Preparing for the Rollout of Pre-Exposure Prophylaxis (PrEP): A Vignette Survey to Identify Intended Sexual Behaviors among Women in Kenya and South Africa if Using PrEP

Introduction

Several clinical trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP) in reducing HIV risk. One concern with introducing PrEP is whether users will engage in riskier sexual behaviors.

Methods

We assessed the effect that PrEP may have on sexual risk behaviors by administering a survey to 799 women in Bondo, Kenya, and Pretoria, South Africa. Participants were asked about their sexual behavior intentions twice — once as if they were taking PrEP and once as if they were not taking PrEP — within four risk situations (vignettes). They responded using a 5-point ordinal scale. We used a series of linear mixed effects models with an unstructured residual covariance matrix to estimate the between- and within-subject differences in the mean likelihood of engaging in risky sexual behavior across the PrEP and non-PrEP contexts. We also calculated the total percentage of participants who reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP, by vignette.

Results

We found statistically significant differences in the mean likelihood of engaging in risky sexual behavior with the between-subject comparison (-0.17, p < 0.01) and with the within-subject comparison (-0.31, p < 0.001). Depending on the vignette, 27% to 40% of participants reported a greater likelihood of engaging in risky sexual behavior if taking PrEP than if not taking PrEP.

Conclusions

Our findings indicate that modest increases in risky sexual behavior could occur with PrEP. Although responses from the majority of participants suggest they would not be more likely to engage in risky sexual behavior if they took PrEP, a substantial proportion might. Programs rolling out PrEP should be prepared to assist similar women in making informed choices about reducing their risk of HIV and about their sexual health beyond HIV prevention.     

Rapid Assessment of Ecosystem Services Provided by Two Mineral Extraction Sites Restored for Nature Conservation in an Agricultural Landscape in Eastern England

Despite growing recognition that mineral sites restored for nature conservation can enhance local biodiversity, the wider societal benefits provided by this type of restoration relative to alternative options are not well understood. This study addresses this research gap by quantifying differences in ecosystem services provision under two common mineral site after-uses: nature conservation and agriculture. Using a combination of site-specific primary field data, benefits transfer and modelling, we show that for our sites restoration for nature conservation provides a more diverse array of ecosystem services than would be delivered under an agricultural restoration scenario. We also explore the effects of addressing different conservation targets, which we find alter the provision of ecosystem services on a service-specific basis. Highly species-focused intervention areas are associated with increased carbon storage and livestock grazing provision, whereas non-intervention areas are important for carbon sequestration, fishing, recreation and flood risk mitigation. The results of this study highlight the wider societal importance of restored mineral sites and may help conservation managers and planners to develop future restoration strategies that provide benefits for both biodiversity and human well-being.     

Adrenal Gland and Lung Lesions in Gulf of Mexico Common Bottlenose Dolphins (Tursiops truncatus) Found Dead following the Deepwater Horizon Oil Spill

A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.     

De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region,Cause Intellectual Disability

To identify further Mendelian causes of intellectual disability (ID), we screened a cohort of 996 individuals with ID for variants in 565 known or candidate genes by using a targeted next-generation sequencing approach. Seven loss-of-function (LoF) mutations—four nonsense (c.1195A>T [p.Lys399^∗], c.1333C>T [p.Arg445^∗], c.1866C>G [p.Tyr622^∗], and c.3001C>T [p.Arg1001^∗]) and three frameshift (c.2177_2178del [p.Thr726Asnfs^∗39], c.3771dup [p.Ser1258Glufs^∗65], and c.3856del [p.Ser1286Leufs^∗84])—were identified in SETD5, a gene predicted to encode a methyltransferase. All mutations were compatible with de novo dominant inheritance. The affected individuals had moderate to severe ID with additional variable features of brachycephaly; a prominent high forehead with synophrys or striking full and broad eyebrows; a long, thin, and tubular nose; long, narrow upslanting palpebral fissures; and large, fleshy low-set ears. Skeletal anomalies, including significant leg-length discrepancy, were a frequent finding in two individuals. Congenital heart defects, inguinal hernia, or hypospadias were also reported. Behavioral problems, including obsessive-compulsive disorder, hand flapping with ritualized behavior, and autism, were prominent features. SETD5 lies within the critical interval for 3p25 microdeletion syndrome. The individuals with SETD5 mutations showed phenotypic similarity to those previously reported with a deletion in 3p25, and thus loss of SETD5 might be sufficient to account for many of the clinical features observed in this condition. Our findings add to the growing evidence that mutations in genes encoding methyltransferases regulating histone modification are important causes of ID. This analysis provides sufficient evidence that rare de novo LoF mutations in SETD5 are a relatively frequent (0.7%) cause of ID.     

