Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis.

Introduction: HIV incidence among women in sub-Saharan Africa (SSA) has declined steadily, but it is unknown whether new infections among women who engage in sex work (WESW) have declined at a similar rate. We synthesised estimates of HIV incidence among WESW in SSA and compared these to the wider female population to understand levels and trends in incidence over time. Methods: We searched Medline, Embase, Global Health, Popline, Web of Science, and Google Scholar from January 1990 to October 2022, and grey literature for estimates of HIV incidence among WESW in SSA. We included studies reporting empirical estimates in any SSA country. We calculated incidence rate ratios (IRR) compared to age-district-year matched total female population incidence estimates. We conducted a meta-analysis of IRRs and used a continuous mixed-effects model to estimate changes in IRR over time. Results: From 32 studies between 1985 and 2020, 2,194 new HIV infections were observed in WESW over 51,000 person-years (py). Median HIV incidence was 4.3/100py (IQR 2.8-7.0/100py), declining from a median of 5.96/100py between 1985 and 1995 to a median of 3.2/100py between 2010 and 2020. Incidence among WESW was nine times higher than in matched total population women (RR 8.6, 95%CI: 5.7-12.9), and greater in Western and Central Africa (RR 22.4, 95%CI: 11.3-44.3) than in Eastern and Southern Africa (RR 5.3, 95%CI: 3.7-7.6). Annual changes in log IRRs were minimal (-0.1% 95%CI: -6.9 to +6.8%). Conclusions: Across SSA, HIV incidence among WESW remains disproportionately high compared to the total female population but showed similar rates of decline between 1990 and 2020. Improved surveillance and standardisation of approaches to obtain empirical estimates of sex worker incidence would enable a clearer understanding of whether we are on track to meet global targets for this population and better support data-driven HIV prevention programming.

Reliability of quantitative sensory testing in the assessment of somatosensory function after high-frequency stimulation-induced sensitisation of central nociceptive pathways.

ABSTRACT: The high frequency stimulation (HFS) model can be used alongside quantitative sensory testing (QST) to assess the sensitisation of central nociceptive pathways. However, the validity and between-session reliability of using QST z -score profiles to measure changes in mechanical and thermal afferent pathways in the HFS model are poorly understood. In this study, 32 healthy participants underwent QST before and after HFS (5× 100 Hz trains; 10× electrical detection threshold) in the same heterotopic skin area across 2 repeated sessions. The only mechanical QST z -score profiles that demonstrated a consistent gain of function across repeated test sessions were mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS), which were associated with moderate and good reliability, respectively. There was no relationship between HFS intensity and MPT and MPS z -score profiles. There was no change in low intensity, but a consistent facilitation of high-intensity pin prick stimuli in the mechanical stimulus response function across repeated test sessions. There was no change in cold pain threshold (CPT) and heat pain threshold (HPT) z -score profiles across session 1 and 2, which were associated with moderate and good reliability, respectively. There were inconsistent changes in the sensitivity to innocuous thermal QST parameters, with cool detection threshold (CDT), warm detection threshold (WDT), and thermal sensory limen (TSL) all producing poor reliability. These data suggest that HFS-induced changes in MPS z -score profiles is a reliable way to assess experimentally induced central sensitisation and associated secondary mechanical hyperalgesia in healthy participants.

Implicit signatures of voluntary action reduce with repeated motor practice.

The sense of controlling one's actions and their consequences is a critical aspect of successful motor activity. While motor performance typically improves with learning, it is unclear whether, how, and why higher order aspects of motor cognition are also affected. Here, we used an implicit measure of sense of agency-the 'intentional binding' effect-as participants learned to make a skilled action involving precise control of thumb adduction. These actions were predictably followed by a tone (the outcome). At pre-test, we showed the perceived time of the tone was shifted towards the thumb action, compared to a control condition in which tones occurred without actions. Next, a relevant training group learned to refine the direction of the thumb movement, while an irrelevant training group was trained on another movement. Manipulation checks demonstrated that, as expected, the relevant training group improved performance of the trained movement, while the irrelevant training group did not. Critically, while both groups still showed binding of the tone towards the thumb action at post-test, the relevant training group showed less binding than the irrelevant training group. Given the link between intentional binding and volitional control of action, we suggest our result demonstrates subjective agency over the outcome of a skilled action decreases as practice makes the skilled action more fluent. We suggest that this reduction in sense of agency over movement outcomes is consistent with the decreasing cognitive engagement, or automatization, that occurs during skill learning.

