Global, regional, and national burden of disorders affecting the nervous system, 1990–2021:a systematic analysis for the Global Burden of Disease Study 2021

Background: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill &amp; Melinda Gates Foundation.</p

Prioritizing Indicators for Rapid Response in Global Health Security:A Bayesian Network Approach

This study explored a Bayesian belief networks (BBNs) approach, developing two distinct models for prioritizing the seven indicators related to the “rapid response to and mitigation of the spread of an epidemic” category within the context of both the specific category and the Global Health Security Index (GHS index). Utilizing data from the 2021 GHS index, the methodology involves rigorous preprocessing, the application of the augmented naive Bayes algorithm for structural learning, and k-fold cross-validation. Key findings show unique perspectives in both BBN models. In the mutual value of information analysis, “linking public health and security authorities” emerged as the key predictor for the “rapid response to and mitigation of the spread of an epidemic” category, while “emergency preparedness and response planning” assumed precedence for the GHS index. Sensitivity analysis highlighted the critical role of “emergency preparedness and response planning” and “linking public health and security authorities” in extreme performance states, with “access to communications infrastructure” and “trade and travel restrictions” exhibiting varied significance. The BBN models exhibit high predictive accuracy, achieving 83.3% and 82.3% accuracy for extreme states in “rapid response to and mitigation of the spread of an epidemic” and the GHS index, respectively. This study contributes to the literature on GHS by modeling the dependencies among various indicators of the rapid response dimension of the GHS index and highlighting their relative importance based on the mutual value of information and sensitivity analyses.</p

Shear Behaviour of Cold-Formed Stainless Steel Lipped Channel Sections with Web Holes

Cold-formed stainless steel structural members are increasingly used in infrastructure for their corrosion resistance, aesthetic appeal, and strain hardening. Accurate design methods are crucial for achieving optimal use of stainless steel, given its high cost. In construction, web holes are commonly introduced to cold-formed stainless-steel sections for service installation like pipes, ducts, and cables. The introduction of web holes can significantly weaken the section, reducing its load-carrying capacity, so it must be carefully considered during the design phase. Despite their importance, there are limited studies investigating the shear strength reduction due to web holes in cold-formed stainless-steel sections and assessing existing Eurocode 3 shear design provisions. To address this gap, shear strength data of cold-formed stainless steel lipped channel sections with circular web holes was collected from the literature. The collected data included austenitic and duplex stainless-steel grades and web hole ratios ranging from 0.1 to 0.85. The collected data was used to assess the applicability of current shear design guidelines in the Eurocode 3 (EN1993-1-4) structural design specification. The comparative assessment revealed that the existing guidelines for solid cold-formed stainless-steel sections cannot be extended to cold-formed stainless steel sections with web holes. The comparison revealed that these guidelines are not suitable for capturing the influence of web holes on the shear strength of cold-formed stainless steel lipped channel sections. Therefore, new shear design proposals specifically for these sections with web holes were developed based on the collected data. The proposed shear design guidelines offer more reliable predictions of ultimate shear strength for cold-formed stainless steel lipped channel sections compared to the existing Eurocode 3 (EN1993-1-3) design rules

Prediction of the torsional capacity of CFDST steel columns using extreme gradient boosting tree-based machine learning technique

This study presents an eXtreme Gradient Boosting (XGBoost) algorithm for predicting the torsional capacity of circular Concrete-Filled Double Skin Tubular (CFDST) steel columns under pure torsion. Utilizing a dataset of 806 columns generated through non-linear finite element analysis, the of XGBoost model outperforms existing empirical models with R² values of 99.5% (training) and 97.6% (testing). SHapley Additive exPlanations (SHAP) framework aided in interpreting predictions at both global and local levels. Key influencing variables include concrete compressive strength, outer steel tube yield strength, outer steel tube thickness, and inner steel tube thickness. The study highlights the effectiveness XGBoost as a promising alternative to traditional empirical models for accurate torsional capacity predictions in CFDST steel columns

Shear Behaviour of Cold-Formed Stainless Steel Lipped Channel Sections with Web Holes

Cold-formed stainless steel structural members are increasingly used in infrastructure for their corrosion resistance, aesthetic appeal, and strain hardening. Accurate design methods are crucial for achieving optimal use of stainless steel, given its high cost. In construction, web holes are commonly introduced to cold-formed stainless-steel sections for service installation like pipes, ducts, and cables. The introduction of web holes can significantly weaken the section, reducing its load-carrying capacity, so it must be carefully considered during the design phase. Despite their importance, there are limited studies investigating the shear strength reduction due to web holes in cold-formed stainless-steel sections and assessing existing Eurocode 3 shear design provisions. To address this gap, shear strength data of cold-formed stainless steel lipped channel sections with circular web holes was collected from the literature. The collected data included austenitic and duplex stainless-steel grades and web hole ratios ranging from 0.1 to 0.85. The collected data was used to assess the applicability of current shear design guidelines in the Eurocode 3 (EN1993-1-4) structural design specification. The comparative assessment revealed that the existing guidelines for solid cold-formed stainless-steel sections cannot be extended to cold-formed stainless steel sections with web holes. The comparison revealed that these guidelines are not suitable for capturing the influence of web holes on the shear strength of cold-formed stainless steel lipped channel sections. Therefore, new shear design proposals specifically for these sections with web holes were developed based on the collected data. The proposed shear design guidelines offer more reliable predictions of ultimate shear strength for cold-formed stainless steel lipped channel sections compared to the existing Eurocode 3 (EN1993-1-3) design rules

Teaching patients about pain: the emergence of Pain Science Education, its learning frameworks and delivery strategies

