Long Duration Exposure Facility (LDEF) structural verification test report

Structural load tests on the Long Duration Exposure Facility's (LDEF) primary structure were conducted. These tests had three purposes: (1) demonstrate structural adequacy of the assembled LDEF primary structure when subjected to anticipated flight loads; (2) verify analytical models and methods used in loads and stress analysis; and (3) perform tests to comply with the Space Transportation System (STS) requirements. Test loads were based on predicted limit loads which consider all flight events. Good agreement is shown between predicted and observed load, strain, and deflection data. Test data show that the LDEF structure was subjected to 1.2 times limit load to meet the STS requirements. The structural adequacy of the LDEF is demonstrated

Antibiotic resistance among clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013

Ureaplasma spp. are associated with numerous clinical sequelae with treatment options being limited due to patient and pathogen factors. This report examines the prevalence and mechanisms of antibiotic resistance among clinical strains isolated from 95 neonates, 32 women attending a sexual health clinic, and 3 patients under investigation for immunological disorders, between 2007 and 2013 in England and Wales. MICs were determined by using broth microdilution assays, and a subset of isolates were compared using the broth microdilution method and the Mycoplasma IST2 assay. The underlying molecular mechanisms for resistance were determined for all resistant isolates. Three isolates carried the tet(M) tetracycline resistance gene (2.3%; confidence interval [CI], 0.49 to 6.86%); two isolates were ciprofloxacin resistant (1.5%; CI, 0.07 to 5.79%) but sensitive to levofloxacin and moxifloxacin, while no resistance was seen to any macrolides tested. The MIC values for chloramphenicol were universally low (2 μg/ml), while inherently high-level MIC values for gentamicin were seen (44 to 66 μg/ml). The Mycoplasma IST2 assay identified a number of false positives for ciprofloxacin resistance, as the method does not conform to international testing guidelines. While antibiotic resistance among Ureaplasma isolates remains low, continued surveillance is essential to monitor trends and threats from importation of resistant clones

MYCO WELL D-ONE detection of Ureaplasma spp. and Mycoplasma hominis in sexual health patients in Wales

The genital mycoplasmas are a unique group of inherently antibiotic-resistant sexually transmitted bacteria, often associated with non-gonococcal urethritis and bacterial vaginosis. The MYCO WELL D-ONE is a culture-based assay that aims to detect these organisms whilst concurrently screening them for antibiotic resistance. Urine and/or swabs from 856 informed and consented participants attending Welsh sexual health clinics were subjected to MYCO WELL D-ONE analysis, alongside qPCR and culture titration methodologies to determine sensitivity, specificity, PPV, NPV and accuracy. Resistance was confirmed by CLSI-compliant susceptibility testing and genetic mechanisms determined. The MYCO WELL D-ONE displayed a sensitivity and specificity of 91.98% and 96.44% for the detection of Ureaplasma spp., with sensitivity and specificity values of 78.23% and 98.84% for Mycoplasma hominis, compared with qPCR. Swabs harboured significantly greater bacterial loads than urine samples for both Ureaplasma spp. and M. hominis. Levofloxacin resistance rates, mediated by Ser83Leu mutation in ParC, for Ureaplasma spp. were 0.54%. Tetracycline resistance rates, mediated by tet(M), were 0.54% and 2% for Ureaplasma spp. and M. hominis, respectively; sequence analysis of tet(M)-positive Ureaplasma spp. and M. hominis strains isolated from a single individual confirmed separate resistance gene origins. The MYCO WELL D-ONE is a sensitive and specific assay for the detection of Ureaplasma spp. and M. hominis in genitourinary medicine samples, facilitating the accurate detection of these organisms within low-technology environments. While good for antibiotic resistance screening, accurate confirmation by MIC determination or molecular methods are required, and more optimally performed on urine samples

Access to Educational Opportunities for Latino Students in Four Massachusetts School Districts

This report was prompted by the pressing concerns over the high failure rates of Latino students on the Massachusetts Comprehensive Assessment System (MCAS) exam. While 27% of White students failed the English portion of the MCAS test and 38% failed the Mathematics portion in 2000, the corresponding rates for Latino students were 66% and 79% respectively (Massachusetts Department of Education, 2000a). There is a great urgency to understand why Latino students score substantially behind students from other racial/ethnic groups. This urgency stems from the reality that students currently enrolled in the 10th grade will be required to pass this exam in order to receive a high school diploma in 2003

