Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessment.

BACKGROUND: Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents' Health (2016-30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. METHODS: For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks' gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. FINDINGS: Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9-2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5-15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8-27·7) per 1000 total births in west and central Africa to 2·9 (2·7-3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7-2·7) from 2000 to 2019, which was lower than the 2·9% (2·5-3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8-4·7) annual rate of reduction in mortality rate among children aged 1-59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0-49·9%, 50 having a decrease of 10·0-24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries, 34 were in sub-Saharan Africa, 16 were in east Asia and the Pacific, and 15 were in Latin America and the Caribbean. INTERPRETATION: Progress in reducing the rate of stillbirths has been slow compared with decreases in the mortality rate of children younger than 5 years. Accelerated improvements are most needed in the regions and countries with high stillbirth rates, particularly in sub-Saharan Africa. Future prevention of stillbirths needs increased efforts to raise public awareness, improve data collection, assess progress, and understand public health priorities locally, all of which require investment. FUNDING: Bill & Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office.

The effects of changes in distance to nearest health facility on under-5 mortality and health care utilization in rural Malawi, 1980-1998.

BACKGROUND: Despite important progress, the burden of under-5 mortality remains unacceptably high, with an estimated 5.3 million deaths in 2018. Lack of access to health care is a major risk factor for under-5 mortality, and distance to health care facilities has been shown to be associated with less access to care in multiple contexts, but few such studies have used a counterfactual approach to produce causal estimates. METHODS: We combined retrospective reports on 18,714 births between 1980 and 1998 from the 2000 Malawi Demographic and Health Survey with a 1998 health facility census that includes the date of construction for each facility, including 335 maternity or maternity/dispensary facilities built in rural areas between 1980 and 1998. We estimated associations between distance to nearest health facility and (i) under-5 mortality, using Cox proportional hazards models, and (ii) maternal health care utilization (antenatal visits prior to delivery, place of delivery, receiving skilled assistance during delivery, and receiving a check-up following delivery), using linear probability models. We also estimated the causal effect of reducing the distance to nearest facility on those outcomes, using a two-way fixed effects approach. FINDINGS: We found that greater distance was associated with higher mortality (hazard ratio 1.007 for one additional kilometer [95%CI 1.001 to 1.014]) and lower health care utilization (for one additional kilometer: 1.2 percentage point (pp) increase in homebirth [95%CI 0.8 to 1.5]; 0.8 pp. decrease in at least three antenatal visits [95% CI - 1.4 to - 0.2]; 1.2 pp. decrease in skilled assistance during delivery [95%CI - 1.6 to - 0.8]). However, we found no effects of a decrease in distance to the nearest health facility on the hazard of death before age 5 years, nor on antenatal visits prior to delivery, place of delivery, or receiving skilled assistance during delivery. We also found that reductions in distance decrease the probability that a woman receives a check-up following delivery (2.4 pp. decrease for a 1 km decrease [95%CI 0.004 to 0.044]). CONCLUSION: Reducing under-5 mortality and increasing utilization of care in rural Malawi and similar settings may require more than the construction of new health infrastructure. Importantly, the effects estimated here likely depend on the quality of health care, the availability of transportation, the demand for health services, and the underlying causes of mortality, among other factors.

Measuring and correcting bias in indirect estimates of under-5 mortality in populations affected by HIV/AIDS: a simulation study.

BACKGROUND: In populations that lack vital registration systems, under-5 mortality (U5M) is commonly estimated using survey-based approaches, including indirect methods. One assumption of indirect methods is that a mother's survival and her children's survival are not correlated, but in populations affected by HIV/AIDS this assumption is violated, and thus indirect estimates are biased. Our goal was to estimate the magnitude of the bias, and to create a predictive model to correct it. METHODS: We used an individual-level, discrete time-step simulation model to measure how the bias in indirect estimates of U5M changes under various fertility rates, mortality rates, HIV/AIDS rates, and levels of antiretroviral therapy. We simulated 4480 populations in total and measured the amount of bias in U5M due to HIV/AIDS. We also developed a generalized linear model via penalized maximum likelihood to correct this bias. RESULTS: We found that indirect methods can underestimate U5M by 0-41% in populations with HIV prevalence of 0-40%. Applying our model to 2010 survey data from Malawi and Tanzania, we show that indirect methods would underestimate U5M by up to 7.7% in those countries at that time. Our best fitting model to correct bias in U5M had a root median square error of 0.0012. CONCLUSIONS: Indirect estimates of U5M can be significantly biased in populations affected by HIV/AIDS. Our predictive model allows scholars and practitioners to correct that bias using commonly measured population characteristics. Policies and programs based on indirect estimates of U5M in populations with generalized HIV epidemics may need to be reevaluated after accounting for estimation bias.

