A trade-off between plant and soil carbon storage under elevated CO2.

Terrestrial ecosystems remove about 30 per cent of the carbon dioxide (CO2) emitted by human activities each year1, yet the persistence of this carbon sink depends partly on how plant biomass and soil organic carbon (SOC) stocks respond to future increases in atmospheric CO2 (refs. 2,3). Although plant biomass often increases in elevated CO2 (eCO2) experiments4-6, SOC has been observed to increase, remain unchanged or even decline7. The mechanisms that drive this variation across experiments remain poorly understood, creating uncertainty in climate projections8,9. Here we synthesized data from 108 eCO2 experiments and found that the effect of eCO2 on SOC stocks is best explained by a negative relationship with plant biomass: when plant biomass is strongly stimulated by eCO2, SOC storage declines; conversely, when biomass is weakly stimulated, SOC storage increases. This trade-off appears to be related to plant nutrient acquisition, in which plants increase their biomass by mining the soil for nutrients, which decreases SOC storage. We found that, overall, SOC stocks increase with eCO2 in grasslands (8 ± 2 per cent) but not in forests (0 ± 2 per cent), even though plant biomass in grasslands increase less (9 ± 3 per cent) than in forests (23 ± 2 per cent). Ecosystem models do not reproduce this trade-off, which implies that projections of SOC may need to be revised.

Pregnancy rates and outcomes in women with cystic fibrosis in the UK: comparisons with the general population before and after the introduction of disease-modifying treatment, 2003-17.

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment. DESIGN: A population-based longitudinal study, 2003-17. SETTING: United Kingdom. POPULATION: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. METHODS: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age. MAIN OUTCOME MEASURES: Pregnancy and live-birth rates and child gestational age. RESULTS: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age. CONCLUSIONS: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor. TWEETABLE ABSTRACT: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate.

Varying aerobic capacity in relation to breeding stage and reproductive success in giant petrels (Macronectes spp.).

Reproduction, and parental care in particular, are among the most energy-demanding activities within the annual cycle of adult birds. Parents that cannot meet the metabolic demands and other physiological costs of raising offspring may opt to abandon chicks in favour of self-maintenance and future reproduction. Recent work examining reproductive trade-offs in birds revealed an important role of oxygen carrying capacity in mediating variation in parental effort. This study explores the aerobic factors underlying the success or failure of parental care in two closely-related petrel species during their breeding season on Bird Island, South Georgia: northern giant petrels (Macronectes halli) and southern giant petrels (M. giganteus). Failed breeders of both sexes and species had significantly lower hematocrit levels (by 5.48 ± 0.64%) than successful breeders, and reticulocyte counts also tended to be lower in failed males, consistent with the hypothesis that parental care and workload depend on aerobic capacity. We discuss these results in relation to differences in the foraging ecology of both species and sexes.

Do genetic variations in proximal tubule transporters influence tenofovir-induced renal dysfunction? An exploratory study in a Ghanaian population.

OBJECTIVES: To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters. PATIENTS AND METHODS: The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05). RESULTS: None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, ß= -0.4), higher baseline CLCR (P = 0.008, ß = 65.2) and lower CLCR after 1 year (P = 0.024, ß= -26.6). CONCLUSIONS: This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort.

Cellular Uptake and Efflux of Palbociclib In Vitro in Single Cell and Spheroid Models.

