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The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. National Institute for Health Research and Oxford Martin School.

Medicine is constantly looking for new and improved treatments for diseases, which need to have a high efficacy and be cost-effective, creating a large demand on scientific research to discover such new treatments. One important aspect of any treatment is the ability to be able to target only the illness and not cause harm to another healthy part of the body. For this reason, metallic nanoparticles have been and are currently being extensively researched for their possible medical uses, including medical imaging, antibacterial and antiviral applications. Superparamagnetic metal nanoparticles possess properties that allow them to be directed around the body with a magnetic field or directed to a magnetic implant, which opens up the potential to conjugate various bio-cargos to the nanoparticles that could then be directed for treatment in the body. Here we report on some of the current bio-medical applications of various metal nanoparticles, including single metal nanoparticles, functionalized metal nanoparticles, and core-shell metal nanoparticles using a core of Fe 3 O 4 as well as synthesis methods of these core-shell nanoparticles.

We compile an IO toolkit for aggregative games with positive and normative comparative statics results for asymmetric oligopoly in the short and long run. We characterize the class of aggregative Bertrand and Cournot oligopoly games, and the subset for which the aggregate is a summary statistic for consumer welfare. We close the model with a monopolistically competitive fringe for long-run analysis. Remarkably, we show strong neutrality properties in the long run across a wide range of market structures. The results elucidate aggregative games as a unifying principle in the literature on merger analysis, privatization, Stackelberg leadership, and cost shocks.

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort ( n =100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment. Here, Richa Saxena and colleagues perform a genome-wide association study (GWAS) of self-reported morningness/eveningness preference in the UKBiobank cohort, and identify new genetic loci that contribute to a person's chronotype.

Standard models of advertising-financed media assume consumers patronise a single-media platform, precluding effective competition for advertisers. Such competition ensues if consumers multi-home. The principle of incremental pricing implies that multi-homing consumers are less valuable to platforms. Then entry of new platforms decreases advertisement prices, while a merger increases them, and advertisement-financed platforms may suffer if a public broadcaster carries advertisements. Platforms may bias content against multi-homing consumers, especially if consumers highly value overlapping content and/or second impressions have low value.

Richa Saxena and colleagues report genome-wide association analyses of sleep disturbance traits in the UK Biobank cohort. They discover loci associated with insomnia symptoms and excessive daytime sleepiness and identify genetic correlations with several neuropsychiatric and metabolic traits. Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality 1 , 2 , affect 25–30% of adults worldwide 3 . Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable 4 , 5 , 6 , 7 , 8 , 9 and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank ( n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1 , TMEM132E , CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR – OPHN1 ) and a composite sleep trait (near PATJ ( INADL ) and HCRTR2 ) and replicate a locus associated with sleep duration (at PAX8 ). We also observe genetic correlation between longer sleep duration and schizophrenia risk ( r g = 0.29, P = 1.90 × 10 −13 ) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): r g = 0.20, P = 3.12 × 10 −9 ; waist circumference: r g = 0.20, P = 2.12 × 10 −7 ).

Background The worldwide outbreak of coronavirus disease‐19 (COVID‐19) has already put healthcare workers (HCWs) at a high risk of infection. The question of how to give HCWs the best protection against infection is a priority. Methods We searched systematic reviews and original studies in Medline (via Ovid) and Chinese Wan Fang digital database from inception to May, 2020, using terms 'coronavirus', 'health personnel', and 'personal protective equipment' to find evidence about the use of full‐body PPEs and other PPEs by HCW exposed highly infectious diseases. Results Covering more of the body could provide better protection for HCWs. Of importance, it is not just the provision of PPE but the skills in donning and doffing of PPE that are important, this being a key time for potential transmission of pathogen to the HCW and in due time from them to others. In relation to face masks, the evidence indicates that a higher‐level specification of face masks and respirators (such as N95) seems to be essential to protect HCWs from coronavirus infection. In community setting, the use of masks in the case of well individuals could be beneficial. Evidence specifically around PPE and protection from the COVID‐19 virus is limited. Conclusion Covering more of the body, and a higher‐level specification of masks and respirators could provide better protection for HCWs. Community mask usecould be beneficial. High quality studies still need to examine the protection of PPE against COVID‐19.

The Information Age has a surfeit of information received relative to what is processed. We model multiple sectors competing for consumer attention, with competition in price within each sector. Sector advertising levels follow a constant elasticity of substitution (CES) form, and within-sector prices are dispersed with a truncated Pareto distribution. The \"information hump\" shows highest ad levels for intermediate attention levels. Overall, advertising is excessive, although the allocation across sectors is optimal. The blame for information overload falls most on product categories with low information transmission costs and low profits.

BackgroundBeneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as first-line treatment are scarce.AimRetrospective comparison of long-term effectiveness and safety of first-line low-dose azathioprine-allopurinol co-therapy (LDAA) with first-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring.MethodsClinical benefit was defined as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events.ResultsIn total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical benefit was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p = 0.0003), 12 months (54% vs. 37%, p = 0.01) and in the long-term (median 36 months; 37% vs. 24%, p = 0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p = 0.001). Only 73% of the effective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200–300 mg/day significantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity.ConclusionsOur poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a long-term safe and more effective profile of first-line LDAA. This co-therapy may therefore be considered standard first-line immunosuppressive.