Bulk genetic characterization of Ghanaian maize landraces using microsatellite markers

Maize (Zea mays L) was first introduced into Ghana over five centuries ago and remains the most important cereal staple, grown in all agro-ecologies across the country. Yield from farmers’ fields are low, which is attributed in part to farmer’s preferences and/or reliance on local landraces for cultivation. Efforts are underway to improve some of these landraces for improved productivity. Seeds of maize landraces cultivated in all agro-ecologies were col¬lected for genetic characterization using a bulked fingerprinting technique and 20 SSR markers. In all, 20 popula¬tions of 15 plants each from Ghana and 4 control populations from Latin America were characterized. The cluster analysis grouped the 20 landraces into two major groups corresponding to the vegetation/climatic conditions of the north and south of the country. Genotypes from Ashanti, which is centrally located, fell into both major clus¬ters, which suggest its importance in maize seed distribution in Ghana and also the diverse climate/vegetation. A Structure analyses grouped the genotypes into two major clusters similar to the UPGMA cluster, and populations were not fully distinct according to F statistics. The results suggest that breeders should make performance data available to seed dealers for better productivity

Availability and price of malaria rapid diagnostic tests in the public and private health sectors in 2011: results from 10 nationally representative cross-sectional retail surveys.

OBJECTIVES: To describe the state of the public and private malaria diagnostics market shortly after WHO updated its guidelines for testing all suspected malaria cases prior to treatment. METHODS: Ten nationally representative cross-sectional cluster surveys were conducted in 2011 among public and private health facilities, community health workers and retail outlets (pharmacies and drug shops) in nine countries (Tanzania mainland and Zanzibar surveyed separately). Eligible outlets had antimalarials in stock on the day of interview or had stocked antimalarials in the past 3 months. RESULTS: Three thousand four hundred and thirty-nine rapid diagnostic test (RDT) products from 39 manufacturers were audited among 12,197 outlets interviewed. Availability was typically highest in public health facilities, although availability in these facilities varied greatly across countries, from 15% in Nigeria to >90% in Madagascar and Cambodia. Private for-profit sector availability was 46% in Cambodia, 20% in Zambia, but low in other countries. Median retail prices for RDTs in the private for-profit sector ranged from $0.00 in Madagascar to$3.13 in Zambia. The reported number of RDTs used in the 7 days before the survey in public health facilities ranged from 3 (Benin) to 50 (Zambia). CONCLUSIONS: Eighteen months after WHO updated its case management guidelines, RDT availability remained poor in the private sector in sub-Saharan Africa. Given the ongoing importance of the private sector as a source of fever treatment, the goal of universal diagnosis will not be achievable under current circumstances. These results constitute national baselines against which progress in scaling-up diagnostic tests can be assessed

Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)

Introduction The BRIGhTMIND study aims to determine the clinical effectiveness, cost effectiveness and mechanism of action of connectivity guided intermittent Theta Burst Stimulation (cgiTBS) versus standard repetitive Transcranial Magnetic Stimulation (rTMS) in adults with moderate to severe treatment resistant depression. Methods and analysis The study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (a) cgiTBS or (b) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital (MGH) Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the United Kingdom. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks post randomisation. Cost effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined

Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight

A male sheep linkage map comprising 191 microsatellites was generated from a single family of 510 Awassi-Merino backcross progeny. Except for ovine chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference greater than 3.0 between the best and second-best map order. The map is on average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map was employed in quantitative trait loci (QTL) analyses on body-weight and growth-rate traits between birth and 98 weeks of age. A custom maximum likelihood program was developed to map QTL in half-sib families for non-inbred strains (QTL-MLE) and is freely available on request. The new analysis package offers the advantage of enabling QTL × fixed effect interactions to be included in the model. Fifty-four putative QTL were identified on nine chromosomes. Significant QTL with sex-specific effects (i.e. QTL × sex interaction) in the range of 0.4 to 0.7 SD were found on ovine chromosomes 1, 3, 6, 11, 21, 23, 24 and 26

Improving access to malaria medicine through private-sector subsidies in seven African countries.

Improving access to quality-assured artemisinin combination therapies (ACTs) is an important component of malaria control in low- and middle-income countries. In 2010 the Global Fund to Fight AIDS, Tuberculosis, and Malaria launched the Affordable Medicines Facility--malaria (AMFm) program in seven African countries. The goal of the program was to decrease malaria morbidity and delay drug resistance by increasing the use of ACTs, primarily through subsidies intended to reduce costs. We collected data on price and retail markups on antimalarial medicines from 19,625 private for-profit retail outlets before and 6-15 months after the program's implementation. We found that in six of the AMFm pilot programs, prices for quality-assured ACTs decreased by US$1.28-$4.34, and absolute retail markups on these therapies decreased by US$0.31-$1.03. Prices and markups on other classes of antimalarials also changed during the evaluation period, but not to the same extent. In all but two of the pilot programs, we found evidence that prices could fall further without suppliers' losing money. Thus, concerns may be warranted that wholesalers and retailers are capturing subsidies instead of passing them on to consumers. These findings demonstrate that supranational subsidies can dramatically reduce retail prices of health commodities and that recommended retail prices communicated to a wide audience may be an effective mechanism for controlling the market power of private-sector antimalarial retailers and wholesalers

Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1×10−9). The improvement varied across diseases with a 16% median increase in χ2 test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci

Methodological developments in qualitative longitudinal research:the advantages and challenges of regular telephone contact with participants in a qualitative longitudinal interview study

BACKGROUND: Qualitative longitudinal research is an evolving methodology, particularly within health care research. It facilitates a nuanced understanding of how phenomena change over time and is ripe for innovative approaches. However, methodological reflections which are tailored to health care research are scarce. This article provides a synthesised and practical account of the advantages and challenges of maintaining regular telephone contact between interviews with participants in a qualitative longitudinal study. METHODS: Participants with metastatic colorectal cancer were interviewed at 3 time points over the course of a year. Half the group also received monthly telephone calls to explore the added value and the feasibility of capturing change as close to when it was occurring as possible. RESULTS: The data gathered from the telephone calls added context to the participants’ overall narrative and informed subsequent interviews. The telephone calls meant we were able to capture change close to when it happened and there was a more evolved, and involved, relationship between the researcher and the participants who were called on a monthly basis. However, ethical challenges were amplified, boundaries of the participant/researcher relationship questioned, and there was the added analytical burden. CONCLUSIONS: The telephone calls facilitated a more nuanced understanding of the illness experience to emerge, when compared with the interview only group. The findings suggest that intensive telephone contact may be justified if retention is an issue, when the phenomena being studied is unpredictable and when participants feel disempowered or lack control. These are potential issues for research involving participants with long-term illness

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression