We report on a deep, multiwavelength study of the galaxy cluster MACS J1931.8−2634 using Chandra X-ray, Subaru optical and Very Large Array 1.4-GHz radio data. This cluster (z= 0.352) harbours one of ...the most X-ray luminous cool cores yet discovered, with an equivalent mass, cooling rate within the central
is ∼700 M⊙ yr−1. Unique features observed in the central core of MACS J1931.8−2634 hint to a wealth of past activity that has greatly disrupted the original cool core. The X-ray and optical data suggest oscillatory motion of the cool core along a roughly north-south direction. We also observe a spiral of relatively cool, dense, X-ray emitting gas connected to the cool core, as well as highly elongated intracluster light (ICL) surrounding the cD galaxy. For a cluster with such a high-nominal cooling rate, this cluster is missing the central metallicity peak almost always seen in the cool-core clusters, which suggest bulk transport of cool gas out to large distances from the centre. Extended radio emission is observed surrounding the central active galactic nucleus (AGN), elongated in the east-west direction, spatially coincident with X-ray cavities. The power input required to inflate these 'bubbles' is estimated from both the X-ray and radio emission to reside between P
jet∼ 4-14 × 1045 erg s−1, putting it among the most powerful jets ever observed. This combination of a powerful AGN outburst and bulk motion of the cool core has resulted in two X-ray bright ridges to form to the north and south of the central AGN at a distance of approximately 25 kpc. The northern ridge has spectral characteristics typical of cool cores: it contains low-temperature high-density metal-rich gas and is consistent with being a remnant of the cool core after it was disrupted by the AGN and bulk motions. It is also the site of Hα filaments and young stars. The X-ray spectroscopic cooling rate associated with this ridge is ∼165 M⊙ yr−1, which agrees with the estimate of the star formation rate from broad-band optical imaging (∼170 M⊙ yr−1). MACS J1931.8−2634 appears to harbour one of the most profoundly disrupted low-entropy cores observed in a cluster, and offers new insights into the survivability of cool cores in the context of hierarchical structure formation.
Thyroid hormones participate in regulating growth and homeostatic processes in vertebrates, including development and adult functioning of the reproductive system. Here we report a new stimulatory ...role of thyroid hormone on the proliferation of Sertoli cells (SCs) and single, type A undifferentiated spermatogonia (Aund) in adult zebrafish testes. A role for T3 in zebrafish testis is suggested by in situ hybridization studies, which localized thyroid receptor α (thrα) in SCs and the β (thrβ) mRNA in Sertoli and Leydig cells. Using a primary zebrafish testis tissue culture system, the effect of T3 on steroid release, spermatogenesis, and the expression of selected genes was evaluated. Basal steroid release and Leydig cell gene expression did not change in response to T3. However, in the presence of FSH, T3 potentiated gonadotropin-stimulated androgen release as well as androgen receptor (ar) and 17α-hydroxylase/17,20 lyase (cyp17a1) gene expression. Moreover, T3 alone stimulated the proliferation of both SCs and Aund, potentially resulting in newly formed spermatogonial cysts. Additional tissue culture studies demonstrated that Igf3, a new, gonad-specific member of the IGF family, mediated the stimulatory effect of T3 on the proliferation of Aund and SCs. Finally, T3 induced changes in connexin 43 mRNA levels in the testis, a known T3-responsive gene. Taken together, our studies suggest that T3 expands the population of SCs and Aund involving Igf signaling and potentiates gonadotropin-stimulated testicular androgen production as well as androgen sensitivity.
Effects of problem-based learning as reported in curricular comparison studies have been shown to be inconsistent over different medical schools. Therefore, we decided to summarize effects of a ...single well-established problem-based curriculum rather than to add up sometimes-conflicting findings from different problem-based curricula. Effect sizes were computed for 270 comparisons. The results suggest that students and graduates from the particular curriculum perform much better in the area of interpersonal skills, and with regard to practical medical skills. In addition, they consistently rate the quality of the curriculum as higher. Moreover, fewer students drop out, and those surviving need less time to graduate. Differences with respect to medical knowledge and diagnostic reasoning were on average positive but small. These outcomes are at variance with expectations voiced in recent contributions to the literature. They demonstrate that constructivist curricula can have positive effects on learning even if they deemphasize direct instruction.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Acute on chronic liver failure (ACLF) has been identified as a distinct syndrome due to acute decompensation of liver cirrhosis accompanied by extra‐hepatic organ failure, primarily caused ...by an overwhelming systemic immune response. Therapeutic plasma exchange (TPE) has been demonstrated in a randomized controlled trial to improve transplant free survival in acute liver failure. Here we investigated if TPE might have comparable beneficial effects in patients with ACLF.
