We explore star formation histories (SFHs) of galaxies based on the evolution of the star formation rate stellar mass relation (SFR-M). Using data from the FourStar Galaxy Evolution Survey (ZFOURGE) ...in combination with far-IR imaging from the Spitzer and Herschel observatories we measure the SFR-M relation at 0.5 < z <. Similar to recent works we find that the average infrared spectral energy distributions of galaxies are roughly consistent with a single infrared template across a broad range of redshifts and stellar masses, with evidence for only weak deviations. We find that these two estimates are in broad qualitative agreement, but that there is room for improvement at a more detailed level. At early times the SFHs suggest mass growth rates that are as much as 10 x higher than inferred from the SMF. However, at later times the SFHs under-predict the inferred evolution, as is expected in the case of additional growth due to mergers.
Objective
In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning.
Methods
Twenty histologic ...features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis OA patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes.
Results
Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others.
Conclusion
Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.
Background
Antenatal care is one of the key preventive health services used around the world. In most Western countries, antenatal care traditionally involves a schedule of one‐to‐one visits with a ...care provider. A different way of providing antenatal care involves use of a group model.
Objectives
1. To compare the effects of group antenatal care versus conventional antenatal care on psychosocial, physiological, labour and birth outcomes for women and their babies.
2. To compare the effects of group antenatal care versus conventional antenatal care on care provider satisfaction.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014), contacted experts in the field and reviewed the reference lists of retrieved studies.
Selection criteria
All identified published, unpublished and ongoing randomised and quasi‐randomised controlled trials comparing group antenatal care with conventional antenatal care were included. Cluster‐randomised trials were eligible, and one has been included. Cross‐over trials were not eligible.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias and extracted data; all review authors checked data for accuracy.
Main results
We included four studies (2350 women). The overall risk of bias for the included studies was assessed as acceptable in two studies and good in two studies. No statistically significant differences were observed between women who received group antenatal care and those given standard individual antenatal care for the primary outcome of preterm birth (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.57 to 1.00; three trials; N = 1888). The proportion of low‐birthweight (less than 2500 g) babies was similar between groups (RR 0.92, 95% CI 0.68 to 1.23; three trials; N = 1935). No group differences were noted for the primary outcomes small‐for‐gestational age (RR 0.92, 95% CI 0.68 to 1.24; two trials; N = 1473) and perinatal mortality (RR 0.63, 95% CI 0.32 to 1.25; three trials; N = 1943).
Satisfaction was rated marginally higher among women who were allocated to group antenatal care, but this 5 point difference is not clinically meaningful on the scale used (mean difference 4.90, 95% CI 3.10 to 6.70; one study; N = 993). No differences in neonatal intensive care admission, initiation of breastfeeding or spontaneous vaginal birth were observed between groups. Several outcomes related to stress and depression were reported in one trial. No differences between groups were observed for any of these outcomes.
No data were available on the effects of group antenatal care on care provider satisfaction.
We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to assess evidence for seven prespecified outcomes; results ranged from low quality (perinatal mortality) to moderate quality (preterm birth, low birthweight, neonatal intensive care unit admission, breastfeeding initiation) to high quality (satisfaction with antenatal care, spontaneous vaginal birth).
Authors' conclusions
Available evidence suggests that group antenatal care is acceptable to women and is associated with no adverse outcomes for them or for their babies. No differences in the rate of preterm birth were reported when women received group antenatal care. This review is limited because of the small numbers of studies and women, and because one study contributed 42% of the women. Most of the analyses are based on a single study. Additional research is required to determine whether group antenatal care is associated with significant benefit in terms of preterm birth or birthweight.
