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A multinutrient-fortified beverage enhances the nutritional status of children in Botswana.

Due to their widespread acceptability, multinutrient-fortified foods and beverages may be useful in reducing micronutrient deficiencies, especially in developing countries. We studied the efficacy of a new fortified beverage in improving the nutritional status of children in Botswana. We screened 311 lower income urban school children, ages 6-11 y, in two primary schools near Gaborone. Children were given seven 240-mL servings weekly of either an experimental beverage (EXP) fortified with 12 micronutrients or an isoenergetic placebo drink (CON) for 8 wk. Weight, mid-upper arm circumference, hemoglobin, retinol, ferritin, vitamin B-12, folate and riboflavin status were measured at baseline and at the end of the study. Plasma zinc and serum transferrin receptors also were measured at study end. A total of 145 children in the EXP group and 118 in the CON group completed the trial. Using multivariate analysis, the changes in mid-upper arm circumference, weight for age and total weight were significantly better in the EXP group than in the CON group (P < 0.01). Ferritin, riboflavin and folate status were significantly better in the EXP group than in the CON group at study end (P < 0.01), but serum vitamin B-12 was not. Zinc was significantly higher and transferrin receptors were significantly lower at the conclusion of the study in the EXP group than in the CON group (P < 0.001). Mean plasma retinol concentrations, which were low (<0.7 micro mol/L) in both groups, did not change. We conclude that a micronutrient-fortified beverage may be beneficial as part of a comprehensive nutritional supplementation program in populations at risk for micronutrient deficiencies.

Anthropometry↗

Political and economic factors influencing contraceptive uptake.

International, national and local level politics influence the uptake of contraception through consensuses, laws, financial and moral support or the creation of an enabling atmosphere. Opposition to contraception generally comes from some churches and groups opposed to particular technologies. Socio-economic factors, particularly education, the health care system and the perceived or actual cost of fertility regulation as compared to benefits expected from children also powerfully influence contraceptive use. For many poor women in developing countries their powerlessness in relation to their male partners is an important obstacle.

Contraception↗

The Wilhelmine E. Key 1994 invitational Lecture. Plant genetic diversity and the struggle to measure selection.

The fundamental research program of population genetics has been to seek a quantitative assessment of the role of the various forces of evolution in shaping patterns of genetic variation. This goal has been pursued on both empirical and theoretical fronts. The introduction of biochemical and molecular techniques into population genetics more than 25 years ago revealed vast stores of genetic variation within populations. This level of genetic diversity is difficult to reconcile with balancing selection, and as a consequence, recent thinking has emphasized the role of mutation and genetic random drift as the primary determinants of genetic diversity. The resulting neutral theory of molecular evolution has dominated population genetic thought for more than 20 years. Nonadaptive theories have also emphasized the role of deleterious mutations in driving evolutionary change. New insights into the relative importance of selection and genetic random drift can now be obtained from samples of DNA sequences of genes drawn from within species. The elaboration of coalescence theory, together with the accumulation of data on gene genealogies, permits an integration over relatively long periods of evolutionary time. The ability to integrate over long periods of evolutionary time permits the detection of small selection intensities and it reveals some information about the mode of selection. When the genealogy is consistent with a neutral process, the effective population size can be estimated, as can the age of the coalescent, thus providing new empirical approaches to the estimation of these important parameters. Applications of these approaches in plant population genetics are still in their infancy, but they have already provided new insights into effective population sizes and they are beginning to illustrate how selection for domestication has affected plant genomes.

Chromosome Mapping↗

Internal dosimetry of uranium isotopes using Bayesian inference methods.

A group of personnel at Los Alamos National Laboratory is routinely monitored for the presence of uranium isotopes by urine bioassay. Samples are analysed by alpha spectroscopy, and the results are examined for evidence of an intake of uranium. Because the measurement uncertainties are often comparable to the quantities of material we wish to detect, statistical considerations are crucial for the proper interpretation of the data. The problem is further complicated by the significant, but highly non-uniform, presence of uranium in local drinking water and, in some cases, food supply. Software originally developed for internal dosimetry of plutonium has been adapted to the problem of uranium dosimetry. The software uses an unfolding algorithm to calculate an approximate Bayesian solution to the problem of characterising any intakes which may have occurred, given the history of urine bioassay results for each individual in the monitored population. The program uses biokinetic models from ICRP Publications 68 and later, and a prior probability distribution derived empirically from the body of uranium bioassay data collected at Los Alamos over the operating history of the laboratory. For each individual, the software creates a posterior probability distribution of intake quantity and solubility type as a function of time. From this distribution, estimates are made of the cumulative committed dose (CEDE) to each individual. Results of the method are compared with those obtained using an earlier classical (non-Bayesian) algorithm for uranium dosimetry. We also discuss the problem of distinguishing occupational intakes from intake of environmental uranium, within a Bayesian framework.

Algorithms↗

National Immunization Survey: the methodology of a vaccination surveillance system.

The National Immunization Survey (NIS) was designed to measure vaccination coverage estimates for the US, the 50 states, and selected urban areas for children ages 19-35 months. The NIS includes a random-digit-dialed telephone survey and a provider record check study. Data are weighted to account for the sample design and to reduce nonresponse and non-coverage biases in order to improve vaccination coverage estimates. Adjustments are made for biases resulting from nonresponse and nontelephone households, and estimation procedures are used to reduce measurement bias. The NIS coverage estimates represent all US children, not just children living in households with telephones. NIS estimates are highly comparable to vaccination estimates derived from the National Health Interview Survey. The NIS allows comparisons between states and urban areas over time and is used to evaluate current and new vaccination strategies.

Data Collection↗

Early warning and NHS Direct: a role in community surveillance?

BACKGROUND: NHS Direct is a nurse-led telephone help line that covers the whole of England and Wales. NHS Direct derived data are being used for community surveillance, the purpose of which is to detect a local or national increase in symptoms reported by callers. The system has the potential to identify an increase in symptoms reported by callers about people in the prodromal stages of illness caused by the deliberate release of a biological or chemical agent. There are no other community surveillance projects existing on a national scale that utilize electronic daily data. METHODS: We describe the surveillance system and calls to NHS Direct between December 2001 and July 2002. Confidence limits have been constructed for 10 key algorithms at each site and control charts devised for five of these algorithms at sites covering the key urban areas. RESULTS: Daily reporting has been achieved from NHS Direct sites in England and Wales. High levels of activity in specific algorithms at both national and regional levels have been detected. A sustained national increase in calls about fever occurred in January 2002. CONCLUSION: Although the project is still at an early stage, daily analysis of NHS Direct data has the potential to detect symptoms in the community that could be related to deliberate releases of chemical or biological agents or to outbreaks of disease. For this surveillance to act as an 'early warning' of illness resulting from a microbiological or chemical cause, the NHS Direct surveillance needs to be fully integrated into an appropriate public health response (which may require diagnostic samples to be taken from callers).

Adolescent↗

The pharmacokinetics of milrinone in pediatric patients after cardiac surgery.

BACKGROUND: Milrinone has been shown to increase cardiac output in children after cardiac surgery, but pharmacokinetic analysis has not been used to identify effective dose regimens. The purpose of this study was to characterize the pharmacokinetics of milrinone in infants and children and to apply the results to the issue of dosing. METHODS: Twenty children were studied after they underwent repair of congenital cardiac defects. Control hemodynamic measurement was made after the children were separated from cardiopulmonary bypass, and each patient was given a loading dose of 50 microg/kg progressively in 5 min. Hemodynamic measurements were recorded again at the end of the loading dose and when a blood sample was taken to determine milrinone plasma concentrations. Further blood samples were taken during the next 16 h for milrinone plasma concentration analysis. The pharmacokinetics of milrinone were analyzed using the population pharmacokinetic program NONMEM. RESULTS: The loading dose of milrinone resulted in a mean decrease in mean blood pressure of 12% and a mean increase in cardiac index of 18% at a mean peak plasma concentration of 235 ng/ml. The pharmacokinetics of milrinone were best described by a three-compartment model. In the optimal model, all volumes and distribution clearances were proportional to weight, and weight-normalized elimination clearance was proportional to age; ie., Cl1 = 2.5 x weight x (1 + 0.058 x age) where Cl1 is expressed as ml/min, and the units of weight and age are kg and months, respectively. CONCLUSIONS: A loading dose of 50 microg/kg effectively increases cardiac index in children after cardiac surgery. Simulations indicate that the peak plasma concentration can be maintained by following the loading dose of 50 microg/kg with an infusion of approximately 3 microg x kg(-1) x min(-1) for 30 min and then a maintenance infusion, which may require adjustment for age.

