Insights into tuberculosis burden in Karachi, Pakistan: A concurrent adult tuberculosis prevalence and child Mycobacterium tuberculosis infection survey.

Pakistan is one of the five highest tuberculosis burden countries globally. We estimated prevalence of adult bacteriologically confirmed pulmonary tuberculosis and annual risk of Mycobacterium tuberculosis (M. tuberculosis) infection in children aged 2-4 years in Karachi, Pakistan. The survey design enabled exploration of tuberculosis burden by whether the population had previously been exposed to widespread tuberculosis active case-finding (ACF) activities or not. We conducted a concurrent adult pulmonary tuberculosis prevalence survey and a child M. tuberculosis infection survey using interferon gamma release assays in four districts (Korangi, South, West and Central). A cluster-based unequal probability random sampling method was employed with the a priori plan to oversample Korangi district which had been the focus of tuberculosis ACF activities since 2011. We defined Korangi district as the 'prior ACF' zone and remaining districts as the 'no prior ACF' zone. Between March 2018 and May 2019, 34,962 adults (78·5% of those eligible) and 1,505 children (59·9%) participated. Overall estimated prevalence of bacteriologically confirmed pulmonary tuberculosis was 387 cases per 100,000 population (95% CI 276-498) with a prevalence of 421 cases [95% CI 276-567] per 100,000 in the 'no prior ACF' and 279 cases [95% CI 155-403] per 100,000 in the 'prior ACF' zone. We estimated the annual risk of M. tuberculosis infection in children to be 1·1% (95% CI 0·7-1·5) in the 'no prior ACF' zone and 0·6% (95% CI 0·3-1·1) in the 'prior ACF' zone. We observed consistent differences in the population distribution of tuberculosis between the 'prior ACF' and 'no prior' ACF zones with a trend towards lower estimates of burden and M. tuberculosis transmission in the 'prior ACF' zone. A plausible explanation is that intensive ACF activities that have been ongoing in Korangi district for the preceding years have noticeably reduced the burden of tuberculosis and transmission.

Changes in Adherence and Viral Load Suppression Among People with HIV in Manila: Outcomes of the Philippines Connect for Life Study.

The Philippines HIV epidemic is among the fastest growing globally. Infections among men who have sex with men are rising at an alarming rate, necessitating targeted evidence-based interventions to retain people living with HIV in care, support adherence, and reach viral suppression. We conducted a 48-week prospective cohort study of 462 participants in which we provided a mobile health (mHealth) adherence support intervention using the Connect for Life platform. We observed an improvement in adherence, with the proportion of participants taking more than 95% of their antiretroviral therapy (ART) doses increasing from 78.6% at baseline to 90.3% at 48 weeks. Among treatment experienced participants, adherence improved significantly (McNemar's test = 21.88, P < 0.001). Viral load suppression did not change, with 92.6% suppression at baseline and 92.0% at 48 weeks. Illicit drug use was associated with reduced adherence (aOR = 0.56, 95%CI 0.31-1.00, P = 0.05) and being on second-line therapy was associated with poor viral load suppression (aOR = 0.33, 95%CI 0.14-0.78, P = 0.01). Quality of life improved following ART initiation, from a mean of 84.6 points (of a possible 120) at baseline to 91.01 at 48 weeks. Due to technical issues, fidelity to the intended intervention was low, with 22.1% (102/462) of participants receiving any voice calls and most others receiving a scaled-back SMS intervention. The mHealth intervention did not have any observed effect on adherence or on viral load suppression. While evidence of effectiveness of mHealth adherence interventions is mixed, these platforms should continue to be explored as part of differentiated treatment support services.

RNA polymerase II dynamics shape enhancer-promoter interactions.

How enhancers control target gene expression over long genomic distances remains an important unsolved problem. Here we investigated enhancer-promoter communication by integrating data from nucleosome-resolution genomic contact maps, nascent transcription and perturbations affecting either RNA polymerase II (Pol II) dynamics or the activity of thousands of candidate enhancers. Integration of new Micro-C experiments with published CRISPRi data demonstrated that enhancers spend more time in close proximity to their target promoters in functional enhancer-promoter pairs compared to nonfunctional pairs, which can be attributed in part to factors unrelated to genomic position. Manipulation of the transcription cycle demonstrated a key role for Pol II in enhancer-promoter interactions. Notably, promoter-proximal paused Pol II itself partially stabilized interactions. We propose an updated model in which elements of transcriptional dynamics shape the duration or frequency of interactions to facilitate enhancer-promoter communication.

Mapping social capital across Wales (UK) using secondary data and spatial analysis.

Social capital, a powerful community resource based on trust, relationships, norms, culture, values, networks and belonging, could shape the acceptance, cooperation, and involvement of citizens towards new policies or interventions. In past, connections of social capital have been studied in relation to human health, wellbeing, social and economic development. More recently, social capital has been studied with respect to human resilience and adaptation to climate change. We argue that social capital could also play a vital role in our efforts to reduce carbon footprint through behaviour change, a shift on shared local renewable energy resources, and adoption of low carbon technologies. In Wales (UK) there is no national scale dataset, reflecting its social capital landscape, that could be used for designing the right policies/interventions in this context, based on an expected level of trust, cooperation, and support within the communities. This paper is an effort to fill this data gap using secondary datasets. Firstly, a literature review is carried out to identify the indicators of social capital (cognitive and participatory). Secondary datasets have then been identified and acquired. Geospatial analysis has been carried out to produce the criterion maps for various indicators of social capital. Finally, Analytical Hierarchy Process is applied to generate a social capital map of Wales combining these indicators together. For validation of the produced data, social capital's known correlations were tested with crime rates, income level and multiple deprivations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43545-023-00639-1.

Evolution of promoter-proximal pausing enabled a new layer of transcription control.

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life. We found that unicellular eukaryotes display a slow acceleration of Pol II near transcription start sites. This proto-paused-like state transitioned to a longer, focused pause in derived metazoans which coincided with the evolution of new subunits in the NELF and 7SK complexes. Depletion of NELF reverts the mammalian focal pause to a proto-pause-like state and compromises transcriptional activation for a set of heat shock genes. Collectively, this work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve.

High level of novelty under the hood of convergent evolution.

Little is known about the extent to which species use homologous regulatory architectures to achieve phenotypic convergence. By characterizing chromatin accessibility and gene expression in developing wing tissues, we compared the regulatory architecture of convergence between a pair of mimetic butterfly species. Although a handful of color pattern genes are known to be involved in their convergence, our data suggest that different mutational paths underlie the integration of these genes into wing pattern development. This is supported by a large fraction of accessible chromatin being exclusive to each species, including the de novo lineage-specific evolution of a modular optix enhancer. These findings may be explained by a high level of developmental drift and evolutionary contingency that occurs during the independent evolution of mimicry.

Deep cis-regulatory homology of the butterfly wing pattern ground plan.

Butterfly wing patterns derive from a deeply conserved developmental ground plan yet are diverse and evolve rapidly. It is poorly understood how gene regulatory architectures can accommodate both deep homology and adaptive change. To address this, we characterized the cis-regulatory evolution of the color pattern gene WntA in nymphalid butterflies. Comparative assay for transposase-accessible chromatin using sequencing (ATAC-seq) and in vivo deletions spanning 46 cis-regulatory elements across five species revealed deep homology of ground plan-determining sequences, except in monarch butterflies. Furthermore, noncoding deletions displayed both positive and negative regulatory effects that were often broad in nature. Our results provide little support for models predicting rapid enhancer turnover and suggest that deeply ancestral, multifunctional noncoding elements can underlie rapidly evolving trait systems.

A butterfly pan-genome reveals that a large amount of structural variation underlies the evolution of chromatin accessibility.

