Sex Differences in HIV Prevalence Persist over Time: Evidence from 18 Countries in Sub-Saharan Africa

Objective

The aim of this study was to examine changes over time in the female: male HIV prevalence ratio in 18 countries in Sub-Saharan Africa, overall and when stratified by area of residence, educational attainment and marital status.

Methodology

We used data from the Demographic and Health Surveys, which are nationally representative household surveys. By using data from 18 countries with at least two survey rounds with HIV testing, and dividing the countries into three regions (Western/Central, Eastern and Southern) we were able to examine cross-country and regional changes in the female: male HIV prevalence ratio over time. Logistic regression was used to estimate female: male HIV prevalence ratios in urban versus rural areas and for different categories of education and marital status. To assess changes over time, we compared the confidence intervals of the prevalence ratios.

Results

The female: male HIV prevalence ratio was above one in all countries in at least one survey round for both ages 15–24 years and 25–49 years. In 13 out of 18 countries the prevalence ratio was higher for the younger age group compared to the age group 25–49 years (3 significant) and this difference in prevalence ratios between the age groups did not change over time. Overall, there was a higher frequency of increasing than decreasing prevalence ratios. The gender disparity was greater among those who were married/living together than among the never-married, and over time, the ratio was more stable among the married/living together. The study found no clear differential changes by education.

Conclusion

Women continue to carry the greater burden of HIV in Sub-Saharan Africa and there is no clear pattern of change in the gap between men and women as the direction and magnitude of change in the prevalence ratios varied greatly.     

Mother-young Relationships in Captive Ungulates: Behavioral Changes over Time

Ungulates are frequently classified into two groups: the “followers”, in which young initially stay close to their mother and the “hiders”, in which young remain at some distance from their mother, often concealed in vegetation. To examine differences in mother-young behavior between the follower and hider groups and among species within these groups, we studied 63 mother-young pairs, representing 22 ungulate species, for 7 weeks after birth of the young. The follower group had consistently higher scores than the hider group on measures of mother-young association, and lower scores on the percentage of time the young spent lying; however, there was considerable variation within each group. In follower species, two measures of mother and young association decreased over time. In hiders, contact between mother and young did not increase over time although the distance between them, while both were lying, decreased. This reduction in the resting distance between mother and young did not always coincide with other changes possibly indicative of the end of the hiding period. The amount of time young hiders spent lying decreased over time.     

Detecting Functional Divergence after Gene Duplication through Evolutionary Changes in Posttranslational Regulatory Sequences

Gene duplication is an important evolutionary mechanism that can result in functional divergence in paralogs due to neo-functionalization or sub-functionalization. Consistent with functional divergence after gene duplication, recent studies have shown accelerated evolution in retained paralogs. However, little is known in general about the impact of this accelerated evolution on the molecular functions of retained paralogs. For example, do new functions typically involve changes in enzymatic activities, or changes in protein regulation? Here we study the evolution of posttranslational regulation by examining the evolution of important regulatory sequences (short linear motifs) in retained duplicates created by the whole-genome duplication in budding yeast. To do so, we identified short linear motifs whose evolutionary constraint has relaxed after gene duplication with a likelihood-ratio test that can account for heterogeneity in the evolutionary process by using a non-central chi-squared null distribution. We find that short linear motifs are more likely to show changes in evolutionary constraints in retained duplicates compared to single-copy genes. We examine changes in constraints on known regulatory sequences and show that for the Rck1/Rck2, Fkh1/Fkh2, Ace2/Swi5 paralogs, they are associated with previously characterized differences in posttranslational regulation. Finally, we experimentally confirm our prediction that for the Ace2/Swi5 paralogs, Cbk1 regulated localization was lost along the lineage leading to SWI5 after gene duplication. Our analysis suggests that changes in posttranslational regulation mediated by short regulatory motifs systematically contribute to functional divergence after gene duplication.     

Microfungal Community Changes in Rodent Food Stores over Space and Time

Abstract This paper reports the changes over time in the microfungal communities that inhabit three rodent species' food stores at two climatically different locations. Results reveal that microfungal diversity values calculated from above-ground food stores are highest in the more commonly disturbed portions of the rodent dens. Interactions among food-inhabiting microbes and between the rodents and food-inhabiting microbes also appear to influence the microfungal communities within the rodent dens. For example, our data suggest that transport by animal vectors, and not by air currents, is more effective at dispersing microbial propagules. Furthermore, although fungal communities inhabiting food stores within dens varied in composition and diversity over time, standardized substrates (sorghum seeds) simultaneously placed within the food stores converged in microfungal composition the longer they were left within the dens. We hypothesize that animal vectors, including rodents, make neighboring fungal communities more alike by introducing similar communities of microbes, which in turn initiate a cascade of biological interactions that, over time, result in similar microfungal communities inhabiting newly stored food items. Received: 14 January 1999; Accepted: 2 April 1999     

Evolutionary Shift from Fighting to Foraging in Blind Cavefish through Changes in the Serotonin Network

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Highlights? Astyanax cavefish have lost aggressive behavior during adaptation to life in the dark ? Astyanax raphe serotonergic neurons control social behavior ? Astyanax hypothalamic serotonergic neurons control homeostatic functions ? The development of a neuronal network links to the behaviors it controls     

When Dread Risks Are More Dreadful than Continuous Risks: Comparing Cumulative Population Losses over Time

People show higher sensitivity to dread risks, rare events that kill many people at once, compared with continuous risks, relatively frequent events that kill many people over a longer period of time. The different reaction to dread risks is often considered a bias: If the continuous risk causes the same number of fatalities, it should not be perceived as less dreadful. We test the hypothesis that a dread risk may have a stronger negative impact on the cumulative population size over time in comparison with a continuous risk causing the same number of fatalities. This difference should be particularly strong when the risky event affects children and young adults who would have produced future offspring if they had survived longer. We conducted a series of simulations, with varying assumptions about population size, population growth, age group affected by risky event, and the underlying demographic model. Results show that dread risks affect the population more severely over time than continuous risks that cause the same number of fatalities, suggesting that fearing a dread risk more than a continuous risk is an ecologically rational strategy.     

When David Beats Goliath: The Advantage of Large Size in Interspecific Aggressive Contests Declines over Evolutionary Time

Body size has long been recognized to play a key role in shaping species interactions. For example, while small species thrive in a diversity of environments, they typically lose aggressive contests for resources with larger species. However, numerous examples exist of smaller species dominating larger species during aggressive interactions, suggesting that the evolution of traits can allow species to overcome the competitive disadvantage of small size. If these traits accumulate as lineages diverge, then the advantage of large size in interspecific aggressive interactions should decline with increased evolutionary distance. We tested this hypothesis using data on the outcomes of 23,362 aggressive interactions among 246 bird species pairs involving vultures at carcasses, hummingbirds at nectar sources, and antbirds and woodcreepers at army ant swarms. We found the advantage of large size declined as species became more evolutionarily divergent, and smaller species were more likely to dominate aggressive contests when interacting with more distantly-related species. These results appear to be caused by both the evolution of traits in smaller species that enhanced their abilities in aggressive contests, and the evolution of traits in larger species that were adaptive for other functions, but compromised their abilities to compete aggressively. Specific traits that may provide advantages to small species in aggressive interactions included well-developed leg musculature and talons, enhanced flight acceleration and maneuverability, novel fighting behaviors, and traits associated with aggression, such as testosterone and muscle development. Traits that may have hindered larger species in aggressive interactions included the evolution of morphologies for tree trunk foraging that compromised performance in aggressive contests away from trunks, and the evolution of migration. Overall, our results suggest that fundamental trade-offs, such as those associated with body size, are more likely to break down over evolutionary time, changing the rules that govern species interactions and structure ecological communities.     

A Biomonitor for Tracking Changes in the Availability of Lakewater Cadmium over Space and Time

Determining the exposure of organisms to contaminants is a key component of Ecological Risk Assessments (ERAs). Effective estimates of exposure consider not only the total concentrations of contaminants in an organism's surroundings but also the availability of the contaminants to organisms. Contaminant availability can be inferred from mechanistic models and verified by measurements of contaminant concentrations in organisms. We evaluated the widespread lake-dwelling insect Chaoborus as a potential biomonitor for use in exposure assessments for three metals: cadmium (Cd), copper (Cu), and zinc (Zn). We show that larvae of this midge maintain constant their concentrations of the essential metals Cu and Zn and thus cannot be used to monitor them. In contrast, larval Cd concentrations varied widely both among lakes and in a given lake over time. We were able to relate these variations in biomonitor Cd to changes in lakewater Cd and pH using the Free Ion Activity Model (FIAM). Our results suggest that Chaoborus larvae could be used as an effective tool for estimating the Cd exposure of organisms in lakes for the purposes of ERAs.     

