Nanodiamond-reinforced aluminum metal matrix composites (ND–Al MMC) powders were synthesized by means of high energy ball milling. We present a systematic study of the effect of various milling ...conditions on the structure and properties of the resulting MMC powders. The described method can be used to control important powder characteristics, including particle size and shape, Al crystal size and residual strain, and structural integrity and dispersion of the nanoparticle inclusions, a crucial requirement for subsequent powder consolidation. Raman spectroscopy was utilized for the first time to directly verify the structural integrity and the dispersion of ND in the Al matrix. For low ball-to-powder ratios (BPR), average particle size and size range of the ND–Al composite powders were found to decrease during milling, while the hardness increases. A BPR of 10:1, a milling time of 10h, and a ND content of 10wt.% were most effective in obtaining small powder particle sizes, small Al crystal sizes, and improved mechanical properties reaching a hardness of 3.46GPa, a 210% increase over the pristine, untreated Al powder (1.10GPa). Finally, we demonstrate that the as-produced composite powders are well-suited for low-temperature consolidation processing by fabricating the first cold-sprayed ND–Al MMC coating.
Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce ...compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored.
We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point.
There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group.
Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.
Mass azithromycin distribution is a core component of trachoma control programmes and could reduce mortality in children younger than 5 years in some settings. In this systematic review we synthesise ...evidence on the emergence of antimicrobial resistance after mass azithromycin distribution. We searched electronic databases for publications up to June 14, 2018. We included studies of any type (excluding modelling studies, surveillance reports, and review articles) on community-wide distribution of oral azithromycin for the prevention and treatment of trachoma that assessed macrolide resistance, without restrictions to the type of organism. We extracted prevalence of resistance from published reports and requested unpublished data from authors of included studies. Of 213 identified studies, 19 met inclusion criteria (12 assessed Streptococcus pneumoniae) and were used for qualitative synthesis. Macrolide resistance after azithromycin distribution was reported in three of the five organisms studied. The lack of resistance in Chlamydia trachomatis suggests that azithromycin might remain effective for trachoma programmes, but evidence is scarce. As mass azithromycin distribution for trachoma continues and is considered for other indications, ongoing monitoring of antimicrobial resistance will be required.
Objective: Neprilysin (NEP), a zinc metalloendopeptidase, has a role in blood pressure control and lipid metabolism. The present study tested the hypothesis that NEP is associated with insulin ...resistance and features of the metabolic syndrome (MetS) in a study of 318 healthy human subjects and in murine obesity, and investigated NEP production by adipocytes in-vitro. Methods and results: In 318 white European males, plasma NEP was elevated in the MetS and increased progressively with increasing MetS components. Plasma NEP activity correlated with insulin, homoeostasis model assessment and body mass index (BMI) in all subjects (P<0.01). Quantitative reverse transcriptase PCR (RT–PCR) and western blotting showed that in human pre-adipocytes NEP expression is upregulated 25- to 30-fold during differentiation into adipocytes. Microarray analysis of mRNA from differentiated human adipocytes confirmed high-NEP expression comparable with adiponectin and plasminogen activator inhibitor-1. In a murine model of diet-induced insulin resistance, plasma NEP levels were significantly higher in high-fat diet (HFD)-fed compared with normal chow diet (NCD)-fed animals (1642+/-529 and 820+/-487 pg microliter-1, respectively; P<0.01). Tissue NEP was increased in mesenteric fat in HFD compared with NCD-fed mice (P<0.05). NEP knockout mice did not display any changes in insulin resistance, glucose tolerance, or body and epididymal fat pad weight compared with wild-type mice. Conclusion: In humans, NEP activity correlated with BMI and measures of insulin resistance with increasing levels in subjects with multiple cardiovascular risk factors. NEP protein production in human adipocytes increased during cell differentiation and plasma and adipose tissue levels of NEP were increased in obese insulin-resistant mice. Our results indicate that NEP associates with cardiometabolic risk in the presence of insulin resistance and increases with obesity.
Glass-fibre reinforced polymer (GFRP) sandwich structures (1.6
m
×
1.3
m) were subject to 30
kg charges of C4 explosive at stand-off distances 8–14
m. Experiments provide detailed data for sandwich ...panel response, which are often used in civil and military structures, where air-blast loading represents a serious threat. High-speed photography, with digital image correlation (DIC), was employed to monitor the deformation of these structures during the blasts. Failure mechanisms were revealed in the DIC data, confirmed in post-test sectioning. The experimental data provides for the development of analytical and computational models. Moreover, it underlines the importance of support boundary conditions with regards to blast mitigation. These findings were analysed further in finite element simulations, where boundary stiffness was, as expected, shown to strongly influence the panel deformation. In-depth parametric studies are ongoing to establish the hierarchy of the various factors that influence the blast response of sandwich composite structures.
Many studies show a link between forced expiratory volume in 1 s (FEV(1)) and survival in the general population and this has been interpreted as a link between airway obstruction and survival. ...However, the observation that vital capacity is also associated with survival weakens this interpretation.
Data on spirometry and survival were taken from the Atherosclerosis Risk in Communities (ARIC) limited access dataset. Survival among 7489 participants with usable spirometry and complete data was regressed against measures of ventilatory function after controlling for many other factors likely to be associated with survival.