Methods
Thirty‐one patients with ACLF that were treated with TPE were enrolled into this retrospective analysis and 1:1 matched to an ACLF cohort treated with standard medical therapy (SMT) only.
Results
Patients considered for a bridge to recovery (n = 21 each group) approach had a 30‐day mortality >90% that was not improved by TPE (P = .185). Deaths occurred in the SMT group at significant earlier time points compared to the patients treated with TPE (mortality at 5 days: 33.3% for TPE and 66.7% for SMT, P = .048). However, patients who received TPE as a bridge to transplant strategy (n = 10) survived in 60% of cases and demonstrated 24 hours after study inclusion a stabilization of organ dysfunction (organ failures at inclusion: 4 (3‐5) vs 24 hours after inclusion: 3 (2‐4), P = .031 and CLIF‐C‐ACLF score: 64 (49‐76) vs 54 (49‐66), P = .043) not seen in SMT patients.
Conclusions
Although these retrospective data need to be interpreted with caution, they suggest that TPE in ACLF patients is feasible but not suitable as a bridge to recovery strategy. In selected patients TPE might assist as bridge to transplant.
We sought to determine if an in‐field gait retraining program can reduce excessive impact forces and peak hip adduction without adverse changes in knee joint work during running. Thirty healthy ...at‐risk runners who exhibited high‐impact forces were randomized to retraining 21.1 (±1.9) years, 22.1 (±10.8) km/week or control groups 21.0 (±1.3) years, 23.2 (±8.7) km/week. Retrainers were cued, via a wireless accelerometer, to increase preferred step rate by 7.5% during eight training sessions performed in‐field. Adherence with the prescribed step rate was assessed via mobile monitoring. Three‐dimensional gait analysis was performed at baseline, after retraining, and at 1‐month post‐retraining. Retrainers increased step rate by 8.6% (P < 0.0001), reducing instantaneous vertical load rate (−17.9%, P = 0.003), average vertical load rate (−18.9%, P < 0.0001), peak hip adduction (2.9° ± 4.2 reduction, P = 0.005), eccentric knee joint work per stance phase (−26.9%, P < 0.0001), and per kilometer of running (−21.1%, P < 0.0001). Alterations in gait were maintained at 30 days. In the absence of any feedback, controls maintained their baseline gait parameters. The majority of retrainers were adherent with the prescribed step rate during in‐field runs. Thus, in‐field gait retraining, cueing a modest increase in step rate, was effective at reducing impact forces, peak hip adduction and eccentric knee joint work.
Motivation: Next-generation sequencing presents several statistical challenges, with one of the most fundamental being determining an individual's genotype from multiple aligned short read sequences ...at a position. Some simple approaches for genotype calling apply fixed filters, such as calling a heterozygote if more than a specified percentage of the reads have variant nucleotide calls. Other genotype-calling methods, such as MAQ and SOAPsnp, are implementations of Bayes classifiers in that they classify genotypes using posterior genotype probabilities. Results: Here, we propose a novel genotype-calling algorithm that, in contrast to the other methods, estimates parameters underlying the posterior probabilities in an adaptive way rather than arbitrarily specifying them a priori. The algorithm, which we call SeqEM, applies the well-known Expectation-Maximization algorithm to an appropriate likelihood for a sample of unrelated individuals with next-generation sequence data, leveraging information from the sample to estimate genotype probabilities and the nucleotide-read error rate. We demonstrate using analytic calculations and simulations that SeqEM results in genotype-call error rates as small as or smaller than filtering approaches and MAQ. We also apply SeqEM to exome sequence data in eight related individuals and compare the results to genotypes from an Illumina SNP array, showing that SeqEM behaves well in real data that deviates from idealized assumptions. Conclusion: SeqEM offers an improved, robust and flexible genotype-calling approach that can be widely applied in the next-generation sequencing studies. Availability and implementation: Software for SeqEM is freely available from our website: www.hihg.org under Software Download. Contact: emartin1@med.miami.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Abstract
We present precise measurements of the X-ray gas mass fraction for a sample of luminous, relatively relaxed clusters of galaxies observed with the Chandra observatory, for which independent ...confirmation of the mass results is available from gravitational lensing studies. Parametrizing the total (luminous plus dark matter) mass profiles using the model of Navarro, Frenk & White, we show that the X-ray gas mass fractions in the clusters asymptote towards an approximately constant value at a radius r
2500, where the mean interior density is 2500 times the critical density of the Universe at the redshifts of the clusters. Combining the Chandra results on the X-ray gas mass fraction and its apparent redshift dependence with recent measurements of the mean baryonic matter density in the Universe and the Hubble constant determined from the Hubble Key Project, we obtain a tight constraint on the mean total matter density of the Universe, , and measure a positive cosmological constant, . Our results are in good agreement with recent, independent findings based on analyses of anisotropies in the cosmic microwave background radiation, the properties of distant supernovae, and the large-scale distribution of galaxies.
