Does global progress on sanitation really lag behind water? An analysis of global progress on community- and household-level access to safe water and sanitation.

Safe drinking water and sanitation are important determinants of human health and wellbeing and have recently been declared human rights by the international community. Increased access to both were included in the Millennium Development Goals under a single dedicated target for 2015. This target was reached in 2010 for water but sanitation will fall short; however, there is an important difference in the benchmarks used for assessing global access. For drinking water the benchmark is community-level access whilst for sanitation it is household-level access, so a pit latrine shared between households does not count toward the Millennium Development Goal (MDG) target. We estimated global progress for water and sanitation under two scenarios: with equivalent household- and community-level benchmarks. Our results demonstrate that the "sanitation deficit" is apparent only when household-level sanitation access is contrasted with community-level water access. When equivalent benchmarks are used for water and sanitation, the global deficit is as great for water as it is for sanitation, and sanitation progress in the MDG-period (1990-2015) outstrips that in water. As both drinking water and sanitation access yield greater benefits at the household-level than at the community-level, we conclude that any post-2015 goals should consider a household-level benchmark for both

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

Measuring coverage in MNCH: indicators for global tracking of newborn care.

Neonatal mortality accounts for 43% of under-five mortality. Consequently, improving newborn survival is a global priority. However, although there is increasing consensus on the packages and specific interventions that need to be scaled up to reduce neonatal mortality, there is a lack of clarity on the indicators needed to measure progress. In 2008, in an effort to improve newborn survival, the Newborn Indicators Technical Working Group (TWG) was convened by the Saving Newborn Lives program at Save the Children to provide a forum to develop the indicators and standard measurement tools that are needed to measure coverage of key newborn interventions. The TWG, which included evaluation and measurement experts, researchers, individuals from United Nations agencies and non-governmental organizations, and donors, prioritized improved consistency of measurement of postnatal care for women and newborns and of immediate care behaviors and practices for newborns. In addition, the TWG promoted increased data availability through inclusion of additional questions in nationally representative surveys, such as the United States Agency for International Development-supported Demographic and Health Surveys and the United Nations Children's Fund-supported Multiple Indicator Cluster Surveys. Several studies have been undertaken that have informed revisions of indicators and survey tools, and global postnatal care coverage indicators have been finalized. Consensus has been achieved on three additional indicators for care of the newborn after birth (drying, delayed bathing, and cutting the cord with a clean instrument), and on testing two further indicators (immediate skin-to-skin care and applications to the umbilical cord). Finally, important measurement gaps have been identified regarding coverage data for evidence-based interventions, such as Kangaroo Mother Care and care seeking for newborn infection

Mathematical models for immunology:current state of the art and future research directions

The advances in genetics and biochemistry that have taken place over the last 10 years led to significant advances in experimental and clinical immunology. In turn, this has led to the development of new mathematical models to investigate qualitatively and quantitatively various open questions in immunology. In this study we present a review of some research areas in mathematical immunology that evolved over the last 10 years. To this end, we take a step-by-step approach in discussing a range of models derived to study the dynamics of both the innate and immune responses at the molecular, cellular and tissue scales. To emphasise the use of mathematics in modelling in this area, we also review some of the mathematical tools used to investigate these models. Finally, we discuss some future trends in both experimental immunology and mathematical immunology for the upcoming years

Methods of nutrition surveillance in low-income countries

Background In 1974 a joint FAO/UNICEF/WHO Expert Committee met to develop methods for nutrition surveillance. There has been much interest and activity in this topic since then, however there is a lack of guidance for practitioners and confusion exists around the terminology of nutrition surveillance. In this paper we propose a classification of data collection activities, consider the technical issues for each category, and examine the potential applications and challenges related to information and communication technology. Analysis There are three major approaches used to collect primary data for nutrition surveillance: repeated cross-sectional surveys; community-based sentinel monitoring; and the collection of data in schools. There are three major sources of secondary data for surveillance: from feeding centres, health facilities, and community-based data collection, including mass screening for malnutrition in children. Surveillance systems involving repeated surveys are suitable for monitoring and comparing national trends and for planning and policy development. To plan at a local level, surveys at district level or in programme implementation areas are ideal, but given the usually high cost of primary data collection, data obtained from health systems are more appropriate provided they are interpreted with caution and with contextual information. For early warning, data from health systems and sentinel site assessments may be valuable, if consistent in their methods of collection and any systematic bias is deemed to be steady. For evaluation purposes, surveillance systems can only give plausible evidence of whether a programme is effective. However the implementation of programmes can be monitored as long as data are collected on process indicators such as access to, and use of, services. Surveillance systems also have an important role to provide information that can be used for advocacy and for promoting accountability for actions or lack of actions, including service delivery. Conclusion This paper identifies issues that affect the collection of nutrition surveillance data, and proposes definitions of terms to differentiate between diverse sources of data of variable accuracy and validity. Increased interest in nutrition globally has resulted in high level commitments to reduce and prevent undernutrition. This review helps to address the need for accurate and regular data to convert these commitments into practice