Despite insertions and deletions being the most common structural variants (SVs) found across genomes, not much is known about how much these SVs vary within populations and between closely related species, nor their significance in evolution. To address these questions, we characterized the evolution of indel SVs using genome assemblies of three closely related Heliconius butterfly species. Over the relatively short evolutionary timescales investigated, up to 18.0% of the genome was composed of indels between two haplotypes of an individual Heliconius charithonia butterfly and up to 62.7% included lineage-specific SVs between the genomes of the most distant species (11 Mya). Lineage-specific sequences were mostly characterized as transposable elements (TEs) inserted at random throughout the genome and their overall distribution was similarly affected by linked selection as single nucleotide substitutions. Using chromatin accessibility profiles (i.e., ATAC-seq) of head tissue in caterpillars to identify sequences with potential cis-regulatory function, we found that out of the 31,066 identified differences in chromatin accessibility between species, 30.4% were within lineage-specific SVs and 9.4% were characterized as TE insertions. These TE insertions were localized closer to gene transcription start sites than expected at random and were enriched for sites with significant resemblance to several transcription factor binding sites with known function in neuron development in Drosophila We also identified 24 TE insertions with head-specific chromatin accessibility. Our results show high rates of structural genome evolution that were previously overlooked in comparative genomic studies and suggest a high potential for structural variation to serve as raw material for adaptive evolution.

Delivering an mHealth Adherence Support Intervention for Patients With HIV: Mixed Methods Process Evaluation of the Philippines Connect for Life Study.

BACKGROUND: The Philippines HIV epidemic is one of the fastest growing epidemics globally, and infections among men who have sex with men are increasing at an alarming rate. Connect for Life Philippines is a mobile health (mHealth) intervention that supports antiretroviral therapy (ART) adherence in this key population through individualized voice calls and SMS text messages. OBJECTIVE: The objective of this process evaluation is to assess the intervention reach, dose delivered and received, fidelity, and acceptability and to describe contextual factors affecting the implementation of an mHealth adherence support intervention for patients on ART in a clinic in Metro Manila, Philippines. METHODS: A mixed methods process evaluation approach was used in an observational cohort study. Quantitative data sources for the process evaluation were call and SMS text message logs obtained from the mHealth platform and questionnaires collected at 12-, 24-, and 48-week study visits. Qualitative data were collected from process reports and through a series of focus group discussions conducted with a subset of participants during the intervention development phase, after an initial 8-week pilot phase, and at the end of the study. RESULTS: The 462 study participants received 31,095 interactive voice calls and 8234 SMS text messages during the study. Owing to technical issues, intervention fidelity was low, with only 22.1% (102/462) of the participants receiving reminders via voice calls and others (360/462, 77.9%) receiving only SMS text messages during the intervention. After 48 weeks in the study, 63.5% (293/462) of the participants reported that they would be quite likely or very likely to recommend the program to a friend, and 53.8% (249/462) of the participants reported that they benefited quite a bit or very much from the intervention. Participants who were on ART for <6 months at the beginning of the study and those who received the daily or weekly pill reminders were more likely to report that they benefited from the intervention (P=.02 and P=.01, respectively). CONCLUSIONS: The Connect for Life intervention had high participant satisfaction and acceptability, especially among those who received high dose of the intervention. However, poor reliability of local telecommunication networks had a large impact on the intervention's usability, fidelity, and dose received.

E-Protein Inhibition in ILC2 Development Shapes the Function of Mature ILC2s during Allergic Airway Inflammation.

E-protein transcription factors limit group 2 innate lymphoid cell (ILC2) development while promoting T cell differentiation from common lymphoid progenitors. Inhibitors of DNA binding (ID) proteins block E-protein DNA binding in common lymphoid progenitors to allow ILC2 development. However, whether E-proteins influence ILC2 function upon maturity and activation remains unclear. Mice that overexpress ID1 under control of the thymus-restricted proximal Lck promoter (ID1tg/WT) have a large pool of primarily thymus-derived ILC2s in the periphery that develop in the absence of E-protein activity. We used these mice to investigate how the absence of E-protein activity affects ILC2 function and the genomic landscape in response to house dust mite (HDM) allergens. ID1tg/WT mice had increased KLRG1- ILC2s in the lung compared with wild-type (WT; ID1WT/WT) mice in response to HDM, but ID1tg/WT ILC2s had an impaired capacity to produce type 2 cytokines. Analysis of WT ILC2 accessible chromatin suggested that AP-1 and C/EBP transcription factors but not E-proteins were associated with ILC2 inflammatory gene programs. Instead, E-protein binding sites were enriched at functional genes in ILC2s during development that were later dynamically regulated in allergic lung inflammation, including genes that control ILC2 response to cytokines and interactions with T cells. Finally, ILC2s from ID1tg/WT compared with WT mice had fewer regions of open chromatin near functional genes that were enriched for AP-1 factor binding sites following HDM treatment. These data show that E-proteins shape the chromatin landscape during ILC2 development to dictate the functional capacity of mature ILC2s during allergic inflammation in the lung.

