Demographic inference under a spatially continuous coalescent model.

In contrast with the classical population genetics theory that models population structure as discrete panmictic units connected by migration, many populations exhibit heterogeneous spatial gradients in population connectivity across semi-continuous habitats. The historical dynamics of such spatially structured populations can be captured by a spatially explicit coalescent model recently proposed by Etheridge (2008) and Barton et al. (2010a, 2010b) and whereby allelic lineages are distributed in a two-dimensional spatial continuum and move within this continuum based on extinction and coalescent events. Though theoretically rigorous, this model, which we here refer to as the continuum model, has not yet been implemented for demographic inference. To this end, here we introduce and demonstrate a statistical pipeline that couples the coalescent simulator of Kelleher et al. (2014) that simulates genealogies under the continuum model, with an approximate Bayesian computation (ABC) framework for parameter estimation of neighborhood size (that is, the number of locally breeding individuals) and dispersal ability (that is, the distance an offspring can travel within a generation). Using empirically informed simulations and simulation-based ABC cross-validation, we first show that neighborhood size can be accurately estimated. We then apply our pipeline to the South African endemic shrub species Berkheya cuneata to use the resulting estimates of dispersal ability and neighborhood size to infer the average population density of the species. More generally, we show that spatially explicit coalescent models can be successfully integrated into model-based demographic inference.

Neonatal early-onset Escherichia coli disease. The effect of intrapartum ampicillin.

BACKGROUND: Maternal intrapartum ampicillin has been recommended for the prevention of neonatal group B streptococcal disease. OBJECTIVES: To assess the effect of this practice, if any, on neonatal early-onset Escherichia coli infection and to delineate the clinical characteristics of infected neonates. PATIENTS AND METHODS: All neonates with early-onset E coli infection who were born at Cook County Children's Hospital, Chicago, Ill, from January 1, 1982, through December 31, 1993, were identified from a microbiological register of all neonatal bacteremias and infections. Because intrapartum ampicillin use increased in our hospital since 1988, infection and case fatality rates from 1982 through 1987 (period 1) were compared with data from 1988 through 1993 (period 2). We studied maternal risk factors, clinical characteristics of infected neonates, and microbiological sensitivities of E coli isolates. RESULTS: Early-onset E coli infection was diagnosed in 30 of 61,498 live births. The overall infection rate (0.49 per 1000 live births) did not change significantly during the 2 time periods (0.37 per 1000 live births during period 1 vs 0.62 per 1000 live births during period 2, P = .21; chi 2 test); however, there was an increase in the infection rate in neonates weighing between 1501 and 2500 g. Infected neonates had a clinical syndrome that was indistinguishable from early-onset group B streptococcal infection; respiratory distress was the single most frequent finding in 73% (22/30) infected neonates. An increase in the proportion of infections caused by ampicillin-resistant E coli was observed during period 2 (12/18) compared with period 1 (3/12, P = .03; Fisher exact test). During period 2, 61% (11/18) of mothers of infected neonates received intrapartum ampicillin compared with 17% (2/12; P = .02) during period 1. Overall, a higher proportion of neonates born to ampicillin-treated women had ampicillin-resistant infection (12/13 vs 3/17; P < .001). Mothers of 10 of 15 neonates with ampicillin-resistant infection had received more than 2 doses of intrapartum ampicillin. The difference between the prevalence of intrapartum fever in mothers with sensitive organisms (40%, or 6/15) and resistant organisms (93%, or 14/15) was also significant (P = .003). All 6 early-onset E coli-related deaths were due to ampicillin-resistant organisms; 4 of the 6 mothers received intrapartum ampicillin. CONCLUSIONS: We have shown a shift of early-onset E coli infection from a less fulminant disease caused by ampicillin-sensitive organisms to a more fulminant disease caused by ampicillin-resistant organisms. Increased use of maternal intrapartum ampicillin therapy may account for these changes. In the absence of evidence for group B streptococcal disease, clinicians should consider the possibility of ampicillin-resistant E coli infection in critically ill neonates born to women with a history of intrapartum fever and treatment with intrapartum ampicillin.

Height at onset of insulin-dependent diabetes in children in southern India.

A total of 250 children with insulin-dependent diabetes mellitus (IDDM), having age at onset of diabetes < or = 18 years were studied. Their height at onset of diabetes was compared with that of the normal age- and sex-matched control population. No differences were observed in the heights of the two groups of children. Therefore, our results were similar to that found in Japan and differed from the reports in European children with IDDM in whom an increased growth velocity was noted before the onset of IDDM.

Delayed onset of diabetes in children of low economic stratum--a study from southern India.

Influence of the socioeconomic status on the age at onset of insulin-dependent diabetes mellitus (IDDM) was analysed in 614 patients who developed diabetes < or = 20 years. The peak occurrence was seen at 11 years in girls (n = 293). The boys (n = 321) showed multiple peaks between 11 and 18 years. In the urban patients (n = 463), the peak was at 11 years in contrast to a delayed peak at 18 years in the rural group (n = 151). When analysed with respect to the family income, the higher income group (HIG) (Rs > 2000/month) showed a sharp peak at 11 years whereas the lower income group (LIG) showed a peak at 18 years (chi 2 = 7.2, P = 0.007). The median body weight of the LIG was lower compared to the HIG. Although the exact cause for the delayed age at onset of IDDM in the rural or LIG is not known, it is likely to be a consequence of the lower socioeconomic and nutritional status (indicated by low body weight) and probably indicates the influence of environmental factors in the pathogenesis of the disease.

Amlodipine in mild and moderate hypertension: initial Indian experience.

In an open, non-comparative, variable-dose study, 20 outpatients with mild to moderate essential hypertension were treated with 5-10 mg amlodipine once daily for 4 weeks, after their blood pressures had stabilized on placebo. Amlodipine produced a significant decrease in blood pressure (P < 0.05) from the initial mean of 162/100 mm Hg to 139/85 mm Hg at 4 weeks. 80% of the patients reached the goal diastolic blood pressure of < or = 90 mm Hg with a once-daily dose of 5 mg amlodipine within 2 weeks. The remaining 20% also attained the goal diastolic blood pressure within 4 weeks, with a one-step increase in the dose to 10 mg at 2 weeks. Amlodipine maintained blood pressure reduction throughout the 24-hours dosing interval with a once-daily dose. Notably, no side effects were observed; pulse rate, electrocardiogram, and laboratory parameters were not significantly altered with therapy. Amlodipine in a single daily dose of 5-10 mg is effective and well tolerated in the treatment of patients with mild to moderate hypertension.

Prevalence of childhood diabetes in an urban population in south India.

The objective of the study was to estimate the prevalence of insulin-dependent diabetes in children less than or equal to 15 years in an urban area in south India, by a population study. Three zones from the northeastern part of the city demarcated by the Directorate of Census were chosen. Ascertainment of the cases from these zones was made (a) by collecting data from the major hospitals and diabetes clinics by personal visit; (b) by questionnaire sent to medical practitioners in the area; and (c) from the chemists and druggists who sell insulin. Recommendations of the Diabetes Epidemiology Research International Registry Group were used. Thirty children with insulin-dependent diabetes with age at diagnosis less than or equal to 15 years were identified. The prevalence was 0.26/1000. The peak age at diagnosis was 12 years. This first population-based study of prevalence of insulin-dependent diabetes in south India shows that insulin-dependent diabetes is not rare. It is higher than reported from many other Asian countries.