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Background It is widely accepted that the risk of hepatitis C virus (HCV) vertical transmission (VT) is 5%–6% in monoinfected women, and that 25%–40% of HCV infection clears spontaneously within 5 years. However, there is no consensus on how VT rates should be estimated, and there is a lack of information on VT rates “net” of clearance. Methods We reanalyzed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates net of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero, and at delivery was estimated from data on the proportion of HCV RNA positive within 3 days of birth, and differences between elective cesarean and nonelective cesarean deliveries. Results Overall VT rates were 7.2% (95% credible interval [CrI], 5.6%–8.9%) in mothers who were human immunodeficiency virus (HIV) negative and 12.1% (95% CrI, 8.6%–16.8%) in HIV-coinfected women. The corresponding rates net of clearance at 5 years were 2.4% (95% CrI, 1.1%–4.1%), and 4.1% (95% CrI, 1.7%–7.3%). We estimated that 24.8% (95% CrI, 12.1%–40.8%) of infections occur early in utero, 66.0% (95% CrI, 42.5%–83.3%) later in utero, and 9.3% (95% CrI, 0.5%–30.6%) during delivery. Conclusions Overall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of interventions to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.

Desegregation in the south had many goals, among them was creating equitable opportunities for students in schools. Much of the literature on desegregation efforts are focused on general education and little research has been done on the effects it had on school orchestra programs. Orchestra programs in Texas schools have had a historically strong presence, but opportunities for Black string players had been rare and limited by segregation. It wasn’t until 1963 that Black students could participate in Texas All-State ensembles and 1968 before school ensemble competitions were integrated. Newspaper articles, archives, and voices of individuals that lived through these experiences were examined to gain a better understanding of what occurred during the time of desegregation in Texas schools. The predominantly Black orchestra program at Dunbar High School in Lubbock thrived despite segregation; however, it would later struggle to recover after integration plans were enacted. In an effort to satisfy desegregation laws, Black students and teachers were bussed to white schools dissolving the Black nucleus that contributed to their previous success. A historical examination of Texas string orchestra programs, competitions, and lived experiences of Black stakeholders revealed issues surrounding representation and the importance of strong role models in music.

Introduction: The COVID-19 pandemic has globally impacted health service access, delivery and resources. There are limited data regarding the impact on the prevention of mother to child transmission (PMTCT) service delivery in low-resource settings. Neotree (www.neotree.org) combines data collection, clinical decision support and education to improve care for neonates. Here we evaluate impacts of COVID-19 on care for HIV-exposed neonates. Methods: Data on HIV-exposed neonates admitted to the neonatal unit (NNU) at Sally Mugabe Central Hospital, Zimbabwe, between 01/06/2019 and 31/12/2021 were analysed, with pandemic start defined as 21/03/2020 and periods of industrial action (doctors (September 2019-January 2020) and nurses (June 2020-September 2020)) included, resulting in modelling during six time periods: pre-doctors’ strike (baseline); doctors’ strike; post-doctors’ strike and pre-COVID; COVID and pre-nurses’ strike ; nurses’ strike; post nurses’ strike. Interrupted time series models were used to explore changes in indicators over time. Results: Of 8,333 neonates admitted to the NNU, 904 (11%) were HIV-exposed. Mothers of 706/765 (92%) HIV-exposed neonates reported receipt of antiretroviral therapy (ART) during pregnancy. Compared to the baseline period when average admissions were 78 per week (95% confidence interval (CI) 70-87), significantly fewer neonates were admitted during all subsequent periods until after the nurses’ strike, with the lowest average number during the nurses’ strike (28, 95% CI 23-34, p0.22) in numbers of admissions or mortality by HIV exposure status. Fewer HIV-exposed neonates received a PCR test during the pandemic (23%) compared to the pre-pandemic periods (40%) (RR 0.59, 95% CI 0.41-0.84, pConclusion: While antiretroviral prophylaxis for HIV-exposed neonates remained high throughout, concerning data on low admissions and increased mortality, similar in HIV-exposed and unexposed neonates, and reduced HIV testing, suggest some aspects of care may have been compromised due to indirect effects of the pandemic.

