Morphological and hemodynamical alterations in brachial artery and cephalic vein. An image‐based study for preoperative assessment for vascular access creation

The current study aims to computationally evaluate the effect of right upper arm position on the geometric and hemodynamic characteristics of the brachial artery (BA) and cephalic vein (CV) and, furthermore, to present in detail the methodology to characterise morphological and hemodynamical healthy vessels. Ten healthy volunteers were analysed in two configurations, the supine (S) and the prone (P) position. Lumen 3D surface models were constructed from images acquired from a non-contrast MRI sequence. Then, the models were used to numerically compute the physiological range of geometric (n = 10) and hemodynamic (n = 3) parameters in the BA and CV. Geometric parameters such as curvature and tortuosity, and hemodynamic parameters based on wall shear stress (WSS) metrics were calculated with the use of computational fluid dynamics. Our results highlight that changes in arm position had a greater impact on WSS metrics of the BA by altering the mean and maximum blood flow rate of the vessel. Whereas, curvature and tortuosity were found not to be significantly different between positions. Inter-variability was associated with antegrade and retrograde flow in BA, and antegrade flow in CV. Shear stress was low and oscillatory shear forces were negligible. This data suggests that deviations from this state may contribute to the risk of accelerated intimal hyperplasia of the vein in arteriovenous fistulas. Therefore, preoperative conditions coupled with post-operative longitudinal data will aid the identification of such relationships

An investigation of exoskeleton robotic systems in assisting construction tasks

Whilst industrial robots have been widely used in many industrial sectors, they are predominantly used in a structured factory environment. In recent years, off-site robotics have been investigated extensively and there are some promising candidates emerging. One such category of robots is exoskeleton robots and this paper provides an in-depth assessment of their suitability in assisting human operators in undertaking manual operations typically found in the construction industry. This work aims to objectively assess the advantages and disadvantages of these two suits and provide recommendations for further improvements of similar system designs. The paper focuses on the passive exoskeleton robotic suits which are commercially available. Three types of activities are designed and a mechatronic methodology has been designed and implemented to capture visual data in order to assess these systems in comparison with normal human operations. The study suggests that these passive suits do reduce the effort required by human operators to undertake the same construction tasks as evidenced by the results from one focused study, though a number of improvements could be made to improve their performance for wider adoption

Protocol for the Foot in Juvenile Idiopathic Arthritis trial (FiJIA): a randomised controlled trial of an integrated foot care programme for foot problems in JIA

<b>Background</b>: Foot and ankle problems are a common but relatively neglected manifestation of juvenile idiopathic arthritis. Studies of medical and non-medical interventions have shown that clinical outcome measures can be improved. However existing data has been drawn from small non-randomised clinical studies of single interventions that appear to under-represent the adult population suffering from juvenile idiopathic arthritis. To date, no evidence of combined therapies or integrated care for juvenile idiopathic arthritis patients with foot and ankle problems exists. <b>Methods/design</b>: An exploratory phase II non-pharmacological randomised controlled trial where patients including young children, adolescents and adults with juvenile idiopathic arthritis and associated foot/ankle problems will be randomised to receive integrated podiatric care via a new foot care programme, or to receive standard podiatry care. Sixty patients (30 in each arm) including children, adolescents and adults diagnosed with juvenile idiopathic arthritis who satisfy the inclusion and exclusion criteria will be recruited from 2 outpatient centres of paediatric and adult rheumatology respectively. Participants will be randomised by process of minimisation using the Minim software package. The primary outcome measure is the foot related impairment measured by the Juvenile Arthritis Disability Index questionnaire's impairment domain at 6 and 12 months, with secondary outcomes including disease activity score, foot deformity score, active/limited foot joint counts, spatio-temporal and plantar-pressure gait parameters, health related quality of life and semi-quantitative ultrasonography score for inflammatory foot lesions. The new foot care programme will comprise rapid assessment and investigation, targeted treatment, with detailed outcome assessment and follow-up at minimum intervals of 3 months. Data will be collected at baseline, 6 months and 12 months from baseline. Intention to treat data analysis will be conducted. A full health economic evaluation will be conducted alongside the trial and will evaluate the cost effectiveness of the intervention. This will consider the cost per improvement in Juvenile Arthritis Disability Index, and cost per quality adjusted life year gained. In addition, a discrete choice experiment will elicit willingness to pay values and a cost benefit analysis will also be undertaken

Rotavirus Serotype G9P[8] and Acute Gastroenteritis Outbreak in Children, Northern Australia

Amino acid substitutions on the VP7 and NSP4 proteins were identified in regions known to influence function and may have contributed to the emergence and increased dominance of the outbreak strains

The Canadian context for evidence-based conservation and environmental management

Canada has strong institutional capacity for science-based decision-making related to natural resource conservation and environmental management. Yet, the concept of using systematic reviews (conducted in accordance with established guidelines) to support evidence-based conservation and environmental management in Canada is in its infancy. Here we discuss the Canadian context for implementing more rigorous evidence-based approaches using systematic reviews. Of particular relevance to Canada is its vast size, broad diversity of ecosystems and heavy economic reliance on natural resources that vary widely in the type and scale of their environmental effects. These factors result in a wide variety of environmental monitoring needs over an extensive area that pose challenges to the scientific community charged with overseeing wise use of the environment. In addition, there are diverse and engaged user groups (e.g., hunters, trappers, fishers, bird watchers, foresters) and indigenous peoples that have constitutional rights to their natural resources. Traditional environmental knowledge is a complementary source of evidence in the Canadian environmental impact assessment process and therefore must be a part of evidence synthesis. Systematic reviews are not intended to replace local field studies, but rather have the opportunity to draw upon a broader suite of evidence that can be interfaced with local perspectives. The existing institutional structures in Canada could easily incorporate systematic reviews into their science advice and decision-making frameworks but to date, there are few examples of where this has occurred. Drawing on the expertise of a growing global collaboration for environmental evidence synthesis, Canadian institutions (federal, provincial and NGO) are poised to more broadly incorporate systematic reviews once their benefits are fully realized and the capacity to undertake such systematic reviews is fully developed. Systematic reviews offer a consolidated view of the available scientific literature on a given question. The results may offer significant value when working with stakeholders and decision makers contributing other sources of information to the question. For example, mechanisms to capture and integrate scientific knowledge with stakeholder and traditional knowledge may benefit from the scientific sources being filtered, interpreted and summarized for discussion. In other cases, wher

An optimistic outlook on the use of evidence syntheses to inform environmental decision-making

Practitioners and policymakers working in environmental arenas make decisions that can have large impacts on ecosystems. Basing such decisions on high‐quality evidence about the effectiveness of different interventions can often maximize the success of policy and management. Accordingly, it is vital to understand how environmental professionals working at the science‐policy interface view and use different types of evidence, including evidence syntheses that collate and summarize available knowledge on a specific topic to save time for decision‐makers. We interviewed 84 senior environmental professionals in Canada working at the science‐policy interface to explore their confidence in, and use of, evidence syntheses within their organizations. Interviewees value evidence syntheses because they increase confidence in decision‐making, particularly for high‐profile or risky decisions. Despite this enthusiasm, the apparent lack of available syntheses for many environmental issues means that use can be limited and tends to be opportunistic. Our research suggests that if relevant, high quality evidence syntheses exist, they are likely to be used and embraced in decision‐making spheres. Therefore, efforts to increase capacity for conducting evidence syntheses within government agencies and/or funding such activities by external bodies have the potential to enable evidence‐based decision‐making.Additional co-authors: Karen E. Smokorowski, Steven M. Alexander, Steven J. Cook

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions