression. WHtR showed the largest effect size (mean change in TPA per one standard deviation (SD) increase in WHtR of 0.665 mm2, 95% confidence interval 0.198, 1.133) while BMI showed the smallest. Effect sizes were substantially reduced after the adjustment for potential mediators. Conclusions Abdominal obesity indirectly measured with WC seems more strongly associated with the progression of TPA than general obesity. These associations appear to be largely mediated by known cardiometabolic markers.

Background/Objectives This study examined whether beliefs about medicines, drug attitudes, and depression independently predicted anticoagulant and antiarrhythmic adherence (focusing on the implementation phase of nonadherence) in patients with atrial fibrillation (AF).Methods This cross-sectional study was part of a larger longitudinal study. Patients with AF (N = 118) completed the Patient Health Questionnaire-8. The Beliefs about Medicines Questionnaire, Drug Attitude Inventory, and Morisky-Green-Levine Medication Adherence Scale (self-report adherence measure), related to anticoagulants and antiarrhythmics, were also completed. Correlation and multiple logistic regression analyses were conducted.Results There were no significant differences in nonadherence to anticoagulants or antiarrhythmics. Greater concerns (r = 0.23, P = .01) were significantly, positively associated with anticoagulant nonadherence only. Depression and drug attitudes were not significantly associated with anticoagulant/antiarrhythmic adherence. Predictors reliably distinguished adherers and nonadherers to anticoagulant medication in the regression model, explaining 14% of the variance, but only concern beliefs (odds ratio, 1.20) made a significant independent contribution to prediction (χ2 = 11.40, P = .02, with df = 4). When entered independently into a regression model, concerns (odds ratio, 1.24) significantly explained 10.3% of the variance (χ2 = 7.97, P = .01, with df = 1). Regressions were not significant for antiarrhythmic medication (P = .30).Conclusions Specifying medication type is important when examining nonadherence in chronic conditions. Concerns about anticoagulants, rather than depression, were significantly associated with nonadherence to anticoagulants but not antiarrhythmics. Anticoagulant concerns should be targeted at AF clinics, with an aim to reduce nonadherence and potentially modifiable adverse outcomes such as stroke.

Mathematical Methods in the Applied Sciences published by John Wiley & Sons, Ltd. We consider a one-dimensional aggregation equation for a non-negative density (Formula presented.) associated with a quartic potential (Formula presented.) ((Formula presented.), (Formula presented.)). We show that for the case of symmetric initial data [(Formula presented.)], the solution of the aggregation equation can be expressed in terms of an explicit function of (Formula presented.), (Formula presented.), and (Formula presented.), where the functions (Formula presented.) and (Formula presented.) are determined by an ordinary differential equation initial value problem, the numerical solution of which is relatively straightforward. The function (Formula presented.), which can be interpreted as an upper bound for the radius of the support of (Formula presented.), is finite for all (Formula presented.), even if the support of (Formula presented.) is unbounded, while (Formula presented.) is a potential related to the time integral of the second spatial moment (Formula presented.) of (Formula presented.). We develop various bounds on (Formula presented.) and (Formula presented.) and a number of results concerning convexity and monotonicity that require no knowledge of (Formula presented.) other than its symmetry. We show that many, but not all, of these results persist if the assumption of symmetry is relaxed. Our general results are tested against numerical solutions for two examples of symmetric (Formula presented.). We also exhibit some counterintuitive behaviour of the model, by finding conditions under which (Formula presented.) as (Formula presented.), even if we start with (Formula presented.) and take (Formula presented.), which ensures ultimate collapse to a single Dirac component at the origin.

Global glaciations have varied in size and magnitude since the Early–Middle Pleistocene transition (~773 ka), despite the apparent regular and high-amplitude 100 ka pacing of glacial–interglacial cycles recorded in marine isotope records. The evidence on land indicates that patterns of glaciation varied dramatically between different glacial–interglacial cycles. For example, Marine Isotope Stages (MIS) 8, 10, and 14 are all noticeably absent from many terrestrial glacial records in North America and Europe. However, globally, the patterns are more complicated, with major glaciations recorded in MIS 8 in Asia and in parts of the Southern Hemisphere, such as Patagonia, for example. This spatial variability in glaciation between glacial–interglacial cycles is likely to be driven by ice volume changes in the West Antarctic Ice Sheet and associated interhemispheric connections through ocean–atmosphere circulatory changes. The weak global glacial imprint in some glacial–interglacial cycles is related to the pattern of global ice buildup. This is caused by feedback mechanisms within glacial systems themselves that partly result from long-term orbital changes driven by eccentricity.