Changes of Diversity Pattern of Proteolytic Bacteria over Time and Space in an Agricultural Soil

The genetic heterogeneity of neutral metalloprotease (npr) gene fragments from soil proteolytic bacteria was investigated at a cultivated field site with four different soil types and at three different depths in April, July, and October. Terminal restriction fragment length polymorphism (T-RFLP) analyses of polymerase chain reaction-amplified npr gene fragments were applied to study the dynamic of the npr gene pool with regard to environmental conditions. The aim of this study was to relate differences in npr community structure and richness to the vertical, site, and seasonal variations naturally occurring at the field site under investigation. T-RFLP analysis revealed a noticeable seasonal variability in the community structure of npr-containing bacteria. The data suggest that the composition of the npr proteolytic bacterial population in July differed from those at the other dates. Additionally, the diversity of npr genes decreased with increasing soil depth revealing the highest values in upper layers. The reasons behind the observed patterns in the community structure might be mainly seasonal and vertical variation of the quantity and heterogeneity of available substrates as well as spatial isolation caused by a varying water amount and the connectivity of soil particles among the soil profile. Sequencing and phylogenetical analysis of 120 npr clones from the top soils collected in July revealed that most of the clones exhibit only poor homology to npr genes of isolates previously obtained from various environments, indicating the presence of until now uncharacterized npr coding proteolytic bacteria at the study site.     

The HIV Care Continuum: Changes over Time in Retention in Care and Viral Suppression

Background

The HIV care continuum (diagnosis, linkage to care, retention in care, receipt of antiretroviral therapy (ART), viral suppression) has been used to identify opportunities for improving the delivery of HIV care. Continuum steps are typically calculated in a conditional manner, with the number of persons completing the prior step serving as the base population for the next step. This approach may underestimate the prevalence of viral suppression by excluding patients who are suppressed but do not meet standard definitions of retention in care. Understanding how retention in care and viral suppression interact and change over time may improve our ability to intervene on these steps in the continuum.

Methods

We followed 17,140 patients at 11 U.S. HIV clinics between 2010-2012. For each calendar year, patients were classified into one of five categories: (1) retained/suppressed, (2) retained/not-suppressed, (3) not-retained/suppressed, (4) not-retained/not-suppressed, and (5) lost to follow-up (for calendar years 2011 and 2012 only). Retained individuals were those completing ≥2 HIV medical visits separated by ≥90 days in the year. Persons not retained completed ≥1 HIV medical visit during the year, but did not meet the retention definition. Persons lost to follow-up had no HIV medical visits in the year. HIV viral suppression was defined as HIV-1 RNA ≤200 copies/mL at the last measure in the year. Multinomial logistic regression was used to determine the probability of patients’ transitioning between retention/suppression categories from 2010 to 2011 and 2010 to 2012, adjusting for age, sex, race/ethnicity, HIV risk factor, insurance status, CD4 count, and use of ART.

Results

Overall, 65.8% of patients were retained/suppressed, 17.4% retained/not-suppressed, 10.0% not-retained/suppressed, and 6.8% not-retained/not-suppressed in 2010. 59.5% of patients maintained the same status in 2011 (kappa=0.458) and 53.3% maintained the same status in 2012 (kappa=0.437).

Conclusions

Not counting patients not-retained/suppressed as virally suppressed, as is commonly done in the HIV care continuum, underestimated the proportion suppressed by 13%. Applying the care continuum in a longitudinal manner will enhance its utility.     

Changes in Physical Activity over Time in Young Children: A Longitudinal Study Using Accelerometers

Previous research has suggested that marked declines in physical activity occur during the preschool years, and across the transition into school. However, longitudinal studies using objective measures of activity have been limited by sample size and length of follow-up. The aims of this study were to determine how overall activity and time in different intensities of activity change in children followed from 3 to 7 years. Children (n = 242) wore Actical accelerometers at 3, 4, 5, 5.5, 6.5 and 7 years of age during all waking and sleeping hours for a minimum of 5 days. Time in sedentary (S), light (L), moderate (M), and vigorous (V) physical activity was determined using available cut points. Data were analyzed using a mixed model and expressed as counts per minute (cpm, overall activity) and the ratio of active time to sedentary time (LMV:S), adjusted for multiple confounders including sex, age, time worn, and weather. At 5 years, physical activity had declined substantially to around half that observed at 3 years. Although starting school was associated with a further short-term (6-month) decline in activity (cpm) in both boys (difference; 95% CI: -98; -149, -46) and girls (-124; -174, -74, both P<0.001), this proved to be relatively transient; activity levels were similar at 6-7 years as they were just prior to starting school. Boys were more physically active than girls as indicated by an overall 12% (95% CI: 2, 22%) higher ratio of active to sedentary time (P = 0.014), but the pattern of this difference did not change from 3 to 7 years. Time worn and weather variables were significant predictors of activity. In conclusion, both boys and girls show a marked decline in activity from 3 to 4 years of age, a decrease that is essentially maintained through to 7 years of age. Factors driving this marked decrease need to be determined to enable the development of targeted interventions.     