Adequate drug distribution through tumors is essential for treatment to be effective. Palbociclib is a cyclin-dependent kinase 4/6 inhibitor approved for use in patients with hormone receptor positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. It has unusual physicochemical properties, which may significantly influence its distribution in tumor tissue. We studied the penetration and distribution of palbociclib in vitro, including the use of multicellular three-dimensional models and mathematical modeling. MCF-7 and DLD-1 cell lines were grown as single cell suspensions (SCS) and spheroids; palbociclib uptake and efflux were studied using liquid chromatography-tandem mass spectrometry. Intracellular concentrations of palbociclib for MCF-7 SCS (C max 3.22 µM) and spheroids (C max 2.91 µM) were 32- and 29-fold higher and in DLD-1, 13- and 7-fold higher, respectively, than the media concentration (0.1 µM). Total palbociclib uptake was lower in DLD-1 cells than MCF-7 cells in both SCS and spheroids. Both uptake and efflux of palbociclib were slower in spheroids than SCS. These data were used to develop a mathematical model of palbociclib transport that quantifies key parameters determining drug penetration and distribution. The model reproduced qualitatively most features of the experimental data and distinguished between SCS and spheroids, providing additional support for hypotheses derived from the experimental data. Mathematical modeling has the potential for translating in vitro data into clinically relevant estimates of tumor drug concentrations. SIGNIFICANCE STATEMENT: This study explores palbociclib uptake and efflux in single cell suspension and spheroid models of cancer. Large intracellular concentrations of palbociclib are found after drug exposure. The data from this study may aid understanding of the intratumoural pharmacokinetics of palbociclib, which is useful in understanding how drug distributes within tumor tissue and optimizing drug efficacy. Biomathematical modelling has the potential to derive intratumoural drug concentrations from plasma pharmacokinetics in patients.

A systematic review of diagnostic criteria for psoriasis in adults and children: evidence from studies with a primary aim to develop or validate diagnostic criteria.

BACKGROUND: The diagnosis of psoriasis in adults and children is made clinically, for both patient management and the selection of participants in research. Diagnostic criteria provide a structure for clinical assessment, which in turn helps standardize patient recruitment into clinical trials and case definitions in observational studies. OBJECTIVES: The aim of this systematic review was to identify and critically appraise the published studies to date that had a primary research aim to develop or validate diagnostic criteria for psoriasis. METHODS: A search of Ovid MEDLINE and Ovid Embase was conducted in October 2016. The primary objective was to record the sensitivity and specificity of diagnostic criteria for psoriasis. Secondary objectives included diagnostic recommendations, applicability to children and study characteristics. Diagnostic accuracy studies were critically appraised for risk of bias using the QUADAS-2 tool. RESULTS: Twenty-three studies met the inclusion criteria. None detailed clinical examination-based diagnostic criteria. The included criteria varied from genetic and molecular diagnostic models to skin imaging, histopathology, and questionnaire-based, computer-aided and traditional Chinese medicine criteria. High sensitivity and specificity (> 90%) were reported in many studies. However, the study authors often did not specify how the criteria would be used clinically or in research. This review identified studies with varying risk of bias, and due to each study developing separate criteria meta-analysis was not possible. CONCLUSIONS: Clinical examination-based diagnostic criteria are currently lacking for psoriasis. Future research could follow an international collaborative approach and employ study designs allowing high-quality diagnostic accuracy testing. Existing and newly developed criteria require validation.

The treatment of anal fistula: second ACPGBI Position Statement - 2018.

It is over 10 years since the first ACPGBI Position Statement on the management of anal fistula was published in 2007. This second edition is the result of scrutiny of the literature published during this time; it updates the original Position Statement and reviews the published evidence surrounding treatments for anal fistula that have been developed since the original publication.

Systematic review and meta-analysis investigating the efficacy and safety of probiotics in people with cancer.