Interventions for children with reactive attachment disorder.

Characterized by aggressive or violent behaviors, reactive attachment disorder (RAD) affects children who have been repeatedly exposed to traumatic experiences. This article discusses the underlying causes of RAD and provides insight on therapies and interventions.

Using census data to measure maternal mortality: A review of recent experience.

BACKGROUND: The Sustainable Development Goals adopted by the United Nations General Assembly in 2015 (United Nations 2015) set national targets for reducing maternal mortality, putting pressure on governments of countries lacking comprehensive statistical systems to find other ways to measure it. One approach tested since the 1990s has been to collect necessary data through national population censuses. OBJECTIVE: This paper reviews maternal mortality data from the 2010 round of censuses for several countries to determine whether the census is useful for monitoring maternal mortality. METHODS: Data on births, deaths, and pregnancy-related deaths from two censuses for 10 countries was evaluated using standard methods; adjustments were applied to the reported numbers if so indicated. RESULTS: In general, the censuses underreported births moderately and underreported deaths by larger amounts; except in one case, proportions of pregnancy-related deaths appeared plausible. Adjusted estimates of the pregnancy-related mortality ratio (PRMR) were generally higher than estimates from Demographic and Health Survey sibling data or estimates of maternal mortality developed by cross-national studies. CONCLUSIONS: Analysis of recent data confirms results of earlier assessments: Census data provides imperfect but still valuable information on maternal mortality. Data requires careful assessment and often adjustment, resulting in estimates with large uncertainty. CONTRIBUTION: This paper provides additional evidence as to whether maternal mortality can usefully be measured by population censuses in countries lacking civil registration data.

Community-Based Health Financing and Child Stunting in Rural Rwanda.

OBJECTIVES: We analyzed the likelihood of rural children (aged 6-24 months) being stunted according to whether they were enrolled in Mutuelles, a community-based health-financing program providing health insurance to rural populations and granting them access to health care, including nutrition services. METHODS: We retrieved health facility data from the District Health System Strengthening Tool and calculated the percentage of rural health centers that provided nutrition-related services required by Mutuelles' minimum service package. We used data from the 2010 Rwanda Demographic and Health Survey and performed multilevel logistic analysis to control for clustering effects and sociodemographic characteristics. The final sample was 1061 children. RESULTS: Among 384 rural health centers, more than 90% conducted nutrition-related campaigns and malnutrition screening for children. Regardless of poverty status, the risk of being stunted was significantly lower (odds ratio = 0.60; 95% credible interval = 0.41, 0.83) for Mutuelles enrollees. This finding was robust to various model specifications (adjusted for Mutuelles enrollment, poverty status, other variables) or estimation methods (fixed and random effects). CONCLUSIONS: This study provides evidence of the effectiveness of Mutuelles in improving child nutrition status and supported the hypothesis about the role of Mutuelles in expanding medical and nutritional care coverage for children.

Deep Neck Fibromatosis After Diskectomy and Cervical Fusion: Case Series and Review of the Literature.

OBJECTIVE: The objective of our study was to report head and neck deep fibromatosis as part of the differential diagnosis of a firm painful neck mass after cervical fusion and diskectomy. CONCLUSION: Although they are rare tumors, fibromatosis tumors or desmoid tumors should be considered in a patient with a painful neck mass; a history of cervical spine surgery; and MRI findings showing a large, avidly enhancing, heterogeneous mass adjacent to surgical hardware that is hyperintense on T2-weighted imaging.

Data on survival of recent births as a source of child mortality estimates in the developing world: An assessment of census data.

In many less developed countries, household surveys collect full and summary birth histories to provide estimates of child mortality. However, full birth histories are expensive to collect and cannot provide precise estimates for small areas, and summary birth histories only provide past child mortality trends. A simple method that provides estimates for the most recent past uses questions about the survival of recent births in censuses or large household surveys. This study examines such data collected by 45 censuses and shows that on average they tend to underestimate under-5 mortality in comparison with alternative estimates, albeit with wide variations. In addition, the high non-sampling uncertainty in this approach precludes its use in providing robust estimates of child mortality at the country level. Given these findings, we suggest that questions about the survival of recent births to collect data on child mortality not be included in census questionnaires.

Maternal mortality in Bangladesh: a Countdown to 2015 country case study.

