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In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. Thus, small resting B cells can function as APC to a variety of T cells. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. Thus, the failure of some other laboratories to observe this phenomenon may be the result of the relative radiosensitivity of the antigen-presenting function of the B cells. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s).

The frequency of murine B lymphocytes that respond to antibodies directed against membrane IgM was measured. These anti-mu antibodies induced all, or almost all, resting B cells to enlarge over the first 24 h of stimulation. This probably represents the transition from the resting state (G0) to active transit through the cell cycle. In contrast, only a fraction of these cells, approximately 60% for BDF1 mice, continued through the cell cycle into S phase. This is consistent with previous experiments that had suggested there were some types of B cells that did not proliferate in response to anti-mu. The results presented here demonstrate that many, perhaps all, of these nonresponding B cells, both from normal mice and from mice with the xid defect, actually do respond to the presence of anti-mu by going through early parts of the cell cycle. These cells appear to become blocked at some point before the beginning of S phase, perhaps requiring a signal from a T cell or a macrophage to continue through the cell cycle. Thus, the role of antigen may be to prepare all B cells for proliferation. Different subpopulations of B cells may then require different regulatory signals before actually proliferating or before differentiating into antibody-secreting cells.

Resting B lymphocytes are activated, proliferate, and differentiate into antibody-secreting cells when cultured with long-term lines of major histocompatibility complex (MHC)-restricted, antigen-specific T cell in the presence of the antigen for which the T cells are specific. Under optimal conditions, essentially all B cells are activated and approximately 35% enter S phase in the absence of antigens for which the B cells are specific. Activation and proliferation are observed in cells from both normal mice and mice with the xid-determined immune defect. Highly purified B cells bearing Ia molecules for which the T cells are "cospecific" can present antigen to T cells with the resulting T cell stimulation leading to the activation and proliferation of the antigen-presenting B cells. However, B cells that do not bear Ia molecules for which the T cells are cospecific are also activated and proliferate if antigen and a source of antigen-presenting B cells or macrophage-rich cells of proper histocompatibility type are present. Thus, resting B cells, both normal and "xid", can be activated by non-MHC restricted factors without receptor cross-linkage. Experiments are presented that support the concept that local production and action of such unrestricted activating factors may be responsible for the MHC-restriction of T cell-B cell interaction seen in many circumstances.

Surgery of the aortic arch remains a complex procedure, with neurological events such as stroke remaining its most dreaded complications. Changes in surgical technique and the continuous innovation in neuroprotective strategies have led to a significant decrease in cerebral and spinal events. Different modes of cerebral perfusion, varying grades of hypothermia, and a number of pharmacological strategies all aim to reduce hypoxic and ischemic cerebral injury, yet there is no evidence indicating the clear superiority of one method over another. While surgical results continue to improve, novel hybrid and interventional techniques are just entering the stage and the question of optimal neuroprotection remains up to date. Within this perspective statement, we want to shed light on the current evidence and controversies of cerebral protection in aortic arch surgery, as well as what is on the horizon in this fast-evolving field. We further present our institutional approach as a large tertiary aortic reference center.

Abstract In this paper, we present the results of lab and pilot-scale testing of a continuously enhanced backscattering, or Rayleigh enhanced fiber cable that can improve distributed acoustic sensing performance. In addition, the Rayleigh-enhanced fiber is embedded within a tight buffered cable configuration to withstand and be compatible for field applications. The sensing fiber cable exhibits a Rayleigh enhancement of 13 dB compared to standard silica single-mode fiber while maintaining low attenuation of ≤ 0.4 dB/km. We built a phase-sensitive optical time domain reflectometry system to interrogate the enhanced backscattering fiber cable both in lab and pilot-scale tests. In the laboratory experiment, we analyzed the vibration performance of the enhanced backscattering fiber cable and compared it with the standard single-mode telecom fiber. Afterward, we field validated for natural gas pipeline vibration monitoring using a 4-inch diameter steel pipeline operating at a fixed pressure level of 1000 psi, and a flow rate of 5, 10, 15, and 20 ft/s. The feasibility of gas pipeline monitoring with the proposed enhanced backscattering fiber cable shows a substantial increase in vibration sensing performance. The pilot-scale testing results demonstrated in this paper enable pipeline operators to perform accurate flow monitoring, leak detection, third-party intrusion detection, and continuous pipeline ground movement.

Abstract Introduction Mental health problems are a considerable public health issue and spending time in nature has been promoted as a way to access a range of psychological benefits leading to the development of nature‐based interventions for people with severe and enduring mental health problems. Less, however, is understood about the potential benefits and efficacy of day‐to‐day routine access to outdoor green and blue spaces for mental health service users. Methods Using a mixed‐methods design between April and October 2021, we explored the benefits and barriers to spending time outdoors with a purposive sample of mental health service users (N = 11) using qualitative interviews and an online general population survey (N = 1791). Qualitative evidence highlighted the restorative benefits of nature and identified a number of barriers associated with fears around personal safety, social anxiety, fatigue and lack of motivation. COVID‐19 had also restricted access to green and blue spaces. Having social contact and support encouraged people to spend time outdoors. In the quantitative survey, self‐report and standardised measures (the Patient Health Questionnaire and the Warwick–Edinburgh Wellbeing Scale) were used to assess past and current mental wellbeing. Findings Statistically significant differences were found between wellbeing and the use of green and blue spaces. Those with mental health problems spent time outdoors because they: felt guilty; wanted to reduce their anxiety; or rely on someone for encouragement. Those without mental health problems endorsed more positively framed reasons including relaxation, improving physical health or getting exercise. Barriers for people with mental health problems involved safety concerns, feeling anxious and having a poor self‐image. These findings give insight into motivations for an outdoor activity to help inform the design of public mental health interventions. Conclusion Further work is required to improve access and safety to promote the benefits of green and blue spaces for everyone. Patient or Public Contribution The research team included expert experienced researchers with a mental health service provider (Praxis Care) and they were involved in the development of the research idea, funding application, design, data collection, analysis, writing up and dissemination activities.

Summary: Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development. Methods: Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analysis using the Olink Oncology-II platform (48% of participants were female; 52% male). To identify proteins which may be altered by the weight-loss intervention, the difference in protein levels between groups at baseline and 1 year was examined using linear regression. Mendelian randomization (MR) was performed to extend these results to evaluate cancer risk and elucidate possible biological mechanisms linking type 2 diabetes and cancer development. MR analyses were conducted using independent datasets, including large cancer meta-analyses, UK Biobank, and FinnGen, to estimate potential causal relationships between proteins modified during intentional weight loss and the risk of colorectal, breast, endometrial, gallbladder, liver, and pancreatic cancers. Findings: Nine proteins were modified by the intervention: glycoprotein Nmb; furin; Wnt inhibitory factor 1; toll-like receptor 3; pancreatic prohormone; erb-b2 receptor tyrosine kinase 2; hepatocyte growth factor; endothelial cell specific molecule 1 and Ret proto-oncogene (Holm corrected P-value

ObjectivesTo date, there is no evidence regarding the safety of automated titanium fastener compared with hand-tied knots for prosthesis fixation in infective endocarditis.MethodsBetween January 2016 and December 2022, a total of 220 patients requiring surgery for infective endocarditis were included in this retrospective analysis. The primary study endpoint was re-endocarditis during follow-up. The secondary study endpoints included stroke onset, all-cause mortality, and a composite outcome of either re-endocarditis, stroke, or all-cause mortality during follow-up.ResultsSuture-securing with an automated titanium fastener was performed in 114 (51.8%) patients, whereas the conventional technique of hand knot-tying was used in 106 (48.2%) patients. The risk of re-endocarditis was significantly lower in the automated titanium fastener group, as shown in a multivariable proportional competing risk regression model (adjusted sub-hazard ratio 0.33, 95% confidence interval 0.11–0.99, p = 0.048). The multivariable Cox proportional hazards regression analysis showed that the automated titanium fastener group was not associated with an increased risk of stroke-onset or attaining the composite outcome, respectively, (adjusted hazard ratio 0.54, 95% confidence interval 0.27–1.08, p = 0.082), (adjusted hazard ratio 0.65, 95% confidence interval 0.42–1.02, p = 0.061). Also, this group was not associated with an increased risk of all-cause mortality, as demonstrated in the multivariable Poisson regression analysis (adjusted incidence-rate ratio 1.42, 95% confidence interval 0.83–2.42, p = 0.202).ConclusionsThe use of automated titanium fastener device seems to be safe for infective endocarditis. Analyses of larger cohorts are required.

