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At least 973 records · Page 54Linked to original sources
PubMed1994

The Western Sydney Stroke Risk in the Elderly Study. A 5-year prospective study.

Aging of the Australian population, as in other developed nations, will ensure that stroke remains one of the most important causes of death and disability. The Stroke Risk in the Elderly (SITE) study aims to measure prospectively the independent contribution of dietary, sociodemographic, blood lipid, blood pressure, and hemostatic factors to risk of stroke and other cardiovascular outcomes. The target population included all independently living men and women aged 65 years and over, residents in several retirement villages in western metropolitan Sydney, New South Wales, Australia. The study cohort consists of 225 men and 787 women, selected as a convenience sample from all eligible residents in the local government areas (LGAs) adjacent to Westmead Hospital. Participants attended a baseline session to complete dietary, life-style, medical, and sociodemographic questionnaires. Anthropomorphic variables and blood pressure were measured. Blood was taken for measurement of serum lipid, glucose, and hemostatic factors. Questionnaire results were compared with an age/sex-stratified, randomly selected sample drawn from the community (in the same LGAs), in order to quantify potential sampling and selection biases. The study cohort will be followed for a minimum of 5 years. The attendance rate of eligible residents for a baseline medical, dietary, life-style, and sociodemographic assessment was 72% for males and 69% for females. The study cohort was older, better educated, less ethnically diverse, and among women, less likely to have ever been married compared to people aged over 65 years in the comparison group. The baseline results suggest that hemostatic factors may be of importance in assessing risk of cardiovascular disease, (CVD), particularly in older men.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

[Social marketing applied to condom promotion: a proposal for intervention in groups at risk for sexually transmitted diseases].

Sexually transmitted diseases (STDs) are an important worldwide health problem. Their association with AIDS an other insidious viral processes have brought them to the foreground of sanitary authorities and general population concern. Often, health services have to struggle with reinfections, which concentrate in pockets of risk that consume large amount of care and constitute an important link in the transmission of these diseases. General publicity have little impact among high risk groups. Thus, it becomes necessary to be more precise and divide into segments the target population we want to reach. Prevention of reinfection in these communities requires the implementation of healthy behaviours through the promotion of a tangible product (condom). Regarding these considerations, social marketing emerges as the right instrument to be used. Through individual focused interviews with prostitutes, homosexual and young promiscuous heterosexual patients from a STDs Prevention, Diagnosis and Treatment Centre, determining factors of the use condoms and related behaviour guidelines have been identified. Also, a social marketing strategy is suggested to prevent these diseases among groups at risk by means of condom promotion.

Adolescent↗
PubMed2006

A study of disruptive behavior disorders in Puerto Rican youth: I. Background, design, and survey methods.

OBJECTIVE: This is the first of two related articles on a study carried out between 2000 and 2003 designed to assess the prevalence, associated comorbidities, and correlates of disruptive behavior disorders in two populations of Puerto Rican children: one in the Standard Metropolitan Areas of San Juan and Caguas in Puerto Rico, and the other in the south Bronx in New York City. METHOD: This article provides the study's background, design, and methodology. Probability samples of children ages 5 to 13 years were drawn at the two sites (n = 2,491). Subjects and their primary caretakers were interviewed using the Diagnostic Interview Schedule for Children-IV and a wide array of risk factor measures. The samples were weighted to correct for differences in the probability of selection resulting from sample design and to adjust for differences from the 2000 U.S. Census in the age/gender distribution. RESULTS: The samples are representative of the populations of Puerto Rican children in the south Bronx and in the Standard Metropolitan Areas in Puerto Rico. Of the 2,940 children identified as eligible for the study, 2,491 participated for an overall compliance rate of 85%. CONCLUSIONS: The study results, to be described in an accompanying report, are generalizable to the two target populations.

Adolescent↗
PubMed1989

Is increased plasma viscosity a risk factor for high blood pressure?

Data from several epidemiologic studies have suggested that, among other variables, hematocrit and fibrinogen may constitute risk factors for high blood pressure. As part of a population survey for cardiovascular risk factors, plasma viscosity and hemoglobin were measured. Blood pressure was determined under standardized conditions according to the recommendations of the AHA. A two-stage age-sex-stratified cluster sample of 5,312 persons, aged twenty-five to sixty-four years, was selected from a mixed urban/rural target population of 282,279 (total population approximately 533,000). A net response of 79.3% was achieved. Multiple logistic regression analyses including plasma viscosity, hemoglobin, body mass index, alcohol consumption, smoking behavior, and total serum cholesterol as independent variables were run controlling for both age and sex. Plasma viscosity appeared as a significant main effect in all analyses and demonstrated the strongest association with high blood pressure next to body mass index. Whether this association implies a causal relationship cannot be answered from cross-sectional data. However, even if plasma hyperviscosity represents a secondary phenomenon in hypertension, it might be of prognostic relevance. There is evidence that increased plasma viscosity may contribute to myocardial hypertrophy. Therefore hypertensives with impaired blood fluidity might constitute a subgroup at particular risk for cardiovascular complications. When antihypertensive drugs are selected, their influence on blood viscosity should be taken into account.

Adult↗
PubMed1984

Oral rehydration therapy: combining anthropological and epidemiological approaches in the evaluation of a Papua New Guinea programme.

The impact of an oral rehydration therapy (ORT) programme for diarrhoeal disease was evaluated by means of continuing surveillance of this Papua New Guinea population. Mortality from diarrhoeal disease in the under-fives fell from 3.3/1000/annum before the ORT programme to 1.3/1000/annum after the programme had become established. However there is evidence that the attendance rate for diarrhoea treatment has begun to fall from its previously high level. These trends are explicable in terms of the target population's expectations of Western treatments. The implications of these findings for the design and evaluation of similar health programmes are discussed.

Attitude to Health↗
PubMed1995

[Evaluation of the nutritional status of a rural child population in a Valencia community: the Pego study].

OBJECTIVE: To evaluate the nutritional state of the child population of Pego (Alicante) in order to define the patterns of normality and check the validity of the anthropometric parameters most commonly used in evaluating nutritional status. DESIGN: A descriptive crossover study. SETTING: Valls de Pego Primary Care Health Centre. PATIENTS: 943 healthy children and adolescents aged 0 to 17 were studied out of a target population of 2,150 who were seen for treatment at the Health Centre for reasons which had nothing to do with nutritional problems. INTERVENTIONS: Between july 1989 and december 1990, a simple anthropometric assessment of each patient was carried out: obtaining weight, height, the nutrition or Shukla index and the Quetelet index. MAIN RESULTS: Nutritional distribution was clearly displaced towards high values on the nutritional scale, with 14% obesity and 15% overweight as against 13% at risk of malnutrition. There was more overweight and obesity at a higher age and in males. CONCLUSIONS: This prevalence of nutritional disturbances is similar to that in other Spanish studies and confirms both the size of the problem of obesity in the prevention of related pathologies in adults and the relevance of the adult's Nutritional History throughout his/her life. The study made clear the good correlation and utility of the Shukla and Quetelet indexes.

Adolescent↗
PubMed2000

Capture-recapture methods to size alcohol related problems in a population.

STUDY OBJECTIVE: To investigate the utility of capture-recapture methods to estimate prevalence of subjects with alcohol related disorders using multiple incomplete lists. DESIGN: This was a cross sectional study of alcohol related disorders in a large community. SETTING: During 1997 identified cases with known alcohol related disorders were independently flagged by four sources (self help volunteering groups; psychiatric ambulatory; public alcohology service; hospital discharges). PATIENTS: 381 records were flagged, corresponding to 349 individual cases from a target population resident in a northern Italy area. MAIN RESULTS: The two sample capture-recapture estimates were clearly biased because of dependencies among sources. Estimates based on log-linear models showed prevalent counts ranged from 2297 (95% confidence intervals: 1524, 3794) to 2523 (95% confidence intervals: 1623, 4627) after adjustment for dependence among sources only or also for heterogeneity in catchability among age categories (< 50 and >/= 50 years), respectively. CONCLUSIONS: The study suggests that capture-recapture is an appropriate approach for estimating prevalence of subjects with alcohol related problems who seek or need treatment and assistance when different lists of alcoholics can be obtained from different types of agencies involved with problematic use of alcohol. Critical factors are the complexity in case definition and the analysis of heterogeneity among people. Accurate estimates are needed to plan and evaluate public health interventions.