BACKGROUND: Bangladesh is one of the only nine Countdown countries that are on track to achieve the primary target of Millennium Development Goal (MDG) 5 by 2015. It is also the only low-income or middle-income country with two large, nationally-representative, high-quality household surveys focused on the measurement of maternal mortality and service use. METHODS: We use data from the 2001 and 2010 Bangladesh Maternal Mortality Surveys to measure change in the maternal mortality ratio (MMR) and from these and six Bangladesh Demographic and Health Surveys to measure changes in factors potentially related to such change. We estimate the changes in risk of maternal death between the two surveys using Poisson regression. FINDINGS: The MMR fell from 322 deaths per 100,000 livebirths (95% CI 253-391) in 1998-2001 to 194 deaths per 100,000 livebirths (149-238) in 2007-10, an annual rate of decrease of 5·6%. This decrease rate is slightly higher than that required (5·5%) to achieve the MDG target between 1990 and 2015. The key contribution to this decrease was a drop in mortality risk mainly due to improved access to and use of health facilities. Additionally, a number of favourable changes occurred during this period: fertility decreased and the proportion of births associated with high risk to the mother fell; income per head increased sharply and the poverty rate fell; and the education levels of women of reproductive age improved substantially. We estimate that 52% of maternal deaths that would have occurred in 2010 in view of 2001 rates were averted because of decreases in fertility and risk of maternal death. INTERPRETATION: The decrease in MMR in Bangladesh seems to have been the result of factors both within and outside the health sector. This finding holds important lessons for other countries as the world discusses and decides on the post-MDG goals and strategies. For Bangladesh, this case study provides a strong rationale for the pursuit of a broader developmental agenda alongside increased and accelerated investments in improving access to and quality of public and private health-care facilities providing maternal health in Bangladesh. FUNDING: United States Agency for International Development, UK Department for International Development, Bill & Melinda Gates Foundation.

Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures.

BACKGROUND: Anti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri antibody may diminish following tumor removal or immunosuppression. METHODS: To study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD. RESULTS: We demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) antibody uptake occurred in living neurons and was not an artifact of antibody diffusion into dead cells; 3) intracellular binding of anti-Hu antibody produced neuronal cell death, whereas uptake of anti-Ri antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of antibody-mediated neuronal death. CONCLUSIONS: Both anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this antibody response. Our results raise questions as to whether anti-Ri antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.

Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

RATIONALE: Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE), are inflammatory disorders of the central nervous system (CNS). The function of platelets in inflammatory and autoimmune pathologies is thus far poorly defined. OBJECTIVE: We addressed the role of platelets in mediating CNS inflammation in EAE. METHODS AND RESULTS: We found that platelets were present in human MS lesions as well as in the CNS of mice subjected to EAE but not in the CNS from control nondiseased mice. Platelet depletion at the effector-inflammatory phase of EAE in mice resulted in significantly ameliorated disease development and progression. EAE suppression on platelet depletion was associated with reduced recruitment of leukocytes to the inflamed CNS, as assessed by intravital microscopy, and with a blunted inflammatory response. The platelet-specific receptor glycoprotein Ibα (GPIbα) promotes both platelet adhesion and inflammatory actions of platelets and targeting of GPIbα attenuated EAE in mice. Moreover, targeting another platelet adhesion receptor, glycoprotein IIb/IIIa (GPIIb/IIIa), also reduced EAE severity in mice. CONCLUSIONS: Platelets contribute to the pathogenesis of EAE by promoting CNS inflammation. Targeting platelets may therefore represent an important new therapeutic approach for MS treatment.

Monitoring child survival in 'real time' using routine health facility records: results from Malawi.

OBJECTIVES: Few developing countries have the accurate civil registration systems needed to track progress in child survival. However, the health information systems in most of these countries do record facility births and deaths, at least in principle. We used data from two districts of Malawi to test a method for monitoring child mortality based on adjusting health facility records for incomplete coverage. METHODS: Trained researchers collected reports of monthly births and deaths among children younger than 5 years from all health facilities in Balaka and Salima districts of Malawi in 2010-2011. We estimated the proportion of births and deaths occurring in health facilities, respectively, from the 2010 Demographic and Health Survey and a household mortality survey conducted between October 2011 and February 2012. We used these proportions to adjust the health facility data to estimate the actual numbers of births and deaths. The survey also provided 'gold-standard' measures of under-five mortality. RESULTS: Annual under-five mortality rates generated by adjusting health facility data were between 35% and 65% of those estimated by the gold-standard survey in Balaka, and 46% and 50% in Salima for four overlapping 12-month periods in 2010-2011. The ratios of adjusted health facility rates to gold-standard rates increased sharply over the four periods in Balaka, but remained relatively stable in Salima. CONCLUSIONS: Even in Malawi, where high proportions of births and deaths occur in health facilities compared with other countries in sub-Saharan Africa, routine Health Management Information Systems data on births and deaths cannot be used at present to estimate annual trends in under-five mortality.