Body Weight↗

Biologic and molecular characterization of non-Hodgkin's lymphoma.

The wide clinicopathologic heterogeneity of non-Hodgkin's lymphoma is reflected by the various molecular pathways underlying non-Hodgkin's lymphoma pathogenesis, including activation of dominantly acting oncogenes, deletion and inactivation of tumor-suppressor genes, viral infection, deregulation of cytokine networks, and chronic antigenic stimulation. Molecular lesions involving protooncogenes include activation of bcl-2 and bcl-1 in specific subsets of low-grade non-Hodgkin's lymphomas and c-myc in a proportion of intermediate- and high-grade non-Hodgkin's lymphomas. The deregulation of these genes promotes cell growth or protects the tumor population from programmed cell death, or both. Additional genetic abnormalities representing putative sites of novel oncogenes contributing to lymphomagenesis include chromosomal breaks at 3q27 in intermediate-grade non-Hodgkin's lymphoma and at 9p13 in small lymphocytic lymphoma. The role of inactivation of tumor-suppressor loci is best exemplified by the frequent inactivation of p53 in Burkitt's lymphoma and by the recurrent deletion of 6q25-q27 and 6q21-q23 in intermediate- and high-grade non-Hodgkin's lymphoma, respectively. Infection by Epstein-Barr virus occurs in a variable fraction of high-grade non-Hodgkin's lymphomas, whereas it is usually absent in other types of non-Hodgkin's lymphoma. Other mechanisms supporting non-Hodgkin's lymphoma growth and development include autocrine or paracrine cytokine loops, or both, and clonal expansion through antigen receptor stimulation. The heterogeneity of non-Hodgkin's lymphoma pathogenesis provides a framework for the development of novel classification methods of potential clinical relevance.

Cyclin D1↗

Increased blood pressure reactivity in children of borderline hypertensive fathers.

OBJECTIVE: To evaluate the influence of heredity on blood pressure levels and reactivity in the offspring of borderline hypertensive and normotensive fathers. PARTICIPANTS AND OUTCOME MEASURES: Borderline hypertensive and normotensive men having normotensive wives (n = 25 and 26) were identified in a population screening program. Their children aged above 12 years were invited to participate. Seventeen having a borderline hypertensive father (BHT+) and 19 with a normotensive father (NT+) were investigated. Clinical and 24 h ambulatory blood pressure was measured, as well as blood pressure reactivity to an arithmetic mental stress test. RESULTS: The BHT+ group had a significantly higher clinical systolic blood pressure than the NT+ group (126 +/- 13 versus 115 +/- 7 mmHg, P< 0.01) but similar 24 h blood pressure levels. Systolic blood pressure variability (standard deviation of systolic blood pressure measurements each hour over 24 h) was significantly higher in the BHT+ group (18 +/- 4 versus 16 +/- 4 mmHg, P< 0.05). During mental stress test the BHT+ group had significantly higher increases in systolic and diastolic blood pressures at 4 min (NT+ 8% and 13% versus BHT+ 16% and 23% above baseline, P< 0.05) and significantly elevated DBP during the period after the stress test (NT+ 1% versus BHT+ 13% above baseline, P < 0.01). CONCLUSION: Even a mild level of hypertensive heredity affects important markers of blood pressure regulation, such as blood pressure variability and reactivity to mental stress. This might have prognostic implications; it also points to the possible importance of these variables as early signs of a familial predisposition to hypertension.

Adolescent↗

Clinical prediction of normotension in borderline hypertensive men--a 10 year study.