Although business model innovation has received increasing attention in recent years, there are gaps in existing literature concerning why innovation occurs. Drawing on the intentions model and knowledge-based view, this study explores the relationship between entrepreneurial alertness and business model innovation, proposing a moderated mediation framework to handle the questions of why some entrepreneurs achieve business model innovation successfully while others do not. Based on a dataset of 150 firms in northwest China, this study finds that (1) entrepreneurial alertness facilitates business model innovation; (2) explorative learning and exploitative learning mediate the relationship between entrepreneurial alertness and business model innovation; and (3) risk perception moderates the mediating effects of different types of learning and then affects the relationship between entrepreneurial alertness and business model innovation. Specifically, with the increase of risk perception, the mediating role through explorative learning is weakened, while the mediating effect through exploitative learning is enhanced.

Purpose The purpose of the paper is to examine processes of entrepreneurial learning and leadership development (ELLD) for women involved in growth-oriented businesses. It considers how ELLD can be supported by building gender-aware ecosystems for growth. Design/methodology/approach Data are from a small-scale study of a growth accelerator program in Canada run by Alberta Women Entrepreneurs. The study uses a mixed-methods approach, drawing on interview, document, and observational data. Findings The study finds that three key activities – formal learning, informal learning and peer / community support – are central to women entrepreneurs’ learning and leadership development. In line with emerging scholarship, entrepreneurial learning is found to be strongly relational, with social capital playing a central role in the formation of human capital. Originality/value This study contributes to the understanding of the micro-foundations of growth, the processes involved in ELLD and the importance of developing gender-aware ecosystems.

Purpose The purpose of in this study is to examine how scholarship on women’s entrepreneurship/gender and entrepreneurship has contributed to understandings of the embeddedness of entrepreneurial activity. The authors review studies from the past four decades (1975-2018) to assess the extent to which research has examined the embeddedness of entrepreneurial activity in two key institutions – the family and the labour market – that remain pervasively and persistently gendered. Design/methodology/approach The authors blend a systematic quantitative analysis of scholarly publications with qualitative analysis, identifying key themes and contributions. The corpus of material comprises over 1,300 scholarly publications, including both empirical and theoretical contributions. Findings This analysis shows that attention to the embeddedness of entrepreneurial activity in gendered social institutions is a clear legacy of women’s entrepreneurship research. The systematic quantitative review found that over one-third (36.6 per cent) of scholarly publications examines questions of family and/or labour market embeddedness in some way. The qualitative analysis identifies a rich array of themes over the past four decades and a growing global reach of scholarship in recent years. Originality/value This paper contributes to knowledge about the embeddedness of entrepreneurial activity. It offers a comprehensive review of how entrepreneurship is shaped by the embedding of such activity in two predominant (and gendered) social institutions – families and labour markets. It will be of use to scholars seeking an overview of this topic and considering new research questions to pursue.

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.

Background Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). Objectives This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. Methods The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life–5 Dimensions–5 Level visual analogue scale at 12 weeks. Results MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). Conclusions Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408)., Central Illustration

Introduction Significant theatre delays were identified in hand trauma lists at our regional adult hand surgery unity. We aimed to improve theatre delays by implementing a golden patient initiative. Method Literature review identified the golden patient initiative, which ensures first patient on the list is identified, communicated to multidisciplinary team, and is optimized for theatre. Multi-stage intervention according to change management models (ADKAR and McKinsey 7s) was used. This included (1) a new protocol, (2) educational intervention, 3) poster and (4) a variety of information dissemination methods. To ensure multidisciplinary staff engagement and reinforce positive change, we used multiple verbal, visual and written prompts: trauma co-ordinator-led daily reminders, senior involvement, new column in handover list, verbal reminders at departmental meetings, posters in key areas and widely-accessible reference booklet. Prospective analysis of theatre utilisation pre- and post-intervention to measure impact of intervention. Results Analysis of emergency general list (EG) and local anaesthetic list (LA) start times identified an average 40 and 20-minute-long delays respectively. Following introduction of golden patient there was a reduction in delays by 9 minutes in LA and 5 minutes in EG. The latest start time improvement by 8 minutes in LA and 50 minutes in EG. There was also a reduction in operation delays by 2.8% in LA and 14.3% in EG. The estimated annual cost saved in EG is approximately £45,200. Conclusions We believe that implementing sustainable change is a complex and challenging process. Implementing the golden patient initiative resulted in a positive impact on hand trauma services.