Abstract Background Critically unwell babies in intensive care units may develop acute renal failure. Options for renal replacement therapy are limited by their small size and available technology. Objectives To determine the clinical efficacy, outcomes and safety profile of the NIDUS® (a novel infant haemodialysis device) for babies under 8 kg, compared with current renal replacement therapy. Design A clinical investigation using a non-blinded cluster stepped wedge design with paediatric intensive care units randomised to sequences. Setting Paediatric intensive care units in six UK hospitals. Participants Children under 8 kg who required renal replacement therapy for fluid overload or biochemical disturbance. Interventions Continuous renal replacement therapy was provided by the usual methods: peritoneal dialysis and continuous haemofiltration (during control periods) and by the NIDUS (during intervention periods), a novel device designed for babies with a smaller circuit and filter and volumetric control of ultrafiltration. Main outcome measures Primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances, accuracy of reported ultrafiltration and mortality. Data sources Bedside study data collected by weighing bags of fluid entering and leaving the device were entered into the study database along with case descriptors. Some secondary outcome data was collected via the Paediatric Intensive Care Audit Network. Results Ninety-seven participants were recruited by study closure, 62 to control and 35 to intervention. The primary outcome was obtained from 62 control but only 21 intervention patients, largely because of technical difficulties using NIDUS. The analysis comparing the available primary outcomes showed that ultrafiltration with NIDUS was closer to that prescribed than with control: standard deviations controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. The mean clearances for creatinine, urea and phosphate were lower on peritoneal dialysis than NIDUS, which were in turn lower than continuous veno-venous haemofiltration. The variability in the clearances was in the same order. Of the 62 control patients, 10 died (2/62 on peritoneal dialysis; 7/13 on continuous haemofiltration) before discharge from paediatric intensive care unit (16%), compared with 12 out of 35 (34%) in the NIDUS group: p = 0.04, 95% confidence interval for difference (0 to 36%). Harms No important adverse events occurred and the NIDUS has an acceptable safety profile compared with other renal replacement therapies in this critically ill population with multi-organ failure. Mortality was lowest for Peritoneal Dialysis, highest for continuous haemofiltration, with the NIDUS in-between. Only one serious adverse device event which was reported to the Medicines and Healthcare products Regulatory Agency. Conclusions NIDUS works effectively, delivering appropriate blood clearances and accurate, controllable fluid removal (ultrafiltration), indicating that it has an important place alongside other dialysis modalities for infant renal replacement therapy. Future work Findings from this study indicate some modifications are required to NIDUS to improve usability. Further studies on use of the NIDUS device in other populations of babies for example those with chronic renal failure, and long-term outcomes are required. Trial registration This trial is registered as ISRCTN 13787486. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/23/26) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary Why do this study? Some children in intensive care are so poorly that their kidneys do not work well, and they need help, called dialysis, to get rid of fluid and chemicals from their blood. For babies, we currently use peritoneal dialysis, where fluid is cycled in and out of the tummy, or adapted machines designed for bigger children (continuous veno-venous haemofiltration). A new machine, the NIDUS® (Allmed, www.allmedgroup.com), was developed specifically for babies weighing under 8 kg with much smaller tubing. NIDUS worked well when studied in Newcastle but needed testing elsewhere. What was the question? How well does NIDUS work compared to other dialysis methods? What are the problems? What did we do? The study was done in six paediatric intensive care units who used their usual dialysis methods (=control) in the first part of the study and then later swapped to using the NIDUS (=intervention). What did we find? We recruited 97 participants, 62 to control (49 peritoneal dialysis, 13 continuous veno-venous haemofiltration) and 35 intervention (NIDUS). We found NIDUS provided much better control of fluid removal. The CVVH machines were more efficient at blood cleaning than NIDUS, which was better than peritoneal dialysis. What does this mean? We learnt a lot about babies needing kidney support in paediatric intensive care units and that all methods have advantages and disadvantages. We showed that NIDUS could be very useful for some participants because it cleans blood effectively and gives accurate, controllable fluid removal. We have gathered important information to help us improve NIDUS to make it easier to use and run. Many parents responded to our questionnaire and most told us they felt it was acceptable to be approached about taking part in research despite the circumstances. This is very important for future research studies. We are very grateful to families for their generosity in becoming involved in this study. Scientific summary Background Critically unwell babies in paediatric intensive care units (PICUs) may develop acute renal failure and require management with renal replacement therapy. Although mortality and morbidity vary and are related to the underlying diagnosis, survival of babies in paediatric intensive care is worse for those with fluid overload. Babies requiring renal replacement treatment present specific therapeutic challenges because of their small size and the current technology available. Difficulties with vascular access and blood flows, fluid balance, loss of circuits, filter clotting and hypotensive episodes at initiation are all described in the literature. The need for new solutions and improved technology is well recognised. Continuous veno-venous haemofiltration (CVVH) machines in use in the UK at the time of this study are not approved for use in babies weighing 80%) were similar. The median (IQR) age in controls 10.5 (7, 38) days was similar to that in the intervention group 11 (7, 61) days; the range of age of participants was between 1 and 477 days (approximately 15 months). The median (IQR) weights 3.2 (2.9, 3.9) and 3.7 (3.1, 5.6) kg were similar between control and intervention. Availability of primary outcome The primary outcome was available on all 62 control patients but only 21 of the 35 intervention patients. This was due to a range of reasons including difficulties in obtaining the information needed to compute the UF rate (accurate timing and weighing data) and technical difficulties using the NIDUS: full details are in the report. Precision of UF Analysis comparing the 62 control patients with the 21 intervention patients with a primary outcome showed that UF with the NIDUS was closer to that prescribed than with control: standard deviations (SDs) controls 18.75, intervention 2.95 (ml/hour), adjusted ratio 0.13, 95% confidence interval (0.03 to 0.71); p = 0.018. For the NIDUS and CVVH devices, an important measure was to compare the difference between the actual fluid removal measured and that reported by the device. This had a mean closer to zero for the NIDUS than CVVH (means −0.44 vs. 11.6 ml/hour, respectively), with less variation in NIDUS than CVVH (SDs 3.2 vs. 28.4 ml/hour). Biochemical clearances The initial intention was to compare clearance rate on NIDUS with the control group. However, for these variables combining PD and CVVH in this way proved to be misleading because NIDUS clearances rates were intermediate between those of PD and CVVH. The clearance for creatinine on PD was smaller and less variable (mean 0.08, SD 0.03 ml/min/kg) than on the NIDUS (mean 0.46, SD 0.30 ml/min/kg), which was in turn smaller and less variable than for CVVH (mean 1.20, SD 0.72 ml/min/kg). The pattern was repeated for urea: PD (0.12, 0.06), NIDUS (0.48, 0.30) and CVVH (1.15, 0.67), all in ml/min/kg, and also for phosphate: PD (0.07, 0.04), NIDUS (0.44, 0.27) and CVVH (1.16, 0.71), all in ml/min/kg. All pairwise treatment comparisons of means and of SDs gave p

In this photo-theoretical article I interrogate portraits generated by NIVIDIA’s StyleGAN2. Even though these portraits are completely artificial and the pictured persons have never existed, they are surprisingly realistic and could even be read as photographs. I therefore ask the question: How do these pictures relate to the photographic and can we consider them as a new aspect of the medium? I will also present an attempt to locate these images on the Internet and discuss how they are used today. The result of this experiential localization shows that the pictures are mostly used in dubious and even criminal ways.

Summary: Background: Studies from Guinea-Bissau and Bangladesh have shown that campaigns with oral polio vaccine (C-OPV) may be associated with 25–31% lower child mortality. Between 1996 and 2015, Ghana had 50 national C-OPVs and numerous campaigns with vitamin A supplementation (VAS), and measles vaccine (MV). We investigated whether C-OPVs had beneficial non-specific effects (NSEs) on child survival in northern Ghana. Methods: We used data from a health and demographic surveillance system in the Navrongo Health Research Centre in rural northern Ghana to examine mortality from day 1–5 years of age. We used Cox models with age as underlying time scale to calculate hazard ratios (HR) for the time-varying covariate “after-campaign” mortality versus “before-campaign” mortality, adjusted for temporal change in mortality, other campaign interventions and stratified for season at risk. Findings: From 1996 to 2015, 75,610 children were followed for 280,156 person-years between day 1 and 5 years of age. In initial analysis, assuming a common effect across all ages, we did not find that OPV-only campaigns significantly reduced all-cause mortality, the HR being 0.96 (95% CI: 0.88–1.05). However, we subsequently found the HR differed strongly by age group, being 0.92 (0.75–1.13), 1.29 (1.10–1.51), 0.79 (0.66–0.94), 0.67 (0.53–0.86) and 1.03 (0.78–1.36) respectively for children aged 0–2, 3–5, 6–8, 9–11 and above 12 months of age (p

(Series Information) European Papers - A Journal on Law and Integration, 2023 8(1), 81-84 | European Forum Highlight of 16 May 2023 | (Abstract) German-speaking scholarship on EU law is coined, to a significant extent, by relevant decisions of constitutional courts in German-speaking countries. The translation of these decisions into other languages contributes strongly to broaden the legal discourse, as it allows also non-German-speaking members of the scientific community or of courts in other Member States to read and to reflect upon them. Against this background, in this Highlight we take a look at the translation policy of the German Bundesverfassungsgericht (BVerfG) and the Austrian Verfassungsgerichtshof (VfGH). For the sake of comparison, we also take a look at how the French Conseil constitutionnel (CC) – as an example for a constitutional court of a non-German-speaking Member State – approaches this question. While in all three cases the number of provided translations has increased considerably over the past 25 years, it turns out that the BVerfG and the VfGH translate mostly into English. The CC, however, does not only translate (proportionally) more decisions, but also it translates them into different languages, very prominently into German, thereby inviting German-speaking scholarship and German-speaking judges to take account of it. The provision of translations by courts seems to be more than a service to ‘interested third parties’. It turns out to be a tool to pursue the specific interests of a court as well.

Abstract Background Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose–response relationship between device-measured PA and incident type 2 diabetes. Methods This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework. Results The median follow-up period was 6.3 years (IQR: 5.7–6.8), with 591 participants developing type 2 diabetes. Compared to those achieving 600 min/week were at 49% (95% CI 62–32%), 62% (95% CI 71–50%) and 71% (95% CI 80–59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving 75 min/week were at 38% (95% CI 48–33%), 48% (95% CI 64–23%) and 64% (95% CI 78–42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively. Conclusions PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction. Trial registration The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011).

Abstract Goal-directed behavior requires integrated mental representations of perceptions and actions. The neurophysiological underpinnings of these processes, however, are not yet understood. It is particularly undetermined, which oscillatory activities in which brain regions are involved in the management of perception-action representations. We examine this question with a focus on response inhibition processes and show that the dynamics of perception-action representations reflected in theta band activity (TBA) are particularly evident in the supplementary motor area and the occipito-temporal cortex. Mental representations coded in alpha band activity (ABA) during perception-action integration are associated with the occipito-temporal cortex. Crucially, perception-action representations are exchanged between theta and alpha frequency bands. The results imply that ABA functions as dynamic top-down control over binding, retrieval and reconfiguration processes during response inhibition, which in turn are reflected by TBA. Our study thus highlights how the interplay of oscillatory activity enables the management of perception-action representations for goal-directed behavior.

Abstract Background This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. Methods A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus–post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. Results After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). Conclusions A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

Abstract Identifying systems failures and contributing to a safety culture is the Association of American Colleges (AAMC’s) thirteenth Entrustable Professional Activity (EPA). While most curricula teach Patient Safety (PS) and Quality Improvement (QI) principles, student participation in live QI/PS activities remains limited. This workshop enabled late Clerkship phase students to apply these Health Systems Science (HSS) principles to real adverse patient event cases through team-based simulation. This 3-h capstone included both a didactic review of QI, PS, and TeamSTEPPS® tools and an experiential component where student-led interactive small group discussions were augmented by resident and faculty preceptors. Collaboratively, students composed an adverse patient event report, conducted a Root Cause Analysis (RCA) during role-play, and proposed error prevention ideas after identifying systems problems. In April 2020, the in-person workshop became fully virtual due to the COVID-19 pandemic. A statistically significant increase in ability to identify Serious Safety Events, Escalation Chain of Command, and define a Plan-Do-Study-Act (PDSA) cycle was observed. Comfort with RCA increased from 48 to 87% and comfort with TeamSTEPPS® principles increased from 68% to 85.5% This novel capstone provided students with the tools to synthesize HSS concepts through problem-solving processes and recognize EPA 13’s importance. Their increased capability to identify appropriate chain of command, escalate concerns, and recognize serious adverse patient events also has training and practice readiness implications.

A sleeper, or more generally a “bearer”, moves vertically under a passing train load. The extent of this motion depends on the static and dynamic load of the train, the train speed, and the support conditions at the bearer and its neighbours. Excessive motion, typically from voiding see-sawing, low support stiffness or possibly excessive stiffness, or even too little stiffness, are all of interest to maintainers. Typically, problems arise around transition zones, switches and crossings, but plain track with poor support can also be a problem. Within the last decade, low-cost micro-electro-mechanical system (MEMS) accelerometers have been used to capture the time history of vertical motion for use in condition monitoring. Existing condition monitoring systems often overlook or sometimes even ignore the possibility of problematic data, which seem to be common in monitored locations. It is essential to understand whether such “bad” data require further attention. Three problematic sites are presented, focussing on examples where the acceleration was higher than expected or the computed displacement was not as expected. Potential causes include wheel defects, hammering of the ballast by a hanging bearer, or high acceleration at some structural resonant frequency. The present paper aims to show the challenges of using MEMS accelerometers to collect data for condition monitoring and offers insights into the sort of problematic data that may be collected from real sites.

Objective: To describe a rare congenital deformity of the phalanges and the surgical details and outcome in a dog with ectrodactyly combined with polydactyly. Study design: Single case report. Animal: A 3.5-month-old male intact mixed breed dog with forelimb lameness and paw malformations. Methods: Surgery was performed on a dog with a congenital limb deformity consisting of resection of the extra bone and soft tissue structure to prevent further subluxation of the remaining metacarpals. Stabilisation consisted of a cortical screw in compression and a K wire across the proximal metacarpals. Results: Postoperative radiographs showed adequate implant positioning and good reduction of the proximal metacarpal row. At six weeks, the dog showed improvement in limb function and weight bearing. Major complications occurred at twelve weeks, and revision surgery with implant removal was required. At six months, the dog showed near normal range of motion and no lameness. Conclusions and Clinical Relevance: The decision to perform surgery on a dog with limb deformity resulted in an almost physiological gait, and the dog showed no abnormalities in daily life. This report adds to the literature on congenital limb deformities by describing the combination of ectrodactyly and polydactylism in a canine species, including the surgical approach and outcome. However, the optimal management of this heterogeneous condition is currently unclear.

Introduction Recurrent infarcts to the internal carotid artery territory in the setting of a corresponding occlusion raises concern for carotid stump syndrome. Over time, robust anastomoses may develop between the patent ipsilateral external carotid artery and the anterior circulation distal to the site of occlusion. A carotid stump’s disturbance of flow uncommonly can form emboli that travel via retrograde flow from the occluded internal carotid artery to the ipsilateral external carotid artery and its collaterals. Stenosis of the external carotid artery in such patients can be a source of atheroembolism or hypoperfusion. We describe a case of external carotid stenting with carotid stump coil occlusion. Methods We present a case report. Verbal consent to share this information was obtained directly from the patient. Results A 75‐year‐old man with aortic stenosis, atrial arrhythmia, multiple prior bi‐hemispheric strokes, on aspirin and clopidogrel, presented with left facial droop, arm weakness, and slurred speech. Magnetic resonance imaging revealed embolic appearing strokes in the right middle cerebral artery territory (Figure 1A). Cerebral angiography revealed complete occlusion of the right internal carotid artery with perfusion of the right middle cerebral artery by external carotid artery anastomoses, and the external carotid was found to be stenosed proximally. Digital subtraction angiography revealed right external carotid – middle cerebral artery anastomoses via the right sphenopalatine artery, middle meningeal artery, internal maxillary artery, and ophthalmic collaterals (Figure 1B). The patient underwent coiling of the right internal carotid artery stump (Figure 1C) followed by stenting of the right external carotid using a 9 mm x 40 mm Cordis precise Pro stent. Post‐stenting angiogram demonstrated good apposition of the stent to the parent vessel walls and improvement of flow into the right external carotid and intracranial circulation (Figure 1D). The patient was treated with aspirin and ticagrelor for 3 months. Repeat imaging at follow up did not show further embolic episodes, with improvement in the patient’s deficits. After three months, he was continued on aspirin alone. Conclusion In patients with an occluded internal carotid artery and recurrent embolic infarcts ipsilateral to the side of the occlusion, carotid stump syndrome may be considered. In this case, we believe the patient’s carotid occlusion served as a nidus for emboli formation, or that there was atheroembolism from the stenosed external carotid artery despite adherence to dual antiplatelet therapy. By coiling the stump, we addressed a possible source of emboli, and stenting of the proximal external carotid optimized anterograde flow and prevented further atheroembolism. Our case showcases an interventional neuroradiology approach to carotid stump emboli and external carotid artery stenosis.

There is large potential to increase cycling participation worldwide. Participation in cycling is associated with lower risk of mortality from any cause, and incidence of cardiovascular disease and type 2 diabetes, as well as positive mental health and well-being. The largest potential for health gains likely to come from increasing participation amongst those who do not currently cycle regularly, rather than encouraging those who already cycle regularly to cycle more. Replacing car journeys with cycling can lead to reductions in air pollution emissions and lower pollutant exposure to the general population. Important gaps and uncertainties in the existing evidence base include: the extent to which the health benefits associated with cycling participation are fully causal due to the observational nature of much of the existing evidence base; the real-world economic cost-benefits of pragmatic interventions to increase cycling participation; and the most effective (combination of) approaches to increase cycling participation. To address these uncertainties, large-scale, long-term randomised controlled trials are needed to: evaluate the effectiveness, and cost-effectiveness, of (combinations of) intervention approaches to induce sustained long-term increases in cycling participation in terms of increases in numbers of people cycling regularly and number of cycling journeys undertaken, across a range of population demographic groups; establish the effects of such interventions on relevant outcomes related to health and wellbeing, economic productivity and wider societal impacts; and provide more robust quantification of potential harms of increasing cycling participation, such as collision risks.

Objectives The aim of this study is to look at spatial and temporal trends in undernutrition in children under 5 years age in Burkina Faso.Setting We used data from annual National Nutrition Surveys using Standardised Monitoring and Assessment of Relief and Transitions methodology (anthropometry, morbidity) over 7 years (2012–2018) in Burkina Faso.Participants Children of under 5 years from households selected through systemic sampling at countrywide level.Main outcome measures Prevalence of stunting (height-for-age z-score,

The European mining bee species Andrena lathyri (Andrenidae) is a narrow specialist of flowers of Lathyrus and Vicia (Fabaceae), from which both females and males gain nectar by primary nectar robbing. Both sexes are equipped with a unique proboscis, which is much longer and more strongly angled than in most other Andrena bees including the most closely related species. The comparison between the shape of the proboscis and the interior of the host flowers combined with field observations revealed that the specialised mouthparts of A. lathyri precisely correspond to the dimensions of the flower interior and the position of the nectary, representing one of the few known examples of a morphological adaptation to primary nectar robbing in bees. For nectar uptake, the bee’s head is inserted laterally under the standard petal before it is moved towards the flower base, thereby slitting the calyx longitudinally to a depth necessary to reach the nectary from inside the flower with the specialised proboscis. Nectar-robbing individuals of A. lathyri are able to adapt their behaviour to the different calyx lengths of their host flower species by slitting the calyx over varying distances. Except for the slit in the calyx, primary nectar robbing by A. lathyri does not damage any flower parts allowing for normal fruit development.