Temporal trends in, and risk factors for, HIV seroconversion among female sex workers accessing Zimbabwe's national sex worker programme, 2009-19: a retrospective cohort analysis of routinely collected HIV testing data.

BACKGROUND: The frequency of new HIV infections among female sex workers in sub-Saharan Africa is poorly understood. We used routinely collected data that enable unique identification of repeat HIV testers to assess temporal trends in seroconversion and identify associated risk factors for female sex workers accessing Sisters with a Voice, Zimbabwe's national sex worker programme. METHODS: We pooled HIV testing data gathered between Sept 15, 2009, and Dec 31, 2019, from 36 Sisters programme sites in Zimbabwe. We included female sex workers aged 16 years or older with an HIV-negative test and at least one subsequent programme test. We calculated HIV seroconversion rates (using the midpoint between the HIV-positive test and the last negative test as the seroconversion date) and estimated rate ratios to compare 2-year periods by using Poisson regression, with robust SEs to account for clustering by site and adjusting for age and testing frequency to assess temporal trends. We did sensitivity analyses to explore assumptions about seroconversion dates and the effects of variation in follow-up time on our conclusions. FINDINGS: Our analysis included data for 6665 female sex workers, 441 (7%) of whom seroconverted. The overall seroconversion rate was 3·8 (95% CI 3·4-4·2) per 100 person-years at risk. Seroconversion rates fell with time since first negative HIV test. After adjustment, there was evidence of a decrease in seroconversion rates from 2009 to 2019 (p=0·0053). In adjusted analyses, being younger than 25 years, and having a sexually transmitted infection diagnosis at a previous visit, were significantly associated with increased seroconversion rates. Our findings were mostly robust to sensitivity analyses, but when 1 month before an HIV-positive test was used as the seroconversion date, seroconversion rates no longer fell with time. INTERPRETATION: We identified high rates of seroconversion shortly after linkage to programme services, which emphasises the need to strengthen HIV prevention programmes from first contact with female sex workers in Zimbabwe. New infections among female sex workers remain challenging to measure, but longitudinal analysis of routine testing data can provide valuable insights into seroconversion rates and associated risk factors. FUNDING: UN Population Fund, Deutsche Gesellschaft für Internationale Zusammenarbeit, the Bill & Melinda Gates Foundation, The Global Fund to Fight AIDS, Tuberculosis and Malaria, US President's Emergency Plan for AIDS Relief, US Agency for International Development, and the Elton John AIDS Foundation.

Similar somatotopy for active and passive digit representation in primary somatosensory cortex.

Scientists traditionally use passive stimulation to examine the organisation of primary somatosensory cortex (SI). However, given the close, bidirectional relationship between the somatosensory and motor systems, active paradigms involving free movement may uncover alternative SI representational motifs. Here, we used 7 Tesla functional magnetic resonance imaging to compare hallmark features of SI digit representation between active and passive tasks which were unmatched on task or stimulus properties. The spatial location of digit maps, somatotopic organisation, and inter-digit representational structure were largely consistent between tasks, indicating representational consistency. We also observed some task differences. The active task produced higher univariate activity and multivariate representational information content (inter-digit distances). The passive task showed a trend towards greater selectivity for digits versus their neighbours. Our findings highlight that, while the gross features of SI functional organisation are task invariant, it is important to also consider motor contributions to digit representation.

Interpreting declines in HIV test positivity: an analysis of routine data from Zimbabwe's national sex work programme, 2009-2019.

INTRODUCTION: Early diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe. METHODS: We analysed HIV test data from Zimbabwe's nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV-positive test after at least one HIV-negative test in the programme. We used logistic regression to analyse test positivity over three time-periods: 2009-2013, 2014-2017 and 2018-2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time-periods. RESULTS: During the 10-year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018-2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009-2013 (aOR 6.08 95% CI 5.52-6.70) and 18.8% for 2014-2017 (aOR 2.17 95% CI 2.06-2.28). Adjusting for time since last test reduced effect estimates for 2009-2013 (aOR 4.03 95% CI 3.64-4.45) and 2014-2017 (aOR 1.97 95% CI 1.86-2.09) compared to 2018-2019. Among 7573 women with an initial HIV-negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5-4.2). CONCLUSIONS: Test positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.