Despite progress toward gender equality in the labor market over the past few decades, gender segregation in labor force composition and labor market outcomes persists. Evidence has shown that job advertisements may express gender preferences, which may selectively attract potential job candidates to apply for a given post and thus reinforce gendered labor force composition and outcomes. Removing gender-explicit words from job advertisements does not fully solve the problem as certain implicit traits are more closely associated with men, such as ambitiousness, while others are more closely associated with women, such as considerateness. However, it is not always possible to find neutral alternatives for these traits, making it hard to search for candidates with desired characteristics without entailing gender discrimination. Existing algorithms mainly focus on the detection of the presence of gender biases in job advertisements without providing a solution to how the text should be (re)worded. To address this problem, we propose an algorithm that evaluates gender bias in the input text and provides guidance on how the text should be debiased by offering alternative wording that is closely related to the original input. Our proposed method promises broad application in the human resources process, ranging from the development of job advertisements to algorithm-assisted screening of job applications.

Background: While surgeons with high caseload volumes deliver higher value care when performing primary anterior cruciate ligament reconstruction (ACLR), the effect of surgeon volume in the revision setting is unknown. Purposes: To determine the percentage of revision ACLR procedures that comprise the practice of high-, medium-, and low-volume surgeons and to analyze associated referral and practice patterns. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We retrospectively investigated all revision ACLR procedures performed between 2015 and 2020 in a single health care system. Surgeons were categorized as low (≤17), medium (18-34), or high (≥35) volume based on the number of annual ACLR procedures performed. Patient characteristics, activity level, referral source, concomitant injuries, graft type, and treatment variables were recorded, and a comparison among surgeon groups was performed. Results: Of 4555 ACLR procedures performed during the study period, 171 (4%) were revisions. The percentage of revision ACLR procedures was significantly higher for high-volume (5%) and medium-volume (4%) surgeons compared with low-volume surgeons (2%) ( P < .01). Patients undergoing revision ACLR by a high-volume surgeon had a significantly higher baseline activity level ( P = .01). Allografts were used significantly more often by low-volume surgeons (70%) compared with medium-volume (35%) and high-volume (25%) surgeons ( P < .01). Bone–patellar tendon–bone (BPTB) and quadriceps tendon (QT) autografts were used significantly more often by high-volume (32% BPTB, 39% QT) and medium-volume (38% BPTB, 14% QT) surgeons compared with low-volume surgeons (15% BPTB, 10% QT) ( P < .01). High-volume surgeons were more likely to perform revision on patients with cartilage injuries ( P = .01), perform staged revision ACLR ( P = .01), and choose meniscal repair (54% high vs 22% medium and 36% low volume; P = .03), despite similar rates of concomitant meniscal tears, compared with low- and medium-volume surgeons. Conclusion: In this registry study of an integrated health care system, high-volume surgeons were more likely to perform revision ACLR on patients with higher activity and competition levels. Additionally, high-volume surgeons more commonly performed staged revision ACLR, chose meniscus-sparing surgery, and favored the use of autografts compared with low-volume surgeons.

To combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer-reviewed articles within the first year. To address the challenge in tracking the vast amount of new research located in separate repositories, we developedoutbreak.infoResearch Library, a standardized, searchable interface of COVID-19 and SARS-CoV-2 resources. Unifying metadata from sixteen repositories, we assembled a collection of over 350,000 publications, clinical trials, datasets, protocols, and other resources as of October 2022. We used a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public API, and R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.