Survival was strongly associated with forced vital capacity (FVC) after adjustment for FEV(1), but not the other way round. The fully adjusted hazard ratio (HR) associated with high FVC was 0.90 in men (95% CI 0.80 to 1.00; p=0.049) and 0.82 in women (95% CI 0.70 to 0.95; p=0.01). This compares with 0.98 for FEV(1) in men (95% CI 0.90 to 1.07; p.0.72) and 1.01 in women (95% CI 0.89 to 1.15; p=0.84). There was no association between survival and airway obstruction as measured by the FEV(1)/FVC ratio.
FVC but not airway obstruction predicts survival in asymptomatic adults without chronic respiratory diagnoses or persistent respiratory symptoms. The association is not explained by age, anthropometry, smoking, income occupation or blood pressure. As FVC later in life, cardiovascular risk, type II diabetes mellitus and low-grade systemic inflammation are all associated with poor fetal growth, these other conditions may be partly responsible for the poor survival in those with low FVC.
Background Great progress has been made toward the elimination of trachoma as a public-health problem. Mathematical and statistical models have been used to forecast when the program will attain the ...goal of the elimination of active trachoma, defined as prevalence of trachomatous inflammation-follicular in 1-9 year olds (TF.sub.1-9) <5%. Here we use program data to create an empirical model predicting the year of attaining global elimination of TF.sub.1-9. Methodology/Principal findings We calculated the mean number of years (95% CI) observed for an implementation unit (IU) to move from a baseline TF.sub.1-9 prevalence greater than or equal to5% to the elimination threshold, based on the region (Ethiopia vs. non-Ethiopia) and baseline prevalence category. Ethiopia IUs had significantly different rates of reaching the TF.sub.1-9 elimination threshold after a trachoma impact survey (TIS) compared to non-Ethiopia IUs across all baseline categories. We used those estimates to predict when remaining active trachoma-endemic IUs (TF.sub.1-9 greater than or equal to5%) would have their last round of mass drug administration (MDA) based on the mean number of years required and number of MDA rounds already completed. Our model predicts that elimination of TF.sub.1-9 will be achieved in 2028 in Ethiopia (95% CI: 2026-2033) and 2029 outside of Ethiopia (95% CI: 2023-2034), with some IUs in East Africa predicted to be the last requiring MDA globally. Conclusions/Significance Our empirical estimate is similar to those resulting from previous susceptible-infectious-susceptible (SIS) and mathematical models, suggesting that the forecast achievement of TF.sub.1-9 elimination is realistic with the caveat that although disease elimination progress can be predicted for most IUs, there is an important minority of IUs that is not declining or has not yet started trachoma elimination activities. These IUs represent an important barrier to the timely global elimination of active trachoma.
We report the first catalytic methods for the transformation of C-H bonds of unactivated arenes into C-Al bonds. The catalytic reactions occur at 25 °C (benzene, toluene and xylenes) with palladium ...loadings as low as 0.1 mol%. Remarkably, the C-H activation of toluene and xylenes proceeds with
- and
-selectivity. This selectivity is highly unusual and complementary to both Friedel-Crafts and the majority of C-H borylation methods. Through a detailed mechanistic analysis (Eyring analysis, KIE, DFT, QTAIM) we show that unusual Pd-Al intermetallic complexes are on the catalytic cycle and that the selectivity is determined by weak attractive dispersion forces in the transition state for C-H bond breaking.
Background Trachoma causes blindness due to repeated conjunctival infection by Chlamydia trachomatis (Ct). Transmission intensity is estimated, for programmatic decision-making, by prevalence of the ...clinical sign trachomatous inflammation-follicular (TF) in children aged 1-9 years. Research into complementary indicators to field-graded TF includes work on conjunctival photography, tests for ocular Ct infection, and serology. The perceived acceptability and feasibility of these indicators among a variety of stakeholders is unknown. Methodology Focus group discussions (FGDs) with community members and in-depth interviews (IDIs) with public health practitioners in Tanzania were conducted. FGDs explored themes including participants' experience with, and thoughts about, different diagnostic approaches. The framework method for content analysis was used. IDIs yielded lists of perceived strengths of, and barriers to, implementation for programmatic use of each indicator. These were used to form an online quantitative survey on complementary indicators distributed to global stakeholders via meetings, mailing lists, and social media posts. Results Sixteen FGDs and 11 IDIs were conducted in October-November 2022. In general, all proposed sample methods were deemed acceptable by community members. Common themes included not wanting undue discomfort and a preference for tests perceived as accurate. Health workers noted the importance of community education for some sample types. The online survey was conducted in April-May 2023 with 98 starting the questionnaire and 81 completing it. Regarding barriers to implementing diagnostics, the highest agreement items related to feasibility, rather than acceptability. No evidence of significant differences was found in responses pertaining to community acceptability based on participant characteristics. Conclusions All of the indicators included were generally deemed acceptable by all stakeholders in Tanzania, although community education around the benefits and risks of different sample types, as well as addressing issues around feasibility, will be key to successful, sustainable integration of these indicators into trachoma programs.
Abstract
Models predict that the negative effects of delayed implementation in trachoma elimination programmes caused by the COVID-19 pandemic will be minimal, except in high prevalence districts ...where progress may be reversed. During times of change we must stand by our principles of evidence-based decision-making, but also be willing to show flexibility. Slow progress to elimination in high prevalence districts was already a significant challenge to the global programme and mitigation of COVID-related delays with enhanced implementation provides an opportunity to simultaneously address an unprecedented challenge and a pre-existing one.
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