The cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side ...effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).
To determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.
Combined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.
The median IQR age was 75.0 69.7-81.1 years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (p<0.001), at a median dose of 50 μg. Levothyroxine did not significantly change the risk of any of the prespecified cardiovascular outcomes, including cardiovascular events (HR 0.74 0.41-1.25), atrial fibrillation (HR 0.69 0.32-1.52), or heart failure (0.41 0.13-1.35), or all-cause mortality (HR 1.28 0.54-3.03), irrespective of history of CVD and age.
Treatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.
ClinicalTrials.gov, identifier NCT01660126 (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+).
Mobile species are particularly affected by artificial barriers requiring large investments to restore connectivity. However, few large‐scale, long‐term studies have investigated the ecological ...outcomes of restoring connectivity for these species. Our study, spanning 15–20 years, quantified response trajectories, which represent temporal trends following disturbance, of three native salmonids colonizing 20 km of protected habitat following restoration of fish passage at Landsburg Dam, Cedar River, WA, in 2003. Built in 1901, the dam blocked the upriver movement of native anadromous coho and Chinook salmon and nonanadromous mountain whitefish for 102 years. Restoration effectiveness was also assessed by comparing temporal trends in freshwater productivity of juvenile coho and Chinook salmon in the Cedar River after restoration to a nearby undammed subbasin. We also compared summer densities of juvenile coho and Chinook salmon, and mountain whitefish above the dam measured a decade after restoration to undammed reference systems. Anadromous salmon and nonanadromous mountain whitefish populations increased linearly or nonlinearly following restoration. The positive, asymptotic response represented by adult Chinook salmon counts indicates a slowing in population recovery rate, plateauing a decade after restoration. In contrast, annual abundance of adult coho salmon increased at a constant rate, indicating additional capacity 15 years post‐restoration. Salmonid compositional diversity, driven largely by juvenile coho salmon, also increased nonlinearly, plateauing in a decade. We observed substantial spatial variation in the temporal response, as juvenile coho salmon and mountain whitefish population expansion slowed linearly with upstream distance from the restoration site. There was evidence that some of the annual variation in salmonid biomass in summer was a result of discharge variability in winter and spring, with biomass declining as flow variability increased. Species reintroduction and establishment had no discernible effect on stream‐rearing salmonids living above the dam before restoration, while increasing coho freshwater productivity at the subbasin scale. Results from our study showed recolonization by three mobile species, each with a unique life history, takes at least a decade or more and was dependent on species and life stage, size of the spawning population, distance from restoration site, and annual variability in streamflow.
During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasite-exported ...proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature.
Context.
The number of super-Earth and Earth-mass planet discoveries has increased significantly in the last two decades thanks to the Doppler radial velocity and planetary transit observing ...techniques. Either technique can detect planet candidates on its own, but the power of a combined photometric and spectroscopic analysis is unique for an insightful characterization of the planets, which in turn has repercussions for our understanding of the architecture of planetary systems and, therefore, their formation and evolution.
Aims.
Two transiting planet candidates with super-Earth radii around the nearby (
d
= 70.64 ± 0.06 pc) K7–M0 dwarf star TOI-1238 were announced by NASA’s Transiting Exoplanet Survey Satellite (TESS), which observed the field of TOI-1238 in four different sectors. We aim to validate their planetary nature using precise radial velocities taken with the CARMENES spectrograph.
Methods.
We obtained 55 CARMENES radial velocity measurements that span the 11 months between 9 May 2020 and 5 April 2021. For a better characterization of the parent star’s activity, we also collected contemporaneous optical photometric observations at the Joan Oró and Sierra Nevada observatories and retrieved archival photometry from the literature. We performed a combined TESS+CARMENES photometric and spectroscopic analysis by including Gaussian processes and Keplerian orbits to account for the stellar activity and planetary signals simultaneously.
Results.
We estimate that TOI-1238 has a rotation period of 40 ± 5 d based on photometric and spectroscopic data. The combined analysis confirms the discovery of two transiting planets, TOI-1238 b and c, with orbital periods of 0.764597
−0.000011
+0.000013
d and 3.294736
−0.000036
+0.000034
d, masses of 3.76
−1.07
+1.15
M
⊕
and 8.32
−1.88
+1.90
M
⊕
, and radii of 1.21
−0.10
+0.11
R
⊕
and 2.11
−0.14
+0.14
R
⊕
. They orbit their parent star at semimajor axes of 0.0137 ± 0.0004 au and 0.036 ± 0.001 au, respectively.The two planets are placed on opposite sides of the radius valley for M dwarfs and lie between the star and the inner border of TOI-1238’s habitable zone. The inner super-Earth TOI-1238 b is one of the densest ultra-short-period planets ever discovered (
ρ
= 11.7
−3.4
+4.2
g cm
−3
). The CARMENES data also reveal the presence of an outer, non-transiting, more massive companion with an orbital period and radial velocity amplitude of ≥600 d and ≥70 m s
−1
, which implies a likely mass of
M
≥ 2 √(1−
e
2
)
M
Jup
and a separation ≥1.1 au from its parent star.