Access to and experience of later abortion: accounts from women in Scotland

Context: Except in the presence of significant medical indications, the legal limit for abortion in Great Britain is 24 weeks’ gestation. Nevertheless, abortion for nonmedical reasons is not usually provided in Scotland after 18–20 weeks, meaning women have to travel to England for the procedure. Methods: In-depth interviews were conducted with 23 women presenting for "later" abortions (i.e., at 16 or more weeks’ gestation) in Scotland. Participants were women who sought an abortion at a participating National Health Service clinic between January and July 2013. Interviews addressed reasons for and consequences of later presentation, as well as women's experiences of abortion. Thematic analysis attended to emerging issues and employed the conceptual tool of candidacy. Results: Delayed recognition of pregnancy, changed life circumstances and conflicting candidacies for motherhood and having an abortion were common reasons for women's presentation for later abortion. Women perceived that the resources required to travel to England for a later abortion were potential barriers to access, and felt that such travel was distressing and stigmatizing. Participants who continued their pregnancy did so after learning they were at a later gestational age than expected or after receiving assurances of support from partners, friends or family. Conclusions: Reasons for seeking later abortion are complex and varied among women in Scotland, and suggest that reducing barriers to access and improving local provision of such abortions are a necessity. The candidacy framework allows for a fuller understanding of the difficulties involved in obtaining abortions

Development of core outcome sets for people undergoing major lower limb amputation for complications of peripheral vascular disease

Objective Every year, thousands of patients with peripheral vascular disease undergo major lower limb amputation. Despite this, evidence for optimal management is weak. Core outcome sets capture consensus on the most important outcomes for a patient group to improve the consistency and quality of research. The aim was to define short and medium term core outcome sets for studies involving patients undergoing major lower limb amputation. Methods A systematic review of the literature and focus groups involving patients, carers, and healthcare professionals were used to derive a list of potential outcomes. Findings informed a three round online Delphi consensus process, where outcomes were rated for both short and medium term studies. The results of the Delphi process were discussed at a face to face consensus meeting, and recommendations were made for each core outcome set. Results A systematic review revealed 45 themes to cazrry forward to the consensus survey. These were supplemented by a further five from focus groups. The consensus survey received responses from 123 participants in round one, and 91 individuals completed all three rounds. In the final round, nine outcomes were rated as “core” for short term studies and a further nine for medium term studies. Wound infection and healing were rated as “core” for both short and medium term studies. Outcomes related to mortality, quality of life, communication, and additional healthcare needs were also rated as “core” for short term studies. In medium term studies, outcomes related to quality of life, mobility, and social integration/independence were rated as “core”. The face to face stakeholder meeting ratified inclusion of all outcomes from the Delphi and suggested that deterioration of the other leg and psychological morbidity should also be reported for both short and medium term studies. Conclusion Consensus was established on 11 core outcomes for short and medium term studies. It is recommended that all future studies involving patients undergoing major lower limb amputation should report these outcomes

Early Postnatal Discharge for Infants: A Meta-analysis

CONTEXT: Postnatal length of hospital stay has reduced internationally but evidence-based abstract policies to support earlier discharge are lacking. OBJECTIVE: To determine the effects of early postnatal discharge on infant outcomes. DATA SOURCES: CENTRAL (Cochrane Central Register of Controlled Trials), Medline, Embase, Cumulative Index to Nursing and Allied Health Literature , and SCI (Science Citation Index) were searched through to January 15, 2018. STUDY SELECTION: Studies reporting infant outcomes with early postnatal discharge versus standard discharge were included if they met Effective Practice and Organisation of Care study design criteria. DATA EXTRACTION: Two authors independently assessed eligibility and extracted data, resolving disagreements by consensus. Data from interrupted time series (ITS) studies were extracted and reanalyzed in meta-analyses. Meta-analyses of randomized controlled trials (RCTs) used random effects models. RESULTS: Of 9298 studies, 15 met the inclusion criteria. RCT meta-analyses revealed that infants discharged ,48 hours after vaginal birth and ,96 hours after cesarean birth were more likely to be readmitted to the hospital within 28 days compared to standard discharge (risk ratio: 1.70; 95% confidence interval [CI] 1.34 to 2.15). ITS meta-analyses revealed a reduction in the proportion of infants readmitted within 28 days after minimum postnatal stay policies and legislation were introduced (change in slope: 20.62; 95% CI 21.83 to 0.60), with increasing impact in the first and second years (effect estimate: 24.27 [95% CI 27.91 to 20.63] and 26.23 [95% CI 210.15 to 22.32]). LIMITATIONS: Withdrawals and crossover limited the value of RCTs in this context but not ITS evidence. CONCLUSIONS: Infants discharged early after birth were more likely to be admitted within 28 days. The introduction of postnatal minimum length of stay policies was associated with a longterm reduction in neonatal hospital readmission rates

Perceptions of long-term impact and change following a midwife-led biomass smoke education program for mothers in rural Uganda: a qualitative study

Introduction: Women and children in Uganda and other low- and middle-income countries are exposed to disproportionately high levels of household air pollution from biomass smoke generated by smoke-producing cookstoves, especially in rural areas. This population is therefore particularly vulnerable to the negative health effects caused by household air pollution, including negative pregnancy outcomes and other health issues throughout life. The Midwife Project, a collaboration between research and health teams in the UK and Uganda, began in 2016 to implement an education program on lung health for mothers in Uganda, to reduce the health risks to women and children. Education materials were produced to guide midwives in the delivery of health messages across four rural health centres, and mixed-methods results of knowledge questionnaires and interviews demonstrated knowledge acquisition, acceptability and feasibility. This qualitative follow-up study aimed to improve understanding of the longer term impact of this education program from the perspective of midwives, village health team members and mothers, in consideration of rolling the program out more widely in rural Uganda. Methods: Purposive sampling was carried out to recruit consenting antenatal or postnatal women, midwives and village health team members who had been involved in an education session. Individual interviews were conducted with 12 mothers and four village health team members, and four focus groups were conducted with 10 midwives in total. Interviews and focus groups were conducted across all four health centres by two researchers and six translators as appropriate depending on language spoken (English or Lusoga). These were semi-structured and directed by topic guides. Reflective and observational notes were also made. A thematic analysis was carried out by two researchers, along with production of a narrative for each mother, to enrich understanding of each individual story. Results: Midwives and village health teams had continued with the program well past the project end date and all mothers expressed making, or intending to make, changes, suggesting long-term feasibility and acceptability. Main themes generated were ability to change and changes made, ability to change dictated by money, importance of practical education, perceived health improvements, and passing on knowledge. Additional findings were that some education topics seemed to be overlooked, and there was a lack of clarity about the village health team role for the purposes of this program. Some mothers had been motivated to overcome financial barriers, for example by reconstructing cooking areas cheaply themselves. However, information given in the program about building advice and potential financial gains was inconsistent. Conclusion: Recommendations for future biomass smoke education should include explicit building advice, emphasis on financial gains, encouragement to share the knowledge acquired and clarification of the village health team role. These program changes will improve focus and relevancy, optimise impact and, with behaviour change and implementation strategy in mind, could be used for widespread rollout in rural Uganda. Future research should include quantitative data collection to objectively examine surprising perceived health benefits, including reduction in malaria and burns, and further qualitative work on why some education content appears neglected

T Cell Cross-Reactivity and Conformational Changes during TCR Engagement

All thymically selected T cells are inherently cross-reactive, yet many data indicate a fine specificity in antigen recognition, which enables virus escape from immune control by mutation in infections such as the human immunodeficiency virus (HIV). To address this paradox, we analyzed the fine specificity of T cells recognizing a human histocompatibility leukocyte antigen (HLA)-A2–restricted, strongly immunodominant, HIV gag epitope (SLFNTVATL). The majority of 171 variant peptides tested bound HLA-A2, but only one third were recognized. Surprisingly, one recognized variant (SLYNTVATL) showed marked differences in structure when bound to HLA-A2. T cell receptor (TCR) recognition of variants of these two peptides implied that they adopted the same conformation in the TCR–peptide–major histocompatibility complex (MHC) complex. However, the on-rate kinetics of TCR binding were identical, implying that conformational changes at the TCR–peptide–MHC binding interface occur after an initial permissive antigen contact. These findings have implications for the rational design of vaccines targeting viruses with unstable genomes

VER-155008 induced Hsp70 proteins expression in fish cell cultures while impeding replication of two RNA viruses

The final publication is available at Elsevier via https://doi.org/10.1016/j.antiviral.2019.01.001 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The heat-shock protein 70 (Hsp70) inhibitor, VER-155008 (VER), was explored as a potential antiviral agent for two RNA viruses important to fish aquaculture, viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Studies were done at a temperature of 14 °C, and with cell lines commonly used to propagate these viruses. These were respectively EPC from fathead minnow for VHSV and CHSE-214 from Chinook salmon embryo for IPNV. Additionally, both viruses were studied with the Atlantic salmon heart endothelial cell line ASHe. For both VHSV and IPNV, 25 μM VER impeded replication. This was evidenced by delays in the development of cytopathic effect (CPE) and the expression of viral proteins, N for VHSV and VP2 for IPNV, and by less production of viral RNA and of viral titre. As VER inhibits the activity of Hsp70 family members, these results suggest that VHSV and IPNV utilize one or more Hsp70s in their life cycles. Yet neither virus induced Hsp70. Surprisingly VER alone induced Hsp70, but whether this induction modulated VER's antiviral effects is unknown. Exploring this apparent paradox in the future should improve the usefulness of VER as an antiviral agent.Natural Science and Engineering Research Council, Grant 468298 - 14Elanco Canada Limite