A case series study on the effect of Ebola on facility-based deliveries in rural Liberia

Abstract Background As communities’ fears of Ebola virus disease (EVD) in West Africa exacerbate and their trust in healthcare providers diminishes, EVD has the potential to reverse the recent progress made in promoting facility-based delivery. Using retrospective data from a study focused on maternal and newborn health, this analysis examined the influence of EVD on the use of facility-based maternity care in Bong Country, Liberia, which shares a boarder with Sierra Leone - near the epicenter of the outbreak. Methods Using a case series design, retrospective data from logbooks were collected at 12 study sites in one county. These data were then analyzed to determine women’s use of facility-based maternity care between January 2012 and October 2014. The primary outcome was the number of facility-based deliveries over time. The first suspected case of EVD in Bong County was reported on June 30, 2014. Heat maps were generated and the number of deliveries was normalized to the average number of deliveries during the full 12 months before the EVD outbreak (March 2013 – February 2014). Results Prior to the EVD outbreak, facility-based deliveries steadily increased in Bong County reaching an all-time high of over 500 per month at study sites in the first half of 2014 – indicating Liberia was making inroads in normalizing institutional maternal healthcare. However, as reports of EVD escalated, facility-based deliveries decreased to a low of 113 in August 2014. Conclusion Ebola virus disease has negatively impacted the use of facility-based maternity services, placing childbearing women at increased risk for morbidity and death.http://deepblue.lib.umich.edu/bitstream/2027.42/114384/1/12884_2015_Article_694.pd

The DANTE trial protocol: a randomised phase III trial to evaluate the Duration of ANti-PD-1 monoclonal antibody Treatment in patients with metastatic mElanoma.

BACKGROUND: Immunotherapy is revolutionising the treatment of patients diagnosed with melanoma and other cancers. The first immune checkpoint inhibitor, ipilimumab (targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4)), showed a survival advantage over standard chemotherapy. Subsequently the anti-programmed cell death protein 1 (PD-1) antibodies, nivolumab and pembrolizumab were shown to be more effective than ipilimumab. Ipilimumab combined with nivolumab gives an incremental gain in overall survival compared with nivolumab alone but increases the risk of severe, potentially life-threatening toxicities. In contrast to ipilimumab monotherapy, anti-PD-1 antibodies are licensed to be continued until disease progression. Follow-up of patients recruited to the first trials evaluating 2 years of pembrolizumab showed that three-quarters of responding patients continue responding after stopping treatment. Suggestive of early response, we hypothesised that continuing anti-PD-1 treatment beyond 1 year in progression-free patients may be unnecessary and so designed the DANTE trial. METHODS: DANTE is a multicentre, randomised, phase III, non-inferiority trial to evaluate the duration of anti-PD-1 therapy in patients with metastatic (unresectable stage III and stage IV) melanoma. It uses a two-stage recruitment strategy, registering patients before they complete 1 year of first-line anti-PD-1 +/- CTLA-4 therapy and randomising eligible patients who have received 12 months of treatment and are progression-free at 1 year. At randomisation, 1208 patients are assigned (1:1) to either 1) continue anti-PD-1 treatment until disease progression/ unacceptable toxicity/ for at least 2 years in the absence of disease progression/ unacceptable toxicity or 2) to stop treatment. Randomisation stratifies for baseline prognostic factors. The primary outcome is progression-free survival at 3, 6, 9 and 12 months and then, 6-monthly for up to 4-years. Secondary outcomes collected at all timepoints include overall survival, response-rate and duration and safety, with quality of life and cost-effectiveness outcomes collected 3-monthly for up to 18-months. Sub-studies include a qualitative analysis of patient acceptance of randomisation and sample collection to inform future translational studies into response/ toxicity biomarkers. DISCUSSION: DANTE is a unique prospective trial investigating the optimal duration of anti-PD-1 therapy in metastatic melanoma patients. Outcomes will inform future use of these high burden drugs. TRIAL REGISTRATION: ISRCTN15837212 , 31 July 2018