BACKGROUND/OBJECTIVES: Probiotics are living microorganisms that confer a health benefit on the host when administered. This systematic review and meta-analysis investigates the efficacy and safety of probiotics in adult and paediatric patients diagnosed with cancer. METHODS: A systematic review and meta-analysis was undertaken (PROSPERO registration: CRD42016050252). Randomised controlled trials (RCT), identified through screening multiple databases were included for analysis of efficacy. Non-randomised controlled trials and case reports were included for safety analysis. Outcomes included the reduction in the incidence and severity of diarrhoea, and adverse events. Where possible, data were combined for meta-analysis using a random-effects model. Planned subgroup analyses were not possible through marked heterogeneity of study characteristics. RESULTS: Twenty one studies (N = 2982 participants) were included for assessment of efficacy. Probiotics may reduce the incidence of diarrhoea in patients with cancer [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.34-0.78, 95% prediction interval (PI) 0.3-0.92, I-sq 36.9%, 5 studies] and the duration of pyrexia [standardised mean difference 0.39 days, 95% CI 0.35-0.43, I-sq 0.01%, 5 studies]. Twenty five studies (N = 2242) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. Definitions and reporting of adverse events were variable and inconsistent. CONCLUSIONS: There remain insufficient studies to assess the true effect of probiotics in people with cancer. Meta-analysis suggests probiotics may be beneficial but further studies are still required. Improved reporting of outcomes and adverse events in clinical trials are required to improve accuracy and confidence of conclusions drawn in future updates.

Parents' voices: "Our process of advocating for our child with autism." A meta-synthesis of parents' perspectives.

BACKGROUND: Advocacy has been described by parents of children with autism as an important coping strategy, enabling them to move forward by redirecting emotions into actions. A key factor in the development of collaborative and constructive partnerships between service providers and parents is having an understanding of how parents engage in advocacy and the support needed to do so. This meta-synthesis was undertaken to consolidate in-depth qualitative data from parents' perspectives of the process that they use to advocate for their children with autism. METHODS: A qualitative meta-synthesis was conducted, whereby 15 databases were systematically searched. Thirty-one studies were identified and appraised using an adapted version of the Critical Appraisal Skills Programme tool. Data were synthesized into themes through the steps of review, meta-aggregation, integration, and interpretation. RESULTS: The voices of 1,662 parents are presented describing the process of advocacy in the stages of seeking a diagnosis, seeking self-education, and taking action. Taking action includes 2 subthemes: seeking, access, and use of support services and community engagement and educating others. CONCLUSIONS: Results highlight the significant impact that positive experiences with first-line professionals have during the diagnosis process and how these experiences lay the foundation for all future relationships with other service providers. Important implications arise from this meta-synthesis for service providers in supporting parents' advocacy and hence building constructive relationships with families with a child with autism.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Natural history of anorectal sepsis.

BACKGROUND: Progression from anorectal abscess to fistula is poorly described and it remains unclear which patients develop a fistula following an abscess. The aim was to assess the burden of anorectal abscess and to identify risk factors for subsequent fistula formation. METHODS: The Hospital Episode Statistics database was used to identify all patients presenting with new anorectal abscesses. Cox regression analysis was undertaken to identify factors predictive of fistula formation. RESULTS: A total of 165 536 patients were identified in the database as having attended a hospital in England with an abscess for the first time between 1997 and 2012. Of these, 158 713 (95·9 per cent) had complete data for all variables and were included in this study, the remaining 6823 (4·1 per cent) with incomplete data were excluded from the study. The overall incidence rate of abscess was 20·2 per 100 000. The rate of subsequent fistula formation following an abscess was 15·5 per cent (23 012 of 148 286) in idiopathic cases and 41·6 per cent (4337 of 10 427 in patients with inflammatory bowel disease (IBD) (26·7 per cent coded concurrently as ulcerative colitis; 47·2 per cent coded as Crohn's disease). Of all patients who developed a fistula, 67·5 per cent did so within the first year. Independent predictors of fistula formation were: IBD, in particular Crohn's disease (hazard ratio (HR) 3·51; P < 0·001), ulcerative colitis (HR 1·82; P < 0·001), female sex (HR 1·18; P < 0·001), age at time of first abscess 41-60 years (HR 1·85 versus less than 20 years; P < 0·001), and intersphincteric (HR 1·53; P < 0·001) or ischiorectal (HR 1·48; P < 0·001) abscess location compared with perianal. Some 2·9 per cent of all patients presenting with a new abscess were subsequently diagnosed with Crohn's disease; the median time to diagnosis was 14 months. CONCLUSION: The burden of anorectal sepsis is high, with subsequent fistula formation nearly three times more common in Crohn's disease than idiopathic disease, and female sex is an independent predictor of fistula formation following abscess drainage. Most fistulas form within the first year of presentation with an abscess.