OBJECTIVE: To investigate 24-h ambulatory blood pressure measurements (ABPM) as a tool for long-term prediction of future blood pressure (BP) status in high normal and low stage 1 hypertensives. DESIGN, SETTING AND PARTICIPANTS: A total of 165 men from a population screening program with diastolic BP (DBP) 85-94 mmHg and a systolic BP (SBP) < 150 mmHg performed a 24-h ABPM. Ten years later, 120 participants (73%) returned for renewed measurements. MAIN OUTCOME MEASURES: Blood pressure status at 10 years. RESULTS: At the 10-year follow-up, 53% of the participants were classified as hypertensive (HT) (BP > or = 140/90 or taking anti-hypertensive medication) and 47% were classified as normotensive (NT) (BP < 140/90 mmHg). There was no significant baseline differences in office SBP levels between those who were normotensive or hypertensive at follow-up (136/91 versus 138/92 mmHg), whereas both SBP and DBP night-time levels were significantly lower in the future normotensives as compared to the future hypertensives (107/69 versus 112/74 mmHg, P < 0.01). Using recommended normalcy night-time ABP levels of < 120/75 mmHg in addition to office BP (140/90) at baseline, over 85% of the subjects were correctly classified provided they met both clinic and ambulatory night-time criteria for HT and NT classification at baseline. CONCLUSION: The use of ABPM in addition to office BP's in patients with borderline hypertension greatly increases the possibility of identifying those individuals who are at a very small risk of developing future hypertension. This could potentially lead to considerable savings in both patient anxiety, physician time and resource consumption.

Adult↗

Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension.

The purpose of this study was to evaluate in a prospective, double-blind, placebo-controlled study the effect of long-term (2-year) lisinopril treatment on cardiovascular end-organ damage in patients with previously untreated isolated systolic hypertension (ISH). All patients with ISH were derived from a population screening program. End-organ damage measurements, done initially and after 6 and 24 months of treatment, included measurements of aortic distensibility and echocardiographic left ventricular mass index (LVMI) and diastolic function. Blood pressure was measured by office and ambulatory measurements. Of the 97 subjects with ISH selected from the screening, 62 (30 lisinopril) completed the study according to protocol. Office blood pressure decreased in both groups, but ambulatory results significantly decreased with lisinopril-treatment only. Aortic distensibility increased significantly with lisinopril, as opposed to a decrease in placebo-treated subjects. The main effect of increased distensibility occurred between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the first 6 months of treatment. LVMI decreased in both treatment groups, with a significantly higher reduction in lisinopril-treated subjects. Left ventricular diastolic function showed no significant changes in either group. The vascular pathophysiologic alterations of ISH-a decreased aortic distensibility-can be improved with long-term lisinopril treatment, whereas values deteriorate further in placebo-treated subjects. These results, in one of the first studies including subjects with previously untreated ISH only, indicate that lisinopril treatment might favorably influence the cardiovascular risk of ISH.

Aged↗

Physician hospital consumer collaboration.

The authors describe a disease management initiative designed to address issues of noncompliance in a diabetic population. The program design was a collaborative effort between a payer and a public health organization representing Hartford Hospital and Hartford Physicians Association. Interventions included a patient self-assessment, phone counseling, and a monetary reward for program participation.

Blue Cross Blue Shield Insurance Plans↗

Infant emmetropization: longitudinal changes in refraction components from nine to twenty months of age.

Rapid emmetropization is described in pediatrically normal infants from 9 months of age during the following year. The infants, obtained from various categories of the Cambridge population screening program, provided a broad range of refractive errors. The large group of 254 nonanisometropic infants studied allowed the mean rate of change and dependence on the initial refraction value to be determined. Refraction was measured by cycloplegic retinoscopy. Rapid emmetropization changes occurred in the following refractive components: mean spherical equivalent (MSE), astigmatism magnitude, the horizontal astigmatism component, the infant's most positive meridian, and the infant's most negative meridian. The MSE and astigmatism rates of change (diopters/year), were highly dependent on their respective initial powers (r = -0.61 and r = -0.76). The percentage weighted mean proportional rate of change for MSE was -30% (SE 4%) and for astigmatism magnitude it was -59% (SE 14%). There was much individual variation, with some exhibiting fast emmetropization and others not. The MSE and astigmatism changes, however, were almost independent of each other. The refractive errors of the most positive and most negative meridians emmetropize because they are both derived from the MSE and half the astigmatism. With-the-rule astigmatism was more prevalent than against-the-rule astigmatism at 9 months of age, and with-the-rule astigmatism exhibited a significantly greater proportional rate of change. The relationship of emmetropization and refractive screening is considered. A new component "MOMS" is introduced, the maximum ocular meridional separation, when both eyes are considered. Thus incorporating astigmatism and anisometropia may be a good single indicator of conditions associated with later amblyopia. The almost independent emmetropization of the MSE and astigmatism components is an important result to consider in theories of emmetropization, refractive screening, clinical prescribing, and the evaluation of infants in treatment trials.

Accommodation, Ocular↗