Since it emerged in the early 2000’s, intensive education about ‘how pain works’, widely known as pain neuroscience education or explaining pain, has evolved into a new educational approach, with new content and new strategies. The substantial differences to the original have led the PETAL collaboration to call the current iteration ‘Pain Science Education’. This review presents a brief historical context for PSE, the clinical trial, consumer perspective and real-world clinical data that have pushed the field to update both content and method. We describe the key role of educational psychology in driving this change, the central role of constructivism and the constructivist learning frameworks around which PSE is now planned and delivered. We integrate terminology and concepts from the learning frameworks currently being used across the PETAL collaboration in both research and practice – the Interactive, Constructive, Active, Passive (ICAP) framework, transformative learning theory, dynamic model of conceptual change. We then discuss strategies that are being used to enhance learning within clinical encounters, which focus on the skill, will and thrill of learning. Finally, we provide practical examples of these strategies so as to assist the reader to drive their own patient pain education offerings towards more effective learnin

The impact of the cost-of-living crisis, self-efficacy and religiosity on health-related quality of life in individuals with sickle cell disease

Aim: This study investigated the role of the individual impact of the cost-of-living crisis, self-efficacy, religiosity, demographic factors, and their collective influence on the health-related quality of life (HRQoL) of individuals with sickle cell disease (SCD).Methods: A correlational online survey with 443 participants living with SCD (51.5% males and 48.8% females) was conducted. HRQoL was assessed with the 12-Item Short Form Survey (SF-12). Independent variables were the individual impact of the cost-of-living crisis (ICoLC), sickle cell self-efficacy, religiosity, and demographic factors (age, gender, education, and country of residence). Quantile regression analysis was employed.Results: Self-efficacy was positively associated with HRQoL, evidencing the importance of self-efficacy in managing SCD. ICoLC was negatively associated with HRQoL, underscoring the challenges faced by individuals with SCD during the cost-of-living crisis. UK participants reported significantly higher HRQoL than US participants, suggesting national disparities. Contrary to previous findings, religiosity was negatively associated with HRQoL.Conclusion: This study highlights the roles of self-efficacy, the cost-of-living crisis, religiosity, and demographic factors in shaping the HRQoL of individuals with SCD. Our findings call for interventions that enhance self-efficacy, mitigate the financial challenges arising from the cost-of-living crisis, and provide tailored support for individuals having differing levels of religiosity. They also emphasize the need for region-specific healthcare delivery and support systems. Future research should explore these relationships qualitatively, aiming to develop interventions that enhance HRQoL for individuals with SCD, regardless of their geographical location, to improve outcomes and overall well-being during the cost-of-living crisis and beyond

Costs of endovascular and open repair of thoracic aortic aneurysms

BACKGROUND: Repair of thoracic aortic aneurysms with either endovascular repair (TEVAR) or open surgical repair (OSR) represents major surgery, is costly and associated with significant complications. The aim of this study was to establish accurate costs of delivering TEVAR and OSR in a cohort of UK NHS patients suitable for open and endovascular treatment for the whole treatment pathway from admission and to discharge and 12-month follow-up.METHODS: A prospective study of UK NHS patients from 30 NHS vascular/cardiothoracic units in England aged ≥18, with distal arch/descending thoracic aortic aneurysms (CTAA) was undertaken. A multicentre prospective cost analysis of patients (recruited March 2014-July 2018, follow-up until July 2019) undergoing TEVAR or OSR was performed. Patients deemed suitable for open or endovascular repair were included in this study. A micro-costing approach was adopted.RESULTS: Some 115 patients having undergone TEVAR and 35 patients with OSR were identified. The mean (s.d.) cost of a TEVAR procedure was higher £26 536 (£9877) versus OSR £17 239 (£8043). Postoperative costs until discharge were lower for TEVAR £7484 (£7848) versus OSR £28 636 (£23 083). Therefore, total NHS costs from admission to discharge were lower for TEVAR £34 020 (£14 301), versus OSR £45 875 (£43 023). However, mean NHS costs for 12 months following the procedure were slightly higher for the TEVAR £5206 (£11 585) versus OSR £5039 (£11 994).CONCLUSIONS: Surgical procedure costs were higher for TEVAR due to device costs. Total in-hospital costs were higher for OSR due to longer hospital and critical care stay. Follow-up costs over 12 months were slightly higher for TEVAR due to hospital readmissions.</p

Rapid Quantification of Oxidized and Reduced Forms of Glutathione Using Ortho-phthalaldehyde in Cultured Mammalian Cells In Vitro

Glutathione has long been considered a key biomarker for determining the antioxidant response of the cell. Hence, it is a primary marker for reactive oxygen species studies. The method utilizes Ortho-phthalaldehyde (OPA) to quantify the cellular concentration of glutathione(s). OPA conjugates with reduced glutathione (GSH) via sulfhydryl binding to subsequently form an isoindole, resulting in a highly fluorescent conjugate. To attain an accurate result of both oxidized glutathione (GSSG) and GSH, a combination of masking agents and reducing agents, which have been implemented in this protocol, are required. Treatments may also impact cellular viability. Hence, normalization via protein assay is presented in this multiparametric assay. The assay demonstrates a pseudo-linear detection range of 0.234 – 30µM (R2=0.9932±0.007 (N=12)) specific to GSH. The proposed assay also allows for the determination of oxidized glutathione with the addition of the masking agent N-ethylmaleimide to bind reduced glutathione, and the reducing agent tris(2-carboxyethyl) phosphine is introduced to cleave the disulfide bond in GSSG to produce two molecules of GSH. The assay is used in combination with a validated bicinchoninic acid assay for protein quantification and an adenylate kinase assay for cytotoxicity assessment