Effects of the EQUIP quasi-experimental study testing a collaborative quality improvement approach for maternal and newborn health care in Tanzania and Uganda.

BACKGROUND: Quality improvement is a recommended strategy to improve implementation levels for evidence-based essential interventions, but experience of and evidence for its effects in low-resource settings are limited. We hypothesised that a systemic and collaborative quality improvement approach covering district, facility and community levels, supported by report cards generated through continuous household and health facility surveys, could improve the implementation levels and have a measurable population-level impact on coverage and quality of essential services. METHODS: Collaborative quality improvement teams tested self-identified strategies (change ideas) to support the implementation of essential maternal and newborn interventions recommended by the World Health Organization. In Tanzania and Uganda, we used a plausibility design to compare the changes over time in one intervention district with those in a comparison district in each country. Evaluation included indicators of process, coverage and implementation practice analysed with a difference-of-differences and a time-series approach, using data from independent continuous household and health facility surveys from 2011 to 2014. Primary outcomes for both countries were birth in health facilities, breastfeeding within 1 h after birth, oxytocin administration after birth and knowledge of danger signs for mothers and babies. Interpretation of the results considered contextual factors. RESULTS: The intervention was associated with improvements on one of four primary outcomes. We observed a 26-percentage-point increase (95% CI 25-28%) in the proportion of live births where mothers received uterotonics within 1 min after birth in the intervention compared to the comparison district in Tanzania and an 8-percentage-point increase (95% CI 6-9%) in Uganda. The other primary indicators showed no evidence of improvement. In Tanzania, we saw positive changes for two other outcomes reflecting locally identified improvement topics. The intervention was associated with an increase in preparation of clean birth kits for home deliveries (31 percentage points, 95% CI 2-60%) and an increase in health facility supervision by district staff (14 percentage points, 95% CI 0-28%). CONCLUSIONS: The systemic quality improvement approach was associated with improvements of only one of four primary outcomes, as well as two Tanzania-specific secondary outcomes. Reasons for the lack of effects included limited implementation strength as well a relatively short follow-up period in combination with a 1-year recall period for population-based estimates and a limited power of the study to detect changes smaller than 10 percentage points. TRIAL REGISTRATION: Pan African Clinical Trials Registry: PACTR201311000681314

Practicing a Musical Instrument in Childhood is Associated with Enhanced Verbal Ability and Nonverbal Reasoning

Background: In this study we investigated the association between instrumental music training in childhood and outcomes closely related to music training as well as those more distantly related. Methodology/Principal Findings: Children who received at least three years (M = 4.6 years) of instrumental music training outperformed their control counterparts on two outcomes closely related to music (auditory discrimination abilities and fine motor skills) and on two outcomes distantly related to music (vocabulary and nonverbal reasoning skills). Duration of training also predicted these outcomes. Contrary to previous research, instrumental music training was not associated with heightened spatial skills, phonemic awareness, or mathematical abilities. Conclusions/Significance: While these results are correlational only, the strong predictive effect of training duration suggests that instrumental music training may enhance auditory discrimination, fine motor skills, vocabulary, and nonverba

Major Reduction in Anti-Malarial Drug Consumption in Senegal after Nation-Wide Introduction of Malaria Rapid Diagnostic Tests

BACKGROUND: While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. METHODS AND FINDINGS: Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases). An estimated 516,576 courses of inappropriate ACT prescription were averted. CONCLUSIONS: The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed flexibility in management of these funds to address increases in other programmatic costs that may accrue from improved diagnosis of febrile disease

Genome-wide association reveals genetic effects on human Aβ₄₂and τ protein levels in cerebrospinal fluids: a case control study

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is common and highly heritable with many genes and gene variants associated with AD in one or more studies, including APOE ε2/ε3/ε4. However, the genetic backgrounds for normal cognition, mild cognitive impairment (MCI) and AD in terms of changes in cerebrospinal fluid (CSF) levels of Aβ_1-42, T-tau, and P-tau_181P, have not been clearly delineated. We carried out a genome-wide association study (GWAS) in order to better define the genetic backgrounds to these three states in relation to CSF levels.</p> <p>Methods</p> <p>Subjects were participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The GWAS dataset consisted of 818 participants (mainly Caucasian) genotyped using the Illumina Human Genome 610 Quad BeadChips. This sample included 410 subjects (119 Normal, 115 MCI and 176 AD) with measurements of CSF Aβ_1-42, T-tau, and P-tau_181PLevels. We used PLINK to find genetic associations with the three CSF biomarker levels. Association of each of the 498,205 SNPs was tested using additive, dominant, and general association models while considering APOE genotype and age. Finally, an effort was made to better identify relevant biochemical pathways for associated genes using the ALIGATOR software.</p> <p>Results</p> <p>We found that there were some associations with APOE genotype although CSF levels were about the same for each subject group; CSF Aβ_1-42levels decreased with APOE gene dose for each subject group. T-tau levels tended to be higher among AD cases than among normal subjects. From adjusted result using APOE genotype and age as covariates, no SNP was associated with CSF levels among AD subjects. <it>CYP19A1 </it>'aromatase' (rs2899472), <it>NCAM2</it>, and multiple SNPs located on chromosome 10 near the <it>ARL5B </it>gene demonstrated the strongest associations with Aβ_1-42in normal subjects. Two genes found to be near the top SNPs, <it>CYP19A1 </it>(rs2899472, p = 1.90 × 10^-7) and <it>NCAM2 </it>(rs1022442, p = 2.75 × 10^-7) have been reported as genetic factors related to the progression of AD from previous studies. In AD subjects, APOE ε2/ε3 and ε2/ε4 genotypes were associated with elevated T-tau levels and ε4/ε4 genotype was associated with elevated T-tau and P-tau_181Plevels. Pathway analysis detected several biological pathways implicated in Normal with CSF β-amyloid peptide (Aβ_1-42).</p> <p>Conclusions</p> <p>Our genome-wide association analysis identified several SNPs as important factors for CSF biomarker. We also provide new evidence for additional candidate genetic risk factors from pathway analysis that can be tested in further studies.</p

Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci

Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. Conclusion: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity

Impact of the RTS,S Malaria Vaccine Candidate on Naturally Acquired Antibody Responses to Multiple Asexual Blood Stage Antigens

Partial protective efficacy lasting up to 43 months after vaccination with the RTS,S malaria vaccine has been reported in one cohort (C1) of a Phase IIb trial in Mozambique, but waning efficacy was observed in a smaller contemporaneous cohort (C2). We hypothesized that low dose exposure to asexual stage parasites resulting from partial pre-erythrocytic protection afforded by RTS,S may contribute to long-term vaccine efficacy to clinical disease, which was not observed in C2 due to intense active detection of infection and treatment. in C2 only (Hazard Ratio [HR]: 0.76, 95% CI 0.66–0.88; HR: 0.75, 95% CI 0.62–0.92, respectively).Vaccination with RTS,S modestly reduces anti-AMA-1 and anti-MSP-1 antibodies in very young children. However, for antigens associated with lower risk of clinical malaria, there were no vaccine group or cohort-specific effects, and age did not influence antibody levels between treatment groups for these antigens. The antigens tested do not explain the difference in protective efficacy in C1 and C2. Other less-characterized antigens or VSA may be important to protection

Phenotypic Diversity and Altered Environmental Plasticity in Arabidopsis thaliana with Reduced Hsp90 Levels

The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to preventing the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by the necessity of reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, increases morphological diversity, and decreases the developmental stability of repeated characters. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment

The use of complementary and alternative medicine by 7427 Australian women with cyclic perimenstrual pain and discomfort: A cross-sectional study

© 2016 Fisher et al. Background: To assess the prevalence of cyclic perimenstrual pain and discomfort and to detail the pattern of complementary and alternative (CAM) use adopted by women for the treatment of these symptoms. Methods: Data from the 2012 national Australian Longitudinal Study of Women's Health (ALSWH) cross-sectional survey of 7427 women aged 34-39 years were analysed to estimate the prevalence of endometriosis, premenstrual syndrome (PMS), irregular or heavy periods and severe dysmenorrhoea and to examine the association between their symptoms and their visits to CAM practitioners as well as their use of CAM therapies and products in the previous 12 months. Results: The prevalence of endometriosis was 3.7 % and of the perimenstrual symptoms assessed, PMS was most prevalent at 41.2 % whilst irregular bleeding (22.2 %), heavy periods (29.8 %) and severe period pain (24.1 %) were reported at lower levels. Women with endometriosis were more likely than non-sufferers to have consulted with a massage therapist or acupuncturist and to have used vitamins/minerals, yoga/meditation or Chinese medicines (p < 0.05). PMS sufferers were more likely to consult with an osteopath, massage therapist, naturopath/herbalist or alternative health practitioner and to have used all forms of CAM therapies except Chinese medicines than women who had infrequent PMS (all p < 0.05). Women with irregular periods did not have different patterns of CAM use from non-sufferers and those with heavy periods did not favour any form of CAM but were less likely to visit a massage therapist or use yoga/meditation than non-sufferers (p < 0.05). For women with severe dysmenorrhoea there was no difference in their visits to CAM practitioners compared to non-sufferers but they were more likely to use aromatherapy oils (p < 0.05) and for more frequent dysmenorrhoea also herbal medicines, Chinese medicines and other alternative therapies compared to non-sufferers (all p < 0.05). Conclusions: There is a high prevalence of cyclic perimenstrual pain and discomfort amongst women in this age group. Women were using CAM differentially when they had specific symptoms of cyclic perimenstrual pain and discomfort. The use of CAM needs to be properly assessed to ensure their safe, effective use and to ascertain their significance as a treatment option enabling women with menstrual problems and their care providers to improve their quality of life