Alcoholism↗
PubMed2006

Addressing the musculoskeletal components of fracture risk with calcium and vitamin D: a review of the evidence.

Osteoporotic fractures are an extremely common and serious health problem in the elderly. This article presents the rationale for calcium and vitamin D supplementation in the prevention and treatment of osteoporotic fractures and reviews the literature evidence on the efficacy of this strategy. Two musculoskeletal risk factors are implicated in osteoporotic fractures in the elderly: the loss of bone mass due to secondary hyperparathyroidism and the increased propensity to falls. Calcium and vitamin D reverse secondary hyperparathyroidism with resultant beneficial effects on bone mineral density (BMD). Additionally, calcium and vitamin D supplementation significantly improves body sway and lower extremity strength, reducing the risk of falls. The effects of combined calcium and vitamin D on parathyroid function and BMD provide a strong rationale for the use of this therapy in the prevention and treatment of osteoporosis and osteoporotic fractures. There is general agreement that, in patients with documented osteoporosis, calcium and vitamin D supplementation should be an integral component of the management strategy, along with antiresorptive or anabolic treatment. Frail elderly individuals constitute another major target population for calcium and vitamin D because evidence from randomized studies in institutionalized elderly subjects demonstrates that these supplements reduce osteoporotic fracture risk, particularly in the presence of dietary deficiencies. However, the results of trials in community-dwelling subjects have been equivocal. Within the primary-care setting, further research is required to establish appropriate target subgroups for calcium and vitamin D supplementation; overall, the data are consistent with a benefit individuals with insufficient calcium and/or vitamin D, although patients with documented osteoporosis will derive further benefit in terms of fracture prevention from the addition of an antiresorptive agent.

Accidental Falls↗
PubMed2002

Infant feeding indicators for use in emergencies: an analysis of current recommendations and practice.

OBJECTIVE: To assess the applicability and use of infant nutrition and health indicators during emergencies. DESIGN: Indicators recommended by international health and nutrition organisations for assessing infant feeding practice were compiled and analysed to evaluate their consistency and applicability for use in surveys of emergency-affected populations. These indicators included measures of breast-feeding status, use of artificial feeding, anthropometric status and morbidity. Health and nutrition surveys performed on the resident or refugee population of Kosovo during the years 1996-1999 were then reviewed and the use of infant feeding and morbidity indicators were compared. RESULTS: A number of recommended indicators exist for assessing infant and child feeding practice which have been generated by different international organisations. A comparison of these indicators revealed a number of inconsistencies, both in target population and measurement method. Their use during the Kosovo crisis was likewise inconsistent and prevented conclusions being drawn about the effectiveness of the international response in protecting infant health and nutrition. CONCLUSIONS: Standard indicators need to be agreed and promoted for use during surveys of emergency-affected populations. Failure to do so will lead to a continued inability to monitor the health and nutrition of infants at a population level during international relief operations.

Breast Feeding↗
PubMed2004

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

Adolescent↗
PubMed1994

Construction of an intrinsic cut-off value for the sero-epidemiological study of Trypanosoma evansi infections in a canine population in Brazil: a new approach towards an unbiased estimation of prevalence.

In the serodiagnosis of tropical infectious diseases, cut-off values are often established by using sera from individuals living under moderate climatic conditions, not exposed to the risk of infection (non-endemic controls). This approach guarantees the disease-free status of the individuals within that control group but leads to an assembly of samples which are not representative for the disease-free individuals of the target population (selection bias). Using data from an epidemiological study of Trypanosoma evansi infection in dogs, two alternative methods to construct cut-off values for a T. evansi antibody ELISA are described which are solely based on a distribution analysis of the data from the endemic animals. By cluster analysis these data could be divided into 'high', 'intermediate' and 'low responders'. High responders could also be identified by using the computer-assisted analysis of mixtures (C.A.MAN). Conventional cut-offs were calculated from a group of non-endemic individuals. A receiver operating characteristic (ROC) analysis was performed to demonstrate the impact of the choice of cut-offs on the test specificity and on the estimated seroprevalence among the endemic population. The data indicate that distribution analysis, especially the mixture analysis (C.A.MAN), are valuable tools for the unbiased estimation of seroprevalence when representative negative controls are not available.

Animals↗
PubMed2002

The DOTS strategy in China: results and lessons after 10 years.

