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Biomedical subjects

J Stover

Publications and source records attributed to J Stover.

At least 19 recordsLinked to original sources

Evidence for population level declines in adult HIV prevalence in Kenya.

The HIV/AIDS epidemic in Kenya has been tracked through annual sentinel surveillance in antenatal clinics since 1990. The system started with 13 sites and now has over 35. Behaviours have been measured through national Demographic and Health Surveys in 1993, 1998, and 2003. The surveillance data indicate that prevalence has declined substantially starting in 1998 in five of the original 13 sites and starting in 2000 in another four sites. No decline is evident in the other five original sites although the 2004 estimate is the lowest recorded. Nationally, adult prevalence has declined from 10% in the late 1990s to under 7% today. Surveys indicate that both age at first sex and use of condoms are rising and that the percentage of adults with multiple partners is falling. It is clear that HIV prevalence is now declining in Kenya in a pattern similar to that seen in Uganda but seven or eight years later. Although the coverage of preventive interventions has expanded rapidly since 2000 this expansion was too late to account for the beginnings of the decline in prevalence. More work is needed to understand fully the causes of this decline, but it is encouraging to see Kenya join the small list of countries experiencing significant declines in HIV prevalence.

Adolescent↗

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti.

OBJECTIVE: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. METHODS: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. RESULTS: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. CONCLUSIONS: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

Adolescent↗

Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples.

OBJECTIVE: Patterns of transmission of HIV are different among different regions of the world and change over time within regions. In order to adapt prevention strategies to changing patterns of risk, we need to understand the behaviours that put people at risk of infection and how new infections are distributed among risk groups. METHODS: A model is described to calculate the expected incidence of HIV infections in the adult population by mode of exposure using the current distribution of prevalent infections and the patterns of risk within different populations. For illustration the model is applied to Thailand and Kenya. RESULTS: New infections in Kenya were mainly transmitted through heterosexual contact (90%), while a small but significant number were related to injecting drug use (4.8%) and men who have sex with men (4.5%). In Thailand, the epidemic has spread over time to the sexual partners of vulnerable groups and in 2005 the majority of new infections occurred among the low risk heterosexual population (43%). Men having sex with men accounted for 21% and sex work (including sex workers, clients, and partners of clients) for 18% of new infections. Medical interventions did not contribute significantly to new infections in either Kenya or Thailand. CONCLUSIONS: The model provides a simple tool to inform the planning of effective, appropriately targeted, country specific intervention programmes. However, better surveillance systems are needed in countries to obtain more reliable biological and behavioural data in order to improve the estimates of incidence by risk group.

Adolescent↗

Projecting the demographic impact of AIDS and the number of people in need of treatment: updates to the Spectrum projection package.

BACKGROUND: In the Joint United Nations Programme on HIV/AIDS (UNAIDS) approach to HIV and AIDS estimates, estimates of adult prevalence produced by the Estimation and Projection Package (EPP) or the Workbook are transferred to Spectrum to estimate the consequences of the HIV/AIDS epidemic, including the number of people living with HIV by age and sex, new infections, AIDS deaths, AIDS orphans, treatment needs, and the impact of treatment on survival. METHODS: The UNAIDS Reference Group on Estimates, Models and Projections recommends updates to the methodology and assumptions based on the latest research findings and international policy and programme guidelines. The latest update to Spectrum has been used in the 2005 round of global estimates. RESULTS: Several new features have been added to Spectrum in the past two years. New patterns of the age distribution of prevalence over time are based on the latest survey data. A more detailed treatment of mother to child transmission of HIV is now based on information about current breastfeeding practices, treatment options offered to prevent mother to child transmission (PMTCT), infant feeding options, and the percentage or number of pregnant women accessing PMTCT services. A new section on child survival includes the effects of cotrimoxazole and ART on child survival. Projections can now be calibrated with national survey data. A new set of outputs is provided for all adults over the age of 15 in addition to the traditional 15-49 age group. New outputs are now available to show plausibility bounds and regional estimates for key indicators. CONCLUSIONS: The latest update to the Spectrum program is intended to incorporate the latest research findings and provide new outputs needed by national and international planners.

Adolescent↗

Improved plausibility bounds about the 2005 HIV and AIDS estimates.

