A-optimal designs for an additive quadratic mixture model

Quadratic models are widely used in the analysis of experiments involving mixtures. This paper gives A-optimal designs for an additive quadratic mixture model for q ≥ 3 mixture components. It is proved that in these A-optimal designs, vertices of the simplex S q-1 are support points, and other support points shift gradually from barycentres of depth 1 to barycentres of depth 3 as q increases. A-optimal designs with minimal support are also discussed.published_or_final_versio

Optimal designs for an additive quadratic mixture model involving the amount of mixture

This paper is concerned with D- and A-optimal designs for a quadratic additive model for experiments with mixtures, in which the response depends not only on the relative proportions but also on the actual amounts of the mixture components. It is found that the origin and vertices of the simplex are support points of these optimal designs, and when the number of mixture components increases, other support points shift gradually from barycentres of depth 1 to barycentres of higher depths. It is shown that the D-optimal designs have high efficiency in terms of A-optimality, and vice versa.published_or_final_versio

A Mobile App Platform for Discovering Learning Profiles and Analytics

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Brief intervention to promote smoking cessation and improve glycemic control in smokers with type 2 diabetes: a randomized controlled trial

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Brief advice and active referral for smoking cessation services among community smokers: a study protocol for randomized controlled trial

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China’s Weibo: is faster different?

The popularization of microblogging in China represents a new challenge to the state’s regime of information control. The speed with which information is diffused in the microblogosphere has helped netizens to publicize and express their discontent with the negative consequences of economic growth, income inequalities and official corruption. In some cases, netizen led initiatives have facilitated the mobilization of online public opinion and forced the central government to intervene to redress acts of lower level malfeasance. However, despite the growing corpus of such cases, the government has quickly adapted to the changing internet ecology and is using the same tools to help it maintain control of society by enhancing its claims to legitimacy, circumscribing dissent, identifying malfeasance in its agents and using online public opinion to adapt policy and direct propaganda efforts. This essay reflects on microblogging in the context of the Chinese internet, and argues that successes in breaking scandals and mobilizing opinion against recalcitrant officials should not mask the reality that the government is utilizing the microblogosphere to its own advantage

"Who are our support networks?" A qualitative study of informal support for carers

There is little information about the types of social support and content of assistance for informal carers. This article aims to fill this knowledge gap by studying 37 informal carers in a region of the UK. It was found that adult children were the main source of support for older carers regardless of ethnic backgrounds, minority ethnic carers supported their husband to fulfill traditional caring duties by taking care of mother-in-law in the same household. Young carers received support mainly from uncles and aunts to look after sick parents while adult carers obtained information and peer support from the internet. Surprisingly, support from neighbors was limited. Additionally, social support for carers was undermined by the stigmatization of drug and alcohol misuse and mental illness. It is proposed that different types of online support services and appropriate educational programs need to be offered to carers to set up self-help groups and tackle stigmatization associated with health problems. It is suggested that future studies can use a large representative sample to give a comprehensive picture on the contents of informal support for different types of caregivers and the impact of social support on helping informal carers to fulfill their duties

Risk of sudden unexplained death after use of dihydroartemisinin-piperaquine for malaria: A systematic review and Bayesian meta-analysis

Background Dihydroartemisinin–piperaquine is an effective and well tolerated artemisinin-based combination therapy that has been assessed extensively for the prevention and treatment of malaria. Piperaquine, similar to several structurally related antimalarials currently used, can prolong cardiac ventricular repolarisation duration and the electrocardiographic QT interval, leading to concerns about its proarrhythmic potential. We aimed to assess the risk of potentially lethal iatrogenic ventricular arrhythmias in individuals receiving dihydroartemisinin–piperaquine. Methods We did a systematic review and Bayesian meta-analysis. We searched clinical bibliographic databases (last on May 24, 2017) for studies of dihydroartemisinin–piperaquine in human beings. Further unpublished studies were identified with the WHO Evidence Review Group on the Cardiotoxicity of Antimalarials. We searched for articles containing “dihydroartemisinin-piperaquine” as title, abstract, or subject heading keywords, with synonyms and variant spellings as additional search terms. We excluded animal studies, but did not apply limits on language or publication date. Eligible studies were prospective, randomised, controlled trials or cohort studies in which individuals received at least one 3-day treatment course of dihydroartemisinin–piperaquine for mass drug administration, preventive therapy, or case management of uncomplicated malaria, with follow-up over at least 3 days. At least two independent reviewers screened titles, abstracts, and full texts, agreed study eligibility, and extracted information about study and participant characteristics, adverse event surveillance methodology, dihydroartemisinin–piperaquine exposures, loss-to-follow up, and any deaths after dihydroartemisinin–piperaquine treatment into a standardised database. The risk of sudden unexplained death after dihydroartemisinin–piperaquine with 95% credible intervals (CI) generated by Bayesian meta-analysis was compared with the baseline rate of sudden cardiac death. Findings Our search identified 94 eligible primary studies including data for 197 867 individuals who had received dihydroartemisinin–piperaquine: 154 505 in mass drug administration programmes; 15 188 in 14 studies of repeated courses in preventive therapies and case management of uncomplicated malaria; and 28 174 as single-course treatments of uncomplicated malaria in 76 case-management studies. There was one potentially drug-related sudden unexplained death: a healthy woman aged 16 in Mozambique who developed heart palpitations several hours after the second dose of dihydroartemisinin–piperaquine and collapsed and died on the way to hospital (no autopsy or ECG was done). The median pooled risk estimate of sudden unexplained death after dihydroartemisinin–piperaquine was 1 in 757 950 (95% CI 1 in 2 854 490 to 1 in 209 114). This risk estimate was not higher than the baseline rate of sudden cardiac death (0·7–11·9 per 100 000 person-years or 1 in 1 714 280 to 1 in 100 835 over a 30-day risk period). The risk of bias was low in most studies and unclear in a few. Interpretation Dihydroartemisinin–piperaquine was associated with a low risk of sudden unexplained death that was not higher than the baseline rate of sudden cardiac death. Concerns about repolarisation-related cardiotoxicity need not limit its current use for the prevention and treatment of malaria

Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa

Background Cryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)–related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. Methods We randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. Results A total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P=0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen. Conclusions One week of amphotericin B plus flucytosine and 2 weeks of fluconazole plus flucytosine were effective as induction therapy for cryptococcal meningitis in resource-limited settings. (ACTA Current Controlled Trials number, ISRCTN45035509.

G12 signaling through c-jun nh 2-terminal kinase promotes breast cancer cell invasion

10.1371/journal.pone.0026085PLoS ONE611