The 'Own Children' fertility estimation procedure: a reappraisal.

The Full Birth History has become the dominant source of estimates of fertility levels and trends for countries lacking complete birth registration. An alternative, the 'Own Children' method, derives fertility estimates from household age distributions, but is now rarely used, partly because of concerns about its accuracy. We compared the estimates from these two procedures by applying them to 56 recent Demographic and Health Surveys. On average, 'Own Children' estimates of recent total fertility rates are 3 per cent lower than birth-history estimates. Much of this difference stems from selection bias in the collection of birth histories: women with more children are more likely to be interviewed. We conclude that full birth histories overestimate total fertility, and that the 'Own Children' method gives estimates of total fertility that may better reflect overall national fertility. We recommend the routine application of the 'Own Children' method to census and household survey data to estimate fertility levels and trends.

Child mortality estimation: methods used to adjust for bias due to AIDS in estimating trends in under-five mortality.

In most low- and middle-income countries, child mortality is estimated from data provided by mothers concerning the survival of their children using methods that assume no correlation between the mortality risks of the mothers and those of their children. This assumption is not valid for populations with generalized HIV epidemics, however, and in this review, we show how the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) uses a cohort component projection model to correct for AIDS-related biases in the data used to estimate trends in under-five mortality. In this model, births in a given year are identified as occurring to HIV-positive or HIV-negative mothers, the lives of the infants and mothers are projected forward using survivorship probabilities to estimate survivors at the time of a given survey, and the extent to which excess mortality of children goes unreported because of the deaths of HIV-infected mothers prior to the survey is calculated. Estimates from the survey for past periods can then be adjusted for the estimated bias. The extent of the AIDS-related bias depends crucially on the dynamics of the HIV epidemic, on the length of time before the survey that the estimates are made for, and on the underlying non-AIDS child mortality. This simple methodology (which does not take into account the use of effective antiretroviral interventions) gives results qualitatively similar to those of other studies.

Child mortality estimation: accelerated progress in reducing global child mortality, 1990-2010.

Monitoring development indicators has become a central interest of international agencies and countries for tracking progress towards the Millennium Development Goals. In this review, which also provides an introduction to a collection of articles, we describe the methodology used by the United Nations Inter-agency Group for Child Mortality Estimation to track country-specific changes in the key indicator for Millennium Development Goal 4 (MDG 4), the decline of the under-five mortality rate (the probability of dying between birth and age five, also denoted in the literature as U5MR and (5)q(0)). We review how relevant data from civil registration, sample registration, population censuses, and household surveys are compiled and assessed for United Nations member states, and how time series regression models are fitted to all points of acceptable quality to establish the trends in U5MR from which infant and neonatal mortality rates are generally derived. The application of this methodology indicates that, between 1990 and 2010, the global U5MR fell from 88 to 57 deaths per 1,000 live births, and the annual number of under-five deaths fell from 12.0 to 7.6 million. Although the annual rate of reduction in the U5MR accelerated from 1.9% for the period 1990-2000 to 2.5% for the period 2000-2010, it remains well below the 4.4% annual rate of reduction required to achieve the MDG 4 goal of a two-thirds reduction in U5MR from its 1990 value by 2015. Thus, despite progress in reducing child mortality worldwide, and an encouraging increase in the pace of decline over the last two decades, MDG 4 will not be met without greatly increasing efforts to reduce child deaths.

Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation.