Background: The multisystem associations between baseline mental health status and coronavirus disease-19 (COVID)-19 illness trajectory are uncertain. Objectives: This article will investigate the associations between baseline mental health status and disease trajectory following COVID-19 hospitalization, which may have implications for practice and future research. Methods: The Chief Scientist Office Cardiovascular and Pulmonary Imaging in severe acute respiratory syndrome (SARS) COVID-19 study is a prospective, observational, multicenter, longitudinal, secondary care cohort study that assessed the time-course of multi-organ injury in posthospital survivors of COVID-19. Patients were assessed in-hospital, at 28–60 days after discharge and in the longer term using electronic health record linkage. Results: One hundred and fifty-two patients (mean ± standard deviation [SD] age 54.3 ± 11.8 years, 43% female, 40% most socio-economically deprived quintile, 33% history of mental health history) were enrolled and had mental health serially assessed using the Patient Health Questionnaire-4 (PHQ-4) questionnaire. Fifty-three (35%) had PHQ-4 score of 6–12 consistent with moderate-severe symptoms of anxiety or depression and this was associated with diagnostic criteria for myocarditis (P = 0.0498). Moderate-severe symptoms of anxiety or depression were positively associated with higher perception of illness, lower health-related quality of life (HRQoL), and poorer physical function. The mean (SD) duration of follow-up after hospital discharge was 428 (86) days (range, 290–627 days). PHQ-4 score was not associated with clinical outcomes at follow-up. Conclusions: In patients who have been hospitalized with COVID-19, moderate-severe symptoms of anxiety or depression were associated with myocarditis, worse HRQoL, higher perception of illness, and lower levels of physical function. Public Registration: ClinicalTrials.gov identifier is NCT04403607.

Abstract High-dose alcohol intoxication reduces cognitive control, including inhibition. Although inhibition deficits may contribute to the behavioral deficits commonly observed in alcohol use disorder (AUD), many questions about potentially modulating factors have remained unanswered. We examined the effects of experimentally induced high-dose alcohol intoxication (~ 1.1 ‰) on the interplay between controlled vs. automatic response selection and inhibition in healthy young men. A holistic EEG-based theta activity analysis that considered both reactive control during task performance and preceding proactive control processes was run. It revealed a previously unknown seesaw relationship, with decreased reactive control, but paradoxically increased proactive control. Most importantly, alcohol-induced increases in proactive occipital theta band power were associated with reductions in negative alcohol effects on reactive control processes associated with decreased activity in the SMA and medial frontal cortex. Our findings demonstrate that research should not solely focus on immediate effects during task performance. Aside from differential neurobiochemical and neuroanatomical effects of alcohol, it is also conceivable that proactive control may have been recruited in a (secondary) response to compensate for alcohol-induced impairments in reactive control. Against this background, it could be promising to investigate changes in such compensatory mechanisms in pronounced alcohol-associated inhibition deficits, like in AUD patients.

Plain English summary Making your own decisions is important. There are disabled people who need support to make some decisions. Supporting disabled people to make decisions is needed so that they are not excluded from society. However, the evidence is limited on disabled people’s experiences of how best to support decision-making. This article will explore the experiences of four researchers with mental health problems or an intellectual disability who worked with other researchers to conduct a project on how people have, or have not been, supported to make their own decisions. These researchers are called peer researchers. The peer researchers interviewed 21 people with mental health problems and 20 people with an intellectual disability. These interviews were conducted in order to gain a detailed understanding of the experiences and preferences for how decision-making should be supported. Blogs written by the peer researchers, discussions in team meetings and a workshop at the end of the study enabled the peer researchers to reflect on their experiences. The peer researchers reported a number of positive effects of being involved in the research project which included improvements in skills and self-confidence. The peer researchers’ involvement challenged assumptions about the inability of people with an intellectual disability and/or mental health problems to participate in a research project whilst also highlighting the importance of training for all team members.

Plain English summary Since the 1970’s, there has been a shift from research on disabled people to research with disabled people. This is often referred to as co-produced research. Co-production has a wide definition but includes disabled people working with academics to produce research and outcomes which neither group could achieve by working in isolation. This paper presents the co-production methodology used to conduct a research project called ‘Getting our Voices Heard’. This project, sought to find the best way to get the voices of people with a learning disability heard inpolicy development in the UK. We explain how this research was carried out, using a co-produced participatory design. We established a research team with professional researchers from a university, who worked with peer researchers. Peer researchers are people who have lived experience of the issue being studied. In this project, we worked with six peer researchers who all had a learning disability. The experiences of the peer researchers, and ways in which the peer researchers were involved at each stage of the project are discussed. The peer researchers described feeling positive about their role and felt involved. We show that working together is important and recommend that additional time and resources are essential for this joint working.