Background Low‐grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high‐sensitivity CRP (C‐reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross‐sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9‐to‐10‐year follow‐up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within‐subject correlation over 9‐to‐10‐year follow‐up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle‐related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow‐mediated dilation=−1.2 [−1.8, −0.7]% per z‐score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z‐score increase for both cohorts) and metabolic syndrome (RR, ≈1.2–1.3 per z‐score increase for both cohorts) in 9‐to‐10‐year follow‐up. Conclusions Low‐grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10‐year follow‐up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

The grazing lands of the High Atlas are vulnerable to climate change and the decline of traditional management practices. However, prior to the mid-20th century, there is little information to examine historical environmental change and resilience to past climate variability. Here, we present a new pollen, non-pollen palynomorph (NPP) and microcharcoal record from a sub-alpine marsh (pozzine) at Oukaïmeden, located in the Marrakech High Atlas, Morocco. The record reveals a history of grazing impacts with diverse non-arboreal pollen assemblages dominant throughout the record as well as recurrent shifts between wetter and drier conditions. A large suite of radiocarbon dates (n = 22) constrains the deposit to the last ~ 1,000 years although multiple reversed ages preclude development of a robust age-depth model for all intervals. Between relatively dry conditions during the Medieval period and in the 20th century, intervening wet conditions are observed, which we interpret as a locally enhanced snowpack during the Little Ice Age. Hydrological fluctuations evidenced by wetland pollen and NPPs are possibly associated with centennial-scale precipitation variability evidenced in regional speleothem records. The pollen record reveals an herbaceous grassland flora resilient against climatic fluctuations through the last millennium, possibly supported by sustainable collective management practices (agdal), with grazing indicators suggesting a flourishing pastoral economy. However, during the 20th century, floristic changes and increases in charcoal accumulation point to a decline in management practices, diversification of land-use (including afforestation) and intensification of human activity.

Objectives Cefiderocol (CFDC) is a novel siderophore cephalosporin approved in Europe for the treatment of infections caused by aerobic Gram-negative (GN) bacteria in adults with limited treatment options. The aim of the ARTEMIS study was to evaluate the in vitro activity of CFDC and comparators against recent clinical isolates collected across five countries in Europe. Here we report susceptibility data from isolates collected in the UK. Methods From January to December 2020, GN clinical isolates were collected from hospitalized patients from all infection sites (excluding the urinary tract). Duplicate isolates of the same species from a single patient were excluded. As a prespecified target, each laboratory collected 75 isolates, with: 20 Klebsiella spp., 20 other Enterobacterales, 20 Pseudomonas aeruginosa and 15 Acinetobacter baumannii isolates expected to be included. CFDC susceptibility testing was conducted using disc diffusion (with 30 μg discs) on Mueller–Hinton agar and Sensititre™ broth microdilution (BMD) panels [EUMDROXF; centrally tested at International Health Management Associates (IHMA)]. Susceptibility by disc diffusion was reported using zone diameter breakpoints (BPs) of ≥22 mm (or ≥17 mm for A. baumannii isolates, corresponding to MIC values below the pharmacokinetic/pharmacodynamic BPs of ≤2 mg/L). Comparator susceptibility was determined using custom research use only Sensititre™ BMD panels (CMP2SHIH) according to the EUCAST method for BMD. Antimicrobial susceptibility was interpreted according to EUCAST clinical BPs (v.11 2021). Results In total, 517 isolates were collected from nine UK hospitals, of which: 308 (59.6%) were Enterobacterales [including 147 (28.4%) Klebsiella spp.], 148 (28.6%) were P. aeruginosa and 33 (6.4%) were A. baumannii. The most common sites of infection were bloodstream (n = 245; 47.4%), respiratory tract (n = 158; 30.6%) and skin (n = 59; 11.4%). A high percentage of Enterobacterales (90.2%), P. aeruginosa (96.6%) and A. baumannii (96.9%) isolates were susceptible to CFDC by disc diffusion. By central laboratory testing (MIC), 99.0% of Enterobacterales, 99.3% of P. aeruginosa and 93.9% of A. baumannii isolates were susceptible to CFDC. High susceptibility rates (>85%) were also observed for all comparator agents (Table 1). A total of 32/517 (6.2%) isolates were carbapenem resistant, the majority of which (22/32, 68.8%) were susceptible to CFDC by disc diffusion. Conclusions Among clinical GN isolates collected from UK hospitals in 2020, a high percentage (98.6%), including carbapenem-resistant isolates, were susceptible to CFDC by BMD. These data support the use of CFDC in patients with GN infections and limited treatment options. The differences identified between EUCAST disc diffusion and BMD using Sensititre™ panels for CFDC highlight that disc diffusion underestimates Enterobacterales susceptibility to CFDC, which is mainly a result of the area of technical uncertainty (where isolates with MIC of 2 mg/L have a zone diameter of

The challenges observed in health service psychology (HSP) training during COVID-19 revealed systemic and philosophical issues that preexisted the pandemic, but became more visible during the global health crisis. In a position paper written by 23 trainees across different sites and training specializations, the authors use lessons learned from COVID-19 as a touchstone for a call to action in HSP training. Historically, trainee voices have been conspicuously absent from literature about clinical training. We describe longstanding dilemmas in HSP training that were exacerbated by the pandemic and will continue to require resolution after the pandemic has subsided. The authors make recommendations for systems-level changes that would advance equity and sustainability in HSP training. This article advances the conversation about HSP training by including the perspective of trainees as essential stakeholders.

BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted ‘wave transmission model’, the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the ‘Windkessel function’ of the elastic arteries. Recently, a ‘reservoir-excess pressure’ model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related ‘reservoir’ pressure and a wave-related ‘excess’ pressure.MethodsIn this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis.ResultsCompared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP.ConclusionThis is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

BackgroundAs people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown.ObjectivesTo examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort.MethodsParticipants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60–64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60–64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60–64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation.ResultsOne thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y with QTc prolongation [respectively: β −0.30 ms/nmol/L, (95% confidence intervals −0.44, −0.17), p < 0.001; β−28.9 ms/unit (-41.93, −15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β −0.04 ms/nmol/L (−0.08, −0.008), p = 0.019; β −2.44 ms/unit (-4.17, −0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y [β −0.21 ms/nmol/L (−0.39, −0.04), p = 0.017; β −20.14 ms/unit (−36.28, −3.99), p = 0.015], steeper decline in ΔIGF-I [β −0.05 ms/nmol/L/10 years (−0.10, −0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β −2.16 ms/unit/10 years (−4.23, −0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β −5.70 ms/mmol/L (−10.23, −1.18) p = 0.014].ConclusionOver a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted.

Significance: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. Aim: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. Approach: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. Results: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. Conclusions: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.

Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression.A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up).56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mmA simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals.

Objectives:We characterised differences in BP control and use of antihypertensive medications in European (EA), South Asian (SA) and African-Caribbean (AC) people with hypertension and investigated the potential role of type 2 diabetes (T2DM), reduced arterial compliance (Ca), and antihypertensive medication use in any differences.Methods:Analysis was restricted to individuals with hypertension [age range 59–85 years; N = 852 (EA = 328, SA = 356, and AC =168)]. Questionnaires, anthropometry, BP measurements, echocardiography, and fasting blood assays were performed. BP control was classified according to UK guidelines operating at the time of the study. Data were analysed using generalised structural equation models, multivariable regression and treatment effect models.Results:SA and AC people were more likely to receive treatment for high BP and received a greater average number of antihypertensive agents, but despite this a smaller proportion of SA and AC achieved control of BP to target [age and sex adjusted odds ratio (95% confidence interval) = 0.52 (0.38, 0.72) and 0.64 (0.43, 0.96), respectively]. Differences in BP control were partially attenuated by controlling for the higher prevalence of T2DM and reduced Ca in SA and AC. There was little difference in choice of antihypertensive agent by ethnicity and no evidence that differences in efficacy of antihypertensive regimens contributed to ethnic differences in BP control.Conclusions:T2DM and more adverse arterial stiffness are important factors in the poorer BP control in SA and AC people. More effort is required to achieve better control of BP, particularly in UK ethnic minorities.

The language used in job advertisements contains explicit and implicit cues, which signal employers’ preferences for candidates of certain ascribed characteristics, such as gender and ethnicity/race. To capture such biases in language use, existing word inventories have focused predominantly on gender and are based on general perceptions of the ‘masculine’ or ‘feminine’ orientations of specific words and socio-psychological understandings of ‘agentic’ and ‘communal’ traits. Nevertheless, these approaches are limited to gender and they do not consider the specific contexts in which the language is used. To address these limitations, we have developed the first comprehensive word inventory for work and employment diversity, (in)equality, and inclusivity that builds on a number of conceptual and methodological innovations. The BIAS Word Inventory was developed as part of our work in an international, interdisciplinary project – BIAS: Responsible AI for Labour Market Equality – in Canada and the United Kingdom (UK). Conceptually, we rely on a sociological approach that is attuned to various documented causes and correlates of inequalities related to gender, sexuality, ethnicity/race, immigration and family statuses in the labour market context. Methodologically, we rely on ‘expert’ coding of actual job advertisements in Canada and the UK, as well as iterative cycles of inter-rater verification. Our inventory is particularly suited for studying labour market inequalities, as it reflects the language used to describe job postings, and the inventory takes account of cues at various dimensions, including explicit and implicit cues associated with gender, ethnicity, citizenship and immigration statuses, role specifications, equality, equity and inclusivity policies and pledges, work-family policies, and workplace context.

Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation.This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age 27 weeks, hemoglobin 85 g/L, and ferritin 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests.Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group.Iron supplementation is effective even among pregnant women with NIDA.NCT01119612 (May 7, 2010).

There is an increasing body of evidence suggesting that vascular disease could contribute to cognitive decline and overt dementia. Of particular interest is atherosclerosis, as it is not only associated with dementia, but could be a potential mechanism through which cardiovascular disease directly impacts brain health. In this work, we evaluated the differences in functional near infrared spectroscopy (fNIRS)-based measures of brain activation, task performance, and the change in central hemodynamics (mean arterial pressure (MAP) and heart rate (HR)) during a Stroop color-word task in individuals with atherosclerosis, defined as bilateral carotid plaques (n = 33) and healthy age-matched controls (n = 33). In the healthy control group, the left prefrontal cortex (LPFC) was the only region showing evidence of activation when comparing the incongruous with the nominal Stroop test. A smaller extent of brain activation was observed in the Plaque group compared with the healthy controls (1) globally, as measured by oxygenated hemoglobin (p = 0.036) and (2) in the LPFC (p = 0.02) and left sensorimotor cortices (LMC)(p = 0.008) as measured by deoxygenated hemoglobin. There were no significant differences in HR, MAP, or task performance (both in terms of the time required to complete the task and number of errors made) between Plaque and control groups. These results suggest that carotid atherosclerosis is associated with altered functional brain activation patterns despite no evidence of impaired performance of the Stroop task or central hemodynamic changes.

We present spectroscopic measurements for 71 galaxies associated with 62 of the brightest high-redshift submillimeter sources from the Southern fields of the Herschel Astrophysical Terahertz Large Area Survey (H-ATLAS), while targeting 85 sources which resolved into 142. We have obtained robust redshift measurements for all sources using the 12-m Array and an efficient tuning of ALMA to optimise its use as a redshift hunter, with 73 per cent of the sources having a robust redshift identification. Nine of these redshift identifications also rely on observations from the Atacama Compact Array. The spectroscopic redshifts span a range $1.41, Comment: 21 pages, 8 figures

Background and aimsRisk of stroke and dementia is markedly higher in people of South Asian and African Caribbean descent than white Europeans in the UK. This is unexplained by cardiovascular risk factors (CVRF). We hypothesized this might indicate accelerated early vascular aging (EVA) and that EVA might account for stronger associations between cerebral large artery characteristics and markers of small vessel disease.Methods360 participants in a tri-ethnic population-based study (120 per ethnic group) underwent cerebral and vertebral MRI. Length and median diameter of the basilar artery (BA) were derived from Time of Flight images, while white matter hyperintensities (WMH) volumes were obtained from T1 and FLAIR images. Associations between BA characteristics and CVRF were assessed using multivariable linear regression. Partial correlation coefficients between WMH load and BA characteristics were calculated after adjustment for CVRF and other potential confounders.ResultsBA diameter was strongly associated with age in South Asians (+11.3 μm/year 95% CI = [3.05; 19.62];p= 0.008), with unconvincing relationships in African Caribbeans (3.4 μm/year [−5.26, 12.12];p= 0.436) or Europeans (2.6 μm/year [−5.75, 10.87];p= 0.543). BA length was associated with age in South Asians (+0.34 mm/year [0.02; 0.65];p= 0.037) and African Caribbeans (+0.39 mm/year [0.12; 0.65];p= 0.005) but not Europeans (+0.08 mm/year [−0.26; 0.41];p= 0.653). BA diameter (rho = 0.210;p= 0.022) and length (rho = 0.261;p= 0.004) were associated with frontal WMH load in South Asians (persisting after multivariable adjustment for CVRF).ConclusionsCompared with Europeans, the basilar artery undergoes more accelerated EVA in South Asians and in African Caribbeans, albeit to a lesser extent. Such EVA may contribute to the higher burden of CSVD observed in South Asians and excess risk of stroke, vascular cognitive impairment and dementia observed in these ethnic groups.