Evolutionary relationships among pollinators and repeated pollinator sharing in sexually deceptive orchids.

The mechanism of pollinator attraction is predicted to strongly influence both plant diversification and the extent of pollinator sharing between species. Sexually deceptive orchids rely on mimicry of species-specific sex pheromones to attract their insect pollinators. Given that sex pheromones tend to be conserved among related species, we predicted that in sexually deceptive orchids, (i) pollinator sharing is rare, (ii) closely related orchids use closely related pollinators and (iii) there is strong bias in the wasp lineages exploited by orchids. We focused on species that are pollinated by sexual deception of thynnine wasps in the distantly related genera Caladenia and Drakaea, including new field observations for 45 species of Caladenia. Specialization was extreme with most orchids using a single pollinator species. Unexpectedly, seven cases of pollinator sharing were found, including two between Caladenia and Drakaea, which exhibit strikingly different floral morphology. Phylogenetic analysis of pollinators using four nuclear sequence loci demonstrated that although orchids within major clades primarily use closely related pollinator species, up to 17% of orchids within these clades are pollinated by a member of a phylogenetically distant wasp genus. Further, compared to the total diversity of thynnine wasps within the study region, orchids show a strong bias towards exploiting certain genera. Although these patterns may arise through conservatism in the chemical classes used in sex pheromones, apparent switches between wasp clades suggest unexpected flexibility in floral semiochemical production. Alternatively, wasp sex pheromones within lineages may exhibit greater chemical diversity than currently appreciated.

Feasibility of early physical therapy for dizziness after a sports-related concussion: A randomized clinical trial.

The purpose of this study was to (a) assess the feasibility of recruitment/retention of participants, protocol/resource management, and participant safety, and (b) estimate the size of the effect between the experimental and control groups. This was a feasibility study conducted as a prospective pilot double-blind randomized clinical trial. Subjects aged 10-23 years old with acute concussion and dizziness were enrolled from sports medicine centers. Forty-one participants were randomized into treatment and were seen for physical therapy beginning at 10 days post-concussion. Subjects in the experimental group received individually tailored, pragmatically delivered progressive interventions. Subjects in the control received prescriptive sham to minimally progressive interventions. The two primary outcomes were medical clearance for return-to-play and symptomatic recovery. The median number of days to medical clearance for the experimental group was 15.5 and for the control was 26. The median number of days to symptomatic recovery was 13.5 for the experimental group and was 17 for the control. According to Cox proportional hazards regression for time to medical release for return-to-play, the experimental group demonstrated a hazard ratio of 2.91 (95% CI: 1.01, 8.43) compared to the control. For time-to-symptomatic recovery, those in the experimental group demonstrated a hazard ratio of 1.99 (95% CI: 0.95, 4.15) compared to the control. The results indicate that it is feasible and safe to complete this type of intervention study. The results provide strong support for the allocation of resources to conduct well-powered randomized clinical trials of this intervention.

Short-term efficacy and safety of three novel sphincter-sparing techniques for anal fistulae: a systematic review.