Interactive Mobile Phone HIV Adherence Support for Men Who Have Sex With Men in the Philippines Connect for Life Study: Mixed Methods Approach to Intervention Development and Pilot Testing.

BACKGROUND: The HIV epidemic in the Philippines is one of the fastest growing epidemics globally, and infections among men who have sex with men are rising at an alarming rate. The World Health Organization recommends the use of mobile health (mHealth) technologies to engage patients in care and ensure high levels of adherence to antiretroviral therapy (ART). Existing mHealth interventions can be adapted and tailored to the context and population served. OBJECTIVE: This study aims to create a locally tailored intervention using a mobile phone platform to support treatment adherence for HIV patients on ART in the Philippines. METHODS: A mixed methods approach guided by the Behavior Change Wheel framework was used to adapt an existing mHealth adherence support platform for the local setting and target population. A literature review, retrospective clinical record review, and focus group discussions with patients were conducted to understand the drivers of ART adherence and tailor the intervention accordingly. The resulting intervention was pilot-tested for 8 weeks, followed by focus group discussions with patients who received the intervention to assess the acceptability of the design. RESULTS: Key issues contributing to nonadherence included side effects, lack of behavioral skills for pill taking, social support, mental health, and substance use. Patients identified mHealth as an acceptable mode of intervention delivery and wanted mHealth services to be highly personalizable. The study team, clinicians, and software developers integrated these findings into the intervention, which included a menu of services as follows: pill reminders, health tips, adherence feedback, appointment reminders, and symptom reporting. During the pilot phase, technical issues in the interactive voice response system (IVRS) were identified and addressed. Patients who participated in the pilot phase expressed a preference for SMS text messaging over the IVRS. Patients responded positively to the appointment reminders and health tips, whereas patient feedback on daily and weekly pill reminders and adherence feedback was mixed. CONCLUSIONS: The mobile phone-based SMS text messaging and IVRS intervention was acceptable to men who have sex with men in Manila, the Philippines, and qualitative analysis suggested that the intervention helped promote ART adherence and appointment attendance.

Multiple stages of evolutionary change in anthrax toxin receptor expression in humans.

The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease may have influenced human evolution, we study changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 is 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observe multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in multiple tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.

Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius.

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.

Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex. This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called 'jumping genes', had inserted itself into the non-coding DNA around the cortex gene, 'flipping' the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.

The Dryas iulia Genome Supports Multiple Gains of a W Chromosome from a B Chromosome in Butterflies.

In butterflies and moths, which exhibit highly variable sex determination mechanisms, the homogametic Z chromosome is deeply conserved and is featured in many genome assemblies. The evolution and origin of the female W sex chromosome, however, remains mostly unknown. Previous studies have proposed that a ZZ/Z0 sex determination system is ancestral to Lepidoptera, and that W chromosomes may originate from sex-linked B chromosomes. Here, we sequence and assemble the female Dryas iulia genome into 32 highly contiguous ordered and oriented chromosomes, including the Z and W sex chromosomes. We then use sex-specific Hi-C, ATAC-seq, PRO-seq, and whole-genome DNA sequence data sets to test if features of the D. iulia W chromosome are consistent with a hypothesized B chromosome origin. We show that the putative W chromosome displays female-associated DNA sequence, gene expression, and chromatin accessibility to confirm the sex-linked function of the W sequence. In contrast with expectations from studies of homologous sex chromosomes, highly repetitive DNA content on the W chromosome, the sole presence of domesticated repetitive elements in functional DNA, and lack of sequence homology with the Z chromosome or autosomes is most consistent with a B chromosome origin for the W, although it remains challenging to rule out extensive sequence divergence. Synteny analysis of the D. iulia W chromosome with other female lepidopteran genome assemblies shows no homology between W chromosomes and suggests multiple, independent origins of the W chromosome from a B chromosome likely occurred in butterflies.