Despite the widespread use of SARS-CoV-2-specific monoclonal antibody (mAb) therapy for the treatment of acute COVID-19, the impact of this therapy on the development of SARS-CoV-2-specific T cell responses has been unknown, resulting in uncertainty as to whether anti-SARS-CoV-2 mAb administration may result in failure to generate immune memory. Alternatively, it has been suggested that SARS-CoV-2-specific mAb may enhance adaptive immunity to SARS-CoV-2 via a "vaccinal effect." Bamlanivimab (Eli Lilly) is a recombinant human IgG1 that was granted FDA emergency use authorization for the treatment of mild to moderate COVID-19 in those at high risk for progression to severe disease. Here, we compared SARS-CoV-2 specific CD4+ and CD8+ T cell responses of 95 individuals from the ACTIV-2/A5401 clinical trial 28 days after treatment with 700 mg bamlanivimab versus placebo. SARS-CoV-2-specific T cell responses were evaluated using activation induced marker (AIM) assays in conjunction with intracellular cytokine staining (ICS). We demonstrate that most individuals with acute COVID-19 develop SARS-CoV-2-specific T cell responses. Overall, our findings suggest that the quantity and quality of SARS-CoV-2-specific T cell memory was not diminished in individuals who received bamlanivimab for acute COVID-19. Receipt of bamlanivimab during acute COVID-19 neither diminished nor enhanced SARS-CoV-2-specific cellular immunity.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Purpose This study explored the feasibility, impact and parent experiences of ENVISAGE (ENabling VISions And Growing Expectations)-Families, a parent-researcher co-designed and co-led program for parents/caregivers raising children with early-onset neurodisabilities. Methods Parents/caregivers of a child with a neurodisability aged ≤6 years, recruited in Australia and Canada, participated in five weekly online workshops with other parents. Self-report measures were collected at baseline, immediately after, and 3 months post-ENVISAGE-Families; interviews were done following program completion. Quantitative data were analyzed with generalized estimating equations and qualitative data using interpretive description methodology. Results Sixty-five parents (86% mothers) were recruited and 60 (92%) completed the program. Strong evidence was found of effects on family empowerment and parent confidence (all p ≤ 0.05 after the program and maintained at 3-month follow-up). The ENVISAGE-Families program was relevant to parents’ needs for: information, connection, support, wellbeing, and preparing for the future. Participants experienced opportunities to reflect on and/or validate their perspectives of disability and development, and how these perspectives related to themselves, their children and family, and their service providers. Conclusions ENVISAGE was feasible and acceptable for parent/caregivers. The program inspired parents to think, feel and do things differently with their child, family and the people who work with them. Implications for rehabilitation • ENVISAGE (ENabling VISions And Growing Expectations)-Families is a co-designed, validated parent/researcher “early intervention and orientation” program for caregivers raising a child with neurodevelopmental disabilities (NDDs). • ENVISAGE-Families empowered parents’ strengths-based approaches to their child, family, disability, and parenting. • ENVISAGE-Families increased caregivers’ confidence in parenting children with NDD’s and provided them tools to support connection, collaboration, and wellbeing. • Raising children with NDD can have a profound impact on caregivers, who can benefit from strengths-based, future focused supports early in their parenting experience.

Capillary malformation-arteriovenous malformation (CM-AVM) is a blood vascular anomaly caused by inherited loss-of-function mutations in RASA1 or EPHB4 genes, which encode p120 Ras GTPase-activating protein (p120 RasGAP/RASA1) and Ephrin receptor B4 (EPHB4). However, whether RASA1 and EPHB4 function in the same molecular signaling pathway to regulate the blood vasculature is uncertain. Here, we show that induced endothelial cell-specific (EC-specific) disruption of Ephb4 in mice resulted in accumulation of collagen IV in the EC ER, leading to EC apoptotic death and defective developmental, neonatal, and pathological angiogenesis, as reported previously in induced EC-specific RASA1-deficient mice. Moreover, defects in angiogenic responses in EPHB4-deficient mice could be rescued by drugs that inhibit signaling through the Ras pathway and drugs that promote collagen IV export from the ER. However, EPHB4-mutant mice that expressed a form of EPHB4 that is unable to physically engage RASA1 but retains protein tyrosine kinase activity showed normal angiogenic responses. These findings provide strong evidence that RASA1 and EPHB4 function in the same signaling pathway to protect against the development of CM-AVM independent of physical interaction and have important implications for possible means of treatment of this disease.