The dawning of a 'Golden era' in lantibiotic bioengineering

There are many examples of highly modified antimicrobial peptides in nature, many of which are non-ribosomally synthesized. However, the bacterial lantibiotics are produced as gene-encoded pre-peptides that are subsequently modified by dedicated enzyme systems to form extraordinarily potent inhibitors. Consequently, they are much more amenable to bioengineering which could lead to the generation of a new arsenal of potent antimicrobials. However, although bioengineering of these compounds has been underway for at least two decades, significant progress has only been reported in recent years. This review charts these recent developments which suggest that we are entering a 'Golden era' of lantibiotic bioengineering.     

Synthesis and in vivo evaluation of bicyclic gababutins

Synthesis of a number of bicyclic five-membered ring derivatives of gabapentin led to the identification of two compounds, (?)-(11A) and (20A) which both had an excellent level of potency against α₂δ and were profiled in an in vivo model of neuropathic pain.     

Amplification of a Cytochrome P450 Gene Is Associated with Resistance to Neonicotinoid Insecticides in the Aphid Myzus persicae

The aphid Myzus persicae is a globally significant crop pest that has evolved high levels of resistance to almost all classes of insecticide. To date, the neonicotinoids, an economically important class of insecticides that target nicotinic acetylcholine receptors (nAChRs), have remained an effective control measure; however, recent reports of resistance in M. persicae represent a threat to the long-term efficacy of this chemical class. In this study, the mechanisms underlying resistance to the neonicotinoid insecticides were investigated using biological, biochemical, and genomic approaches. Bioassays on a resistant M. persicae clone (5191A) suggested that P450-mediated detoxification plays a primary role in resistance, although additional mechanism(s) may also contribute. Microarray analysis, using an array populated with probes corresponding to all known detoxification genes in M. persicae, revealed constitutive over-expression (22-fold) of a single P450 gene (CYP6CY3); and quantitative PCR showed that the over-expression is due, at least in part, to gene amplification. This is the first report of a P450 gene amplification event associated with insecticide resistance in an agriculturally important insect pest. The microarray analysis also showed over-expression of several gene sequences that encode cuticular proteins (2–16-fold), and artificial feeding assays and in vivo penetration assays using radiolabeled insecticide provided direct evidence of a role for reduced cuticular penetration in neonicotinoid resistance. Conversely, receptor radioligand binding studies and nucleotide sequencing of nAChR subunit genes suggest that target-site changes are unlikely to contribute to resistance to neonicotinoid insecticides in M. persicae.     

Fire history and the global carbon budget: a 1°× 1° fire history reconstruction for the 20th century

A yearly global fire history is a prerequisite for quantifying the contribution of previous fires to the past and present global carbon budget. Vegetation fires can have both direct (combustion) and long‐term indirect effects on the carbon cycle. Every fire influences the ecosystem carbon budget for many years, as a consequence of internal reorganization, decomposition of dead biomass, and regrowth. We used a two‐step process to estimate these effects. First we synthesized the available data available for the 1980s or 1990s to produce a global fire map. For regions with no data, we developed estimates based on vegetation type and history. Second, we then worked backwards to reconstruct the fire history. This reconstruction was based on published data when available. Where it was not, we extrapolated from land use practices, qualitative reports and local studies, such as tree ring analysis. The resulting product is intended as a first approximation for questions about consequences of historical changes in fire for the global carbon budget. We estimate that an average of 608 Mha yr^?1 burned (not including agricultural fires) at the end of the 20th century. 86% of this occurred in tropical savannas. Fires in forests with higher carbon stocks consumed 70.7 Mha yr^?1 at the beginning of the century, mostly in the boreal and temperate forests of the Northern Hemisphere. This decreased to 15.2 Mha yr^?1 in the 1960s as a consequence of fire suppression policies and the development of efficient fire fighting equipment. Since then, fires in temperate and boreal forests have decreased to 11.2 Mha yr^?1. At the same time, burned areas increased exponentially in tropical forests, reaching 54 Mha yr^?1 in the 1990s, reflecting the use of fire in deforestation for expansion of agriculture. There is some evidence for an increase in area burned in temperate and boreal forests in the closing years of the 20th century.     

A resource-based conceptual model of plant diversity that reassesses causality in the productivity–diversity relationship

Biogeographical studies frequently reveal positive correlations between species richness and estimates of environmental water and/or energy. A popular interpretation of this relationship relates the supply of water and energy to productivity, and then, in turn, to richness. Productivity–diversity theories are now legion, yet none has proved sufficiently intuitive to gain broad acceptance. Like productivity, heterogeneity is known to influence diversity at fine spatial scales, yet the possibility that richness might relate to water–energy dynamics at coarse spatial scales via a heterogeneity‐generating mechanism has received little attention. In this paper we outline such a conceptual model for plants that is internally consistent and testable. We believe it may help to explain the capacity of environments receiving different inputs of water and energy to support variable numbers of species at a range of spatial scales, the pervasive correlation between productivity and richness, some exceptions to the productivity–diversity relationship, the form of productivity–diversity curves and the link between richness and environmental ‘harshness’. The model may also provide an answer to one of the most venerable puzzles in the field of diversity studies: why high inputs of water and energy correspond to more species rather than simply more individuals.