BACKGROUND: Since 1998 the Joint United Nations Programme on HIV/AIDS and the World Health Organization has provided estimates on the magnitude of the HIV epidemic for individual countries. Starting with the 2003 estimates, plausibility bounds about the estimates were also reported. The bounds are intended to serve as a guide as to what reasonable or plausible ranges are for the uncertainty in HIV incidence, prevalence, and mortality. METHODS: Plausibility bounds were developed for three situations: for countries with generalised epidemics, for countries with low level or concentrated epidemics (LLC), and for regions. The techniques used build on those developed for the previous reporting round. However the current bounds are based on the available surveillance and survey data from each individual country rather than on data from a few prototypical countries. RESULTS: The uncertainty around the HIV estimates depends on the quality of the surveillance system in the country. Countries with population based HIV seroprevalence surveys have the tightest plausibility bounds (average relative range about the adult HIV prevalence (ARR) of -18% to +19%.) Generalised epidemic countries without a survey have the next tightest ranges (average ARR of -46% to +59%). Those LLC countries which have conducted multiple surveys over time for HIV among the populations most at risk have the bounds similar to those in generalised epidemic countries (ARR -40% to +67%). As the number and quality of the studies in LLC countries goes down, the plausibility bounds increase (ARR of -38% to +102% for countries with medium quality data and ARR of -53% to +183% for countries with poor quality data). The plausibility bounds for regions directly reflect the bounds for the countries in those regions. CONCLUSIONS: Although scientific, the plausibility bounds do not represent and should not be interpreted as formal statistical confidence intervals. However in order to make the bounds as meaningful as possible the authors have tried to apply reasonable statistical approaches and assumptions to their derivation. An understanding of the uncertainty in the HIV estimates may help policy makers take better informed decisions to address the epidemic in their respective countries.

Adolescent↗

Edema and brain trauma.

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury (TBI) as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" due to blood-brain barrier (BBB) disruption resulting in extracellular water accumulation and "cytotoxic/cellular" due to sustained intracellular water collection. A third type, "osmotic" brain edema is caused by osmotic imbalances between blood and tissue. Rarely after TBI do we encounter a "hydrocephalic edema/interstitial" brain edema related to an obstruction of cerebrospinal fluid outflow. Following TBI, various mediators are released which enhance vasogenic and/or cytotoxic brain edema. These include glutamate, lactate, H(+), K(+), Ca(2+), nitric oxide, arachidonic acid and its metabolites, free oxygen radicals, histamine, and kinins. Thus, avoiding cerebral anaerobic metabolism and acidosis is beneficial to control lactate and H(+), but no compound inhibiting mediators/mediator channels showed beneficial results in conducted clinical trials, despite successful experimental studies. Hence, anti-edematous therapy in TBI patients is still symptomatic and rather non-specific (e.g. mannitol infusion, controlled hyperventilation). For many years, vasogenic brain edema was accepted as the prevalent edema type following TBI. The development of mechanical TBI models ("weight drop," "fluid percussion injury," and "controlled cortical impact injury") and the use of magnetic resonance imaging, however, revealed that "cytotoxic" edema is of decisive pathophysiological importance following TBI as it develops early and persists while BBB integrity is gradually restored. These findings suggest that cytotoxic and vasogenic brain edema are two entities which can be targeted simultaneously or according to their temporal prevalence.

Acidosis, Lactic↗

Projecting the demographic consequences of adult HIV prevalence trends: the Spectrum Projection Package.

This paper describes the software package Spectrum, which is a modular program that is used to examine the consequences of current trends and future program interventions in reproductive health. It is used to determine the consequences of the HIV/AIDS epidemic, including the number of people living with HIV/AIDS by age and sex, the number of AIDS deaths, and the number of orphans as a result of AIDS, as well as other demographic indicators of interest, such as life expectancy and <5 mortality. The core of Spectrum is a demographic projection model called DemProj, which projects the population by age and sex. Other modules interact with the demographic projection. The HIV/AIDS projections are added to the demographic projections using a module called AIDS Impact Model. This module uses the projection of adult HIV prevalence over time, which is prepared using the Estimation and Projection Package model or the projection workbook. It also requires assumptions about the epidemiology of HIV, including the ratio of female:male prevalence, the distribution of infection by age, the distribution of the time from infection until AIDS death, and the effect of HIV on fertility.

Acquired Immunodeficiency Syndrome↗

The UNAIDS Estimation and Projection Package: a software package to estimate and project national HIV epidemics.

This paper describes the Estimation and Projection Package (EPP) for estimating and projecting HIV prevalence levels in countries with generalised epidemics. The paper gives an overall summary of the software and interface. It describes the process of defining and modelling a national epidemic in terms of locally relevant sub-epidemics and the four epidemiological parameters used to fit a curve to produce the prevalence trends in the epidemic. It also provides an example of using the EPP in a country with a generalised epidemic. The paper discusses the strengths and weaknesses of the software and its envisaged future developments.