Chromosome Fusion Affects Genetic Diversity and Evolutionary Turnover of Functional Loci but Consistently Depends on Chromosome Size.

Major changes in chromosome number and structure are linked to a series of evolutionary phenomena, including intrinsic barriers to gene flow or suppression of recombination due to chromosomal rearrangements. However, chromosome rearrangements can also affect the fundamental dynamics of molecular evolution within populations by changing relationships between linked loci and altering rates of recombination. Here, we build chromosome-level assembly Eueides isabella and, together with a recent chromosome-level assembly of Dryas iulia, examine the evolutionary consequences of multiple chromosome fusions in Heliconius butterflies. These assemblies pinpoint fusion points on 10 of the 20 autosomal chromosomes and reveal striking differences in the characteristics of fused and unfused chromosomes. The ten smallest autosomes in D. iulia and E. isabella, which have each fused to a longer chromosome in Heliconius, have higher repeat and GC content, and longer introns than predicted by their chromosome length. When fused, these characteristics change to become more in line with chromosome length. The fusions also led to reduced diversity, which likely reflects increased background selection and selection against introgression between diverging populations, following a reduction in per-base recombination rate. We further show that chromosome size and fusion impact turnover rates of functional loci at a macroevolutionary scale. Together these results provide further evidence that chromosome fusion in Heliconius likely had dramatic effects on population level processes shaping rates of neutral and adaptive divergence. These effects may have impacted patterns of diversification in Heliconius, a classic example of an adaptive radiation.

An Integrated eDiagnosis Approach (IeDA) versus standard IMCI for assessing and managing childhood illness in Burkina Faso: a stepped-wedge cluster randomised trial.

BACKGROUND: The Integrated eDiagnosis Approach (IeDA), centred on an electronic Clinical Decision Support System (eCDSS) developed in line with national Integrated Management of Childhood Illness (IMCI) guidelines, was implemented in primary health facilities of two regions of Burkina Faso. An evaluation was performed using a stepped-wedge cluster randomised design with the aim of determining whether the IeDA intervention increased Health Care Workers' (HCW) adherence to the IMCI guidelines. METHODS: Ten randomly selected facilities per district were visited at each step by two trained nurses: One observed under-five consultations and the second conducted a repeat consultation. The primary outcomes were: overall adherence to clinical assessment tasks; overall correct classification ignoring the severity of the classifications; and overall correct prescription according to HCWs' classifications. Statistical comparisons between trial arms were performed on cluster/step-level summaries. RESULTS: On average, 54 and 79% of clinical assessment tasks were observed to be completed by HCWs in the control and intervention districts respectively (cluster-level mean difference = 29.9%; P-value = 0.002). The proportion of children for whom the validation nurses and the HCWs recorded the same classifications (ignoring the severity) was 73 and 79% in the control and intervention districts respectively (cluster-level mean difference = 10.1%; P-value = 0.004). The proportion of children who received correct prescriptions in accordance with HCWs' classifications were similar across arms, 78% in the control arm and 77% in the intervention arm (cluster-level mean difference = - 1.1%; P-value = 0.788). CONCLUSION: The IeDA intervention improved substantially HCWs' adherence to IMCI's clinical assessment tasks, leading to some overall increase in correct classifications but to no overall improvement in correct prescriptions. The largest improvements tended to be observed for less common conditions. For more common conditions, HCWs in the control districts performed relatively well, thus limiting the scope to detect an overall impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT02341469 ; First submitted August 272,014, posted January 19, 2015.

Performance of GeneXpert MTB/RIF for Diagnosing Tuberculosis Among Symptomatic Household Contacts of Index Patients in South Africa.