I’m not joking! The strategic use of humour in stories of racism

This study examines the use of humour by Black football coaches in England as a rhetorical device against racism. The paper draws on humour studies and critical race theory to illustrate signs of humour as defence. Research on humour has popularly explored the ambiguities and qualities of humour and, in particular, joke telling through its use as a foil to stem racial ills is less well understood. Where previous work has focused on explicit joke telling/banter in sport, this paper examines how techniques of humour are used in everyday racialised experiences. The use of techniques of humour enables feelings of subordination, and humiliation to be transposed into forms of resistance, while its physiological and psychological benefits can lead to inter-racial relief and catharsis. The paper concludes that techniques of humour remain underexplored as important tools of resistance to everyday racism

Effectiveness of a nurse-led intensive home-visitation programme for first-time teenage mothers (Building Blocks):a pragmatic randomised controlled trial

SummaryBackgroundMany countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children. The Family Nurse Partnership (FNP) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in England that involves up to 64 structured home visits from early pregnancy until the child's second birthday by specially recruited and trained family nurses. We aimed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth.MethodsWe did a pragmatic, non-blinded, randomised controlled, parallel-group trial in community midwifery settings at 18 partnerships between local authorities and primary and secondary care organisations in England. Eligible participants were nulliparous and aged 19 years or younger, and were recruited at less than 25 weeks' gestation. Field-based researchers randomly allocated mothers (1:1) via remote randomisation (telephone and web) to FNP plus usual care (publicly funded health and social care) or to usual care alone. Allocation was stratified by site and minimised by gestation (<16 weeks vs ≥16 weeks), smoking status (yes vs no), and preferred language of data collection (English vs non-English). Mothers and assessors (local researchers at baseline and 24 months' follow-up) were not masked to group allocation, but telephone interviewers were blinded. Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy, birthweight of the baby, the proportion of women with a second pregnancy within 24 months post-partum, and emergency attendances and hospital admissions for the child within 24 months post-partum. Analyses were by intention to treat. This trial is registered with ISRCTN, number ISRCTN23019866.FindingsBetween June 16, 2009, and July 28, 2010, we screened 3251 women. After enrolment, 823 women were randomly assigned to receive FNP and 822 to usual care. All follow-up data were retrieved by April 25, 2014. 304 (56%) of 547 women assigned to FNP and 306 (56%) of 545 assigned to usual care smoked at late pregnancy (adjusted odds ratio [AOR] 0·90, 97·5% CI 0·64–1·28). Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g (SD 618·0), whereas birthweight of 768 babies assigned to usual care was 3197·5 g (SD 581·5; adjusted mean difference 20·75 g, 97·5% CI −47·73 to 89·23. 587 (81%) of 725 assessed children with mothers assigned to FNP and 577 (77%) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday (AOR 1·32, 97·5% CI 0·99–1·76). 426 (66%) of 643 assessed women assigned to FNP and 427 (66%) 646 assigned to usual care had a second pregnancy within 2 years (AOR 1·01, 0·77–1·33). At least one serious adverse event (mainly clinical events associated with pregnancy and infancy period) was reported for 310 (38%) of 808 participants (mother–child) in the usual care group and 357 (44%) of 810 in the FNP group, none of which were considered related to the intervention.InterpretationAdding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes. Programme continuation is not justified on the basis of available evidence, but could be reconsidered should supportive longer-term evidence emerge.FundingDepartment of Health Policy Research Programme

Implicit and explicit pedagogical practices related to sociocultural issues and social justice in physical education teacher education programs