BACKGROUND: The surgical treatment of complex anal fistulae, particularly those involving a significant portion of the anal sphincter in which fistulotomy would compromise continence, is challenging. Video-assisted anal fistula treatment (VAAFT), fistula tract laser closure (FiLaC™) and over-the-scope clip (OTSC®) proctology system are all novel sphincter-sparing techniques targeted at healing anal fistulae. In this study, all published articles on these techniques were reviewed to determine efficacy, feasibility and safety. METHODS: A systematic search of major databases was performed using defined terms. All studies reporting on experience of these techniques were included and outcomes (fistula healing and safety) evaluated. RESULTS: Eighteen studies (VAAFT-12, FiLaC™-3, OTSC®-3) including 1245 patients were analysed. All were case series, and outcomes were heterogeneous with follow-up ranging from 6 to 69 months and short-term (< 1 year) healing rates of 64-100%. Morbidity was low with only minor complications reported. There was one report of minor incontinence following the first reported study of FiLaC™, and this was treated successfully at 6 months with rubber band ligation of hypertrophied prolapsed mucosa. There are inconsistencies in the technique in studies of VAAFT and FiLaC™. CONCLUSIONS: All three techniques appear to be safe and feasible options in the management of anal fistulae, and short-term healing rates are acceptable with no sustained effect on continence. There is, however, a paucity of robust data with long-term outcomes. These techniques are thus welcome additions; however, their long-term place in the colorectal surgeon's armamentarium, whether diagnostic or therapeutic, remains uncertain.

Unravelling the relative roles of top-down and bottom-up forces driving population change in an oceanic predator.

In the open ocean ecosystem, climate and anthropogenic changes have driven biological change at both ends of the food chain. Understanding how the population dynamics of pelagic predators are simultaneously influenced by nutrient-driven processes acting from the "bottom-up" and predator-driven processes acting from the "top-down" is therefore considered an urgent task. Using a state-space demographic model, we evaluated the population trajectory of an oceanic predator, the Macaroni Penguin (Eudyptes chrysolophus), and numerically assessed the relative importance of bottom-up and top-down drivers acting through different demographic rates. The population trajectory was considerably more sensitive to changes in top-down control of survival compared to bottom-up control of survival or productivity. This study integrates a unique set of demographic and covariate data and highlights the benefits of using a single estimation framework to examine the links between covariates, demographic rates and population dynamics.

Paternity analysis reveals wide pollen dispersal and high multiple paternity in a small isolated population of the bird-pollinated Eucalyptus caesia (Myrtaceae).

Optimal foraging behaviour by nectavores is expected to result in a leptokurtic pollen dispersal distribution and predominantly near-neighbour mating. However, complex social interactions among nectarivorous birds may result in different mating patterns to those typically observed in insect-pollinated plants. Mating system, realised pollen dispersal and spatial genetic structure were examined in the bird-pollinated Eucalyptus caesia, a species characterised by small, geographically disjunct populations. Nine microsatellite markers were used to genotype an entire adult stand and 181 seeds from 28 capsules collected from 6 trees. Mating system analysis using MLTR revealed moderate to high outcrossing (tm=0.479-0.806) and low estimates of correlated paternity (rp=0.136±s.e. 0.048). Paternity analysis revealed high outcrossing rates (mean=0.72) and high multiple paternity, with 64 different sires identified for 181 seeds. There was a significant negative relationship between the frequency of outcross mating and distance between mating pairs. Realised mating events were more frequent than expected with random mating for plants <40 m apart. The overall distribution of pollen dispersal distances was platykurtic. Despite extensive pollen dispersal within the stand, three genetic clusters were detected by STRUCTURE analysis. These genetic clusters were strongly differentiated yet geographically interspersed, hypothesised to be a consequence of rare recruitment events coupled with extreme longevity. We suggest that extensive polyandry and pollen dispersal is a consequence of pollination by highly mobile honeyeaters and may buffer E. caesia against the loss of genetic diversity predicted for small and genetically isolated populations.

The construction of Chasma Boreale on Mars.