BACKGROUND: We describe the performance of GeneXpert MTB/RIF (Xpert) for diagnosing tuberculosis (TB) among symptomatic household contacts (HHCs) of rifampicin-resistant and drug-sensitive index cases. METHODS: We conducted a cross-sectional study among HHCs of recently diagnosed (<2 weeks) smear-positive and Xpert-positive index cases in the Bojanala District, South Africa. The HHCs were screened for TB symptoms; persons with ≥1 TB symptom provided 1 sputum for smear microscopy, Xpert, and mycobacterial growth indicator tube (MGIT) culture. Diagnostic test performance of Xpert was determined using MGIT as the reference standard. RESULTS: From August 2013 to July 2015, 619 HHCs from 216 index cases were enrolled: 60.6% were female, median age was 22 years (interquartile range, 9-40), and 126 (20.4%) self-reported/tested human immunodeficiency virus positive. A total of 54.3% (336 of 619) of contacts had ≥1 TB symptom (cough, fever, night sweats, weight loss), 297 of 336 (88.4%) of which provided a sputum; 289 (97.3%) had complete testing and 271 were included in the analysis. In total, 42 (6.8%) of 619 HHCs had microbiologically confirmed TB. The MGIT identified 33 HHCs as positive for Mycobacterium tuberculosis; of these, 7 were positive on Xpert resulting in a sensitivity of 21.2% (95% confidence interval [CI], 9.0-38.9), specificity of 98.3% (95% CI, 95.6-99.5), positive predictive value of 63.6% (95% CI, 30.8-89.1), and negative predictive value of 90.0 (95% CI, 85.7-93.4). CONCLUSIONS: Among symptomatic HHCs investigated for TB, Xpert performed suboptimally compared with MGIT culture. The poor performance of Xpert for diagnosing TB suggests that a more sensitive test, such a Xpert Ultra or culture, may be needed to improve yield of contact investigation, where feasible.

Heliconius butterflies: a window into the evolution and development of diversity.

Butterflies have become prominent models for studying the evolution and development of phenotypic variation. In Heliconius, extraordinary within species divergence and between species convergence in wing color patterns has driven decades of comparative genetic studies. However, connecting genetic patterns of diversification to the molecular mechanisms of adaptation has remained elusive. Recent studies are bridging this gap between genome and function and have driven substantial advances in deciphering the genetic architecture of diversification in Heliconius. While only a handful of large-effect genes were initially identified in the diversification of Heliconius color patterns, recent experiments have begun to unravel the underlying gene regulatory networks and how these have evolved. These results reveal an evolutionary story of many interacting loci and partly independent genetic architectures that underlie convergent evolution.

Risk factors affecting adherence to antiretroviral therapy among HIV patients in Manila, Philippines: a baseline cross-sectional analysis of the Philippines Connect for Life Study.

Background The Philippines HIV epidemic is one of the fastest growing, globally. Infections among men who have sex with men (MSM) are rising at an alarming rate, necessitating targeted evidence-based interventions to reach epidemic control. Treatment as prevention is a key strategy to end AIDS, making it a priority to explore novel approaches to retain people living with HIV (PLHIV) in care, support adherence, and reach viral suppression. METHODS: This cross-sectional analysis describes HIV-related risk behaviours and adherence to antiretroviral therapy (ART) in a population of HIV-positive patients at a clinic in Metro Manila, Philippines participating in the Philippines Connect for LifeTM cohort study. RESULTS: Among 426 HIV-positive adults taking ART, 79% reported ≥95% adherence over the prior 30 days. Longer time on treatment was associated with reduced adherence to ART (adjusted odds ratio (AOR) = 0.87 per year, P = 0.027). Being in a serodiscordant relationship, in which the subject's primary partner was HIV negative, increased adherence (AOR = 3.19, P = 0.006). Inconsistent condom use (AOR = 0.50, P = 0.103) and injection drug use (AOR = 0.54, P = 0.090) are potentially associated with reduced adherence to ART. Patients used drugs and alcohol at significantly higher rates than the general population.? CONCLUSIONS: The study found that patients in this setting require intervention to address treatment fatigue. Interventions to improve social support of PLHIV, as well as harm-reduction approaches for drug and alcohol use, could improve adherence in this population, strengthening the test-and-treat strategy to control the epidemic.