Survival of neonates in rural Southern Tanzania: does place of delivery or continuum of care matter?

\ud The concept of continuum of care has recently been highlighted as a core principle of maternal, newborn and child health initiatives, and as a means to save lives. However, evidence has consistently revealed that access to care during and post delivery (intra and postpartum) remains a challenge in the continuum of care framework. In places where skilled delivery assistance is exclusively available in health facilities, access to health facilities is critical to the survival of the mother and her newborn. However, little is known about the association of place of delivery and survival of neonates. This paper uses longitudinal data generated in a Health and Demographic Surveillance System in rural Southern Tanzania to assess associations of neonatal mortality and place of delivery. Three cohorts of singleton births (born 2005, 2006 and 2007) were each followed up from birth to 28 days. Place of birth was classified as either "health facility" or "community". Neonatal mortality rates were produced for each year and by place of birth. Poisson regression was used to estimate crude relative risks of neonatal death by place of birth. Adjusted ratios were derived by controlling for maternal age, birth order, maternal schooling, sex of the child and wealth status of the maternal household. Neonatal mortality for health facility singleton deliveries in 2005 was 32.3 per 1000 live births while for those born in the community it was 29.7 per 1000 live births. In 2006, neonatal mortality rates were 28.9 and 26.9 per 1,000 live births for deliveries in health facilities and in the community respectively. In 2007 neonatal mortality rates were 33.2 and 27.0 per 1,000 live births for those born in health facilities and in the community respectively. Neonates born in a health facility had similar chances of dying as those born in the community in all the three years of study. Adjusted relative risks (ARR) for neonatal death born in a health facility in 2005, 2006 and 2007 were 0.99 (95% CI: 0.58 - 1.70), 0.98 (95% CI: 0.62 - 1.54) and 1.18 (95% CI: 0.76 - 1.85) respectively. We found no evidence to suggest that delivery in health facilities was associated with better survival chances of the neonates.\u

Educational outreach in an integrated clinical management tool for nurse-led non-communicable chronic disease management in primary care in South Africa: pragmatic cluster randomised controlled trial

Background: In many low-income countries, care for patients with non-communicable diseases (NCDs) and mental health conditions is provided by nurses. The benefits of nurse substitution and supplementation in NCD care in high income settings are well recognised, but evidence from low- and middle-income countries is limited. Primary Care 101 (PC101) is a programme designed to support and expand nurses’ role in NCD care, comprising a clinical management tool with enhanced prescribing provisions for nurses, and educational outreach. We evaluated the effectiveness of the programme on primary care nurses’ capacity to manage NCDs (ISRCTN20283604). Methods and findings: In a cluster randomised controlled trial design, 38 public sector primary care clinics in the Western Cape province, South Africa, were randomised. Nurses in the intervention clinics were trained to use the PC101 management tool during educational outreach sessions delivered by health department trainers and authorised to prescribe an expanded range of drugs for several NCDs. Control clinics continued use of the Practical Approach to Lung Health and HIV /AIDS in South Africa (PALSA PLUS) management tool and usual training. Patients attending these clinics with one or more of hypertension (3227), diabetes (1842), chronic respiratory disease (1157) or screened positive for depression (2466), totalling 4393 patients, were enrolled between March 2011 and October 2011. Primary outcomes were treatment intensification for hypertension, diabetes, and chronic respiratory disease cohorts, defined as the proportion of patients in whom treatment was escalated during follow-up over 14 months, and case detection in the depression cohort. Primary outcome data were analysed for 2110 (97%) intervention and 2170 (97%) control group patients. Treatment intensification rates in intervention clinics were not superior to those in the control group clinics [hypertension: 44% in the intervention group versus 40% in the controls, risk ratio (RR) 1.08 (95% CI: 0.94 to 1.24; p=0.252); diabetes: 57% v 50%, RR 1.10 (0.97 to 1.24;p=0.126); chronic respiratory disease: 14% v 12%, RR 1.08 (0.75 to 1.55; p=0.674); and case detection of depression: 18% v 24%, RR 0.76 (0.53 to 1.10; p=0.142)]. No adverse effects of the nurses’ expanded scope of practice were observed. Limitations of the study include dependence on self-reported diagnoses for inclusion in the patient cohorts, limited data on uptake of PC101 by users, reliance on process outcomes, and insufficient resources to measure important health outcomes, such as HbA1c, at follow-up. Conclusions: Educational outreach to primary care nurses through use of a management tool involving an expanded role in managing NCDs, is feasible and safe but was not associated with treatment intensification or case detection for index diseases. This notwithstanding, the intervention, with adjustments to improve its effectiveness, has been adopted for implementation in primary care clinics throughout South Africa

The contribution of 7q33 copy number variations for intellectual disability

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. One family presents a small duplication in cis affecting CALD1 and AGBL3 genes, while the other four patients carry two larger deletions encompassing EXOC4, CALD1, AGBL3, and CNOT4. This work helps to refine the phenotype and narrow the minimal critical region involved in 7q33 CNVs. Comparison with similar cases and functional studies should help us clarify the relevance of the deleted genes for ID and behavioral alterations.FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects PIC/IC/83026/2007, PIC/IC/83013/2007, and POCI-01-0145-FEDER-007038. This work has also been funded by the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)info:eu-repo/semantics/publishedVersio

Epithelial Neutrophil-Activating Peptide (ENA-78), Acute Coronary Syndrome Prognosis, and Modulatory Effect of Statins

Endothelial inflammation with chemokine involvement contributes to acute coronary syndromes (ACS). We tested the hypothesis that variation in the chemokine gene CXCL5, which encodes epithelial neutrophil-activating peptide (ENA-78), is associated with ACS prognosis. We also investigated whether statin use, a potent modulator of inflammation, modifies CXCL5's association with outcomes and characterized the in vitro effect of atorvastatin on endothelial ENA-78 production. Using a prospective cohort of ACS patients (n = 704) the association of the CXCL5 −156 G>C polymorphism (rs352046) with 3-year all-cause mortality was estimated with hazard ratios (HR). Models were stratified by genotype and race. To characterize the influence of statins on this association, a statin*genotype interaction was tested. To validate ENA-78 as a statin target in inflammation typical of ACS, endothelial cells (HUVECs) were treated with IL-1β and atorvastatin with subsequent quantification of CXCL5 expression and ENA-78 protein concentrations. C/C genotype was associated with a 2.7-fold increase in 3-year all-cause mortality compared to G/G+G/C (95%CI 1.19–5.87; p = 0.017). Statins significantly reduced mortality in G/G individuals only (58% relative risk reduction; p = 0.0009). In HUVECs, atorvastatin dose-dependently decreased IL-1β-stimulated ENA-78 concentrations (p<0.0001). Drug effects persisted over 48 hours (p<0.01). CXCL5 genotype is associated with outcomes after ACS with potential statin modification of this effect. Atorvastatin lowered endothelial ENA-78 production during inflammation typical of ACS. These findings implicate CXCL5/ENA-78 in ACS and the statin response

An Ultra Deep Field survey with WFIRST

Studying the formation and evolution of galaxies at the earliest cosmic times, and their role in reionization, requires the deepest imaging possible. Ultra-deep surveys like the HUDF and HFF have pushed to mag \mAB$\,\sim\,$30, revealing galaxies at the faint end of the LF to $z$$\,\sim\,$9$\,-\,$11 and constraining their role in reionization. However, a key limitation of these fields is their size, only a few arcminutes (less than a Mpc at these redshifts), too small to probe large-scale environments or clustering properties of these galaxies, crucial for advancing our understanding of reionization. Achieving HUDF-quality depth over areas $\sim$100 times larger becomes possible with a mission like the Wide Field Infrared Survey Telescope (WFIRST), a 2.4-m telescope with similar optical properties to HST, with a field of view of $\sim$1000 arcmin$^2$, $\sim$100$\times$ the area of the HST/ACS HUDF. This whitepaper motivates an Ultra-Deep Field survey with WFIRST, covering $\sim$100$\,-\,$300$\times$ the area of the HUDF, or up to $\sim$1 deg$^2$, to \mAB$\,\sim\,$30, potentially revealing thousands of galaxies and AGN at the faint end of the LF, at or beyond $z$\,$\sim$\,9$\,-\,$10 in the epoch of reionization, and tracing their LSS environments, dramatically increasing the discovery potential at these redshifts. (Note: This paper is a somewhat expanded version of one that was submitted as input to the Astro2020 Decadal Survey, with this version including an Appendix (which exceeded the Astro2020 page limits), describing how the science drivers for a WFIRST Ultra Deep Field might map into a notional observing program, including the filters used and exposure times needed to achieve these depths.

Assessment of coronary atherosclerosis by IVUS and IVUS-based imaging modalities: progression and regression studies, tissue composition and beyond

Cardiovascular disease remains the leading cause of mortality, morbidity and disability in the developed world, predominantly affecting the adult population. In the early 1990s coronary heart disease (CHD) was established as affecting one in two men and one in three women by the age of forty. Despite the dramatic progress in the field of cardiovascular medicine in terms of diagnosis and treatment of heart disease, modest improvements have only been achieved when the reduction of cardiovascular mortality and morbidity indices are assessed. To better understand coronary atherosclerosis, new imaging modalities have been introduced. These novel imaging modalities have been used in two ways: (1) for the characterization of plaque types; (2) for the assessment of the progression and regression of tissue types. These two aspects will be discussed in this review