The polar layered deposits of Mars contain the planet's largest known reservoir of water ice and the prospect of revealing a detailed Martian palaeoclimate record, but the mechanisms responsible for the formation of the dominant features of the north polar layered deposits (NPLD) are unclear, despite decades of debate. Stratigraphic analyses of the exposed portions of Chasma Boreale-a large canyon 500 km long, up to 100 km wide, and nearly 2 km deep-have led most researchers to favour an erosional process for its formation following initial NPLD accumulation. Candidate mechanisms include the catastrophic outburst of water, protracted basal melting, erosional undercutting, aeolian downcutting and a combination of these processes. Here we use new data from the Mars Reconnaissance Orbiter to show that Chasma Boreale is instead a long-lived, complex feature resulting primarily from non-uniform accumulation of the NPLD. The initial valley that later became Chasma Boreale was matched by a second, equally large valley that was completely filled in by subsequent deposition, leaving no evidence on the surface to indicate its former presence. We further demonstrate that topography existing before the NPLD began accumulating influenced successive episodes of deposition and erosion, resulting in most of the present-day topography. Long-term and large-scale patterns of mass balance achieved through sedimentary processes, rather than catastrophic events, ice flow or highly focused erosion, have produced the largest geomorphic anomaly in the north polar ice of Mars.

Haemorrhoids: modern diagnosis and treatment.

Haemorrhoids present often to primary and secondary care, and haemorrhoidal procedures are among the most common carried out. They may co-exist with more serious pathology, and correct evaluation is important. In most cases a one-off colonoscopy in patients aged 50 or above with flexible sigmoidoscopy in younger patients is reasonable. Many people with haemorrhoids do not require treatment. Topical remedies provide no more than symptomatic relief-and even evidence for this is poor. Bulk laxatives alone may improve symptoms of both bleeding and prolapse and seem as effective as injection sclerotherapy. Rubber band ligation is effective in 75% of patients in the short term, but does not treat prolapsed haemorrhoids or those with a significant external component. Conventional haemorrhoidectomy remains the most effective treatment in the long term, the main limitation being post-operative pain. Metronidazole, topical sphincter relaxants and operative technique have all been shown to reduce pain. Stapled haemorrhoidectomy and haemorrhoidal artery ligation techniques are probably less effective but less painful. Long-term data are poor for all procedures, with many studies reporting only 1-3 years of follow-up data. Haemorrhoids are common in pregnancy, occurring in 40% of women. They can usually be treated conservatively during pregnancy, with any treatment delayed until after delivery. Acutely strangulated haemorrhoids may be treated either conservatively or operatively. There is an increased risk of anal stenosis after acute surgery, but the risks of sepsis and sphincter damage are less significant than previously thought. The majority of patients who are treated conservatively will still require definitive treatment at a later date.

Parents' voices: 'why and how we advocate'. A meta-synthesis of parents' experiences of advocating for their child with autism spectrum disorder.

Parenting a child with autism spectrum disorder (ASD) can be stressful, and accessing services can add to this stress. Self-efficacy, agency and advocacy are important for parents when accessing and using services. To develop insight into parental advocacy, a meta-synthesis was undertaken to consolidate the literature focussing on parents' experiences of advocating for their child with ASD. A qualitative meta-synthesis was conducted. Fifteen databases were systematically searched by using key terms related to ASD, children, parents/carers, advocacy and qualitative studies. Twenty-four studies were identified and appraised using an adapted version of the Critical Appraisal Skills Programme tool. Data were synthesized into themes through the steps of review, meta-aggregation, integration and interpretation. Two overarching concepts emerged, illustrating both the challenging nature of advocacy and the associated personal and societal benefits. These two concepts are supported by eight themes: a life-long, all-encompassing challenge; advocacy as a parental coping strategy; advocacy involving working to create a future; balancing roles and needs; isolation versus support; personal impacts of advocacy; benefits of advocacy; and the barriers to advocacy. The experience of advocacy for parents with a child with ASD is complex and intensive, presenting both personal and societal benefits, as well as challenges for parents. In supporting individuals with ASD and family well-being, service providers need to have an understanding of the advocating role of parents and ensure that opportunities exist for their voices to be heard during service delivery.

Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.

HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.