Countdown to 2015 country case studies: What have we learned about processes and progress towards MDGs 4 and 5?

BACKGROUND: Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. METHODS: Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). RESULTS: The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns - which require higher-level health workers, more infrastructure, and increased community engagement - showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. CONCLUSIONS: These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts

Serological evidence for transmission of multiple dengue virus serotypes in Papua New Guinea and West Papua prior to 1963

Little is known about the natural history of dengue in Papua New Guinea (PNG). We assessed dengue virus (DENV)-specific neutralizing antibody profiles in serum samples collected from northern and southern coastal areas and the highland region of New Guinea between 1959 and 1963. Neutralizing antibodies were demonstrated in sera from the northern coast of New Guinea: from Sabron in Dutch New Guinea (now known as West Papua) and from four villages in East Sepik in what is now PNG. Previous monotypic infection with DENV-1, DENV-2, and DENV-4 was identified, with a predominance of anti-DENV-2 neutralizing antibody. The majority of positive sera demonstrated evidence of multiple previous DENV infections and neutralizing activity against all four serotypes was detected, with anti-DENV-2 responses being most frequent and of greatest magnitude. No evidence of previous DENV infection was identified in the Asmat villages of the southern coast and a single anti-DENV-positive sample was identified in the Eastern Highlands of PNG. These findings indicate that multiple DENV serotypes circulated along the northern coast of New Guinea at different times in the decades prior to 1963 and support the notion that dengue has been a significant yet neglected tropical infection in PNG for many decades

Gastric variceal bleeding caused by an intrahepatic arterioportal fistula that formed after liver biopsy: a case report and review of the literature

An intrahepatic arterioportal fistula is a rare cause of portal hypertension and variceal bleeding. We report on a patient with an intrahepatic arterioportal fistula following liver biopsy who was successfully treated by hepatectomy after unsuccessful arterial embolization. We also review the literature on symptomatic intrahepatic arterioportal fistulas after liver biopsy. A 48-year-old male with bleeding gastric varices and hepatitis B virus-associated liver cirrhosis was transferred to our hospital; this patient previously underwent percutaneous liver biopsies 3 and 6 years ago. Abdominal examination revealed a bruit over the liver, tenderness in the right upper quadrant, and splenomegaly. Ultrasonographic examination, computed tomography, and angiography confirmed an arterioportal fistula between the right hepatic artery and the right portal vein with portal hypertension. After admission, the patient suffered a large hematemesis and developed shock. He was treated with emergency transarterial embolization using microcoils. Since some collateral vessels bypassed the obstructive coils and still fed the fistulous area, embolization was performed again. Despite the second embolization, the collateral vessels could not be completely controlled. Radical treatment involving resection of his right hepatic lobe was performed. For nearly 6 years postoperatively, this patient has had no further episodes of variceal bleeding

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR

Oxidation of DJ-1 Induced by 6-Hydroxydopamine Decreasing Intracellular Glutathione

DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported to undergo preferential oxidation of the cysteine residue at position 106 (Cys-106) under oxidative stress; however, details of the molecular mechanisms are not well known. In the present study, mechanisms of DJ-1 oxidation induced by 6-hydroxydopamine (6-OHDA) were investigated by using SH-SY5Y cells. The treatment of these cells with 6-OHDA caused an obvious acidic spot sift of DJ-1 due to its oxidation. However, when catalase, which is an hydrogen peroxide (H2O2)-removing enzyme, was added during the treatment, it failed to prevent the oxidation induced by 6-OHDA, suggesting that electrophilic p-quinone formed from 6-OHDA, but not H2O2, was responsible for the DJ-1 oxidation. Benzoquinone, another electrophilic p-quinone, also induced DJ-1 oxidation. The intracellular glutathione (GSH) levels were significantly decreased by 6-OHDA, irrespective of the presence or absence of catalase. The inhibition of GSH synthesis by buthionine sulfoximine resulted in a decrease in GSH levels and enhancement of DJ-1 oxidation. The pretreatment of cells with N-acetyl-cysteine prevented the loss of intracellular GSH and subsequently DJ-1 oxidation induced by 6-OHDA. Collectively, these results suggest that electrophilic p-quinone formed from 6-OHDA induces DJ-1 oxidation by decreasing intracellular GSH