Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal ...follow-up, with inconsistent results.
The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality.
Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions.
Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio OR: 1.60; 95% confidence interval CI: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD.
Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.
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The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated ...interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O ≥ 1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T > 2,500 K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.
Pediatric bone and soft tissue sarcomas often display increased Akt phosphorylation through up regulation of insulin-like growth factor (IGF1) signaling. Additionally, Akt signaling has been linked ...to resistance to IGF1 receptor (IGF1R) and mTOR (mammalian target of rapamycin) inhibitors in sarcoma, further demonstrating the role of Akt in tumor survival. This suggests targeting components of the PI3K/Akt pathway may be an effective therapeutic strategy. Here, we investigated the in vitro activity of the pan-class I PI3K inhibitor buparlisib (BKM120) in pediatric bone and soft tissue sarcomas. Buparlisib inhibited activation of Akt and signaling molecules downstream of mTORC1 (mTOR complex 1) in Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma cell lines. Anti-proliferative effects were observed in both anchorage dependent and independent conditions and apoptosis was induced within 24 hours of drug treatment. Buparlisib demonstrated cytotoxicity as a single agent, but was found to be more effective when used in combination. Synergy was observed when buparlisib was combined with the IGF1R inhibitor NVP-AEW541 and the mTORC1 inhibitor rapamycin. The addition of NVP-AEW541 also further reduced phospho-Akt levels and more potently induced apoptosis compared to buparlisib treatment alone. Additionally, the combination of buparlisib with the MEK1/2 inhibitor trametinib resulted in synergy in sarcoma cell lines possessing MAPK pathway mutations. Taken together, these data indicate buparlisib could be a novel therapy for the treatment of pediatric bone and soft tissue sarcomas.
Wetlands enrolled in the Agricultural Conservation Easement Program (ACEP) are established as a means of restoring wetland ecosystems and wildlife habitat on private, agricultural land. In West ...Virginia, USA, ACEP wetlands have never been evaluated to determine how they function as wildlife habitat in comparison to other available wetland habitat in the state. We measured the wintering occupancy of Passerellidae species and apparent avian species richness on ACEP wetlands and a set of reference wetlands located on public land in West Virginia to evaluate if ACEP wetlands are being used similarly by avian species to other available wetland habitat in the state. Apparent avian species richness and the occupancy probability of four Passerellidae species-song sparrows (Melospiza melodia), dark-eyed juncos (Junco hyemalis), swamp sparrows (Melospiza georgiana), and white-throated sparrows (Zonotrichia albicollis)-did not differ between ACEP and reference sites. In addition to other vegetative and habitat associations for each species, dark-eyed junco occupancy was negatively correlated with wetland size while swamp sparrow occupancy and apparent avian species richness were positively associated with wetland size. These results indicate that ACEP wetlands are providing winter avian habitat as well as another source of wetland habitat in the state. Maintaining and expanding ACEP wetlands in West Virginia would continue to provide wetland systems in areas that are otherwise lacking these habitats.
Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical ...hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40–200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores > 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy.
Understanding survival probabilities is critical for the sustainable harvest of wildlife and fisheries populations. Age‐ and stage class‐specific survival probabilities are needed to inform a suite ...of population models used to estimate abundance and track population trends. However, current techniques for estimating survival probabilities using age‐at‐harvest methods require restrictive assumptions or incorporate potentially unknown parameters within the model.
Using a Bayesian approach, we developed a flexible age‐at‐harvest model that incorporates either age‐ or stage‐structured populations, while accounting for uncertainty in age structure, population growth rates and relative selectivity. Survival probabilities can vary by age or stage class, as well as by environmental covariates, and both population growth rates and selectivity for each age or stage class can be specified as fixed and known or these parameters can be specified as informative priors, allowing for the incorporation of expert opinion. We evaluated our model with simulations and empirical data from harvested bobcats Lynx rufus and American paddlefish Polyodon spathula.
Models fit to simulated age‐at‐harvest data yielded unbiased estimates of survival probability when population growth rates and selectivity were centered on the data‐generating parameter. We obtained unbiased estimates of survival probability even with biased prior estimates of selectivity and random departures from the assumed stage distribution, although the latter increased uncertainty in those estimates. We found biased estimates of survival probability when the prior distribution for population growth rate was not centered on the data‐generating value. When fit to empirical harvest data, our proposed age‐at‐harvest model produced estimates of survival probability congruent to those reported in the literature within similar geographic regions.
We demonstrate the utility of a novel age‐at‐harvest model that estimates survival probability and realistically account for uncertainty in model parameters, transcending the restrictive assumptions and auxiliary data requirements of other methods. Furthermore, we advise collecting information about population trends and age structure alongside age‐at‐harvest data to help reduce bias. Although our model cannot replace more rigorous methods, we believe our model will be transformative for wildlife and fisheries practitioners who collect age‐at‐harvest data to estimate age‐ or stage‐specific survival probabilities to help inform management decisions.
•MEG beta-band power suppression characterizes functional cortical engagement.•Time-resolved analysis reveals bilateral temporal regions over a narrative.•Progressive right-hemispheric dominance can ...be linked to social inference.
PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults. The protocol consisted of two runs, each interleaving 7 blocks of the story comprehension task with 15 blocks of an auditorily presented math task as a control for phonological processing, working memory, and attention processes. Sources at the cortical surface were estimated with a frequency-resolved beamformer. Beta-band power was estimated in the frequency range of 16–24 Hz over 1-sec epochs starting from 400 msec after stimulus onset until the end of a story or math problem presentation. These power estimates were compared to 1-second epochs of data before the stimulus block onset. The task-related cortical engagement was inferred from beta-band power decrements. Group-level source activations were statistically compared using non-parametric permutation testing. A story-math contrast of beta-band power changes showed greater bilateral cortical engagement within the fusiform gyrus, inferior and middle temporal gyri, parahippocampal gyrus, and left inferior frontal gyrus (IFG) during story comprehension. A math-story contrast of beta power decrements showed greater bilateral but left-lateralized engagement of the middle frontal gyrus and superior parietal lobule. The evolution of cortical engagement during five temporal windows across the presentation of stories showed significant involvement during the first interval of the narrative of bilateral opercular and insular regions as well as the ventral and lateral temporal cortex, extending more posteriorly on the left and medially on the right. Over time, there continued to be sustained right anterior ventral temporal engagement, with increasing involvement of the right anterior parahippocampal gyrus, STG, MTG, posterior superior temporal sulcus, inferior parietal lobule, frontal operculum, and insula, while left hemisphere engagement decreased. Our findings are consistent with prior imaging studies of narrative comprehension, but in addition, they demonstrate increasing right-lateralized engagement over the course of narratives, suggesting an important role for these right-hemispheric regions in semantic integration as well as social and pragmatic inference processing.
Eolian dust is a significant source of iron and other nutrients that are essential for the health of marine ecosystems and potentially a controlling factor of the high nutrient-low chlorophyll status ...of the Subarctic North Pacific. We map the spatial distribution of dust input using three different geochemical tracers of eolian dust, 4He, 232Th and rare earth elements, in combination with grain size distribution data, from a set of core-top sediments covering the entire Subarctic North Pacific. Using the suite of geochemical proxies to fingerprint different lithogenic components, we deconvolve eolian dust input from other lithogenic inputs such as volcanic ash, ice-rafted debris, riverine and hemipelagic input. While the open ocean sites far away from the volcanic arcs are dominantly composed of pure eolian dust, lithogenic components other than eolian dust play a more crucial role along the arcs. In sites dominated by dust, eolian dust input appears to be characterized by a nearly uniform grain size mode at ∼4 μm.
Applying the 230Th-normalization technique, our proxies yield a consistent pattern of uniform dust fluxes of 1–2 g/m2/yr across the Subarctic North Pacific. Elevated eolian dust fluxes of 2–4 g/m2/yr characterize the westernmost region off Japan and the southern Kurile Islands south of 45° N and west of 165° E along the main pathway of the westerly winds. The core-top based dust flux reconstruction is consistent with recent estimates based on dissolved thorium isotope concentrations in seawater from the Subarctic North Pacific. The dust flux pattern compares well with state-of-the-art dust model predictions in the western and central Subarctic North Pacific, but we find that dust fluxes are higher than modeled fluxes by 0.5–1 g/m2/yr in the northwest, northeast and eastern Subarctic North Pacific. Our results provide an important benchmark for biogeochemical models and a robust approach for downcore studies testing dust-induced iron fertilization of past changes in biological productivity in the Subarctic North Pacific.
•Spatial survey of dust tracers 4Heterr, 232Th and REE in the Subarctic North Pacific.•Sedimentary lithogenic components are deconvolved with dust and volcanic endmembers.•High dust fluxes in the southwest SNP and constant lower fluxes elsewhere are found.•Sedimentary and dissolved Th-based dust fluxes from seawater show good consistency.•A constant eolian dust grain size mode at 4 μm over the entire SNP is observed.
Abstract We present the first star formation history (SFH) and age–metallicity relation (AMR) derived from resolved stellar populations imaged with the JWST NIRCam instrument. The target is the Local ...Group star-forming galaxy WLM at 970 kpc. The depth of the color–magnitude diagram (CMD) reaches below the oldest main sequence turnoff with a signal-to-noise ratio = 10 at M F090W = + 4.6 mag. This is the deepest CMD for any galaxy that is not a satellite of the Milky Way. We use Hubble Space Telescope (HST) optical imaging that overlaps with the NIRCam observations to directly evaluate the SFHs derived based on data from the two great observatories. The JWST and HST-based SFHs are in excellent agreement. We use the metallicity distribution function measured from stellar spectra to confirm the trends in the AMRs based on the JWST data. Together, these results confirm the efficacy of recovering an SFH and AMR with the NIRCam F090W−F150W filter combination, and validate the sensitivity and accuracy of stellar evolution libraries in the near-infrared relative to the optical for SFH recovery work. From the JWST data, WLM shows an early onset to star formation, followed by an extended pause post-reionization before star formation reignites, which is qualitatively similar to what has been observed in the isolated galaxies Leo A and Aquarius. Quantitatively, 15% of the stellar mass formed in the first Gyr, while only 10% formed over the next ∼5 Gyr. The stellar mass then rapidly doubled in ∼2.5 Gyr, followed by constant star formation over the last ∼5 Gyr.
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