OBJECTIVE: To analyse the five-point tuberculosis (TB) strategy, DOTS, 10 years after its implementation in one-half of China's population, and to suggest lessons for future implementation of the DOTS strategy. METHODS: We analysed trends in case-finding and treatment outcome over time following implementation of the DOTS strategy in each county, using routine reporting data from the Infectious and Endemic Disease Control (IEDC) project (1991 - 2000). We also determined the proportion of counties with different levels of case-finding for the fifth and sixth years of DOTS implementation. FINDINGS: From 1991 to 1995, DOTS expanded rapidly to cover more than 90% of target population and counties. By 2000, 8 million TB suspects had received free diagnostic evaluation: 1.8 million TB cases were diagnosed, free treatment was provided to 1.3 million smear-positive cases, and more than 90% were cured. During DOTS implementation, the percentage of previously treated cases decreased among all smear-positive cases and treatment outcomes improved. Despite these achievements, the detection rate for new smear-positive cases in the project was estimated to be only 54% in 1998, and 41.2% of the counties had a below average or low level of case-finding (with substantial variation between provinces). CONCLUSIONS: The IEDC project demonstrated that it is feasible to rapidly expand DOTS on a large scale. The global target of an 85% cure rate was quickly achieved, and the level of drug-resistance was probably reduced by this project. However, case-detection did not reach the 70% global target, and more research is needed on how to enhance this.

Antitubercular Agents↗
PubMed2005

Mortality from dementia in a community-dwelling Brazilian population.

BACKGROUND: The influence of dementia on mortality has not yet been reported for a Latin American country. OBJECTIVES: To evaluate the influence of dementia on mortality of a community-dwelling elderly population in Brazil, and to verify the extent to which the diagnosis of dementia is reported on death certificates. METHODS: A cohort of 1,656 individuals, aged 65 and over, was screened for dementia at their domiciles, in 1997. The same population was re-evaluated in 2000, and information on deaths was obtained from relatives and from the municipal obituary service. Kaplan-Meier curves were used for the survival analysis, and the mortality risk ratio (MMR) was calculated using Cox proportional hazards models. RESULTS: We obtained data from 1,393 subjects, corresponding to 84.1% of the target population. The number of deaths was 58 (51.3%) among the patients with dementia and 163 (12.7%) among those without dementia in 1997 (p <0.0001). Dementia and Alzheimer's disease (AD) decreased survival, with hazards ratios of 5.16 [95% Confidence Interval (CI): 3.74-7.12] for dementia and 4.76 (95% CI: 3.16-7.18) for AD. The Cox proportional hazards model identified dementia (MMR=3.92, 95% CI: 2.80-5.48) as the most significant predictor of death, followed by age, history of stroke, complaints of visual impairment and heart failure and by severe arterial hypertension in the baseline evaluation. Dementia and/or AD were mentioned in only 12.5% of the death certificates of individuals with dementia. CONCLUSIONS: Dementia causes a significant decrease in survival, and the diagnosis of dementia is rarely reported on death certificates in Brazil.

Activities of Daily Living↗
PubMed1992

Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of specific populations of hepatocytes.

Hepatocyte proliferation was analyzed in vivo during the time course of continuous administration to rats of the liver tumor promoter ethinyl estradiol (EE) at 10 p.p.m. in the diet. EE-induced acute liver hyperplasia was detected in male and female Sprague-Dawley rats as an increased mitotic index of hepatocytes after 2 days of treatment. 5'-Bromodeoxyuridine (BrdU) labeling showed that proliferating hepatocytes were randomly distributed throughout the hepatic lobule. Subsequently, and still during the first few days of continuous EE treatment, hepatocyte proliferation decreased to control levels, and a transient increase in the incidence of apoptosis in the liver was detected. Although consistent with the concept of liver growth regression after mitogen-induced hyperplasia, these results differ from others reported to date in that, in our experiments, the cessation of cell proliferation and the subsequent growth regression occurred without withdrawal of EE in our experiments. After returning to control levels, hepatocellular proliferation again increased between 3 and 6 months of chronic treatment and remained activated during the following months of continuous treatment, as seen by accumulative BrdU labeling. Proliferating hepatocytes were predominantly located in zone 2 of the hepatic lobule at this time, surrounding a periportal zone of vacuolated hepatocytes, which were also induced by the treatment. Moreover, hyperplasia of basophilic hepatocytes was also seen around some portal spaces. In another set of experiments, chronic EE-induced activation was characterized by flow cytometry on hepatocytes isolated from male Fischer rats. Ploidy analysis of hepatocyte cell suspensions showed that the normal polyploid pattern of hepatocytes was altered by EE, the proportion of diploid hepatocytes rising considerably. The results also showed that these diploid cells were the most susceptible hepatocyte population to EE-induced proliferation, as shown by a combination of BrdU labeling and cell sorting methods. In contrast to Sprague-Dawley rats, no vacuolated cells were found histologically in the livers of these animals and the proliferating hepatocytes were located adjacent to the portal areas. These results taken together support the existence of cell target populations in the liver responding to the effects of tumor promoters. The finding that a subpopulation of diploid hepatocytes was the liver cell class most susceptible to proliferation during chronic EE treatment may explain, at least in part, the behavior of EE as a tumor promoter in hepatocarcinogenesis.

Animals↗
PubMed1999

Genetics of osteoporosis.

There is clear evidence of genetic modulation of bone phenotype parameters including bone density, quantitative ultrasound, bone size, and bone turnover. At any particular age and phase of life, genetic factors explain about 70% of the variance in bone phenotype after adjustment for major medical and disease factors. Hormonal factors, diet, and lifestyle interact with those genetic factors over time. Common allelic variation in the VDR was the first of several genes and now chromosomal loci to be implicated in the genetic determination of bone phenotype. The VDR polymorphisms have an effect weaker than originally reported, and part of the allelic effects may be mediated by effects on body size and development and even other hormonal regulators such as PTH or insulin. Irrespective of the strength or mechanism of these associations, these initial findings on the VDR stimulated the field of the genetics of osteoporosis with targeted genetic studies and now genome scan approaches. Intronic polymorphisms of the collagen I alpha 1 gene have been shown to be related to bone density and to fracture risk in several studies, although not all findings concur. Common allelic variations have now been associated with bone density for the estrogen receptor, TGF beta receptor, and TGF beta 1, for the insulin-like growth factor-I pathway, for interleukin-4 and -6 and the interleukin-1 receptor antagonist, for calcitonin and the PTH receptors and for apolipoprotein E. Of considerable interest, chromosomal loci, notably 11q 12-13, have now been linked to bone phenotypes in human and mouse studies. The mouse strain studies seem likely to be powerful tools providing insight to important human loci based on the mouse-human chromosomal synteny. Variability of genetic findings across studies seems to be the rule rather than the exception. This variability may relate to interaction of particular loci with specific environmental or even other genetic loci. The importance of genetic heterogeneity, including ethnicity, as well as environmental and hormonal confounders, such as calcium and vitamin D intake, hormonal status and skeletal and body size, will need to be taken into account in future gene search approaches. Genome scans in relation to bone density and fracture end-points will need to account for such important potential confounders in each target population. Interactions between genetic and environmental factors, including lifestyle, have been investigated initially for the VDR polymorphisms in relation to the response of bone density and turnover to calcium intake and treatment with simple vitamin D and active vitamin D compounds. Gene-gene and gene-environment interactions in human and animal models will be critical targets for future research. Further genes with positive and negative effects on bone phenotype are certain to be identified in the near future. Each of these will need to be evaluated in relation to potential environmental modulators in pharmacogenetic models. Understanding the molecular physiology of such gene effects is likely to lead to more specific treatments and to allow the selection of more appropriate and effective treatment options.

Animals↗
PubMed2004

Conserved hierarchy of helper T cell responses in a chimpanzee during primary and secondary hepatitis C virus infections.

Control of hepatitis C virus (HCV) infection could be influenced by the timing and magnitude of CD4+ T cell responses against individual epitopes. We characterized CD4+ T cells targeting seven Pan troglodytes (Patr) class II-restricted epitopes during primary and secondary HCV infections of a chimpanzee. All Patr-DR-restricted HCV epitopes bound multiple human HLA-DR molecules, indicating the potential for overlap in epitopes targeted by both species. Some human MHC class II molecules efficiently stimulated IL-2 production by chimpanzee virus-specific T cell clones. Moreover, one conserved epitope designated NS3(1248) (GYKVLVLNPSV) overlapped a helper epitope that is presented by multiple HLA-DR molecules in humans who spontaneously resolved HCV infection. Resolution of primary infection in the chimpanzee was associated with an initial wave of CD4+ T cells targeting a limited set of dominant epitopes including NS3(1248.) A second wave of low-frequency CD4+ T cells targeting other subdominant epitopes appeared in blood several weeks later after virus replication was mostly contained. During a second infection 7 years later, CD4+ T cells against all epitopes appeared in blood sooner and at higher frequencies but the pattern of dominance was conserved. In summary, primary HCV infection in this individual was characterized by T cell populations targeting two groups of MHC class II-restricted epitopes that differed in frequency and kinetics of appearance in blood. The hierarchial nature of the CD4+ T cell response, if broadly applicable to other HCV-infected chimpanzees and humans, could be a factor governing the outcome of HCV infection.

Amino Acid Sequence↗
PubMedDate not supplied

OptDesign: extending optimizable k-dissimilarity selection to combinatorial library design.

Optimizable k-dissimilarity (OptiSim) selection entails drawing a series of subsamples of size k from a population and choosing the "best" candidate from each such subsample for inclusion in the selection set. By varying the size of the subsample, one can control the balance between representativeness and diversity in the selection set obtained. In the original formulation, a uniform random sampling from among valid candidates was used to draw the subsamples from a single target population. Here we describe in detail two key modifications that serve to extend the OptiSim methodology to vector selection for interdependent variables, specifically as applied to the design of combinatorial sublibraries. The first modification involves pivoting between variables: subsamples are drawn from each reagent pool in turn, with the viability of each candidate being evaluated in isolation as well as in terms of the products it will produce from complementary reagents already selected. The filters applied may be static or dynamic in nature, with molecular weight and hydrophobicity being examples of the former and structural diversity with respect to reagents already selected being an example of the latter. The second key modification is adding the ability to bias the selection of candidate reagents for inclusion in the subsamples. Taken together, these modifications support the efficient generation of multiblock and other sparse matrix designs that are both representative and diverse, and for which "backfilling" of designs edited to remove undesirable reagents or products is straightforward. The method is intrinsically fast and efficient, since enumeration of the full combinatorial is not required- only those candidates actually considered for inclusion need be evaluated. Moreover, because the subsample selection step is separate from the diversity-based selection of the "best" candidate, incorporating such bias in favor of a competing criterion such as low price provides a "natural," nonparametric mechanism for generating designs that are likely to be "good" in a double-objective, Pareto sense.

Journal Article↗
PubMed2005

Cytolytic T lymphocytes (CTLs) from HIV-1 subtype C-infected Indian patients recognize CTL epitopes from a conserved immunodominant region of HIV-1 Gag and Nef.

Analysis of the human immunodeficiency virus type 1 (HIV-1) cytolytic T lymphocyte (CTL) epitopes recognized by the targeted population is critical for HIV-1 vaccine design. Peripheral blood mononuclear cells from 47 Indian subjects at different stages of HIV-1 infection were tested for HIV-1 Gag-, Nef-, and Env-specific T cell responses by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay, using pools of overlapping peptides. The Gag and Nef antigens were targeted by 83% and 36% of responders. Five immunodominant regions, 4 in Gag and 1 in Nef, were identified in the study; these regions are conserved across clades, including the African subtype C clade. Three antigenic regions were also found to be recognized by CTLs of the study participants. These regions were not identified as immunodominant regions in studies performed in Africa, which highlights the importance of differential clustering of responses within HIV-1 subtype C. Twenty-six putative epitopes--15 Gag (10 in p24 and 5 in p17), 10 Nef, and 1 Env (gp 41)--were predicted using a combination of peptide matrix ELISPOT assay and CTL epitope-prediction software. Ninety percent of the predicted epitopes were clustered in the conserved immunodominant regions of the Gag and Nef antigens. Of 26 predicted epitopes, 8 were promiscuous, 3 of which were highly conserved across clades. Three Gag and 4 Nef epitopes were novel. The identification of conserved epitopes will be important in the planning of an HIV-1 vaccine strategy for subtype C-affected regions.

AIDS Vaccines↗