EEG Responses to TMS Are Sensitive to Changes in the Perturbation Parameters and Repeatable over Time

Background

High-density electroencephalography (hd-EEG) combined with transcranial magnetic stimulation (TMS) provides a direct and non-invasive measure of cortical excitability and connectivity in humans and may be employed to track over time pathological alterations, plastic changes and therapy-induced modifications in cortical circuits. However, the diagnostic/monitoring applications of this technique would be limited to the extent that TMS-evoked potentials are either stereotypical (non-sensitive) or random (non-repeatable) responses. Here, we used controlled changes in the stimulation parameters (site, intensity, and angle of stimulation) and repeated longitudinal measurements (same day and one week apart) to evaluate the sensitivity and repeatability of TMS/hd-EEG potentials.

Methodology/Principal Findings

In 10 volunteers, we performed 92 single-subject comparisons to evaluate the similarities/differences between pairs of TMS-evoked potentials recorded in the same/different stimulation conditions. For each pairwise comparison, we used non-parametric statistics to calculate a Divergence Index (DI), i.e., the percentage of samples that differed significantly, considering all scalp locations and the entire post-stimulus period. A receiver operating characteristic analysis showed that it was possible to find an optimal DI threshold of 1.67%, yielding 96.7% overall accuracy of TMS/hd-EEG in detecting whether a change in the perturbation parameters occurred or not.

Conclusions/Significance

These results demonstrate that the EEG responses to TMS essentially reflect deterministic properties of the stimulated neuronal circuits as opposed to stereotypical responses or uncontrolled variability. To the extent that TMS-evoked potentials are sensitive to changes and repeatable over time, they may be employed to detect longitudinal changes in the state of cortical circuits.     

A Technique to Identify Changes in Hemlock Forest Health over Space and Time Using Satellite Image Data

The objective of this study was to develop a technique to classify health of eastern hemlock stands using historical satellite images. While remote sensing and geographic information systems have been used successfully to classify forest health using recent images, applying this process to older images is problematic because contemporaneous field data are not available to measure the accuracy of the classification of historical images. Data ranges were established for each hemlock health class using a contemporary image and field data. These ranges were used to level-slice archived images to create a series of health-class maps that show changes in forest health over time. By applying cross-tabulation procedures to pairs of classified images, it is possible to construct a transition map that indicates how the hemlock health class of each pixel in the images of the study area has changed over time. The resulting maps provide a look back at forest conditions of the past and can be used to identify areas of special interest.     

Linking Transcriptional Changes over Time in Stimulated Dendritic Cells to Identify Gene Networks Activated during the Innate Immune Response

The innate immune response is primarily mediated by the Toll-like receptors functioning through the MyD88-dependent and TRIF-dependent pathways. Despite being widely studied, it is not yet completely understood and systems-level analyses have been lacking. In this study, we identified a high-probability network of genes activated during the innate immune response using a novel approach to analyze time-course gene expression profiles of activated immune cells in combination with a large gene regulatory and protein-protein interaction network. We classified the immune response into three consecutive time-dependent stages and identified the most probable paths between genes showing a significant change in expression at each stage. The resultant network contained several novel and known regulators of the innate immune response, many of which did not show any observable change in expression at the sampled time points. The response network shows the dominance of genes from specific functional classes during different stages of the immune response. It also suggests a role for the protein phosphatase 2a catalytic subunit α in the regulation of the immunoproteasome during the late phase of the response. In order to clarify the differences between the MyD88-dependent and TRIF-dependent pathways in the innate immune response, time-course gene expression profiles from MyD88-knockout and TRIF-knockout dendritic cells were analyzed. Their response networks suggest the dominance of the MyD88-dependent pathway in the innate immune response, and an association of the circadian regulators and immunoproteasomal degradation with the TRIF-dependent pathway. The response network presented here provides the most probable associations between genes expressed in the early and the late phases of the innate immune response, while taking into account the intermediate regulators. We propose that the method described here can also be used in the identification of time-dependent gene sub-networks in other biological systems.     

Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time

Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time.