Life cycle adaptation to latitudinal and seasonal variation in photoperiod and temperature is a major determinant of evolutionary success in flowering plants. Whereas the life cycle of the ...dicotyledonous model species Arabidopsis thaliana is controlled by two epistatic genes, FLOWERING LOCUS C and FRIGIDA 1–3, three unrelated loci (VERNALIZATION 1–3) determine the spring and winter habits of monocotyledonous plants such as temperate cereals 4–6. In the core eudicot species Beta vulgaris, whose lineage diverged from that leading to Arabidopsis shortly after the monocot-dicot split 140 million years ago 7, 8, the bolting locus B 9 is a master switch distinguishing annuals from biennials. Here, we isolated B and show that the pseudo-response regulator gene BOLTING TIME CONTROL 1 (BvBTC1), through regulation of the FLOWERING LOCUS T genes 10, is absolutely necessary for flowering and mediates the response to both long days and vernalization. Our results suggest that domestication of beets involved the selection of a rare partial loss-of-function BvBTC1 allele that imparts reduced sensitivity to photoperiod that is restored by vernalization, thus conferring bienniality, and illustrate how evolutionary plasticity at a key regulatory point can enable new life cycle strategies.
► Map-based cloning of B in beet led to isolation of the PRR gene BvBTC1 ► BvBTC1 controls life cycle through differential regulation of the BvFT1/BvFT2 module ► BvBTC1 mediates floral transition in response to both long days and vernalization ► Beet domestication involved selection of a rare Bvbtc1 allele conferring bienniality
Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT
) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. ...We aimed to define the optimal healthy ranges of TSH and FT
based on the risk of cardiovascular disease and mortality.
This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT
, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT
, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576.
We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT
with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L IQR 11·2-13·9) to 40th percentiles (median 14·8 pmol/L 12·3-15·0) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT
in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT
greater than the 85th percentile (median 17·6 pmol/L IQR 15·0-18·3), and men with FT
greater than the 75th percentile (16·7 pmol/L 14·0-17·4). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L IQR 1·68-2·25) to 80th percentiles (2·90 mIU/L 2·41-3·32) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality.
There was a J-shaped association of FT
with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT
and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT
greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes.
None.
Low energy fission of 234,235,236,238U and 237,238Np radioactive beams, provided by the GSI/FRS facility, has been studied using the R3B/SOFIA setup. The latter allows, on an event-by-event basis, to ...simultaneously identify, in terms of their mass and atomic numbers, the fissioning nucleus in coincidence with both fission fragments after prompt-neutron emission. This presentation reports on new results on elemental, isobaric and isotopic yields.
Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought ...to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents.
Advancements in the field of oncology are allowing patients to live longer, with enhanced quality of life (QoL). Accordingly, more patients with cancer are expressing the desire to return to work ...(RTW). Previous research has indicated that patients with a rare or advanced cancer can experience unique problems in the RTW process.
This pilot study evaluated the outcomes and feasibility of the occupational care programme TERRA (i.e., recalibraTe lifE and woRk with and afteR cAncer) for patients with a rare or advanced cancer. Four rare cancer patients and 3 advanced cancer patients completed TERRA; a supportive occupational care programme consisting of five online group sessions over a two-month period. Pre- and post-intervention outcomes were collected using validated self-report questionnaires. The primary outcome was work ability. Secondary outcomes included QoL, anxiety and depression, fatigue, unmet needs, self-efficacy, readiness for RTW, work intention, work involvement, and work-life conflict. Feasibility was assessed using the RE-AIM model.
Changes in work ability scores were inconsistent across participants. Well-being outcomes generally improved following the intervention. Feasibility was evaluated positively by both participants and trainers.
A multidisciplinary approach may further improve outcomes of occupational interventions supporting rare and advanced cancer patients. An effectiveness study to evaluate the outcomes and feasibility of the programme is deemed necessary.
The primary objective of the study was a change in left ventricular end-systolic volume index (LVESVi) from baseline to 6 months of spinal cord stimulation (SCS) therapy in the treatment arm compared ...to the control arm as measured by echocardiography. Secondary objectives were changes in peak oxygen uptake and N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the treatment arm and control arm from baseline through 6 months.
Abnormal neurohormonal activation is often responsible for progression of heart failure (HF). Treatment has often included drug therapy to modulate the neurohormonal axis. The purpose of the DEFEAT-HF (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure) clinical study was to evaluate whether direct modulation of the nervous system through SCS improved HF metrics, including heart size, biomarkers, functional capacity, and symptoms.