Abstract
Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatiotemporal patterns of ...genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterize variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.
OBJECTIVE Overlapping surgery-the performance of parts of 2 or more surgical procedures at the same time by a single lead surgeon-has recently come under intense scrutiny, although data on the ...effects of overlapping procedures on patient outcomes are lacking. The authors examined the impact of overlapping surgery on complication rates in neurosurgical patients. METHODS The authors conducted a retrospective review of consecutive nonemergent neurosurgical procedures performed during the period from May 12, 2014, to May 12, 2015, by any of 5 senior neurosurgeons at a single institution who were authorized to schedule overlapping cases. Overlapping surgery was defined as any case in which 2 patients under the care of a single lead surgeon were under anesthesia at the same time for any duration. Information on patient demographics, premorbid conditions, surgical variables, and postoperative course were collected and analyzed. Primary outcome was the occurrence of any complication from the beginning of surgery to 30 days after discharge. A secondary outcome was the occurrence of a serious complication-defined as a life-threatening or life-ending event-during this same period. RESULTS One thousand eighteen patients met the inclusion criteria for the study. Of these patients, 475 (46.7%) underwent overlapping surgery. Two hundred seventy-one patients (26.6%) experienced 1 or more complications, with 134 (13.2%) suffering a serious complication. Fourteen patients in the cohort died, a rate of 1.4%. The overall complication rate was not significantly higher for overlapping cases than for nonoverlapping cases (26.3% vs 26.9%, p = 0.837), nor was the rate of serious complications (14.7% vs 11.8%, p = 0.168). After adjustments for surgery type, surgery duration, body mass index, American Society of Anesthesiologists (ASA) physical classification grade, and intraoperative blood loss, overlapping surgery remained unassociated with overall complications (OR 0.810, 95% CI 0.592-1.109, p = 0.189). Similarly, after adjustments for surgery type, surgery duration, body mass index, ASA grade, and neurological comorbidity, there was no association between overlapping surgery and serious complications (OR 0.979, 95% CI 0.661-1.449, p = 0.915). CONCLUSIONS In this cohort, patients undergoing overlapping surgery did not have an increased risk for overall complications or serious complications. Although this finding suggests that overlapping surgery can be performed safely within the appropriate framework, further investigation is needed in other specialties and at other institutions.
Autologous stem cell transplantation (ASCT) with subsequent lenalidomide maintenance is standard consolidation therapy for multiple myeloma, and a subset of patients achieve durable progression-free ...survival that is suggestive of long-term immune control. Nonetheless, most patients ultimately relapse, suggesting immune escape. TIGIT appears to be a potent inhibitor of myeloma-specific immunity and represents a promising new checkpoint target. Here we demonstrate high expression of TIGIT on activated CD8+ T cells in mobilized peripheral blood stem cell grafts from patients with myeloma. To guide clinical application of TIGIT inhibition, we evaluated identical anti-TIGIT antibodies that do or do not engage FcγR and demonstrated that anti-TIGIT activity is dependent on FcγR binding. We subsequently used CRBN mice to investigate the efficacy of anti-TIGIT in combination with lenalidomide maintenance after transplantation. Notably, the combination of anti-TIGIT with lenalidomide provided synergistic, CD8+ T cell-dependent, antimyeloma efficacy. Analysis of bone marrow (BM) CD8+ T cells demonstrated that combination therapy suppressed T cell exhaustion, enhanced effector function, and expanded central memory subsets. Importantly, these immune phenotypes were specific to the BM tumor microenvironment. Collectively, these data provide a logical rationale for combining TIGIT inhibition with immunomodulatory drugs to prevent myeloma progression after ASCT.
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