Malleability of the cortical hand map following a finger nerve block.

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand's fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping.

Interplay of tactile and motor information in constructing spatial self-perception.

During active movement, there is normally a tight relation between motor command and sensory representation about the resulting spatial displacement of the body. Indeed, some theories of space perception emphasize the topographic layout of sensory receptor surfaces, while others emphasize implicit spatial information provided by the intensity of motor command signals. To identify which has the primary role in spatial perception, we developed experiments based on everyday self-touch, in which the right hand strokes the left arm. We used a robot-mediated form of self-touch to decouple the spatial extent of active or passive right hand movements from their tactile consequences. Participants made active movements of the right hand between unpredictable, haptically defined start and stop positions, or the hand was passively moved between the same positions. These movements caused a stroking tactile motion by a brush along the left forearm, with minimal delay, but with an unpredictable spatial gain factor. Participants judged the spatial extent of either the right hand's movement, or of the resulting tactile stimulation to their left forearm. Across five experiments, we found that movement extent strongly interfered with tactile extent perception, and vice versa. Crucially, interference in both directions was stronger during active than passive movements. Thus, voluntary motor commands produced stronger integration of multiple sensorimotor signals underpinning the perception of personal space. Our results prompt a reappraisal of classical theories that reduce space perception to motor command information.

Human perceptual learning is delayed by the N-methyl-D-aspartate receptor partial agonist D-cycloserine.

BACKGROUND: The optimisation of learning has long been a focus of scientific research, particularly in relation to improving psychological treatment and recovery of brain function. Previously, partial N-methyl-D-aspartate agonists have been shown to augment reward learning, procedural learning and psychological therapy, but many studies also report no impact of these compounds on the same processes. AIMS: Here we investigate whether administration of an N-methyl-D-aspartate partial agonist (D-cycloserine) modulates a previously unexplored process - tactile perceptual learning. Further, we use a longitudinal design to investigate whether N-methyl-D-aspartate-related learning effects vary with time, thereby providing a potentially simple explanation for apparent mixed effects in previous research. METHODS: Thirty-four volunteers were randomised to receive one dose of 250 mg D-cycloserine or placebo 2 h before tactile sensitivity training. Tactile perception was measured using psychophysical methods before and after training, and 24/48 h later. RESULTS: The placebo group showed immediate within-day tactile perception gains, but no further improvements between-days. In contrast, tactile perception remained at baseline on day one in the D-cycloserine group (no within-day learning), but showed significant overnight gains on day two. Both groups were equivalent in tactile perception by the final testing - indicating N-methyl-D-aspartate effects changed the timing, but not the overall amount of tactile learning. CONCLUSIONS: In sum, we provide first evidence for modulation of perceptual learning by administration of a partial N-methyl-D-aspartate agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains.

Paediatric Dentistry and Orthodontics interface: When should we consider balancing and compensating extractions?

The guidelines regarding balancing and compensating extractions, published by the Royal College of Surgeons of England,1 are based on relatively low-level evidence and it is highlighted in the guidance that further research into these areas is required. This paper aims to appraise the current evidence base regarding balancing and compensating extractions, to aid general dental practitioners in their decision making. General and clinical factors that should be considered in the treatment planning process are discussed throughout.

Association between HIV stigma and antiretroviral therapy adherence among adults living with HIV: baseline findings from the HPTN 071 (PopART) trial in Zambia and South Africa.