Abstract
We study galactic star formation activity as a function of environment and stellar mass over 0.5 <
z
< 2.0 using the FourStar Galaxy Evolution (ZFOURGE) survey. We estimate the galaxy ...environment using a Bayesian-motivated measure of the distance to the third nearest neighbor for galaxies to the stellar mass completeness of our survey,
at
z
= 1.3 (2.0). This method, when applied to a mock catalog with the photometric-redshift precision (
) of ZFOURGE, accurately recovers galaxies in low- and high-density environments. We quantify the environmental quenching efficiency and show that at
, it depends on galaxy stellar mass, demonstrating that the effects of quenching related to (stellar) mass and environment are not separable. In high-density environments, the mass and environmental quenching efficiencies are comparable for massive galaxies (
) at all redshifts. For lower-mass galaxies (
), the environmental quenching efficiency is very low at
, but increases rapidly with decreasing redshift. Environmental quenching can account for nearly all quiescent lower-mass galaxies (
), which appear primarily at
. The morphologies of lower-mass quiescent galaxies are inconsistent with those expected of recently quenched star-forming galaxies. Some environmental process must transform the morphologies on similar timescales as the environmental quenching itself. The evolution of the environmental quenching favors models that combine gas starvation (as galaxies become satellites) with gas exhaustion through star formation and outflows (“overconsumption”), and additional processes such as galaxy interactions, tidal stripping, and disk fading to account for the morphological differences between the quiescent and star-forming galaxy populations.
Medical journals use social media to distribute the findings of published articles. Whether social media exposure to original articles improves article impact metrics is uncertain.
Articles were ...randomized to receive targeted social media exposure from Circulation, including postings on the journal's Facebook and Twitter feeds. The primary end point was 30-day article page views. We conducted an intention-to-treat analysis comparing article page views by the Wilcoxon Rank sum test between articles randomized to social media as compared with those in the control group, which received no social media from Circulation. Prespecified subgroups included article type (population/clinical/basic), US versus non-US corresponding author, and whether the article received an editorial. Overall, 243 articles were randomized: 121 in the social media arm and 122 in the control arm. There was no difference in median 30-day page views (409 social media versus 392 control, P=0.80). No differences were observed by article type (clinical, population, or basic science; P=0.19), whether an article had an editorial (P=0.87), or whether the corresponding author was from the United States (P=0.73).
A social media strategy for a cardiovascular journal did not increase the number of times an article was viewed. Further research is necessary to understand and quantify the ways in which social media can increase the impact of published cardiovascular research.
We study the effects of galaxy environment on the evolution of the stellar mass function (SMF) over 0.2 < z < 2.0 using the FourStar Galaxy Evolution (ZFOURGE) Survey and NEWFIRM Medium-Band Survey ...(NMBS) down to the stellar mass completeness limit, (9.5) at z = 1.0 (2.0). We compare the SMFs for quiescent and star-forming galaxies in the highest and lowest environments using a density estimator based on the distance to the galaxies' third-nearest neighbors. For star-forming galaxies, at all redshifts there are only minor differences with environment in the shape of the SMF. For quiescent galaxies, the SMF in the lowest densities shows no evolution with redshift other than an overall increase in number density (φ*) with time. This suggests that the stellar mass dependence of quenching in relatively isolated galaxies both is universal and does not evolve strongly. While at , the SMF of quiescent galaxies is indistinguishable in the highest and lowest densities, at lower redshifts, it shows a rapidly increasing number density of lower-mass galaxies, , in the highest-density environments. We argue that this evolution can account for all the redshift evolution in the shape of the total quiescent galaxy SMF. This evolution in the quiescent galaxy SMF at higher redshift (z > 1) requires an environmental quenching efficiency that decreases with decreasing stellar mass at 0.5 < z < 1.5 or it would overproduce the number of lower-mass quiescent galaxies in denser environments. This requires a dominant environmental process such as starvation combined with rapid gas depletion and ejection at z > 0.5-1.0 for galaxies in our mass range. The efficiency of this process decreases with redshift, allowing other processes (such as galaxy interactions and ram-pressure stripping) to become more important at later times, z < 0.5.
CRISPR-Cas9-based genetic screens have successfully identified cell type-dependent liabilities in cancer, including acute myeloid leukemia (AML), a devastating hematologic malignancy with poor ...overall survival. Because most of these screens have been performed
using established cell lines, evaluating the physiologic relevance of these targets is critical. We have established a CRISPR screening approach using orthotopic xenograft models to validate and prioritize AML-enriched dependencies
, including in CRISPR-competent AML patient-derived xenograft (PDX) models tractable for genome editing. Our integrated pipeline has revealed several targets with translational value, including
as a metabolic vulnerability for AML addicted to exogenous myo-inositol and
as a critical guardian to prevent apoptosis in AML. MARCH5 repression enhanced the efficacy of BCL2 inhibitors such as venetoclax, further highlighting the clinical potential of targeting
in AML. Our study provides a valuable strategy for discovery and prioritization of new candidate AML therapeutic targets. SIGNIFICANCE: There is an unmet need to improve the clinical outcome of AML. We developed an integrated
screening approach to prioritize and validate AML dependencies with high translational potential. We identified
as a metabolic vulnerability and
as a critical apoptosis regulator in AML, both of which represent novel therapeutic opportunities.