BACKGROUND: The Sustainable Development Goals (SDGs), set in 2015 by the UN General Assembly, call for all countries to reach an under-5 mortality rate (U5MR) of at least as low as 25 deaths per 1000 livebirths and a neonatal mortality rate (NMR) of at least as low as 12 deaths per 1000 livebirths by 2030. We estimated levels and trends in under-5 mortality for 195 countries from 1990 to 2019, and conducted scenario-based projections of the U5MR and NMR from 2020 to 2030 to assess country progress in, and potential for, reaching SDG targets on child survival and the potential under-5 and neonatal deaths over the next decade. METHODS: Levels and trends in under-5 mortality are based on the UN Inter-agency Group for Child Mortality Estimation (UN IGME) database on under-5 mortality, which contains around 18 000 country-year datapoints for 195 countries-nearly 10 000 of those datapoints since 1990. The database includes nationally representative mortality data from vital registration systems, sample registration systems, population censuses, and household surveys. As with previous sets of national UN IGME estimates, a Bayesian B-spline bias-reduction model (B3) that considers the systematic biases associated with the different data source types was fitted to these data to generate estimates of under-5 (age 0-4 years) mortality with uncertainty intervals for 1990-2019 for all countries. Levels and trends in the neonatal mortality rate (0-27 days) are modelled separately as the log ratio of the neonatal mortality rate to the under-5 mortality rate using a Bayesian model. Estimated mortality rates are combined with livebirths data to calculate the number of under-5 and neonatal deaths. To assess the regional and global burden of under-5 deaths in the present decade and progress towards SDG targets, we constructed several scenario-based projections of under-5 mortality from 2020 to 2030 and estimated national, regional, and global under-5 mortality trends up to 2030 for each scenario. FINDINGS: The global U5MR decreased by 59% (90% uncertainty interval [UI] 56-61) from 93·0 (91·7-94·5) deaths per 1000 livebirths in 1990 to 37·7 (36·1-40·8) in 2019, while the annual number of global under-5 deaths declined from 12·5 (12·3-12·7) million in 1990 to 5·2 (5·0-5·6) million in 2019-a 58% (55-60) reduction. The global NMR decreased by 52% (90% UI 48-55) from 36·6 (35·6-37·8) deaths per 1000 livebirths in 1990, to 17·5 (16·6-19·0) in 2019, and the annual number of global neonatal deaths declined from 5·0 (4·9-5·2) million in 1990, to 2·4 (2·3-2·7) million in 2019, a 51% (47-54) reduction. As of 2019, 122 of 195 countries have achieved the SDG U5MR target, and 20 countries are on track to achieve the target by 2030, while 53 will need to accelerate progress to meet the target by 2030. 116 countries have reached the SDG NMR target with 16 on track, leaving 63 at risk of missing the target. If current trends continue, 48·1 million under-5 deaths are projected to occur between 2020 and 2030, almost half of them projected to occur during the neonatal period. If all countries met the SDG target on under-5 mortality, 11 million under-5 deaths could be averted between 2020 and 2030. INTERPRETATION: As a result of effective global health initiatives, millions of child deaths have been prevented since 1990. However, the task of ending all preventable child deaths is not done and millions more deaths could be averted by meeting international targets. Geographical and economic variation demonstrate the possibility of even lower mortality rates for children under age 5 years and point to the regions and countries with highest mortality rates and in greatest need of resources and action. FUNDING: Bill & Melinda Gates Foundation, US Agency for International Development.

Streamlined process for the chemical synthesis of RNA using 2'-O-thionocarbamate-protected nucleoside phosphoramidites in the solid phase.

An improved method for the chemical synthesis of RNA was developed utilizing a streamlined method for the preparation of phosphoramidite monomers and a single-step deprotection of the resulting oligoribonucleotide product using 1,2-diamines under anhydrous conditions. The process is compatible with most standard heterobase protection and employs a 2'-O-(1,1-dioxo-1λ(6)-thiomorpholine-4-carbothioate) as a unique 2'-hydroxyl protective group. Using this approach, it was demonstrated that the chemical synthesis of RNA can be as simple and robust as the chemical synthesis of DNA.

Observation of cocurrent toroidal rotation in the EAST tokamak with lower-hybrid current drive.

Lower-hybrid waves have been shown to induce a cocurrent change in toroidal rotation of up to 40 km/s in the L-mode plasma core region and 20 km/s in the edge of the EAST tokamak. This modification of toroidal rotation develops on different time scales. For the edge, the time scale is no more than 100 ms, but for the core the time scale is around 1 s. A simple model based on turbulent equipartition and thermoelectric pinch predicts the experimental results.

Maternal mortality estimation at the subnational level: a model-based method with an application to Bangladesh.

OBJECTIVE: To provide a model-based method of estimating maternal mortality at the subnational level and illustrate its use in estimating maternal mortality rates (MMrates) and maternal mortality ratios (MMRs) in all 64 districts of Bangladesh. METHODS: Knowing that mortality is more pronounced among the poorer segments of a population, in rural areas and in areas with poor availability and utilization of maternal care, we used an empirical Bayesian prediction method to estimate maternal mortality at the subnational level from the spatial distribution of such factors. FINDINGS: MMRs varied significantly by district in Bangladesh, from 158 maternal deaths per 100,000 live births at Dhaka district to 782 in the northern coastal regions. Maternal mortality was consistently higher in the eastern and northern regions, which are known to be culturally conservative and to have poor transportation systems. CONCLUSION: Bangladesh has made noteworthy strides in reducing maternal mortality since 1990, even though the utilization of skilled birth attendants has increased very little. However, several areas still show alarmingly high maternal mortality figures and need to be prioritized and targeted by health administrators and policy-makers.