Abstract Background Whether women’s physical function in mid-life is related to their reproductive age is not known. The objectives of this study were to examine and compare changes in physical function in women by reproductive age, measured as time since final menstrual period (FMP), and chronological age, and to explore associations with repeatedly assessed levels of reproductive hormones. Methods We used data from 2319 UK women with up to three repeated measurements of physical function (median length of follow up: 2 years), focusing on changes occurring in women experiencing a natural menopausal transition. The main outcome was a composite physical function score that incorporated assessments of strength (grip strength), balance (one-leg stand) and cardiorespiratory fitness (timed chair rises). Associations with time since FMP, age, and time-updated measures of anti-Müllerian hormone, follicle-stimulating hormone and luteinizing hormone were assessed by multilevel models and generalised estimating equations models adjusted for the underlying effects of chronological age and confounding by education, age at first birth and smoking. Results The results showed that, adjusted for these confounders, time since FMP (− 0.21 SD per 10 years, 95% CI − 0.37, − 0.06) and chronological age (− 0.31 SD per 10 years, 95% CI − 0.46, − 0.15) were inversely associated with the physical function composite score. Grip strength seemed to be the main contributor to the decline in the composite score by time since FMP. There was no strong evidence of associations between any of the three reproductive hormones and the composite score. Conclusions Physical function in women in mid-life declined with both chronological and reproductive age. The decline with reproductive age was independent of chronological age but did not seem to be driven by changes in reproductive hormones.

Abstract Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein–protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

No presente artigo busca-se introduzir uma discussão sobre a unidade da obra musical a partir dos sentidos primordiais propostos pelo filósofo na Metafísica. O problema é: Em que sentido a obra musical pode ser una, considerando os significados primordiais de uno discutidos por Aristóteles? A discussão se inicia em torno da noção de obra musical. A seguir, são introduzidos alguns aspectos do pensamento musical aristotélico para abordar, mais tarde, a continuidade como sentido primordial de unidade e posteriormente desdobrar a contemplação do problema da unidade musical em apontamentos distintos concentrados na noção de variedade e no problema do belo. Por fim, sobre essas bases, também são introduzidas algumas questões relativas ao problema da unidade enquanto valor representado. Espera-se que este trabalho estimule reflexões filosóficas sobre problemas composicionais e contribua na discussão sobre a unidade da obra musical.

Background: Even though physiotherapists attempt to match care to the patient’s needs, there is little knowledge about which treatments are applied in daily practice and which treatments have the most potential to improve ROM in patients with non-specific neck pain with a limited ROM. The objective of this study was 1) to establish the measurement error of the Sensamove cervical training accelerometer (SCT); 2) to describe the applied treatments for patients with non-specific neck pain with an identified restriction in cervical Range of Motion (ROM) in primary care physiotherapy clinics; 3) to explore if the cervical ROM, pain, (perceived) disability and motor control improved after one manual therapy treatment. Methods: The standard error of measurement (SEM) and the smallest detectable difference (SDD) were calculated based on a test-retest study. Second, an explorative, longitudinal study design (follow-up one week) was performed. Inclusion criterion: nonspecific neck pain with an identified restriction in cervical ROM. Measurements: pre- (T0) and post-treatment (T1), and one-week post-treatment (T2). Outcomes: ROM, motor control movement task, Numerical Pain Rating Scale (NPRS), and Patient Specific Function Scale (PSFS). Results: The SEM varied from 1.62° (lateral flexion right) to 3.46° (extension). The SDD varied from 4.49° (lateral flexion right) to 9.58° (extension). Four physiotherapists included 24 patients and used eight different treatments. The T0-T2 improvement in cervical ROM ranged from 2.95° (SD 6.09) (right lateral flexion) to 11.00° (SD11.87) (left rotation). The movement task was performed 3.96 (SD 4.24) seconds faster. The NPRS decreased by 3.08 (SD 1.82) points, and PSFS improved by 7.71 (SD 5.34) points. Conclusion: The measurement error has been established. Moreover, this study illustrates that matched treatments, as applied in daily practice, have the potential to induce short-term improvements.

The full optical response of twisted bilayer graphene at the neutrality point close to the magic angle within the continuum model (CM) is discussed. First, three different channels consistent with the underlying D 3 symmetry are identified, yielding the total, magnetic, and chiral response. Second, the full optical response in the immediate vicinity of the magic angle θ m is numerically calculated, which provides a direct mapping of the CM onto an effective two‐band model. It is, further, shown that the ground state of the CM in the immediate vicinity of θ m is unstable toward transverse current fluctuations, a so‐called Condon instability. Third, due to the large counterflow, the acoustic plasmonic excitations with typical wave numbers have larger energies than the optical ones and their energy density may be largely enhanced at certain frequencies which are denominated as chiral resonances. Finally, symmetry relations for the optical response and their consequences for the chiral response are discussed.

Abstract. Objectives:. The objective of this study was to describe the relationship between positive toxicology screens and measures of preinjury mental health and physical function in an orthopaedic trauma population Design:. This was a cross-sectional study. Setting:. Urban Level 1 trauma center. Patients:. A total of 125 trauma patients gave written consent for this study. Main Outcome Measurements:. Questionnaires such as, Patient Health Questionnaire-9, General Anxiety Disorder-7, PCL-5, and Short Musculoskeletal Function Assessment, were used to survey patients after surgical intervention. Results:. Patient Health Questionnaire-9 (P = 0.05) and PCL-5 (P = 0.04) were not found to have significant differences between positive and negative toxicology screens. Both General Anxiety Disorder-7 (P = 0.004) and Short Musculoskeletal Function Assessment function (P = 0.006) were significantly higher in patients with positive toxicology screens. Conclusions:. Positive toxicology seems to be associated with preinjury anxiety. Patient reported preinjury function was not adversely affected by the presence of illicit substances or alcohol, nor were levels of post-traumatic stress disorder and depression found to be higher in patients with positive toxicology screens. Level of Evidence:. Level IV Cross-Sectional Study.

Occupational exposure to airborne nanoparticles in semiconductor-manufacturing facilities is of growing concern. Currently, comprehensive information regarding atmospheric concentrations, potential origins, and the physical and chemical properties of nanoparticles in these industrial settings is lacking. This study investigated the occurrence of airborne nanoparticles within a semiconductor-research and -manufacturing facility, during both routine operation and maintenance activities. A Scanning Mobility Particle Sizer was used to monitor size-resolved airborne-nanoparticle number concentrations spanning the range of 6 to 220 nm. Breathing zone filter samples were also collected during maintenance processes and underwent subsequent analyses via Transmission Electron Microscopy and Inductively Coupled Plasma Mass Spectrometry, to discover the size, morphology, and chemical composition of the observed nanoparticles. The findings reveal low levels of airborne nanoparticles during routine operations, but maintenance tasks resulted in substantial concentration surges particularly for plasma-enhanced chemical vapor deposition tools with concentrations up to 11,800 particles/cm3. More than 80% of observed particles were smaller than 30 nm. These smallest particles were predominately composed of metals such as iron, nickel, and copper. Moreover, larger particles above 100 nm were also identified, comprising process-related materials such as silicon and indium. Comparative assessment against established mass-based exposure limits did not yield any exceedances. Current exposure limits do not typically consider size though, and the preponderance of small nanoparticles (

The emergence of facial masks as a critical health intervention to prevent the spread of airborne disease and protect from occupational nanomaterial exposure highlights the need for fundamental insights into the interaction of nanoparticles (f) in the range of −10 V to −800 V were measured by an electrostatic voltmeter and used for testing. Results show that the mask filtration efficiency is highly dependent on the mask surface potential as well as the charge on the challenge aerosol, ranging from 60% to 98%. Eliminating the surface charge results in a maximum 43% decrease in filtration efficiency, emphasizing the importance of electrostatic charge interactions during the particle capture process. Moreover, increased humidity can decrease the surface charge on filters, thereby decreasing the mask filtration efficiency. The knowledge gained from this study provides insight into the critical role of electrostatic attraction in nanoparticle capture mechanisms and benefits future occupational and environmental health studies.

Abstract Background Out-of-pocket payment (OOPP) is reported to be a major barrier to seeking maternal health care especially among the poor and can expose households to a risk of catastrophic expenditure and impoverishment.This study examined the OOPPs women made during childbirth in the Upper West region of Ghana. Methods We carried out a cross-sectional study and interviewed women who gave birth between January 2013 and December 2017. Data on socio-demographic characteristics, place of childbirth, as well as direct cost (medical and non-medical) were collected from respondents. The costs of childbirth were estimated from the patient perspective. Logistics regression was used to assess the factors associated with catastrophic payments cost. All analyses were done using STATA 16.0. Results Out of the 574 women interviewed, about 71% (406/574) reported OOPPs on their childbirth. The overall average direct medical and non-medical expenditure women made on childbirth was USD 7.5. Cost of drugs (USD 8.0) and informal payments (UDD 5.7) were the main cost drivers for medical and non-medical costs respectively. Women who were enrolled into the National Health Insurance Scheme (NHIS) spent a little less (USD 7.5) than the uninsured women (USD 7.9). Also, household childbirth expenditure increased from primary health facilities level (community-based health planning and services compound = USD7.2; health centre = USD 6.0) to secondary health facilities level (hospital = USD11.0); while home childbirth was USD 4.8. Overall, at a 10% threshold, 21% of the respondents incurred catastrophic health expenditure. Regression analysis showed that place of childbirth and household wealth were statistically significant factors associated with catastrophic payment. Conclusions The costs of childbirth were considerably high with a fifth of households spending more than one-tenth of their monthly income on childbirth and therefore faced the risk of catastrophic payments and impoverishment. Given the positive effect of NHIS on cost of childbirth, there is a need to intensify efforts to improve enrolment to reduce direct medical costs as well as sensitization and monitoring to reduce informal payment. Also, the identified factors that influence cost of childbirth should be considered in strategies to reduce cost of childbirth.

Abstract Background Women experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated. The aim of this study was to examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age. Methods We used data from 1702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause. Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche). In addition, we looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-menopause, peri-menopause and post-menopause) using information from women who had and had not experienced menopause (N = 3892). Results There was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 μm/year, 95% CI − 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 μm/year, 95% CI 6.3, 8.9). Consistent with this, we found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (− 0.1 mmHg/year, 95% CI − 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively). In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI − 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI − 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age. Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively). Conclusions Our results suggest that going through the menopausal transition does not further increase women’s risk of atherosclerosis (measured by CIMT) beyond effects of ageing. Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

Abstract Background Canine relationship is a key reference identifying anterior malocclusion and an important implication for evaluating preimplantation bone morphology at maxillary esthetic zone. This study aimed to compare the differences of maxillary central incisor-related measurements (alveolar bone thickness and tooth sagittal angulation) between Class I and Class III canine relationship and further explore the risk factors for immediate implant placement in the anterior maxilla based on cone beam computed tomography (CBCT) data. Methods CBCT digital imaging and communications in medicine (DICOM) files of 107 patients (54 with Class I canine relationship and 53 with Class III canine relationship) were collected and the alveolar bone thickness at mid-root (mid-root buccal thickness/MBT; palatal/MPT), apical regions (apical buccal thickness/ABT; palatal/APT) and sagittal angulation (SA) of the maxillary central incisor at the examined side were measured on the mid-sagittal observation plane. Descriptive statistical analysis and frequency distributions of the measurements based on Class I or Class III canine relationship were established. Statistical analyses were performed using Fisher’s exact test, independent samples t test and Pearson correlation test with the significance level set at p