.
Denitrification is a form of anaerobic respiration wherein nitrate (NO
) is sequentially reduced via nitrite (NO
), nitric oxide, and nitrous oxide (N
O) to dinitrogen gas (N
) by four reductase ...enzymes. Partial denitrifying bacteria possess only one or some of these four reductases and use them as independent respiratory modules. However, it is unclear if partial denitrifiers sense and respond to denitrification intermediates outside of their reductase repertoire. Here, we tested the denitrifying capabilities of two purple nonsulfur bacteria,
CGA0092 and
SB1003. Each had denitrifying capabilities that matched their genome annotation; CGA0092 reduced NO
to N
, and SB1003 reduced N
O to N
. For each bacterium, N
O reduction could be used both for electron balance during growth on electron-rich organic compounds in light and for energy transformation via respiration in darkness. However, N
O reduction required supplementation with a denitrification intermediate, including those for which there was no associated denitrification enzyme. For CGA0092, NO
served as a stable, non-catalyzable molecule that was sufficient to activate N
O reduction. Using a β-galactosidase reporter, we found that NO
acted, at least in part, by stimulating N
O reductase gene expression. In SB1003, NO
but not NO
activated N
O reduction, but NO
was slowly removed, likely by a promiscuous enzyme activity. Our findings reveal that partial denitrifiers can still be subject to regulation by denitrification intermediates that they cannot use.IMPORTANCEDenitrification is a form of microbial respiration wherein nitrate is converted via several nitrogen oxide intermediates into harmless dinitrogen gas. Partial denitrifying bacteria, which individually have some but not all denitrifying enzymes, can achieve complete denitrification as a community by cross-feeding nitrogen oxide intermediates. However, the last intermediate, nitrous oxide (N2O), is a potent greenhouse gas that often escapes, motivating efforts to understand and improve the efficiency of denitrification. Here, we found that at least some partial denitrifying N2O reducers can sense and respond to nitrogen oxide intermediates that they cannot otherwise use. The regulatory effects of nitrogen oxides on partial denitrifiers are thus an important consideration in understanding and applying denitrifying bacterial communities to combat greenhouse gas emissions.
ABSTRACT
Background Methamphetamine (Meth) abuse continues to be a major illicit drug of abuse. Neuroimaging findings suggest that Meth is neurotoxic and may alter various brain structures, but the ...effect of Meth on the aging brain has not been studied.
Aim The aim was to determine regional volumes of cortical gray matter in the brains of adult Meth users versus healthy control subjects, and their interaction with age and Meth‐usage variables.
Design Cross‐sectional study
Setting Magnetic resonance imaging (MRI) Research Center located in a university‐affiliated hospital.
Participants Thirty‐four Meth‐dependent subjects (21 men and 13 women; ages 33.1 ± 8.9 years), diagnosed according to DSM‐IV criteria, and 31 healthy non‐Meth user comparison subjects (23 men and 8 women ages 35.7 ± 8.4 years).
Measurement Regional gray matter volumes were segmented automatically in all subjects and evaluated in relation to age, using high‐resolution MRIs at 3.0 Tesla.
Findings After adjustment for the effects of cranium size, the Meth users showed enhanced cortical gray matter volume loss with age in the frontal (analysis of covariance interaction P = 0.02), occipital (interaction P = 0.01), temporal (interaction P < 0.001) and the insular lobes (interaction P = 0.01) compared to controls, independently of Meth‐usage patterns. Additionally, Meth users showed smaller gray matter volumes than control subjects in several subregions (dorsolateral prefrontal: P = 0.02; orbitofrontal: P = 0.03; prefrontal: P = 0.047; superior temporal: P = 0.04).
Conclusions Methamphetamine users appear to show increased cortical gray matter loss with age which raises the possibility of accelerated decline in mental functioning.
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