Improving a Mother to Child HIV Transmission Programme through Health System Redesign: Quality Improvement, Protocol Adjustment and Resource Addition

Health systems that deliver prevention of mother to child transmission (PMTCT) services in low and middle income countries continue to underperform, resulting in thousands of unnecessary HIV infections of newborns each year. We used a combination of approaches to health systems strengthening to reduce transmission of HIV from mother to infant in a multi-facility public health system in South Africa.All primary care sites and specialized birthing centers in a resource constrained sub-district of Cape Metro District, South Africa, were enrolled in a quality improvement (QI) programme. All pregnant women receiving antenatal, intrapartum and postnatal infant care in the sub-district between January 2006 and March 2009 were included in the intervention that had a prototype-innovation phase and a rapid spread phase. System changes were introduced to help frontline healthcare workers to identify and improve performance gaps at each step of the PMTCT pathway. Improvement was facilitated and spread through the use of a Breakthrough Series Collaborative that accelerated learning and the spread of successful changes. Protocol changes and additional resources were introduced by provincial and municipal government. The proportion of HIV-exposed infants testing positive declined from 7.6% to 5%. Key intermediate PMTCT processes improved (antenatal AZT increased from 74% to 86%, PMTCT clients on HAART at the time of labour increased from 10% to 25%, intrapartum AZT increased from 43% to 84%, and postnatal HIV testing from 79% to 95%) compared to baseline.System improvement methods, protocol changes and addition/reallocation of resources contributed to improved PMTCT processes and outcomes in a resource constrained setting. The intervention requires a clear design, leadership buy-in, building local capacity to use systems improvement methods, and a reliable data system. A systems improvement approach offers a much needed approach to rapidly improve under-performing PMTCT implementation programmes at scale in sub-Saharan Africa

Knock-in models related to Alzheimer’s disease: synaptic transmission, plaques and the role of microglia

Background: Microglia are active modulators of Alzheimer’s disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. Methods: AppNL-F and AppNL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer’s disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Results: Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in AppNL-F mice but was not evident in AppNL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Conclusions: Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer’s disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer’s disease

High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission

BACKGROUND. Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF. METHODS AND RESULTS. As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight. CONCLUSIONS. Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children's lives. TRIAL REGISTRATION. ClinicalTrials.gov NCT00310726National Institute of Child Health and Human Development; National Institutes of Health (R01 HD 39611, R01 HD 40777); Centers for Disease Control and Prevention; Global AIDS Program; Glaser Pediatric AIDS Foundation; USAID Country Research (GHS-A-00-00020-00

Preservation and recovery of mangrove ecosystem carbon stocks in abandoned shrimp ponds

Mangrove forests capture and store exceptionally large amounts of carbon and are increasingly recognised as an important ecosystem for carbon sequestration. Yet land-use change in the tropics threatens this ecosystem and its critical ‘blue carbon’ (carbon stored in marine and coastal habitats) stores. The expansion of shrimp aquaculture is among the major causes of mangrove loss globally. Here, we assess the impact of mangrove to shrimp pond conversion on ecosystem carbon stocks, and carbon losses and gains over time after ponds are abandoned. Our assessment is based on an intensive field inventory of carbon stocks at a coastal setting in Thailand. We show that although up to 70% of ecosystem carbon is lost when mangroves are converted to shrimp ponds, some abandoned ponds contain deep mangrove soils (>2.5 m) and large carbon reservoirs exceeding 865 t carbon per hectare. We also found a positive recovery trajectory for carbon stocks in the upper soil layer (0-15 cm) of a chronosequence of abandoned ponds, associated with natural mangrove regeneration. Our data suggest that mangrove carbon pools can rebuild in abandoned ponds over time in areas exposed to tidal flushing

A theoretical account of cue averaging in the rodent head direction system

Head direction (HD) cell responses are thought to be derived from a combination of internal (or idiothetic) and external (or allothetic) sources of information. Recent work from the Jeffery laboratory shows that the relative influence of visual versus vestibular inputs upon the HD cell response depends on the disparity between these sources. In this paper, we present simulation results from a model designed to explain these observations. The model accurately replicates the Knight et al. data. We suggest that cue conflict resolution is critically dependent on plastic remapping of visual information onto the HD cell layer. This remap results in a shift in preferred directions of a subset of HD cells, which is then inherited by the rest of the cells during path integration. Thus, we demonstrate how, over a period of several minutes, a visual landmark may gain cue control. Furthermore, simulation results show that weaker visual landmarks fail to gain cue control as readily. We therefore suggest a second longer term plasticity in visual projections onto HD cell areas, through which landmarks with an inconsistent relationship to idiothetic information are made less salient, significantly hindering their ability to gain cue control. Our results provide a mechanism for reliability-weighted cue averaging that may pertain to other neural systems in addition to the HD system

Effectiveness of Journal Ranking Schemes as a Tool for Locating Information

BACKGROUND: The rise of electronic publishing, preprint archives, blogs, and wikis is raising concerns among publishers, editors, and scientists about the present day relevance of academic journals and traditional peer review. These concerns are especially fuelled by the ability of search engines to automatically identify and sort information. It appears that academic journals can only remain relevant if acceptance of research for publication within a journal allows readers to infer immediate, reliable information on the value of that research. METHODOLOGY/PRINCIPAL FINDINGS: Here, we systematically evaluate the effectiveness of journals, through the work of editors and reviewers, at evaluating unpublished research. We find that the distribution of the number of citations to a paper published in a given journal in a specific year converges to a steady state after a journal-specific transient time, and demonstrate that in the steady state the logarithm of the number of citations has a journal-specific typical value. We then develop a model for the asymptotic number of citations accrued by papers published in a journal that closely matches the data. CONCLUSIONS/SIGNIFICANCE: Our model enables us to quantify both the typical impact and the range of impacts of papers published in a journal. Finally, we propose a journal-ranking scheme that maximizes the efficiency of locating high impact research