Impaired respiratory burst contributes to infections in PKCδ-deficient patients

Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients' circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype

Modelling the Innate Immune Response against Avian Influenza Virus in Chicken

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -β and -γ, lung (i.e. pulmonary) cells and Natural Killer cells. We use recent results from experimentally infected chickens to validate some of the model predictions. The model includes an initial exponential increase of the viral load, which we show to be consistent with experimental data. Using this exponential growth model we show that the duration until a given viral load is reached in experiments with different inoculation doses is consistent with a model assuming a linear relationship between initial viral load and inoculation dose. Subsequent to the exponential-growth phase, the model results show a decline in viral load caused by both target-cell limitation as well as the innate immune response. The model results suggest that the temporal viral load pattern in the lungs displayed in experimental data cannot be explained by target-cell limitation alone. For biologically plausible parameter values the model is able to qualitatively match to data on viral load in chicken lungs up until approximately 4 days post infection. Comparison of model predictions with data on CD107-mediated degranulation of Natural Killer cells yields some discrepancy also for earlier days post infection

Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses

Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection

Socioeconomic Inequalities in Newborn Care During Facility and Home Deliveries: A Cross Sectional Analysis of Data from Demographic Surveillance Sites in Rural Bangladesh, India and Nepal

Background: In Bangladesh, India and Nepal, neonatal outcomes of poor infants are considerably worse than those of better-off infants. Understanding how these inequalities vary by country and place of delivery (home or facility) will allow targeting of interventions to those who need them most. We describe socio-economic inequalities in newborn care in rural areas of Bangladesh, Nepal and India for all deliveries and by place of delivery. Methods: We used data from surveillance sites in Bangladesh, India and from Makwanpur and Dhanusha districts in Nepal, covering periods from 2001 to 2011. We used literacy (ability to read a short text) as indicator of socioeconomic status. We developed a composite score of nine newborn care practices (score range 0–9 indicating infants received no newborn care to all nine newborn care practices). We modeled the effect of literacy and place of delivery on the newborn care score and on individual practices. Results: In all study sites (60,078 deliveries in total), use of facility delivery was higher among literate mothers. In all sites, inequalities in newborn care were observed: the difference in new born care between literate and illiterate ranged 0.35–0.80. The effect of literacy on the newborn care score reduced after adjusting for place of delivery (range score difference literate-illiterate: 0.21–0.43). Conclusion: Socioeconomic inequalities in facility care greatly contribute to inequalities in newborn care. Improving newborn care during home deliveries and improving access to facility care are a priority for addressing inequalities in newborn care and newborn mortality

A Mathematical Model of Mitotic Exit in Budding Yeast: The Role of Polo Kinase

Cell cycle progression in eukaryotes is regulated by periodic activation and inactivation of a family of cyclin–dependent kinases (Cdk's). Entry into mitosis requires phosphorylation of many proteins targeted by mitotic Cdk, and exit from mitosis requires proteolysis of mitotic cyclins and dephosphorylation of their targeted proteins. Mitotic exit in budding yeast is known to involve the interplay of mitotic kinases (Cdk and Polo kinases) and phosphatases (Cdc55/PP2A and Cdc14), as well as the action of the anaphase promoting complex (APC) in degrading specific proteins in anaphase and telophase. To understand the intricacies of this mechanism, we propose a mathematical model for the molecular events during mitotic exit in budding yeast. The model captures the dynamics of this network in wild-type yeast cells and 110 mutant strains. The model clarifies the roles of Polo-like kinase (Cdc5) in the Cdc14 early anaphase release pathway and in the G-protein regulated mitotic exit network