OBJECTIVES: Adherence to antiretroviral therapy (ART) leads to viral suppression for people living with HIV (PLHIV) and is critical for both individual health and reducing onward HIV transmission. HIV stigma is a risk factor that can undermine adherence. We explored the association between HIV stigma and self-reported ART adherence among PLHIV in 21 communities in the HPTN 071 (PopART) trial in Zambia and the Western Cape of South Africa. METHODS: We conducted a cross-sectional analysis of baseline data collected between 2013 and 2015, before the roll-out of trial interventions. Questionnaires were conducted, and consenting participants provided a blood sample for HIV testing. Poor adherence was defined as self-report of not currently taking ART, missing pills over the previous 7 days or stopping treatment in the previous 12 months. Stigma was categorised into three domains: community, health setting and internalised stigma. Multivariable logistic regression was used for analysis. RESULTS: Among 2020 PLHIV self-reporting ever taking ART, 1888 (93%) were included in multivariable analysis. Poor ART adherence was reported by 15.8% (n = 320) of participants, and 25.7% (n = 519) reported experiencing community stigma, 21.5% (n = 434) internalised stigma, and 5.7% (n = 152) health setting stigma. PLHIV who self-reported previous experiences of community and internalised stigma more commonly reported poor ART adherence than those who did not (aOR 1.63, 95% CI 1.21 -2.19, P = 0.001 and aOR 1.31, 95% CI 0.96-1.79, P = 0.09). CONCLUSIONS: HIV stigma was associated with poor ART adherence. Roll-out of universal treatment will see an increasingly high proportion of PLHIV initiated on ART. Addressing HIV stigma could make an important contribution to supporting lifelong ART adherence.

OBJECTIFS: L'adhésion à la thérapie antirétrovirale (ART) conduit à la suppression virale pour les personnes vivant avec le VIH (PVVIH) et est essentielle à la fois pour la santé individuelle et pour réduire la transmission du VIH. La stigmatisation du VIH est un facteur de risque qui peut compromettre l'adhésion. Nous avons exploré l'association entre la stigmatisation du VIH et l'adhésion autodéclarée à l'ART chez les PVVIH dans 21 communautés dans l'essai HPTN 071 (PopART) en Zambie et dans le Western Cape en Afrique du Sud. MÉTHODES: Nous avons effectué une analyse transversale des données de base collectées entre 2013-2015, avant le déploiement des interventions d'essai. Des questionnaires ont été réalisés et les participants consentants ont fourni un échantillon de sang pour le dépistage du VIH. Une mauvaise adhésion a été définie comme l'autodéclaration de ne pas prendre actuellement l'ART, d'omettre des comprimés au cours des 7 jours précédents ou d'arrêter le traitement au cours des 12 mois précédents. La stigmatisation a été classée en trois domaines: communautaire, en milieu de santé et stigmatisation intériorisée. Une régression logistique multivariée a été utilisée pour l'analyse. RÉSULTATS: Parmi les 2.020 PVVIH autodéclarant avoir déjà pris un ART, 1.888 (93%) ont été inclus dans l'analyse multivariée. Une mauvaise adhésion à l'ART a été signalée par 15,8% (n = 320) des participants, 25,7% (n = 519) ont déclaré avoir subi une stigmatisation communautaire, 21,5% (n = 434) une stigmatisation internalisée et 5,7% (n = 152) une stigmatisation en milieu de santé. Les PVVIH qui ont auto-déclaré des expériences antérieures de stigmatisation communautaire et intériorisée ont plus souvent rapporté une mauvaise adhésion à l'ART que ceux qui ne l'ont pas fait (aOR 1,63 ; IC95%: 1,21-2,19 ; P = 0,001 et aOR 1,31 ; IC95%: 0,96-1,79 ; P = 0,09). CONCLUSIONS: La stigmatisation du VIH était associée à une mauvaise adhésion à l'ART. Le déploiement du traitement universel verra une proportion de plus en plus élevée de PVVIH initiées à l'ART. Lutter contre la stigmatisation du VIH pourrait apporter une contribution importante au soutien de l'adhésion à l'ART au cours de la vie. NUMÉRO D'ESSAI CLINIQUE: NCT01900977.

Organized Toe Maps in Extreme Foot Users.

Although the fine-grained features of topographic maps in the somatosensory cortex can be shaped by everyday experience, it is unknown whether behavior can support the expression of somatotopic maps where they do not typically occur. Unlike the fingers, represented in all primates, individuated toe maps have only been found in non-human primates. Using 1-mm resolution fMRI, we identify organized toe maps in two individuals born without either upper limb who use their feet to substitute missing hand function and even support their profession as foot artists. We demonstrate that the ordering and structure of the artists' toe representation mimics typical hand representation. We further reveal "hand-like" features of activity patterns, not only in the foot area but also similarly in the missing hand area. We suggest humans may have an innate capacity for forming additional topographic maps that can be expressed with appropriate experience.