The DEFEAT-HF study was a prospective, multicenter randomized (3:2), parallel, single-blind, controlled study to investigate whether SCS was a feasible therapy for the treatment of systolic HF for patients with New York Heart Association functional class III HF, left ventricular ejection fraction (LVEF) ≤35%, QRS duration <120 ms, and left ventricular end-diastolic dimension ≥55 mm. The primary objective of the DEFEAT-HF study was to evaluate the reduction in LVESVi after 6 months of SCS therapy in the treatment arm compared to the control arm.
In total, 81 patients were enrolled, with 66 successfully randomized and implanted with the SCS device system. Seventy-six percent (50 of 66) had an implantable cardioverter-defibrillator at the baseline visit. Among randomized patients, the mean age was 61 years, 79% were male, mean LVEF was 27%, and mean QRS duration was 105 ms. The change in LVESVi over 6 months was not significantly different between randomization arms (SCS OFF: -2.2 95% confidence interval: -9.1 to 4.6 vs.
2.1 95% confidence interval: -2.7 to 6.9; p = 0.30). Analyses of secondary endpoints for the study were also not significantly different.
The present study does not provide evidence to support a meaningful change in clinical outcomes for HF patients receiving SCS. (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure DEFEAT-HF; NCT01112579).
► Lorentz Invariance Violation as an observational window on Quantum Gravity (QG). ► Reanalysis of PKS 2155-304 flare in 2006 by H.E.S.S. ► Use of a precise likelihood fit procedure on individual ...photons. ► Previous limits on QG energy scale improved by a factor of 3.
Several models of Quantum Gravity predict Lorentz Symmetry breaking at energy scales approaching the Planck scale (∼10
19
GeV). With present photon data from the observations of distant astrophysical sources, it is possible to constrain the Lorentz Symmetry breaking linear term in the standard photon dispersion relations. Gamma Ray Bursts (GRB) and flaring Active Galactic Nuclei (AGN) are complementary to each other for this purpose, since they are observed at different distances in different energy ranges and with different levels of variability. Following a previous publication of the High Energy Stereoscopic System (H.E.S.S.) collaboration
1, a more sensitive event-by-event method consisting of a likelihood fit is applied to PKS 2155-304 flare data of MJD 53944 (July 28, 2006) as used in the previous publication. The previous limit on the linear term is improved by a factor of ∼3 up to
M
QG
l
>
2.1
×
10
18
GeV and is currently the best result obtained with blazars. The sensitivity to the quadratic term is lower and provides a limit of
M
QG
q
>
6.4
×
10
10
GeV, which is the best value obtained so far with an AGN and similar to the best limits obtained with GRB.
Context. Multiwavelength (MWL) observations of the blazar PKS 2155-304 during two weeks in July and August 2006, the period when two exceptional flares at very high energies (VHE, E ≳ 100 GeV) ...occurred, provide a detailed picture of the evolution of its emission. The complete data set from this campaign is presented, including observations in VHE γ-rays (H.E.S.S.), X-rays (RXTE, Chandra, Swift XRT), optical (Swift UVOT, Bronberg, Watcher, ROTSE), and in the radio band (NRT, HartRAO, ATCA). Optical and radio light curves from 2004 to 2008 are compared to the available VHE data from this period, to put the 2006 campaign into the context of the long-term evolution of the source. Aims. The data set offers a close view of the evolution of the source on different time scales and yields new insights into the properties of the emission process. The predictions of synchrotron self-Compton (SSC) scenarios are compared to the MWL data, with the aim of describing the dominant features in the data down to the hour time scale. Methods. The spectral variability in the X-ray and VHE bands is explored and correlations between the integral fluxes at different wavelengths are evaluated. SSC modelling is used to interpret the general trends of the varying spectral energy distribution. Results. The X-ray and VHE γ-ray emission are correlated during the observed high state of the source, but show no direct connection with longer wavelengths. The long-term flux evolution in the optical and radio bands is found to be correlated and shows that the source reaches a high state at long wavelengths after the occurrence of the VHE flares. Spectral hardening is seen in the Swift XRT data. Conclusions. The nightly averaged high-energy spectra of the non-flaring nights can be reproduced by a stationary one-zone SSC model, with only small variations in the parameters. The spectral and flux evolution in the high-energy band during the night of the second VHE flare is modelled with multi-zone SSC models, which can provide relatively simple interpretations for the hour time-scale evolution of the high-energy emission, even for such a complex data set. For the first time in this type of source, a clear indication is found for a relation between high activity at high energies and a long-term increase in the low frequency fluxes.
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