Background: For many years, scholars in PETE have argued for the importance of educating pre-service teachers (PSTs) about equality (e.g., Evans 1990), sociocultural perspectives and issues (e.g., Cliff, Wright and Clarke, 2009; Author 2014) and critical pedagogy (e.g., Fernandez-Balboa 1997; Philpot 2015). Despite this advocacy, we would argue that there are significant differences in how faculty teach about sociocultural issues, and for, social justice. The pedagogical actions through which Physical Education Teacher Educators (PETEs) do this work is the focus of this paper. Purpose: We investigated the pedagogical approaches and strategies used by PETE faculty to address and educate PSTs about social justice and sociocultural issues related to gender, race, sexuality, (dis)ability, socioeconomic status and religion in their individual PETE programs. In this study, we draw on transformational pedagogy (Ukpokodu 2009; Ovens 2017) as a framework for theorizing the data. Through this study, we highlight the pedagogical practices espoused as those that engender transformative learning. Data collection and analysis: Data for this interpretive qualitative research study was collected primarily through in-depth semi-structured interviews with over 70 PETEs who work in 48 PETE programs across Australia, Canada, England, Ireland New Zealand, Sweden, and the United States. Furthermore, an informational survey was used to gather demographic data of the participants. The participants, all current PETEs, had a wide range of professional experiences, which included the length of time in the profession, the type of institution employed, educational backgrounds and courses taught. Data analysis was completed using the processes of content analysis and the constant comparative method (Corbin and Strauss 2008). Findings: Three major themes represent the findings. In the first theme, ‘Intentional and Explicit Pedagogies’ we provide descriptions of the approaches and strategies used by PETEs in this study that were planned in advance of the learning experiences. In the second theme, ‘Teachable Moments’ we provide examples of how PETEs utilized ‘teachable moments’ in implicit and explicit ways to educate PSTs about sociocultural issues. The third theme, ‘Resistance and Constraints’ captures the individual challenges PETE faculty faced within their courses if, and when, they teach for equity and social justice. The findings suggest that social justice struggles to find an explicit presence within many PETE programs and that educating PSTs about sociocultural issues and social justice is lacking in many PETE programs

Conceptualising social justice and sociocultural issues within physical education teacher education: international perspectives

Background: Physical education (PE) and physical education teacher education (PETE) have a substantial literature base that advocates for students to develop a critical consciousness, appreciate multiple perspectives, and engage in actions to enhance social justice (Tinning 2016). Analysing sociocultural issues, critically reflecting on beliefs, knowledge, biography and values, and developing a sense of agency to enact change, have been recognised as an integral part of the PETE knowledge base for some time (Fernández-Balboa 1997). However, there remain differences in how social justice itself is conceptualised and enacted. Social justice is aligned heavily with critical and ‘post’ theories where taking action for justice, democracy and power are central; but social justice is also found in humanist beliefs in student-centredness and equality and has been co-opted by neoliberal forces that promote individual responsibility. While a lack of consensus is not in itself a problem (Bialystok 2014), diverse definitions might contribute to confusion (Randall and Robinson 2016) and lead to uncertainty over what and how to teach for social justice. Purpose: In order to work towards greater certainty around concepts of social justice in the PETE community, this project sought to map variations in definition and conceptualisation of social justice and sociocultural issues among physical education teacher educators (PETEs) and physical education and sport pedagogy (PESP) educators, as part of a wider project on social justice and sociocultural perspectives and practices in PETE. Methods: PETE and PESP faculty (n=72) in North America, Europe, and Australasia engaged in an in-depth interview, during which they were asked how they define social justice and sociocultural issues. Additional information about participants’ social identity was collected. A constant comparative method of analysing participants’ definitions mapped a range of concepts building on the theoretical framework of neoliberal, humanist, critical and ‘post’ approaches to social justice. Findings: The data demonstrate that there are a range of understandings about sociocultural issues and social justice. Most commonly, some participants articulated a humanist approach to social justice by encouraging their pre-service teachers (PSTs) to have awareness of equality of opportunity in relation to gender, sexuality and/or racism. Less prevalent, but strongly stated by those who conceptualised social justice in these terms, was the importance to take action for democracy, empowerment or critical reflection. The terms diversity and equality, framed in neoliberal and humanist discourses, were most commonly used within the United States (US), while critical pedagogy and alignment with critical and ‘post’ theories were more prevalent in Australia and New Zealand. Conclusion: Differences exist in the ways social justice is conceptualised in PETE. While this can be attributed to the influence of local issues, it is also reflective of what intellectual tools, such as humanism or critical theory, are available for problematising social issues. The range of non-critical concepts found raises concern that PSTs are not getting the tools to enact social justice or tackle sociocultural issues.

Valacyclovir in the treatment of acute retinal necrosis

Background: To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN). Methods: This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease. Results: Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks). Conclusions: Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovi

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN