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© 2020 Viol et al.OBJECTIVES An unexpected drug-drug interaction has been recently reported between dolutegravir, an HIV integrase inhibitor, and valproic acid. Despite there being several potential underlying mechanisms, plasma protein displacement has been suggested. The aim of this study was to assess plasma concentrations of several antiretrovirals when administered with or without valproic acid. METHODS We performed a therapeutic drug monitoring registry analysis and identified patients concomitantly taking antiretrovirals and valproic acid and without clinical affecting conditions or interacting drugs. RESULTS One hundred and thirty-four patients were identified. Median (IQR) age and BMI were 49.7 years (45-56) and 23.4 kg/m2 (20.8-26.3) and 78 were male (58.2%). Despite small groups, we observed no major effect on antiretroviral exposure, even when considering highly protein-bound compounds (such as etravirine), with the exception of dolutegravir trough concentrations [median (IQR) = 132 ng/mL (62-227) in individuals on valproic acid versus 760 ng/mL (333-1407) in those not receiving valproic acid]. CONCLUSIONS Valproic acid does not have a major effect on antiretrovirals other than dolutegravir. The mechanism of this unexpected drug-drug interaction may be the combination of protein displacement, reduced absorption and CYP3A4 induction. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email [email protected] When comparing mammography-screening participants and non-participants, estimates of reduction in breast-cancer mortality may be biased by poor baseline comparability. We used negative controls to detect uncontrolled confounding. METHODS We designed a closed cohort of Danish women invited to a mammography-screening programme at age 50-52 years in Copenhagen or Funen from 1991 through 2001. We included women with a normal screening result in their first-invitation round. Based on their second-invitation round, women were divided into participants and non-participants and followed until death, emigration or 31 December 2014, whichever came first. We estimated hazard ratios (HRs) of death from breast cancer, causes other than breast cancer and external causes. We added dental-care participation as an exposure to test for an independent association with breast-cancer mortality. We adjusted for civil status, parity, age at first birth, educational attainment, income and hormone use. RESULTS Screening participants had a lower hazard of breast-cancer death [HR 0.47, 95% confidence interval (CI) 0.32, 0.69] compared with non-participants. Participants also had a lower hazard of death from other causes (HR 0.43, 95% CI 0.39, 0.46) and external causes (HR 0.35, 95% CI 0.23, 0.54). Reductions persisted after covariate adjustment. Dental-care participants had a lower hazard of breast-cancer death (HR 0.75, 95% CI 0.56, 1.01), irrespective of screening participation. CONCLUSIONS Negative-control associations indicated residual uncontrolled confounding when comparing breast-cancer mortality among screening participants and non-participants. © The Author(s) 2020. Published by Oxford University Press on behalf of the International Epidemiological Association.Lensless Fourier transform holography has been developed. By treating Bragg diffraction waves as object waves and a transmitted spherical wave as a reference wave, these two waves are interfered and recorded as holograms away from the reciprocal plane. In this method, reconstruction of holograms requires only one Fourier transform. Application of this method to analyze vortex beams worked well and their amplitude and phase distributions were obtained on the reciprocal plane. By combining the conventional holography with the developed lensless Fourier transform holography, we can reconstruct and analyze electron waves from the real to reciprocal space continuously. © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Society of Microscopy.BACKGROUND Few long-term data are available in subjects having initiated ART with an NRTI-sparing regimen. OBJECTIVES Outcomes of subjects enrolled in the NEAT 001/ANRS 143 randomized clinical trial (comparing ritonavir-boosted darunavir + raltegravir versus ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were retrospectively collected, through anonymized electronic case report forms, up to 6 years post-enrolment. METHODS The last NEAT 001 visit (Week 96) was conducted in 745/805 randomized subjects (363/401 ritonavir-boosted darunavir + raltegravir and 382/404 ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine). Of these, 430 were enrolled in NEAT 001/ANRS 143 LONG TERM (NLT) study (201 raltegravir, 229 tenofovir disoproxil fumarate/emtricitabine), with a median follow-up of 44.4 months. RESULTS During NLT follow-up, the proportion of AIDS, non-AIDS events, virological rebound and serious adverse events, discontinuation for virological failure and for adversehe British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email [email protected] AND OBJECTIVES This article explores care relationships as they are represented within "The Lady in the Van," a sequence of interconnected texts by English writer Alan Bennett. RESEARCH AND METHODS By mainly taking the memoirs and film of the same title as primary sources, and in the light of key concepts related to care theory and aging studies, the article shows the extent to which Bennett goes beyond the accustomed portrayal of domestic relationships of care by placing himself as the protagonist of a narrative-and a relationship-in which caring for and about a complete stranger entails coming to terms with both social and personal issues. DISCUSSION The article examines the ways in which the relationship of care portrayed by Bennett entails exploring forms of Otherness that both caring and aging unveil, which are related to age, gender, and sexuality, and that in Bennett's narrative end up favoring a dialogue of which the author himself is the main beneficiary. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail [email protected] form 2 groups based on their innate immunity to Epstein-Barr virus (EBV). Group 1 makes a strong natural killer (NK)-cell and γδ T-cell response, whereas group 2 makes a strong NK-cell response, but a weak γδ T-cell response. To investigate the underlying basis for this difference in γδ T-cell immunity to EBV, we used next-generation sequencing to compare the γδ T-cell receptor (TCR) repertoires of groups 1 and 2. buy H2DCFDA In the absence of EBV, group 1 TCRγ chains are enriched for complementarity determining region 3 (CDR3s) containing JγP, whereas group 2 TCRγ chains are enriched for CDR3s containing Jγ2. In group 1 donors, EBV activates many γδ T cells expressing Vγ9JγP, inducing proliferation that produces a large population of activated effector cells. The TCRs using Vγ9JγP are closely related to the TCRs of γδ T cells that respond to phosphoantigens. In group 2 donors, EBV activates a small subpopulation of γδ T cells, most expressing Vγ9JγP. In conclusion, we find that differences in the TCRγ-chain repertoire underlie the differential response of group 1 and group 2 to EBV. © 2020 by The American Society of Hematology.Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment for stage I-II NLPHL is undefined. We conducted a multi-center retrospective study including patients ≥16 years with stage I-II NLPHL diagnosed from 1995-2018 receiving all forms of management including radiotherapy (RT), combined modality therapy (CMT=RT+chemotherapy), chemotherapy (CT), observation after excision, rituximab and RT, and single agent rituximab (R). End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age 39 years, 72.3% being male, and 54.9% having stage I disease. Median follow up was 5.5 years (IQR=3.1-10.1). 5-year PFS and OS for the entire cohort were 87.1% (95%CI=83.6-90.0%) and 98.3% (95%CI=96.4-99.2%), respectively. Primary management was RT alone (n=257, 46.0%), CMT (n=184, 32.9%), CT alone (n=47, 8.4%), observation (n=37, 6.6%), rituximab and RT (n=19, 3.4%), and rituximab alone (n=15, 2.7%). 5-year PFS rates were 91.1% (95%CI=85.3-94.7%) after RT, 90.5% (95%CI=84.8-94.1%) after CMT, 77.8% (95%CI=61.3-88.0%) after chemotherapy, 73.5% (95%CI=50.6-87.0%) after observation, 80.8% (95%CI=41.0-95.1%) after rituximab and RT, and 38.5% (95%CI=14.0-62.8%) after rituximab alone. For the RT cohort but not the CMT cohort, variant immunoarchitectural pattern and number of sites>2 were associated with worse PFS (P2 (P=0.0006). OS for patients with stage I-II NLPHLwas excellent following all managements. Copyright © 2020 American Society of Hematology.BACKGROUND AND OBJECTIVES We examined the association between turnover of registered nurses (RNs) and certified nurse assistants (CNAs) and perceived patient safety culture (PSC) in nursing homes (NHs). RESEARCH DESIGN AND METHODS In 2017, we conducted PSC survey using the Agency for Healthcare Research and Quality- developed and -validated instrument for NHs. A random sample of 2,254 U.S. NHs was identified. Administrators, directors of nursing (DONs), and nurse unit leaders served as respondents. Responses were obtained for 818 facilities from 1,447 individuals. The instrument contained 42 items relating to 12 PSC domains and turnover rates. PSC domains were based on five-point Likert scale items. A positive response was defined as "agree" or "strongly agree" (4-5 on the Likert scale). For CNAs low turnover was defined as less then 35%, and for RNs less then 15%. Facility-level and market-competition characteristics were included. Bivariate comparisons employed analysis of variance and chi-square tests. In multivariable models, we fit separate linear regressions for the average positive PSC score and for each of the 12 PSC domains, including turnover rates, NH, and market factors. RESULTS In NHs with low turnover, the overall PSC scores were 4.04% (RNs) and 6.28% (CNAs) higher than in NHs with high turnover. Teamwork, staffing, and training/skills were associated with CNA but not RN turnover. DISCUSSION AND IMPLICATIONS The effect of turnover on PSC depends on who leaves and to a lesser extent on the organizational characteristics. In NHs, improvements in PSC may depend on the ability to retain a well-trained and skilled nursing staff. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail [email protected] Sleep problems are common in eating disorders (EDs). PURPOSE We evaluated whether sleep-phasing regularity associates with the regularity of daily eating events. METHODS ED patients (n = 29) completed hourly charts of mood and eating occasions for 2 weeks. Locomotor activity was recorded continuously by wrist actigraphy for a minimum of 10 days, and sleep was calculated based on periods of inactivity. We computed the center of daily inactivity (CenDI) as a measure of sleep phasing and consolidation of the daily inactivity (ConDI) as a measure of daily sleep rhythm strength. We assessed interday irregularities in the temporal structure of food intake using the standard deviation (SD) of frequency (IFRQ), timing (ITIM), and interval (IINT) of food intake. A self-evaluation of other characteristics included mood, anxiety, and early trauma. RESULTS A later phasing of sleep associated with a lower frequency of eating (eating frequency with the CenDI rho = -0.49, p = .007). The phasing and rhythmic strength of sleep correlated with the degree of eating irregularity (CenDI with ITIM rho = 0.
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