The First Act

The First Act is a creative thesis which explores the boundaries of biography and autobiography, fact and fiction, as the life of my mother, Deborah Wolfe, and my own, intersect in prose and drama. My purpose in writing this thesis was to examine and seek an understanding of my own relationship with the past and the present, as I explored the roots of my family history, specifically through the eyes of my mother, while using aspects of my family’s West Virginian and Mormon heritage. By reading the following story, you will, in a way, go on that journey with me and my mother, and will provide us with an audience to listen to the voice of the hidden feminine psyches found within my mother and within myself

A Systematic Review of Research Syntheses for Students with Mathematics Learning Disabilities and Difficulties

The purpose of this document is to provide readers with the coding protocol that authors used to code 36 research syntheses (including meta-analyses, evidence-based reviews, and quantitative systematic reviews) focused on mathematics interventions for students with learning disabilities (LD), mathematics learning disabilities (MLD), and mathematics difficulties (MD). The purpose of the systematic review of mathematics intervention syntheses was to identify patterns and gaps in content areas, instructional strategies, effect sizes, and definitions of LD, MLD, and MD. We searched the literature for research syntheses published between 2000 and 2020 and used rigorous inclusion criteria in our literature review process. We evaluated 36 syntheses that included 836 studies with 32,495 participants. We coded each synthesis for variables across seven categories including: publication codes (authors, year, journal), inclusion and exclusion criteria, content area focus, instructional strategy focus, sample size, methodological information, and results. The mean interrater reliability across all codes using this coding protocol was 90.3%. Although each synthesis stated a focus on LD, MLD, or MD, very few students with LD or MLD were included, and authors’ operational definitions of disability and risk varied. Syntheses predominantly focused on word problem solving, fractions, computer- assisted learning, and schema-based instruction. Syntheses reported wide variation in effectiveness, content areas, and instructional strategies. Finally, our results indicate the majority of syntheses report achievement outcomes, but very few syntheses report on other outcomes (e.g., social validity, strategy use). We discuss how the results of this comprehensive review can guide researchers in expanding the knowledge base on mathematics interventions. The systematic review that results from this coding process is accepted for publication and in press at Learning Disabilities Research and Practice

Forecasting scenarios for UK household expenditure and associated GHG emissions : Outlook to 2030

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Incidence and Predictors of Pregnancy among a Cohort of HIV-Positive Women Initiating Antiretroviral Therapy in Mbarara, Uganda

Objective: Many people living with HIV in sub-Saharan Africa desire biological children. Implementation of HIV preventionstrategies that support the reproductive goals of people living with HIV while minimizing HIV transmission risk to sexualpartners and future children requires a comprehensive understanding of pregnancy in this population. We analyzedprospective cohort data to determine pregnancy incidence and predictors among HIV-positive women initiatingantiretroviral therapy (ART) in a setting with high HIV prevalence and fertility.Methods:Participants were enrolled in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort of HIV-positiveindividuals initiating ART in Mbarara. Bloodwork (including CD4 cells/mm3, HIV viral load) and questionnaires (includingsocio-demographics, health status, sexual behavior, partner dynamics, HIV history, and self-reported pregnancy) werecompleted at baseline and quarterly. Our analysis includes 351 HIV-positive women (18–49 years) who enrolled between2005–2011. We measured pregnancy incidence by proximal and distal time relative to ART initiation and used multivariableCox proportional hazards regression analysis (with repeated events) to identify baseline and time-dependent predictors ofpregnancy post-ART initiation.Results:At baseline (pre-ART initiation), median age was 33 years [IQR: 27–37] and median prior livebirths was four [IQR: 2–6]. 38% were married with 61% reporting HIV-positive spouses. 73% of women had disclosed HIV status to a primary sexualpartner. Median baseline CD4 was 137 cells/mm3[IQR: 81–207]. At enrolment, 9.1% (31/342) reported current pregnancy.After ART initiation, 84 women experienced 105 pregnancies over 3.8 median years of follow-up, yielding a pregnancyincidence of 9.40 per 100 WYs. Three years post-ART initiation, cumulative probability of at least one pregnancy was 28%and independently associated with younger age (Adjusted Hazard Ratio (AHR): 0.89/year increase; 95%CI: 0.86–0.92) and HIVserostatus disclosure to primary sexual partner (AHR: 2.45; 95%CI: 1.29–4.63).Conclusions:Nearly one-third of women became pregnant within three years of initiating ART, highlighting the need forintegrated services to prevent unintended pregnancies and reduce periconception-related risks for HIV-infected womenchoosing to conceive. Association with younger age and disclosure suggests a role for early and couples-based safer conception counselling

Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density

BACKGROUND: Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge. METHODS: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia. RESULTS: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities. CONCLUSION: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density

Comparing the Costs and Acceptability of Three Fidelity Assessment Methods for Assertive Community Treatment

Successful implementation of evidence-based practices requires valid, yet practical fidelity monitoring. This study compared the costs and acceptability of three fidelity assessment methods: on-site, phone, and expert-scored self-report. Thirty-two randomly selected VA mental health intensive case management teams completed all fidelity assessments using a standardized scale and provided feedback on each. Personnel and travel costs across the three methods were compared for statistical differences. Both phone and expert-scored self-report methods demonstrated significantly lower costs than on-site assessments, even when excluding travel costs. However, participants preferred on-site assessments. Remote fidelity assessments hold promise in monitoring large scale program fidelity with limited resources

A comparison of liquid and solid culture for determining relapse and durable cure in phase III TB trials for new regimens

Supported by the Global Alliance for TB Drug Development with support from the Bill & Melinda Gates Foundation, the Medical Research Council (MC_UU_12023/27), the European and Developing Countries Clinical Trials Partnership (grant IP.2007.32011.011), the US Agency for International Development, the UK Department for International Development, the Directorate General for International Cooperation of the Netherlands, Irish Aid, the Australia Department of Foreign Affairs and Trade and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636 and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin; and Sanofi for the donation of rifampin. Additional grants were from Chief Scientist Office, Scottish Government, British Society of Antimicrobial Chemotherapy.Background:  Tuberculosis kills more people than any other infectious disease, and new regimens are essential. The primary endpoint for confirmatory phase III trials for new regimens is a composite outcome that includes bacteriological treatment failure and relapse. Culture methodology is critical to the primary trial outcome. Patients in clinical trials can have positive cultures after treatment ends that may not necessarily indicate relapse, which was ascribed previously to laboratory cross-contamination or breakdown of old lesions. Löwenstein-Jensen (LJ) medium was the previous standard in clinical trials, but almost all current and future trials will use the Mycobacteria Growth Indicator Tube (MGIT) system due to its simplicity and consistency of use, which will affect phase III trial results. LJ was used for the definition of the primary endpoint in the REMoxTB trial, but every culture was also inoculated in parallel into the MGIT system. The data from this trial, therefore, provide a unique opportunity to investigate and compare the incidence of false ‘isolated positives’ in liquid and solid media and their potential impact on the primary efficacy results. Methods:  All post-treatment positive cultures were reviewed in the REMoxTB clinical trial. Logistic regression models were used to model the incidence of isolated positive cultures on MGIT and LJ. Results:  A total of 12,209 sputum samples were available from 1652 patients; cultures were more often positive on MGIT than LJ. In 1322 patients with a favourable trial outcome, 126 (9.5%) had cultures that were positive in MGIT compared to 34 (2.6%) patients with positive cultures on LJ. Among patients with a favourable outcome, the incidence of isolated positives on MGIT differed by study laboratory (p < 0.0001) with 21.9% of these coming from one laboratory investigating only 4.9% of patients. No other baseline factors predicted isolated positives on MGIT after adjusting for laboratory. There was evidence of clustering of isolated positive cultures in some patients even after adjusting for laboratory, p < 0.0001. The incidence of isolated positives on MGIT did not differ by treatment arm (p = 0.845, unadjusted). Compared to negative MGIT cultures, positive MGIT cultures were more likely to be associated with higher grade TB symptoms reported within 7 days either side of sputum collection in patients with an unfavourable primary outcome (p < 0.0001) but not in patients with a favourable outcome (p = 0.481). Conclusions:  Laboratory cross-contamination was a likely cause of isolated positive MGIT cultures which were clustered in some laboratories. Certain patients had repeated positive MGIT cultures that did not meet the definition of a relapse. This pattern was too common to be explained by cross-contamination only, suggesting that host factors were also responsible. We conclude that MGIT can replace LJ in phase III TB trials, but there are implications for the definition of the primary outcome and patient management in trials in such settings. Most importantly, the methodologies differ in the incidence of isolated positives and in their capacity for capturing non-tuberculosis mycobacteria. It emphasises the importance of effective medical monitoring after treatment ends and consideration of clinical signs and symptoms for determining treatment failure and relapse.Publisher PDFPeer reviewe

Trauma-induced coagulopathy

Acknowledgements E.E.M. and A.S. appreciate the generous support from the National Institutes of Health for their inflammation and coagulation research over the past 35 years (NIGMS: 1-6 P50 GM49222, 1-6 T32 GM08315, 1-2 U54 GM 62119, RM1 GM 131968 and NHLBI: UM1 HL120877). H.B.M. acknowledges the generous support from the National Institutes of Health (NHBLI: K99HL1518870) L.Z.K. acknowledges the generous support from the National Institutes of Health for her platelet biology research (NIGMS: K23GM130892-01). M.D.N. acknowledges the generous support by the National Institutes of Health (NIGMS: R35 GM119526 and NHLBI R01 HL141080).Peer reviewedPostprin