Implementing prevention policies for mother-to-child transmission of HIV in rural Malawi, South Africa and United Republic of Tanzania, 2013-2016.

OBJECTIVE: To assess adoption of World Health Organization (WHO) guidance into national policies for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) and to monitor implementation of guidelines at facility level in rural Malawi, South Africa and the United Republic of Tanzania. METHODS: We summarized national PMTCT policies and WHO guidance for 15 indicators across the cascades of maternal and infant care over 2013-2016. Two survey rounds were conducted (2013-2015 and 2015-2016) in 46 health facilities serving five health and demographic surveillance system populations. We administered structured questionnaires to facility managers to describe service delivery. We report the proportions of facilities implementing each indicator and the frequency and durations of stock-outs of supplies, by site and survey round. FINDINGS: In all countries, national policies influencing the maternal and infant PMTCT cascade of care aligned with WHO guidelines by 2016; most inter-country policy variations concerned linkage to routine HIV care. The proportion of facilities delivering post-test counselling, same-day antiretroviral therapy (ART) initiation, antenatal care and ART provision in the same building, and Option B+ increased or remained at 100% in all sites. Progress in implementing policies on infant diagnosis and treatment varied across sites. Stock-outs of HIV test kits or antiretroviral drugs in the past year declined overall, but were reported by at least one facility per site in both rounds. CONCLUSION: Progress has been made in implementing PMTCT policy in these settings. However, persistent gaps across the infant cascade of care and supply-chain challenges, risk undermining infant HIV elimination goals.

Blocking tactile input to one finger using anaesthetic enhances touch perception and learning in other fingers.

Brain plasticity is a key mechanism for learning and recovery. A striking example of plasticity in the adult brain occurs following input loss, for example, following amputation, whereby the deprived zone is "invaded" by new representations. Although it has long been assumed that such reorganization leads to functional benefits for the invading representation, the behavioral evidence is controversial. Here, we investigate whether a temporary period of somatosensory input loss to one finger, induced by anesthetic block, is sufficient to cause improvements in touch perception ("direct" effects of deafferentation). Further, we determine whether this deprivation can improve touch perception by enhancing sensory learning processes, for example, by training ("interactive" effects). Importantly, we explore whether direct and interactive effects of deprivation are dissociable by directly comparing their effects on touch perception. Using psychophysical thresholds, we found brief deprivation alone caused improvements in tactile perception of a finger adjacent to the blocked finger but not to non-neighboring fingers. Two additional groups underwent minimal tactile training to one finger either during anesthetic block of the neighboring finger or a sham block with saline. Deprivation significantly enhanced the effects of tactile perceptual training, causing greater learning transfer compared with sham block. That is, following deafferentation and training, learning gains were seen in fingers normally outside the boundaries of topographic transfer of tactile perceptual learning. Our results demonstrate that sensory deprivation can improve perceptual abilities, both directly and interactively, when combined with sensory learning. This dissociation provides novel opportunities for future clinical interventions to improve sensation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Obtaining and maintaining cortical hand representation as evidenced from acquired and congenital handlessness.

A key question in neuroscience is how cortical organisation relates to experience. Previously we showed that amputees experiencing highly vivid phantom sensations maintain cortical representation of their missing hand (Kikkert et al., 2016). Here, we examined the role of sensory hand experience on persistent hand representation by studying individuals with acquired and congenital hand loss. We used representational similarity analysis in primary somatosensory and motor cortex during missing and intact hand movements. We found that key aspects of acquired amputees' missing hand representation persisted, despite varying vividness of phantom sensations. In contrast, missing hand representation of congenital one-handers, who do not experience phantom sensations, was significantly reduced. Across acquired amputees, individuals' reported motor control over their phantom hand positively correlated with the extent to which their somatosensory hand representation was normally organised. We conclude that once cortical organisation is formed, it is remarkably persistent, despite long-term attenuation of peripheral signals.

The psychosocial and service delivery impact of genomic testing for inherited retinal dystrophies.

Next-generation sequencing (NGS) provides diagnostic information for many rare conditions. The evolution of NGS for panel, exome, and genome testing is set to be the platform for transforming genomic diagnosis in the National Health Service (NHS). Inherited retinal dystrophies (IRDs) are a highly genetically heterogeneous disease group causing progressive visual impairment. IRDs are ideal for an NGS panel approach due to phenotypic overlap and were one of the first diagnostic panels to be developed in the NHS. While diagnostic yield for patients with IRD has improved significantly with NGS, a proportion of patients remain without a diagnosis. The clinical value of NGS testing is well understood; however, the patient experience of panel testing is not well documented. Semi-structured qualitative telephone interviews were conducted with 23 participants with IRD who had undergone NGS testing. Interviews were transcribed verbatim and analysed using interpretative phenomenological analysis. Participants' experiences were interpreted to explore the psychosocial and service delivery impact of this testing technology, inclusive of those who received a pathogenic, negative, carrier status or variant of uncertain significance result. Collectively, three core themes were identified: (1) the journey towards a genomic diagnosis, (2) the impact of NGS testing, (3) service delivery of NGS tests. Disclosure of results had no reported adverse implications. Participants appreciated an open discussion about the potential for an uncertain or unexpected result, prior to testing. They valued pre-test counselling discussions, expert opinions and on-going care from genomic services.

Handedness modulates proprioceptive drift in the rubber hand illusion.

Preference for use of either the left or right hand ('handedness') has been linked with modulations of perception and sensory processing-both of space and the body. Here we ask whether multisensory integration of bodily information also varies as a function of handedness. We created a spatial disparity between visual and somatosensory hand position information using the rubber hand illusion, and use the magnitude of illusory shifts in hand position (proprioceptive 'drift') as a tool to probe the weighted integration of multisensory information. First, we found drift was significantly reduced when the illusion was performed on the dominant vs. non-dominant hand. We suggest increased manual dexterity of the dominant hand causes greater representational stability and thus an increased resistance to bias by the illusion induction. Second, drift was generally greatest when the hand was in its habitual action space (i.e., near the shoulder of origin), compared to when it laterally displaced towards, or across the midline. This linear effect, however, was only significant for the dominant hand-in both left- and right-handed groups. Thus, our results reveal patterns of habitual hand action modulate drift both within a hand (drift varies with proximity to action space), and between hands (differences in drift between the dominant and non-dominant hands). In contrast, we were unable to find conclusive evidence to support, or contradict, an overall difference between left- and right-handers in susceptibility to RHI drift (i.e., total drift, collapsed across hand positions). In sum, our results provide evidence that patterns of daily activity-and the subsequent patterns of sensory input-shape multisensory integration across space.

Implementing prevention policies for mother-to-child transmission of HIV in rural Malawi, South Africa and United Republic of Tanzania, 2013­2016

Objective To assess adoption of World Health Organization (WHO) guidance into national policies for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) and to monitor implementation of guidelines at facility level in rural Malawi, South Africa and the United Republic of Tanzania. Methods : We summarized national PMTCT policies and WHO guidance for 15 indicators across the cascades of maternal and infant care over 2013­2016. Two survey rounds were conducted (2013­2015 and 2015­2016) in 46 health facilities serving five health and demographic surveillance system populations. We administered structured questionnaires to facility managers to describe service delivery. We report the proportions of facilities implementing each indicator and the frequency and durations of stock-outs of supplies, by site and survey round.Findings In all countries, national policies influencing the maternal and infant PMTCT cascade of care aligned with WHO guidelines by 2016; most inter-country policy variations concerned linkage to routine HIV care. The proportion of facilities delivering post-test counselling, same-day antiretroviral therapy (ART) initiation, antenatal care and ART provision in the same building, and Option B+ increased or remained at 100% in all sites. Progress in implementing policies on infant diagnosis and treatment varied across sites. Stock-outs of HIV test kits or antiretroviral drugs in the past year declined overall, but were reported by at least one facility per site in both rounds. Conclusion Progress has been made in implementing PMTCT policy in these settings. However, persistent gaps across the infant cascade of care and supply-chain challenges, risk undermining infant HIV elimination goals