Exempting low-risk health and medical research from ethics reviews: Comparing Australia, the United Kingdom, the United States and the Netherlands

Background: Disproportionate regulation of health and medical research contributes to research waste. Better understanding of exemptions of research from ethics review in different jurisdictions may help to guide modification of review processes and reduce research waste. Our aim was to identify examples of low-risk human health and medical research exempt from ethics reviews in Australia, the United Kingdom, the United States and the Netherlands. Methods: We examined documents providing national guidance on research ethics in each country, including those authored by the National Health and Medical Research Council (Australia), National Health Service (United Kingdom), the Office for Human Research Protections (United States) and the Central Committee on Research Involving Humans (the Netherlands). Examples and types of research projects exempt from ethics reviews were identified, and similar examples and types were grouped together. Results: Nine categories of research were exempt from ethics reviews across the four countries; these were existing data or specimen, questionnaire or survey, interview, post-marketing study, evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, audit and service evaluation, and other exemptions. Existing non-identifiable data and specimens were exempt in all countries. Four categories - evaluation of public benefit or service programme, randomised controlled trials, research with staff in their professional role, and audit and service evaluation - were exempted by one country each. The remaining categories were exempted by two or three countries. Conclusions: Examples and types of research exempt from research ethics reviews varied considerably. Given the considerable costs and burdens on researchers and ethics committees, it would be worthwhile to develop and provide clearer guidance on exemptions, illustrated with examples, with transparent underpinning rationales

Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders

Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders

Probiotics for preventing acute otitis media in children

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: to assess the effects of probiotics to prevent the occurrence and reduce the severity of acute otitis media in children.</p

The Fate of Binaries in the Galactic Center: The Mundane and the Exotic

The Galactic Center (GC) is dominated by the gravity of a super-massive black hole (SMBH), Sagittarius A$^*$, and is suspected to contain a sizable population of binary stars. Such binaries form hierarchical triples with the SMBH, undergoing Eccentric Kozai-Lidov (EKL) evolution, which can lead to high eccentricity excitations for the binary companions' mutual orbit. This effect can lead to stellar collisions or Roche-lobe crossings, as well as orbital shrinking due to tidal dissipation. In this work we investigate the dynamical and stellar evolution of such binary systems, especially with regards to the binaries' post-main-sequence evolution. We find that the majority of binaries (~75%) is eventually separated into single stars, while the remaining binaries (~25%) undergo phases of common-envelope evolution and/or stellar mergers. These objects can produce a number of different exotic outcomes, including rejuvenated stars, G2-like infrared-excess objects, stripped giant stars, Type Ia supernovae (SNe), cataclysmic variables (CVs), symbiotic binaries (SBs), or compact object binaries. We estimate that, within a sphere of 250 Mpc radius, about 7.5 to 15 Type Ia SNe per year should occur in galactic nuclei due to this mechanism, potentially detectable by ZTF and ASAS-SN. Likewise we estimate that, within a sphere of 1 Gpc$^3$ volume, about 10 to 20 compact object binaries form per year that could become gravitational wave sources. Based on results of EKL-driven compact object binary mergers in galactic nuclei by Hoang at al. (2018), this compact object binary formation rate translates to about 15 to 30 events per year detectable by Advanced LIGO.Comment: 8 pages, 3 figures, accepted by Ap

With development, list recall includes more chunks, not just larger ones.

The nature of the childhood development of immediate recall has been difficult to determine. There could be a developmental increase in either the number of chunks held in working memory or the use of grouping to make the most of a constant capacity. In 3 experiments with children in the early elementary school years and adults, we show that improvements in the immediate recall of word and picture lists come partly from increases in the number of chunks of items retained in memory. This finding was based on a distinction between access to a studied group of items (i.e., recall of at least 1 item from the group) and completion of the accessed group (i.e., the proportion of the items recalled from the group). Access rates increased with age, even with statistical controls for completion rates, implicating development of capacity in chunks. (PsycINFO Database Record (c) 2010 APA, all rights reserved

Detectability of CO2 Flux Signals by a Space-Based Lidar Mission

Satellite observations of carbon dioxide (CO2) offer novel and distinctive opportunities for improving our quantitative understanding of the carbon cycle. Prospective observations include those from space-based lidar such as the Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. Here we explore the ability of such a mission to detect regional changes in CO2 fluxes. We investigate these using three prototypical case studies, namely the thawing of permafrost in the Northern High Latitudes, the shifting of fossil fuel emissions from Europe to China, and changes in the source-sink characteristics of the Southern Ocean. These three scenarios were used to design signal detection studies to investigate the ability to detect the unfolding of these scenarios compared to a baseline scenario. Results indicate that the ASCENDS mission could detect the types of signals investigated in this study, with the caveat that the study is based on some simplifying assumptions. The permafrost thawing flux perturbation is readily detectable at a high level of significance. The fossil fuel emission detectability is directly related to the strength of the signal and the level of measurement noise. For a nominal (lower) fossil fuel emission signal, only the idealized noise-free instrument test case produces a clearly detectable signal, while experiments with more realistic noise levels capture the signal only in the higher (exaggerated) signal case. For the Southern Ocean scenario, differences due to the natural variability in the ENSO climatic mode are primarily detectable as a zonal increase

Impact of alpha-tocopherol deficiency and supplementation on sacrocaudalis and gluteal muscle fiber histopathology and morphology in horses.

BackgroundA subset of horses deficient in alpha-tocopherol (α-TP) develop muscle atrophy and vitamin E-responsive myopathy (VEM) characterized by mitochondrial alterations in the sacrocaudalis dorsalis medialis muscle (SC).ObjectivesTo quantify muscle histopathologic abnormalities in subclinical α-TP deficient horses before and after α-TP supplementation and compare with retrospective (r)VEM cases.AnimalsProspective study; 16 healthy α-TP-deficient Quarter Horses. Retrospective study; 10 retrospective vitamin E-responsive myopathy (rVEM) cases .MethodsBlood, SC, and gluteus medius (GM) biopsy specimens were obtained before (day 0) and 56 days after 5000 IU/450 kg horse/day PO water dispersible liquid α-TP (n = 8) or control (n = 8). Muscle fiber morphology and mitochondrial alterations were compared in samples from days 0 and 56 and in rVEM cases.ResultsMitochondrial alterations more common than our reference range (&lt;2.5% affected fibers) were present in 3/8 control and 4/8 treatment horses on day 0 in SC but not in GM (mean, 2.2; range, 0%-10% of fibers). Supplementation with α-TP for 56 days did not change the percentage of fibers with mitochondrial alterations or anguloid atrophy, or fiber size in GM or SC. Clinical rVEM horses had significantly more mitochondrial alterations (rVEM SC, 13% ± 7%; GM, 3% ± 2%) and anguloid atrophy compared to subclinical day 0 horses.Conclusions and clinical importanceClinically normal α-TP-deficient horses can have mitochondrial alterations in the SC that are less severe than in atrophied VEM cases and do not resolve after 56 days of α-TP supplementation. Preventing α-TP deficiency may be of long-term importance for mitochondrial viability

Detectability of CO2 flux signals by a space‐based lidar mission

Satellite observations of carbon dioxide (CO2) offer novel and distinctive opportunities for improving our quantitative understanding of the carbon cycle. Prospective observations include those from space‐based lidar such as the active sensing of CO2 emissions over nights, days, and seasons (ASCENDS) mission. Here we explore the ability of such a mission to detect regional changes in CO2 fluxes. We investigate these using three prototypical case studies, namely, the thawing of permafrost in the northern high latitudes, the shifting of fossil fuel emissions from Europe to China, and changes in the source/sink characteristics of the Southern Ocean. These three scenarios were used to design signal detection studies to investigate the ability to detect the unfolding of these scenarios compared to a baseline scenario. Results indicate that the ASCENDS mission could detect the types of signals investigated in this study, with the caveat that the study is based on some simplifying assumptions. The permafrost thawing flux perturbation is readily detectable at a high level of significance. The fossil fuel emission detectability is directly related to the strength of the signal and the level of measurement noise. For a nominal (lower) fossil fuel emission signal, only the idealized noise‐free instrument test case produces a clearly detectable signal, while experiments with more realistic noise levels capture the signal only in the higher (exaggerated) signal case. For the Southern Ocean scenario, differences due to the natural variability in the El Niño–Southern Oscillation climatic mode are primarily detectable as a zonal increase.Key PointsDetectability of regional changes in CO2 fluxes by space‐based lidarPermafrost thawing flux perturbation readily detectable by ASCENDS‐like missionSouthern Ocean ENSO‐related flux variability detectable as zonal changePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110893/1/jgrd51945.pd

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations