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A summary of data and results from the first neutron images produced by the National Ignition Facility (NIF), Lawrence Livermore National Laboratory, Livermore, CA, USA are presented. An overview of the neutron imaging technique is presented, as well as a synopsis of data and measurements made to date. Data from directly driven, DT filled microballoons, as well as indirectly driven, cryogenically layered ignition experiments are presented. The data show that the primary cores from directly driven implosions are approximately twice as large, 64 ± 3 μm, as indirectly driven cores, 25 ± 4 and 29 ± 4 μm and more asymmetric, P2/P0 = 47% vs. − 14% and 7%. Further, comparison with the size and shape of X-ray image data on the same implosions show good agreement, indicating X-ray emission is dominated by the hot regions of the implosion.

Inertial Confinement Fusion experiments at the National Ignition Facility (NIF) are designed to understand and test the basic principles of self-sustaining fusion reactions by laser driven compression of deuterium-tritium (DT) filled cryogenic plastic (CH) capsules. The experimental campaign is ongoing to tune the implosions and characterize the burning plasma conditions. Nuclear diagnostics play an important role in measuring the characteristics of these burning plasmas, providing feedback to improve the implosion dynamics. The Neutron Imaging (NI) diagnostic provides information on the distribution of the central fusion reaction region and the surrounding DT fuel by collecting images at two different energy bands for primary (13–15 MeV) and downscattered (10–12 MeV) neutrons. From these distributions, the final shape and size of the compressed capsule can be estimated and the symmetry of the compression can be inferred. The first downscattered neutron images from imploding ICF capsules are shown in this paper.

Abstract Background Many older people in long-term care do not receive evidence-based diagnosis or management for heart failure; it is not known whether this can be achieved for this population. We initiated an onsite heart failure service, compared with ‘usual care’ with the aim of establishing the feasibility of accurate diagnosis and appropriate management. Methods A pilot randomised controlled trial which randomised residents from 33 care facilities in North-East England with left ventricular systolic dysfunction (LVSD) to usual care or an onsite heart failure service. The primary outcome was the optimum prescription of angiotensin-converting enzyme inhibitors and beta-adrenergic antagonists at 6 months. Results Of 399 echocardiographically-screened residents aged 65–100 years, 30 subjects with LVSD were eligible; 28 (93%) consented and were randomised (HF service: 16; routine care: 12). Groups were similar at baseline; six month follow-up was completed for 25 patients (89%); 3 (11%) patients died. Results for the primary outcome were not statistically significant but there was a consistent pattern of increased drug use and titration to optimum dose in the intervention group (21% compared to 0% receiving routine care, p=0.250). Hospitalisation rates, quality of life and mortality at 6 months were similar between groups. Conclusions This study demonstrated the feasibility of an on-site heart failure service for older long-term care populations. Optimisation of medication appeared possible without adversely affecting quality of life; this questions clinicians’ concerns about adverse effects in this group. This has international implications for managing such patients. These methods should be replicated in a large-scale study to quantify the scale of benefit. Trial registration ISRCTN19781227 http://www.controlled-trials.com/ISRCTN19781227

Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22). Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

Abstract Background Delay in the diagnosis of tuberculosis (TB) results in excess morbidity and mortality, particularly among HIV-infected individuals. This study was conducted at a secondary level hospital serving communities with a high HIV prevalence in Cape Town, South Africa. The aim was to describe patient and provider delay in the diagnosis of TB in patients with suspected TB requiring admission, and to determine the risk factors for this delay and the consequences. Methods A cross-sectional study was conducted. Patients admitted who were TB suspects were interviewed using a structured questionnaire to assess history of their symptoms and health seeking behaviour. Data regarding TB diagnosis and outcome were obtained from the medical records. Bivariate associations were described using student's T-tests (for means), chi-square tests (for proportions), and Wilcoxon rank-sum tests (for medians). Linear regression models were used for multivariate analysis. Results One hundred twenty-five (125) patients were interviewed. In 104 TB was diagnosed and these were included in the analysis. Seventy of 83 (84%) tested were HIV-infected. Provider delay (median = 30 days, interquartile range (IQR) = 10.3–60) was double that of patient delay (median = 14 days, IQR = 7–30). Patients had a median of 3 contacts with formal health care services before referral. Factors independently associated with longer patient delay were male gender, cough and first health care visit being to public sector clinic (compared with private general practitioner). Patient delay ≥ 14 days was associated with increased need for transfer to a TB hospital. Provider delay ≥ 30 days was associated with increased mortality. Conclusion Delay in TB diagnosis was more attributable to provider than patient delay, and provider delay was associated with increased mortality. Interventions to expedite TB diagnosis in primary care need to be developed and evaluated in this setting.

Abstract Background Childhood injury is the leading cause of mortality, morbidity and permanent disability in children in the developed world. This research examines relationships between socio-economic status (SES), demographics, and types of childhood injury in the province of Alberta, Canada. Methods Secondary analysis was performed using administrative health care data provided by Alberta Health and Wellness on all children, aged 0 to 17 years, who had injuries treated by a physician, either in a physician's office, outpatient department, emergency room and/or as a hospital inpatient, between April 1st. 1995 to March 31st. 1996. Thirteen types of childhood injury were assessed with respect to age, gender and urban/rural location using ICD9 codes, and were related to SES as determined by an individual level SES indicator, the payment status of the Alberta provincial health insurance plan. The relationships between gender, SES, rural/urban status and injury type were determined using logistic regression. Results Twenty-four percent of Alberta children had an injury treated by physician during the one year period. Peak injury rates occurred about ages 2 and 13–17 years. All injury types except poisoning were more common in males. Injuries were more frequent in urban Alberta and in urban children with lower SES (receiving health care premium assistance). Among the four most common types of injury (78.6% of the total), superficial wounds and open wounds were more common among children with lower SES, while fractures and dislocations/sprains/strains were more common among children receiving no premium assistance. Conclusion These results show that childhood injury in Alberta is a major health concern especially among males, children living in urban centres, and those living on welfare or have Treaty status. Most types of injury were more frequent in children of lower SES. Analysis of the three types of the healthcare premium subsidy allowed a more comprehensive picture of childhood injury with children whose families are on welfare and those of Treaty status presenting more frequently for an injury-related physician's consultation than other children. This report also demonstrates that administrative health care data can be usefully employed to describe injury patterns in children.

Abstract Background Tuberculosis (TB) is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH) is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH) urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. Methods Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. Results 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0) of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001). In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043). Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007). Belief in INH safety was associated with a positive test (p = 0.021). In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086). Conclusion Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.

We examined the lived experiences of male undergraduates on the campus of a high-research-activity university in the northeastern United States. Interviews with 8 male undergraduates with a grade-point average lower than 2.0 revealed that their poor academic performances resulted from a combination of the following experiences: a disconnect between high school and university academic expectations, adherence to rigid male gender roles, an inability to set priorities and engage with faculty and staff, and the manifestation of mental health issues. We implemented the study as a front-end analysis to understand better these learners and their learning contexts. Recommendations for advising intervention are offered.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease driven by gain-of-function variants in activin receptor–like kinase 2 (ALK2), the most common variant being ALK2R206H. In FOP, ALK2 variants display increased and dysregulated signaling through the bone morphogenetic protein (BMP) pathway resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of BLU-782 (IPN60130), a small-molecule ALK2R206H inhibitor developed for the treatment of FOP. A small-molecule library was screened in a biochemical ALK2 binding assay to identify potent ALK2 binding compounds. Iterative rounds of structure-guided drug design were used to optimize compounds for ALK2R206H binding, ALK2 selectivity, and other desirable pharmacokinetic properties. BLU-782 preferentially bound to ALK2R206H with high affinity, inhibiting signaling from ALK2R206H and other rare FOP variants in cells in vitro without affecting signaling of closely related homologs ALK1, ALK3, and ALK6. In vivo efficacy of BLU-782 was demonstrated using a conditional knock-in ALK2R206H mouse model, where prophylactic oral dosing reduced edema and prevented cartilage and heterotopic ossification (HO) in both muscle and bone injury models. BLU-782 treatment preserved the normal muscle-healing response in ALK2R206H mice. Delayed dosing revealed a short 2-day window after injury when BLU-782 treatment prevented HO in ALK2R206H mice, but dosing delays of 4 days or longer abrogated HO prevention. Together, these data suggest that BLU-782 may be a candidate for prevention of HO in FOP. Editor's summary: Fibrodysplasia ossificans progressiva results in ectopic bone formation through heterotopic ossification (HO), which causes fused joints and early death. Gain-of-function variants in the gene encoding the activin receptor–like kinase 2 (ALK2) protein cause the disorder. Davis et al. screened a library of small-molecule kinase inhibitors and developed a compound, BLU-782, to inhibit ALK2 and prevent HO in a mouse model expressing the most common disease-causing variant of ALK2 in humans. Muscle pinch or bone break caused HO in the mice, and prophylactic treatment with BLU-782 prevented HO formation in the injured tissue. BLU-782 treatment was required starting 2 days after injury and no later than 4 days after injury to prevent HO in these mice. This study characterizes a promising potential therapy to prevent HO in fibrodysplasia ossificans progressiva. —Brandon Berry [ABSTRACT FROM AUTHOR]

This quasiexperimental investigation describes the relative effects of a technology-driven course redesign on retention and achievement in a developmental writing program at a large, urban community college in the southwest United States. The new program focused on student learning and included online as well as face-to-face components that allowed students to complete the program in half the usual time in most cases. On average, students enrolled in the new program had lower placement test scores compared to students in the old program, but the gap was closed in the subsequent test and English course. Details of the redesign and challenges to conducting educational research and data analysis in community colleges are provided for other 2-year colleges considering course redesigns intended to impact student success.

The purpose of this study was to understand the experience of students as they progressed through three specific online graduate courses in health promotion studies delivered primarily by asynchronous computer conferencing. Focused teleconference discussions were conducted with approximately 45 students from the different courses and the transcripts subjected to qualitative analysis. Themes that emerged included what new students appreciated most when adapting to learning online, factors that contributed to learner satisfaction, and the difficulties encountered by students taking a course when the content was not as well suited to the instructional method. The findings are discussed in relation to the three components of Garrison, Anderson and Archer's (2000) Community of Inquiry model of learning: cognitive, social and teacher presence. Implications are presented for assisting students with the process of adapting to online learning and enhancing the "fit" between course content and online instructional methods.

Author(s): Tami D Lieberman [1, 2]; Douglas Wilson [3]; Reshma Misra [4]; Lealia L Xiong [1]; Prashini Moodley [4]; Ted Cohen (corresponding author) [5, 6, 7]; Roy Kishony (corresponding author) [...]