Cosmic-ray electrons and positrons (CREs) at GeV-TeV energies are a unique probe of our local Galactic neighborhood. CREs lose energy rapidly via synchrotron radiation and inverse-Compton scattering ...processes while propagating within the Galaxy, and these losses limit their propagation distance. For electrons with TeV energies, the limit is on the order of a kiloparsec. Within that distance, there are only a few known astrophysical objects capable of accelerating electrons to such high energies. It is also possible that the CREs are the products of the annihilation or decay of heavy dark matter (DM) particles. VERITAS, an array of imaging air Cherenkov telescopes in southern Arizona, is primarily utilized for gamma-ray astronomy but also simultaneously collects CREs during all observations. We describe our methods of identifying CREs in VERITAS data and present an energy spectrum, extending from 300 GeV to 5 TeV, obtained from approximately 300 hours of observations. A single power-law fit is ruled out in VERITAS data. We find that the spectrum of CREs is consistent with a broken power law, with a break energy at 710±40stat±140syst GeV.
Organic nitrates in both gas and condensed (aerosol) phases were measured during the Uintah Basin Winter Ozone Study from January to February in 2012. A high degree of correlation between total ...aerosol volume at diameters less than 500 nm and the particulate organic nitrate concentration indicates that organic nitrates are a consistent, if not dominant, fraction of fine aerosol mass. In contrast, a similar correlation with sub-2.5 μm aerosol volume is weaker. The C : N atomic ratio inferred from field measurements of PM2.5 and particulate organic nitrate is 34 : 1. Calculations constrained by the observations indicate that both condensation of gas-phase nitrates and heterogeneous reactions of NO3 / N2O5 are responsible for introducing organic nitrate functionality into the aerosol and that the source molecules are alkanes. Extrapolating the results to urban aerosol suggests organic nitrate production from alkanes may be a major secondary organic aerosol source.
Questionable authorship practices in scientific publishing are detrimental to research quality and management. The existing literature dealing with the prevalence, and perceptions, of such practices ...has focused on the medical sciences, and on experienced researchers. In contrast, this study investigated how younger researchers (PhD students) from across the faculties view fair authorship attribution, their experience with granting guest authorships to more powerful researchers and their reasons for doing so. Data for the study were collected in a survey of European PhD students. The final dataset included 1,336 participants from five European countries (Denmark, Hungary, Ireland, Portugal, and Switzerland) representing all major disciplines. Approximately three in ten reported that they had granted at least one guest authorship to "a person in power". Half of these indicated that they had done so because they had been told to do so by the person in power. Participants from the medical, natural and technical sciences were much more likely to state that they had granted a guest authorship than those from other faculties. We identified four general views about what is sufficient for co-authorship. There were two dominant views. The first (inclusive view) considered a broad range of contributions to merit co-authorship. The second (strongly writing-oriented) emphasised that co-authors must have written a piece of the manuscript text. The inclusive view dominated in the natural, technical, and medical sciences. Participants from other faculties were more evenly distributed between the inclusive and writing oriented view. Those with an inclusive view were most likely to indicate that they have granted a guest authorship. According to the experiences of our participants, questionable authorship practices are prevalent among early-career researchers, and they appear to be reinforced through a combination of coercive power relations and dominant norms in some research cultures, particularly in the natural, technical, and medical sciences.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We previously reported enhanced expression of the p67 and gp91 components of NAD(P)H oxidase in angiotensin (Ang) II–induced hypertension, suggesting de novo assembly in response to Ang II. To ...examine the direct involvement of NAD(P)H oxidases in Ang II–induced O2 production, we designed a chimeric peptide that inhibits p47 association with gp91 in NAD(P)H oxidase (gp91ds-tat). This was achieved by linking a 9-amino acid peptide (aa) derived from HIV-coat protein (tat) to a 9-aa sequence of gp91 (known to interact with p47). As a control, we constructed a chimera containing tat and a scrambled gp91 sequence (scramb-tat). We found that gp91ds-tat decreased O2 levels in aortic rings treated with Ang II (10 pmol/L) but had no effect on either the O2-generating enzyme xanthine oxidase or potassium superoxide–generated O2. We infused vehicle, Ang II (0.75 mg · kg · d), Ang II+gp91ds-tat (10 mg · kg · d), or Ang II+scramb-tat intraperitoneally in C57Bl/6 mice and measured systolic blood pressure (SBP) on days 0, 3, 5, and 7 of infusion. SBP increased by day 3 in mice given Ang II and Ang II+scramb-tat but was significantly lower with Ang II+gp91-tat. On day 7, SBP was still significantly inhibited in mice given Ang II+gp91ds-tat, whereas Ang II–induced O2 production was inhibited throughout the aorta as detected by dihydroethidium staining, consistent with the ability of this inhibitor to block the various vascular NAD(P)H oxidase isoforms. These data support the hypothesis that inhibition of the interaction of p47 and gp91 (or its homologues) can block O2 production and attenuate blood pressure elevation in mice.
Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported ...symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research.
BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid.
To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received.
The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.
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