Summary
A state-transition microsimulation model was used to project the substantial economic burden to the Chinese healthcare system of osteoporosis-related fractures. Annual number and costs of ...osteoporosis-related fractures were estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55) million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050. Consequently, cost-effective intervention policies must urgently be identified in an attempt to minimize the impact of fractures.
Introduction
The aim of the study was to project the osteoporosis-related fractures and costs for the Chinese population aged ≥50 years from 2010 to 2050.
Methods
A state-transition microsimulation model was used to simulate the annual incident fractures and costs. The simulation was performed with a 1-year cycle length and from the Chinese healthcare system perspective. Incident fractures and annual costs were estimated from 100 unique patient populations for year 2010, by multiplying the age- and sex-specific annual fracture risks and costs of fracture by the corresponding population totals in each of the 100 categories. Projections for 2011–2050 were performed by multiplying the 2010 risks and costs of fracture by the respective annual population estimates. Costs were presented in 2013 US dollars.
Results
Approximately 2.33 (95 % CI 2.08, 2.58) million osteoporotic fractures were estimated to occur in 2010, costing $9.45 (95 % CI 8.78, 10.11) billion. Females sustained approximately three times more fractures than males, accounting for 76 % of the total costs from 1.85 (95 % CI 1.68, 2.01) million fractures. The annual number and costs of osteoporosis-related fractures were estimated to double by 2035 and will increase to 5.99 (95 % CI 5.44, 6.55) million fractures costing $25.43 (95 % CI 23.92, 26.95) billion by 2050.
Conclusions
Our study demonstrated that osteoporosis-related fractures cause a substantial economic burden which will markedly increase over the coming decades. Consequently, healthcare resource planning must consider these increasing costs, and cost-effective screening and intervention policies must urgently be identified in an attempt to minimize the impact of fractures on the health of the burgeoning population as well as the healthcare budget.
Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum ...human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.
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•Binding to all influenza A subtypes neutralizing seasonal and pandemic strains•Utilizes a rare VH (VH6-1) and carries a low level of somatic mutations•Highly conserved epitope encompassing fusion peptide and hydrophobic groove•Superior therapeutic window compared to oseltamivir in animals
Identification of a human monoclonal antibody that reacts effectively with all influenza A hemagglutinin subtypes paves the way for developing immunotherapy for people infected with the flu virus.
The mosquito midgut is a hostile environment that vector‐borne parasites must survive to be transmitted. Commensal bacteria in the midgut can reduce the ability of mosquitoes to transmit disease, ...either by having direct anti‐parasite effects or by stimulating basal immune responses of the insect host. As different bacteria have different effects on parasite development, the composition of the bacterial community in the mosquito gut is likely to affect the probability of disease transmission. We investigated the diversity of mosquito gut bacteria in the field using 454 pyrosequencing of 16S rRNA to build up a comprehensive picture of the diversity of gut bacteria in eight mosquito species in this population. We found that mosquito gut typically has a very simple gut microbiota that is dominated by a single bacterial taxon. Although different mosquito species share remarkably similar gut bacteria, individuals in a population are extremely variable and can have little overlap in the bacterial taxa present in their guts. This may be an important factor in causing differences in disease transmission rates within mosquito populations.
Rationale
Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy ...risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non‐allergen‐specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring.
Methods
We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case‐control studies and meta‐analysis performed from RCTs.
Results
We identified 95 papers: 17 RCTs and 78 observational (case‐control, cross‐sectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta‐analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56‐0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega‐3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45‐1.08). Omega‐3 supplementation was also associated with a non‐significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56‐1.04). Neither vitamin D nor omega‐3 fatty acids were associated with an altered risk of AD or food allergy.
Conclusions
Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.
Our systematic review focused on the maternal diet in pregnancy and allergy outcomes in the offspring. Results from the observational studies provided no conclusive evidence on whether the mother’s diet when pregnant affects the development of offspring allergic disease. Data from the randomized controlled trials indicated that vitamin D supplementation in doses higher than recommended by most countries, lead to a 30% reduction in offspring asthma. As a result, no recommendations about what pregnant women should eat or which supplements to take, to prevent their offspring from developing allergic disease can be made at this stage. Further studies should be performed, using standardised methods focusing on the total diet rather than one nutrient, using validated instruments to measure dietary intake and clearly defining the phenotype ad genetic characteristics of each woman.
Cancer-related fatigue (CRF) is the most common symptom in patients with advanced cancer. The primary objective of this prospective, randomized, double-blind, placebo-controlled study was to compare ...the effect of dexamethasone and placebo on CRF.
Patients with advanced cancer with ≥ three CRF-related symptoms (ie, fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days. The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) subscale from baseline to day 15. Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores.
A total of 84 patients were evaluable (dexamethasone, 43; placebo, 41). Mean (± standard deviation) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group (9 ± 10.3 v 3.1 ± 9.59; P = .008). The improvement in FACIT-F total quality-of-life scores was also significantly better for the dexamethasone group at day 15 (P = .03). The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group (P = .013, respectively). No differences were observed for ESAS overall symptom distress (P = .22) or psychological distress score (P = .76). Frequency of adverse effects was not significantly different between groups (41 of 62 v 44 of 58; P = .14).
Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.
Black men, underrepresented in engineering, constitute a missing segment of the population who could contribute to the global knowledge economy. To address this national concern, stakeholders need ...additional research on strategies that aid in Black men's persistence. This study explores the experiences of 30 Black men in engineering graduate programs. Three factors are identified as helping them persist from year to year, and in many cases through completion of the doctorate: the role of family, spirituality and faith-based community, and undergraduate mentors. The article concludes with implications for future research and professional practice that may improve the experiences of Black men in engineering graduate programs, which may also increase the chances that they will remain in the engineering workforce.
Face pareidolia is the phenomenon of seeing facelike structures in everyday objects. Here, we tested the hypothesis that face pareidolia, rather than being limited to a cognitive or mnemonic ...association, reflects the activation of visual mechanisms that typically process human faces. We focused on sensory cues to social attention, which engage cell populations in temporal cortex that are susceptible to habituation effects. Repeated exposure to “pareidolia faces” that appear to have a specific direction of attention causes a systematic bias in the perception of where human faces are looking, indicating that overlapping sensory mechanisms are recruited when we view human faces and when we experience face pareidolia. These cross-adaptation effects are significantly reduced when pareidolia is abolished by removing facelike features from the objects. These results indicate that face pareidolia is essentially a perceptual phenomenon, occurring when sensory input is processed by visual mechanisms that have evolved to extract specific social content from human faces.
Multicellularity has coincided with the evolution of microRNAs (miRNAs), small regulatory RNAs that are integrated into cellular differentiation and homeostatic gene-regulatory networks. However, the ...regulatory mechanisms underpinning miRNA activity have remained largely obscured because of the precise, and thus difficult to access, cellular contexts under which they operate. To resolve these, we have generated a genome-wide map of active miRNAs in Caenorhabditis elegans by revealing cell-type-specific patterns of miRNAs loaded into Argonaute (AGO) silencing complexes. Epitope-labelled AGO proteins were selectively expressed and immunoprecipitated from three distinct tissue types and associated miRNAs sequenced. In addition to providing information on biological function, we define adaptable miRNA:AGO interactions with single-cell-type and AGO-specific resolution. We demonstrate spatial and temporal dynamicism, flexibility of miRNA loading, and suggest miRNA regulatory mechanisms via AGO selectivity in different tissues and during ageing. Additionally, we resolve widespread changes in AGO-regulated gene expression by analysing translatomes specifically in neurons.
Details of current UK anaesthetic practice are unknown and were needed for interpretation of reports of accidental awareness during general anaesthesia (GA) within the 5th National Audit Project.
We ...surveyed NHS anaesthetic activity to determine numbers of patients managed by anaesthetists and details of ‘who, when, what, and where': activity included GA, local anaesthesia, sedation, or patients managed awake. Anaesthetists in NHS hospitals collected data on all patients for 2 days. Scaling enabled estimation of annual activity.
Hospital response rate was 100% with 20 400 returns. The median return rate within departments was 98% (inter-quartile range 0.95–1). Annual numbers (% of total) of general anaesthetics, sedation, and awake cases were 2 766 600 (76.9%), 308 800 (8.6%), and 523 100 (14.5%), respectively. A consultant or career grade anaesthetist was present in more than 87% of cases. Emergency cases accounted for 23.1% of workload, 75% of which were undertaken out of hours. Specialties with the largest workload were orthopaedics/trauma (22.1%), general surgery (16.1%), and gynaecology (9.6%): 6.2% of cases were non-surgical. The survey data describe: who anaesthetized patients according to time of day, urgency, and ASA grade; when anaesthesia took place by day and by weekday; the distribution of patient types, techniques, and monitoring; where patients were anaesthetized. Nine patients out of 15 460 receiving GA died intraoperatively.
Anaesthesia in the UK is currently predominantly a consultant-delivered service. The low mortality rate supports the safety of UK anaesthetic care. The survey data should be valuable for planning and monitoring anaesthesia services.
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