Adolescent↗

The workbook approach to making estimates and projecting future scenarios of HIV/AIDS in countries with low level and concentrated epidemics.

This paper describes an approach to making estimates and short term projections of future scenarios of HIV/AIDS in countries with low level and concentrated epidemics. This approach focuses on identifying populations which through their behaviour are at higher risk of infection with HIV or who are exposed through the risk behaviour of their sexual partners. Estimates of the size and HIV prevalence of these populations allow the total number of HIV infected people in a country or region to be estimated. Subsequently, assumptions about the possible level and timing of saturation of HIV prevalence among each population can be used to explore future scenarios of HIV prevalence. The basic structure of the software used to make estimates and projections is described. This software includes a set of consistency and audit checks to help exclude unrealistic projections. The paper also discusses the strengths and weakness to this approach to making estimates and projections of HIV/AIDS in countries with low level and concentrated epidemics.

Acquired Immunodeficiency Syndrome↗

Uncertainty in estimates of HIV/AIDS: the estimation and application of plausibility bounds.

OBJECTIVES: To establish the accuracy of the country specific estimates of HIV prevalence, incidence, and AIDS mortality published every 2 years by UNAIDS and WHO. METHODS: We review sources of error in the data used to generate national HIV/AIDS and where possible estimate their statistical properties. We use numerical and approximate analytic methods to estimate the combined impact of these errors on HIV/AIDS estimates. Heuristic rules are then derived to produce plausible bounds about these estimates for countries with different types of epidemic and different qualities of surveillance system. RESULTS: Although 95% confidence intervals (CIs) can be estimated for some sources of error, the sizes of other sources of error must be based on expert judgment. We therefore produce plausible bounds about HIV/AIDS estimates rather than statistical CIs. The magnitude of these bounds depends on the stage of the epidemic and the quality and coverage of the sentinel HIV surveillance system. The bounds for adult estimates are narrower than those for children, and those for prevalence are narrower than those for new infections. CONCLUSIONS: This paper presents a first attempt at a rigorous description of the errors associated with estimation of global statistics of an infectious disease. The proposed methods work well in countries with generalised epidemics (>1% adult HIV prevalence) where the quality of surveillance is good. Although methods have also been derived for countries with low level or concentrated epidemics, more data on the biases in the estimation process are required.

Acquired Immunodeficiency Syndrome↗

Influence of mathematical modeling of HIV and AIDS on policies and programs in the developing world.

BACKGROUND: A number of simulation models have been developed to explore the dynamics of the AIDS epidemic. There seems to be minimal impact of these models on policies and programs. GOAL: To describe the major findings from simulation modeling and the impact of these findings on policies and programs. STUDY DESIGN: A literature review to summarize the major findings that are supported by more than one modeling group. RESULTS: Simulation modeling has contributed to improved understanding of a number of issues including the demographic impact of AIDS, the value of targeting prevention efforts to high-risk behavior, the importance of controlling STDs, the benefits of early intervention, and the need for combined interventions. CONCLUSIONS: Modeling has played a major role in increasing our understanding of the dynamics of the epidemic and in demonstrating how much we still need to learn. Its impact on policies and programs has been limited. The need for better translation of modeling findings to policy action will be even greater in the future.

Acquired Immunodeficiency Syndrome↗

Empirically based conversion factors for calculating couple-years of protection.

Couple-years of protection (CYP) is one of several commonly used indicators to assess international family planning efforts. It has been the subject of much debate, relating in part to the specific conversion factors used to translate the quantity of the respective contraceptive methods distributed to a single measure of protection. This article outlines a comprehensive effort to revisit those conversion factors based on the best available empirical evidence. In most instances, the analysis supports previously established standard conversion factors. However, there are two notable departures. Fewer condoms and spermicides are recommended for each CYP (120 vs. 150), primarily because coital frequency among condom users is lower than previously assumed. Furthermore, for sterilization, the authors recommend the use of country or region-specific conversion factors. Every program evaluation indicator has strengths and weaknesses, and the best program evaluation efforts use a variety of indicators. If CYP is used to evaluate programs, however, the authors believe that the conversion factors presented reflect the best available evidence.

Adolescent↗

Halicephalobus gingivalis (Nematoda) infection in a Grevy's zebra (Equus grevyi).

A 6-yr-old female Grevy's zebra (Equus grevyi) with a disseminated rhabditiform nematode infection is described. Antemortem clinical signs were limited to blindness and abnormal behavior believed to be caused by a recurrent nematode-induced uveitis. Histologic examination of the kidneys, heart, eyes, uterus, and lymph nodes revealed granulomas containing multiple sections of rhabditiform nematodes. Most of the recovered nematodes were larval stages with only a few adult females noted. The adults measured 243-297 microm x 11-16 microm (x = 269 x 14 microm). The distinctive rhabditiform esophagi had corpus:isthmus:bulb proportions of 19:11:5. On the basis of adult morphology, the nematode was identified as Halicephalobus gingivalis. This is the first report of this parasite in a zebra and indicates that this parasitic granulomatous disease should be considered in zebras with neurologic disease.

Animals↗

Projecting the impact of AIDS on mortality.

OBJECTIVE: To illustrate the magnitude of the impact of AIDS on projections of mortality, to explain the reasons for the differences in projections by major international organizations and to provide a simple approach to estimating the impact of AIDS on life expectancy. RESULTS: AIDS has already had significant impacts on mortality in a number of countries in the developing world and this impact is expected to grow substantially in the next 10 years. By 2005 the population of the most severely affected countries in Africa will be 13-59 million less than it would have been without AIDS. Life expectancy may decline by as much as 27% in these countries. Country specific projections made by the United Nations (UN) and the US Census Bureau differ significantly in their estimates of the impact of AIDS. The UN projects that AIDS will reduce the population growth of the most severely affected countries in Africa by 13 million by 2005 and 30 million by 2025, while the US Census Bureau projects the reduction to be four times larger (59 million by 2005 and 120 million by 2025). These differences are due largely to the use of different methodologies for projecting future levels of adult HIV prevalence. Other factors contributing to the different projections are different estimates of current levels of HIV prevalence and different assumptions about the length of the incubation period (from initial infection until death from AIDS) and the perinatal transmission rate. In addition to the number of deaths caused by AIDS, useful indicators of mortality include life expectancy at birth, the under five mortality rate and the life-time risk of dying from AIDS. An equation for estimating the impact of AIDS on life expectancy is presented and its use is illustrated. CONCLUSION: It is clear that AIDS has already increased mortality significantly in many countries and will continue to do so in the coming decades. Uncertainty about current and future levels of HIV prevalence among adults leads to differences in the projections of future AIDS-related mortality. As data and projection methodologies improve, the differences in projections may be reduced for sub-Saharan Africa, but the growing epidemic in some of the largest countries of Asia may increase uncertainty about future global impacts.

Acquired Immunodeficiency Syndrome↗

Revising the proximate determinants of fertility framework: what have we learned in the past 20 years?

The proximate determinants of fertility framework, developed in its current form by Bongaarts, has been used extensively by researchers for the past 20 years. Since the initial framework was developed, a wealth of new survey data on the proximate determinants has become available. This article reviews the new data and past experiences and suggests modifications to the framework that would take advantage of this experience. The major modifications suggested are (1) the use of sexual activity rather than marriage to indicate exposure to pregnancy; (2) a revision of the sterility index to measure infecundity from all causes; (3) a revised index of contraception that accounts for the fact that users of sterilization may become infecund before age 49; and (4) a revised definition and estimate of total fecundity.

Adolescent↗

A genetic selection for isolating cDNAs encoding secreted proteins.

We describe a simple, rapid technique for simultaneously isolating large numbers of cDNAs encoding secreted proteins. The technique makes use of a facile genetic selection performed in a strain of Saccharomyces cerevisiae deleted for its endogenous invertase gene. A cDNA cloning vector which carries a modified invertase gene lacking its leader sequence is used in conjunction with this strain. Heterologous secreted genes fused appropriately upstream of this defective invertase provide the necessary signals to restore secretion, allowing the yeast to grow on sugars such as sucrose or raffinose. This microbial growth selection facilitates scanning cDNA libraries containing millions of clones, enabling the wholesale identification of novel secreted proteins without the need for specific bioassays. The technique is similar to one previously described (Klein et al. (1996) Proc. Natl. Acad. Sci. USA 93, 7108-7113). We describe results using a cDNA library derived from activated human peripheral blood mononuclear cells (PBMC). Genes identified from this library encoded signal sequences of proteins of diverse structure, function, and cellular location such as cytokines, type 1 and type 2 transmembrane proteins, and proteins found in intracellular organelles. In addition, a number of novel secreted proteins were identified, including a chemokine and a novel G-protein-coupled receptor. Since signal sequences possess features conserved throughout evolution, the procedure can be used to isolate genes encoding secreted proteins from both eukaryotes and prokaryotes.

Amino Acid Sequence↗