From the mid twentieth century, second-wave feminism prompted interest from both historians and novelists in recovering the voices of women from the past. Where only sparse archival records were extant, a revised practice of biography was necessary, but differences arising from disciplinary approaches have led to debate on how this is best achieved. This essay analyses two contemporary publications that draw attention to lesser-known women’s experiences in colonial Australia: Melissa Ashley’s The Birdman’s Wife (2016) and Kiera Lindsey’s The Convict’s Daughter (2016). Marketed as fiction and biography respectively, these two texts nonetheless use similar techniques to recover the voices of these women from the archives and to share their stories with broad audiences: Immersive research; imaginative interpretation of documented records; character development through dialogue, emotions, thoughts and sensory details; use of literary techniques of imagery and dramatisation as signposts of fictionality. Through these techniques, and despite their generic differences, Ashley and Lindsey’s works evoke a powerful sense of their female subjects’ experiences and inner lives.

The average age of survivors from Hiroshima and Nagasaki (hibakusha) is now over 80. There is an urgent need to hear the survivors' stories while they are still alive to tell. This article focuses ...

Kumiko Kakehashi was born in 1961 in Kumamoto Prefecture and graduated from Hokkaido University with a degree in Japanese Literature. She won the Soichi Oya Non-fiction Award for So Sad to Fall in ...

Women played an integral, but understated and often unrecognised, part in Baptist missions such as Jamaica during the early nineteenth century. Yet they are largely absent from extant correspondenc...

String musicians put a high priority on ear training in order to be successful on their instruments. Research suggests that delaying music reading to teach by ear does not negatively affect sight-reading performance in the long term, may improve music literacy skills, and also may improve student perceptions of accomplishment. The pedagogy of learning by ear, which is distinctly different than learning by rote, may be unfamiliar to many string teachers, regardless of their experience in the classroom. The purpose of this research-to-resource article is to provide string teachers with strategies to teach repertoire by ear with the intention of strengthening students’ aural acuity, problem-solving skills, and knowledge of the fingerboard.

Background Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. Methods Data on children aged Results 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) 3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens–Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. Conclusion Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

BackgroundCurrent guidelines recommend that infants born to women with hepatitis C (HCV) viremia are screened for HCV antibody at age 18 months, and if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based in part on analyses suggesting 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years.MethodsData on 179 infants with RNA and/or anti-HCV evidence of vertically acquired viraemia (single PCR+) or confirmed infection (2 PCR+ or anti-HCV beyond 18 months) in three prospective European cohorts were investigated. Ages at clearance of viremia and confirmed infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in infants in whom RNA was not detectable until after 6 weeks.ResultsClearance rates decline rapidly over the first 6 months. An estimated 90.6% (95%CrI: 83.5-95.9) of viremia cleared by 5 years, most within 3 months, and 65.9% (50.1-81.6) of confirmed infection cleared by 5 years, at a median 12.4 (7.1-18.9) months. If treatment began at age 6 months, 18 months or 3 years, at least 59.0% (42.0-76.9), 39.7 (17.9-65.9), and 20.9 (4.6-44.8) of those treated would clear without treatment. In seven (6.6%) confirmed infections, RNA was not detectable until after 6 weeks, and in 2 (1.9%) not until after 6 months. However, all such cases subsequently cleared.ConclusionsMost viraemia clears within 3 months, and most confirmed infection by 3 years. Delaying treatment avoids but does not eliminate over-treatment and should be balanced against loss to follow-up.Key pointsBased on a re-analysis of the largest purely prospective dataset assembled so far, 66% (50-82) of confirmed vertically acquired HCV clears spontaneously by age 5 years, rather than the 25-40% assumed in guidelines.

Background: The risk of vertical transmission of hepatitis C virus (HCV) is ≈6%, and evidence suggests HCV negatively affects pregnancy and infant outcomes. Despite this, universal antenatal HCV screening is not available in most settings, and direct acting antivirals (DAA) are yet to be approved for use in pregnancy or breastfeeding period. Larger safety and efficacy trials are needed. At current there is limited understanding of the acceptability of routine HCV screening and use of DAAs in pregnancy but only among women in high HCV burden countries. Methods: We conducted a cross-sectional survey of pregnant or post-partum (

BackgroundIt is widely accepted that the risk of HCV vertical transmission (VT) is 5-6% in mono-infected women, and that 25-40% of HCV infection clears spontaneously within 5 years. However, VT and clearance rates have not been estimated from the same datasets, and there is a lack of information on VT rates “net” of clearance.MethodsWe re-analysed data on 1749 children in 3 prospective cohorts to obtain coherent estimates of overall VT rate and VT rates “net” of clearance at different ages. Clearance rates were used to impute the proportion of uninfected children who had been infected and then cleared before testing negative. The proportion of transmission early in utero, late in utero and at delivery was estimated from data on the proportion of RNA positives in samples tested within three days of birth, and differences between elective caesarean and non-elective caesarean deliveries.FindingsOverall VT rates were 7.2% (95% credible interval 5.6-8.9) in mothers who were HIV negative and 12.1% (8.6-16.8) in HIV-co-infected women. The corresponding rates net of clearance at 5 years were 2.4% (1.1-4.1) and 4.1% (1.7-7.3). We estimated that 24.8% (12.1-40.8) of infections occur early in utero, 66.0% (42.5-83.3) later in utero, and 9.3% (0.5-30.6) during delivery.ConclusionOverall VT rates are about 24% higher than previously assumed, but the risk of infection persisting beyond age 5 years is about 38% lower. The results can inform design of trials of to prevent or treat pediatric HCV infection, and strategies to manage children exposed in utero.Key pointsTaking account of infections that would have cleared spontaneously before detection, the rate of HCV vertical transmission is 7.2% (95%CrI 5.6-8.9) in mono-infected women, but transmission “net” of clearance is 3.1% (1.8-4.4) at 3 years, and 2.4% (1.1-4.1) at 5.

Background Early infant HIV diagnosis (EID) is critical to ensuring timely diagnosis of HIV-exposed infants, and treatment in those found to be infected. However estimates of coverage vary considerably, depending on data sources used. We used 4 methods to estimate coverage among a historical cohort of HIV-exposed infants in rural South Africa, between 2010–2016. Methods We estimated the proportion of infants ever tested (methods 1–3) and tested by 7 weeks of age (1–4) as follows: (1) infants born to women identified as HIV-positive in demographic surveillance were linked to those with ≥1 EID result in routine laboratory surveillance; (2) the number of infants with ≥1 EID result in laboratory surveillance divided by the estimated number of HIV-exposed infants, calculated as total live births multiplied by antenatal HIV seroprevalence; (3) the number of infants with ≥1 EID result in routine laboratory surveillance, divided by the number of HIV-exposed infants as estimated by the district health service; (4) from documentation in infants’ Road-to-Health-booklets. Results The proportion ever tested was 43%, 88% and 138% for methods 1–3, and by 7 weeks of age was 25%, 49%, 86% and 46% for methods 1–4 respectively. Conclusions The four methods, applied to a range of routine data sources, resulted in estimates varying considerably, and the true coverage of EID remains unclear. Our findings highlight the importance of developing unique patient identifiers, improving training of healthcare providers using reporting systems, and ensuring the accuracy of healthcare records, to ensure the best possible health outcomes for HIV-exposed infants.

Elizabeth Chappell, Simon King and Dominique Baron-Bonarjee made a film, The Day War Broke Out, in the summer of 2019 as part of a CHASE film making training course led by film-maker Karen Boswall at The University of Sussex. The film focuses on the way in which the Mass Observation (MO) Archive came about. The film brings to life the materiality of the archive through voice, music, hand-written letters, historical objects and setting as well as through an interview with one of Mass Observation’s curators, Kirsty Pattrick. But what can we understand from the stated intentions of MO’s founders for anonymous volunteer contributors to write diaries ‘so that their [the public’s] environment may be understood and thus constantly transformed.’? This article takes the view that the ‘single voice’, i.e. in this case the personal reflective narrative, can offer a ‘way in’ to understanding collective lived experience. Exploring the research questions through three case studies, it offers a dialogical approach to the parallel and overlapping questions of how past lived experience can be brought to life on film as well as how researchers can use materiality to access the context of lived experience. It asks, how does the creative exploration of the archive through film offer the possibility of a more open dialogue to occur between researchers and curators? And finally, how can film making open up new vistas and avenues for researchers to share findings as well as to transform their own field of research?

The Btla inhibitory receptor limits innate and adaptive immune responses, both preventing the development of autoimmune disease and restraining anti-viral and anti-tumor responses. It remains unclear how the functions of Btla in diverse lymphocytes contributes to immunoregulation. Here, we show that Btla inhibits activation of genes regulating proliferation and cytokine signaling including the transcription factor Myc, indicating a regulatory role in humoral immunity. Within mucosal Peyer’s Patches, we found T cell-expressed Btla regulated Tfh, while Btla in T or B cells regulated GC B cell numbers. Treg-expressed Btla was required for cell-intrinsic Treg homeostasis, that subsequently controlled GC B cells. Loss of Btla in lymphocytes resulted in increased IgA bound to intestinal bacteria, correlating with altered microbial homeostasis and elevations in commensal and pathogenic bacteria. Together our studies provide important insights into how Btla functions as a checkpoint in diverse conventional and regulatory lymphocyte subsets to influence systemic immune responses.