Entanglements of faith: Discourses, practices of care and homeless people in an Italian City of Saints

This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/0042098013514620This paper investigates how Catholic-inspired services for homeless people are delivered in Turin, Italy. The purpose is to critically interrogate particular faith-based organisations’ moral discourses on homelessness, and to show how they are enacted through practices of care directed at the homeless subject. The paper contributes to the geographical literature on faith-based organisations addressing its shortcomings – namely the lack of critical and contextual focus on faith-based organisations’ ‘love for the poor’. To address this point, the paper takes a vitalist perspective on the urban and introduces the notion of the ‘entanglements of faith’, which allows an integrated and grounded perspective on faith-based organisations’ interventions. The outcomes of the work suggest that these faith-based organisations propose standardised services that, producing particular assemblages and affective atmospheres, have deep emotional and relational effects on their recipients. Further lines of research are sketched in the conclusions

Improving the coverage of the PMTCT programme through a participatory quality improvement intervention in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite several years of implementation, prevention of mother-to-child transmission (PMTCT) programmes in many resource poor settings are failing to reach the majority of HIV positive women. We report on a data driven participatory quality improvement intervention implemented in a high HIV prevalence district in South Africa.</p> <p>Methods</p> <p>A participatory quality improvement intervention was implemented consisting of an initial assessment undertaken by a team of district supervisors, workshops to assess results, identify weaknesses and set improvement targets and continuous monitoring to support changes.</p> <p>Results</p> <p>The assessment highlighted weaknesses in training and supervision. Routine data revealed poor coverage of all programme indicators except HIV testing. Monthly support to all facilities took place including an orientation to the PMTCT protocol, review of local data and identification of bottlenecks to optimal coverage using a continuous quality improvement approach. One year following the intervention large improvements in programme indicators were observed. Coverage of CD4 testing increased from 40 to 97%, uptake of maternal nevirapine from 57 to 96%, uptake of infant nevirapine from 15 to 68% and six week PCR testing from 24 to 68%.</p> <p>Conclusion</p> <p>It is estimated that these improvements in coverage could avert 580 new infant infections per year in this district. This relatively simple participatory assessment and intervention process has enabled programme managers to use a data driven approach to improve the coverage of this important programme.</p

Fibre Distribution and the Process-Property Dilemma

The options for the fibre reinforcement of polymer matrix composites cover a range from short-fibre chopped strand mat, through woven fabric to unidirectional pre-impregnated (prepreg) reinforcements. The modelling of such materials may be simplified by assumptions such as perfect regular packing of fibres and the total absence of fibre waviness. However, these and other features such as the crimp or waviness in woven fabrics make real materials more complex than the simplified models. Clustering of fibres creates fibre-rich and resin-rich volumes (FRV and RRV respectively) in the composites. Prior to impregnation, large RRV will be pore-space that can expedite the flow of resin in liquid composite moulding processes (especially resin transfer moulding (RTM) and resin infusion under flexible tooling (RIFT). In the composite, the clustering of fibres tends to reduce the mechanical properties. The use of image processing and analysis can permit micro-/meso-structural characterisation which may correlate to the respective properties. This chapter considers the quantification of microstructure images in the context of the process-property dilemma for woven carbon-fibre reinforced composites with the aim of increasing understanding of the balance between processability and mechanical performance

Preliminary analysis of immune activation in early onset type 2 diabetes

Introduction. First Nations and other Aboriginal children are disproportionately affected by cardiometabolic diseases, including type 2 diabetes (T2D). In T2D, the disruption of insulin signalling can be driven by pro-inflammatory immunity. Pro-inflammatory responses can be fueled by toll-like receptors (TLR) on immune cells such as peripheral blood mononuclear cells (PBMC, a white blood cell population). TLR4 can bind to lipids from bacteria and food sources activating PBMC to produce cytokines tumour necrosis factor (TNF)-&#x03B1; and interleukin (IL)-1&#x03B2;. These cytokines can interfere with insulin signalling. Here, we seek to understand how TLR4 activation may be involved in early onset T2D. We hypothesized that immune cells from youth with T2D (n=8) would be more reactive upon TLR4 stimulation relative to cells from age and body mass index (BMI)-matched controls without T2D (n=8). Methods. Serum samples were assayed for adipokines (adiponectin and leptin), as well as cytokines. Freshly isolated PBMC were examined for immune reactivity upon culture with TLR4 ligands bacterial lipopolysaccharide (LPS, 2 and 0.2 ng/ml) and the fatty acid palmitate (200 &#x00B5;M). Culture supernatants were evaluated for the amount of TNF-&#x03B1; and IL-1&#x03B2; produced by PBMC. Results. Youth with T2D displayed lower median serum adiponectin levels compared to controls (395 vs. 904 ng/ml, p&#x003C;0.05). PBMC isolated from youth with and without T2D produced similar levels of TNF-&#x03B1; and IL-1&#x03B2; after exposure to the higher LPS concentration. However, at the low LPS dose the T2D cohort exhibited enhanced IL-1&#x03B2; synthesis relative to the control cohort. Additionally, exposure to palmitate resulted in greater IL-1&#x03B2; synthesis in PBMCs isolated from youth with T2D versus controls (p&#x003C;0.05). These differences in cytokine production corresponded to greater monocyte activation in the T2D cohort. Conclusion. These preliminary results suggest that cellular immune responses are exaggerated in T2D, particularly with respect to IL-1&#x03B2; activity. These studies aim to improve the understanding of the biology behind early onset T2D and its vascular complications that burden First Nations people