ObjectivesTo assess the effectiveness of radiofrequency denervation (RD) of lumbosacral anatomical targets for the management of chronic back pain.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).MethodsA database search (Medline, Medline in Process, Embase, CINHAL and the Cochrane library) was conducted from January 2014 to April 2019 for placebo or no-treatment controlled trials of RD for the management of chronic back pain. Included trials were quality assessed using the Cochrane Risk-of-Bias Tool and the quality of outcomes assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Meta-analysis was conducted to calculate mean difference (MD) in post-treatment Pain Score.ResultsNineteen RCTs were included in the review. There appears to be short-term pain relief (1–3 months) provided by RD of the sacroiliac joint (five trials, MD −1.53, CI −2.62 to 0.45) and intervertebral discs (four trials, MD −0.98, CI −1.84 to 0.12), but the placebo effect is large and additional intervention effect size is small (6 months) is uncertain.ConclusionsRD of selected lumbosacral targets appears to have a small, short-term, positive effect for the management of patients with chronic back pain. However, the quality of evidence for the majority of outcomes is low or very low quality and there is still a degree of uncertainty, particularly around the duration of effect.

This special issue of Wasafiri takes a wide interpretation of the verb ‘to remember’ as both a conscious act and a process. Memory is necessarily individual and selective, and it cannot exist in is...

Introduction: The UNAIDS 90‐90‐90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland. / Methods: Utilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow‐up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression (

Genome-wide co-expression analysis is often used for annotating novel gene functions from high-dimensional data. Here, we developed an R package with a Shiny visualization app that creates immuno-networks from RNAseq data using a combination of Weighted Gene Co-expression Network Analysis (WGCNA), xCell immune cell signatures, and Bayesian Network Learning. Using a large publicly available RNAseq dataset we generated a Gene Module-Immune Cell (GMIC) network that predicted causal relationships between DEAH-box RNA helicase (DHX)15 and genes associated with humoral immunity, suggesting that DHX15 may regulate B cell fate. Deletion of DHX15 in mouse B cells led to impaired lymphocyte development, reduced peripheral B cell numbers, and dysregulated expression of genes linked to antibody-mediated immune responses similar to the genes predicted by the GMIC network. Moreover, antigen immunization of mice demonstrated that optimal primary IgG1 responses required DHX15. Intrinsic expression of DHX15 was necessary for proliferation and survival of activated of B cells. Altogether, these results support the use of co-expression networks to elucidate fundamental biological processes.

High proportion of children with MDR-TB had favourable outcome (90%) with early diagnosis and treatment initiation http://ow.ly/2eq5302gWmr

Mucosal immunity in the gut is achieved in part through cellular connections between lymphoid cells such as regulatory-T cells (Treg), T follicular helper cells (Tfh), T follicular regulatory cells (Tfr) and Germinal Center B cells (GC B). Btla (B and T Lymphocyte Attenuator) is a receptor mainly expressed on B and T cells that is activated by its ligand Hvem (Herpesvirus entry mediator; Tnfrsf14) to inhibit cellular activation. However, the role of these specific immune checkpoints in the regulation of mucosal immunity in the gut is still unknown. In mice containing genetic ablation of Btla in T cells, we observed an increased frequency of Tfh and GC B cells in Peyer’s Patches (PP), and a decreased frequency of Treg and Tfr cells in these tissues. Interestingly, in mice with a B-cell-specific deletion of the Btla ligand Tnfrsf14 (Hvem), we observe similar increases in GC B cells and Tfh cells and decreased in Treg. Moreover, these mice are characterized by an increase of mucosal IgA bound to bacteria in fecal pellets, indicating a functional outcome of Btla regulation of the GC. Finally, treating wild-type mice with an antibody agonist for Btla increases the frequency of regulatory T cells in PP demonstrating the potential therapeutic effect of activating Btla inhibitory signaling in mucosal immunity. Together, we show that T cell-expressed Btla interacts with B cell-expressed Hvem to regulate GC responses in Peyer’s Patches. A disruption of the balance effector T cell/regulatory T cell is responsible for many inflammatory autoimmune diseases. It will be crucial to understand the role of Btla and its ligand in these populations in mucosal tissues to understand how immunity is regulated, and to develop potential novel therapeutics to treat disease.

SETTING: Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil. OBJECTIVE: To describe the incidence, presentation, treatment and treatment outcomes of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children. DESIGN: Observational study of TB diagnosed in HIV-infected children in 2011–2013. RESULTS: Of 4265 children aged

Summary Background Tuberculosis is the most common serious co-infection in people living with HIV worldwide, but little is known about its incidence in HIV-infected children living in high-resource settings with low tuberculosis prevalence. We aimed to assess the incidence and prevalence of tuberculosis in children with HIV living in the UK and Ireland to understand rates, risk factors, and outcomes of the disease in this group. Methods We did an analysis of children enrolled in CHIPS, an observational multicentre cohort of children receiving HIV care in the UK and Ireland. We assessed characteristics and prevalence of tuberculosis at baseline, measured incidence of disease through the follow-up period using the CHIPS database, and calculated associated risk factors in these children with multivariable logistic and Cox regression models. Findings Between Jan 1, 1996, to Sept 18, 2014, data for 1848 children with 14 761 years of follow-up were reported to CHIPS. 57 (3%) children were diagnosed with tuberculosis: 29 children had tuberculosis at presentation (prevalent tuberculosis) and 29 had the disease diagnosed during follow-up (incident tuberculosis), including one child with recurrent tuberculosis events. Median age at diagnosis was 9 years (IQR 5–12). 25 (43%) children had pulmonary tuberculosis, 24 (41%) had extrapulmonary tuberculosis with or without pulmonary involvement, and the remainder (n=9; 16%) had unspecified-site tuberculosis. The overall incidence rate for the follow-up period was 196 cases per 100 000 person-years (95% CI 137–283). In our multivariable model, tuberculosis at presentation was associated with more severe WHO immunological stage at baseline (odds ratio 0·25, 95% CI 0·08–0·74; p=0·0331; for none vs severe) and being born abroad (odds ratio 0·28, 0·10–0·73; p=0·0036; for UK and Ireland vs abroad). Incident tuberculosis was associated with time-updated more severe WHO immunological stage (hazard ratio 0·15, 95% CI 0·06–0·41; p=0·0056; for none vs severe) and older age at baseline (1·11, 0·47–2·63; p=0·0027; for age >10 years vs 5–9 years). Interpretation Tuberculosis rates in HIV-infected children in the UK and Ireland were higher than those reported in the general paediatric population. Further study is warranted of tuberculosis screening and preventive treatment for children at high-risk of this disease to avoid morbidity and mortality in this population. Funding NHS England, PENTA Foundation.

Three-dimensional whole body scan data from a single static pose of a subject was processed to create a three-dimensional whole body surface model for anthropometric and biomechanical evaluation of space hardware. While this static surface model had benefits over traditional anthropometric measurements, the single scanned posture was not an ideal pose for evaluating the biomechanical requirements of specific tasks. Therefore, the ability to reposition the whole body surface data into various postures without sacrificing the integrity of kinematic parameters (such as segment lengths, widths, depths, etc) was required. The surface data for the upper extremities has been successfully repositioned using a technique that combines thin-plate spline theory and a kinematic model. The accuracy of this technique is being validated by creating representative models of cross-sections near each joint and performing an analysis of the shape and position of each section.

We developed a Wilms' tumor-cell culture system to investigate the molecular basis of nephrogenesis and oncogenesis. Several distinct fractions of cells were isolated and characterized from the same tumor specimen. The cells exhibited striking differences in morphology, immunocytochemical staining profiles and cytogenetics. One fraction contained cells with features of epithelium; other cell fractions resembled partially differentiated mesenchyme (blastema or stroma). While the Wilms' tumor-suppressor gene WT1 was not altered, loss of heterozygosity (LOH) and an insertion in intron I of the p53 tumor-suppressor gene occurred in the tumor and the cultured cell types. LOH for RB was detected only in the cultured cells. These findings are consistent with a model of tumor initiation in a pluripotent cell that is able to undergo subsequent differentiation along multiple different lines and which mimics normal nephrogenesis.

Jennifer, a 3-year-old from Memphis, had laryngeal papilloma of such severity that she required laser surgery every two or three weeks. Tracey, 5 years old, was being treated for asthma in Kansas City and nearly died of asphyxia before laryngeal papilloma was diagnosed. A tracheotomy had to be performed. Chris, 24 years old, is an unusually "old" laryngeal papilloma patient living in St Louis. He had endured countless laryngoscopies and surgical procedures throughout his life, with little hope for a better existence. Until now. These patients are participants in a multi-institutional study to determine the effects of a synthetic interferon-α (Wellferon—made by Burroughs Wellcome Co) in the treatment of laryngeal papilloma. All have shown improvement. Jennifer, in fact, can go more than twice as long between surgeries; after two months, she is only beginning to show signs of relapse. The coordinating center for the study is at the Johns Hopkins

Contains fulltext : 249078.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged