Abstract
The origin of magnetic fields in clusters of galaxies is still a matter of debate. Observations for intracluster magnetic fields over a wide range of redshifts are crucial to constrain ...possible scenarios for the origin and evolution of the fields. Differences in Faraday rotation measures (RMs) of an embedded double radio source, i.e., a pair of lobes of mostly Fanaroff–Riley type II radio galaxies, are free from the Faraday rotation contributions from the interstellar medium inside the Milky Way and the intergalactic medium between radio galaxies and us, and hence provide a novel way to estimate average magnetic field within galaxy clusters. We have obtained a sample of 627 pairs whose RMs and redshifts are available in the most updated RM catalogs and redshift databases. The RM differences of the pairs are derived. The statistically large RM differences for pairs of redshifts
z
> 0.9 indicate that intracluster magnetic fields are as strong as about 4
μ
G. Such strong magnetic fields in the intracluster medium at the half age of the universe, comparable to the intracluster field strength in nearby galaxy clusters, pose a challenge to the theories of the origin of cosmic magnetic fields.
Abstract
Background
According to a landmark study by the Institute of Medicine, patients with cancer often receive poorly coordinated care in multiple settings from many providers. Lack of ...coordination is associated with poor symptom control, medical errors, and higher costs.
Purpose
The aims of this systematic review and meta-analysis were to (1) synthesize the findings of studies addressing cancer care coordination, (2) describe study outcomes across the cancer continuum, and (3) obtain a quantitative estimate of the effect of interventions in cancer care coordination on service system processes and patient health outcomes.
Methods
Of 1241 abstracts identified through MEDLINE, EMBASE, CINAHL, and the Cochrane Library, 52 studies met the inclusion criteria. Each study had US or Canadian participants, comparison or control groups, measures, times, samples, and/or interventions. Two researchers independently applied a standardized search strategy, coding scheme, and online coding program to each study. Eleven studies met the additional criteria for the meta-analysis; a random effects estimation model was used for data analysis.
Results
Cancer care coordination approaches led to improvements in 81 % of outcomes, including screening, measures of patient experience with care, and quality of end-of-life care. Across the continuum of cancer care, patient navigation was the most frequent care coordination intervention, followed by home telehealth; nurse case management was third in frequency. The meta-analysis of a subset of the reviewed studies showed that the odds of appropriate health care utilization in cancer care coordination interventions were almost twice (OR = 1.9, 95 % CI = 1.5–3.5) that of comparison interventions.
Conclusions
This review offers promising findings on the impact of cancer care coordination on increasing value and reducing healthcare costs in the USA.
Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis-with death within 3 years of diagnosis-most often due to transformation to ...aggressive disease.
In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.
At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4-positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present.
These results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.
Uncertainty and affect are fundamental and interrelated aspects of the human condition. Uncertainty is often associated with negative affect, but in some circumstances, it is associated with positive ...affect. In this article, we review different explanations for the varying relationship between uncertainty and affect. We identify “mental simulation” as a key process that links uncertainty to affective states. We suggest that people have a propensity to simulate negative outcomes, which result in a propensity toward negative affective responses to uncertainty. We also propose the existence of several important moderators of this process, including context and individual differences such as uncertainty tolerance, as well as emotion regulation strategies. Finally, we highlight important knowledge gaps and promising areas for future research, both empirical and conceptual, to further elucidate the relationship between uncertainty and affect.
Summary
Background Psoriasis has been linked to cardiovascular comorbidities in cross‐sectional studies, but evidence regarding the association between psoriasis and incident cardiovascular disease ...(CVD) is limited.
Objectives To make a prospective evaluation of the association between psoriasis and risk of incident nonfatal CVD.
Methods Participants (n = 96 008) were included from the Nurses’ Health Study II, and followed for 18 years. Information on physician‐diagnosed psoriasis was obtained by self‐report and diagnosis was confirmed by supplementary questionnaires. We included 2463 individuals with self‐reported psoriasis and a subsample of 1242 with validated psoriasis. The main outcome was incident nonfatal CVD events nonfatal myocardial infarction (MI) and nonfatal stroke, ascertained by biennial questionnaires and confirmed.
Results During 1 709 069 person‐years of follow‐up, 713 incident nonfatal CVD events were confirmed. Psoriasis was associated with a significantly increased multivariate‐adjusted hazard ratio (HR) of nonfatal CVD, 1·55 95% confidence interval (CI): 1·04–2·31. HRs for nonfatal MI and stroke were 1·70 (95% CI: 1·01–2·84) and 1·45 (95% CI: 0·80–2·65), respectively. The association remained consistent in a sensitivity analysis of confirmed psoriasis (HR: 2·06, 95% CI: 1·31–3·26). For individuals with concomitant psoriatic arthritis, the risk of nonfatal CVD was even higher (HR: 3·47; 95% CI: 1·85–6·51). Women diagnosed with psoriasis at < 40 years of age or with duration of psoriasis ≥ 9 years had substantial elevations in CVD risk: HR: 3·26 (95% CI: 1·21–8·75) and 3·09 (95% CI: 1·15–8·29), respectively.
Conclusions Psoriasis is an independent predictor for nonfatal CVD among women, with particularly high risk for those with longer duration of psoriasis and concomitant psoriatic arthritis.
Does psi exist? D. J. Bem (2011) conducted 9 studies with over 1,000 participants in an attempt to demonstrate that future events retroactively affect people's responses. Here we discuss several ...limitations of Bem's experiments on psi; in particular, we show that the data analysis was partly exploratory and that one-sided p values may overstate the statistical evidence against the null hypothesis. We reanalyze Bem's data with a default Bayesian t test and show that the evidence for psi is weak to nonexistent. We argue that in order to convince a skeptical audience of a controversial claim, one needs to conduct strictly confirmatory studies and analyze the results with statistical tests that are conservative rather than liberal. We conclude that Bem's p values do not indicate evidence in favor of precognition; instead, they indicate that experimental psychologists need to change the way they conduct their experiments and analyze their data.
Classical Hodgkin lymphoma (cHL) represents a B-cell lymphoproliferative disease characterized by clonal immunoglobulin gene rearrangements and recurrent genomic aberrations in the Hodgkin ...Reed–Sternberg cells in a reactive inflammatory background. Several methods are available for the molecular analysis of cHL on both tissue and cell-free DNA isolated from blood, which can provide detailed information regarding the clonal composition and genetic alterations that drive lymphoma pathogenesis. Clonality testing involving the detection of immunoglobulin and T cell receptor gene rearrangements, together with mutation analysis, represent valuable tools for cHL diagnostics, especially for patients with an atypical histological or clinical presentation reminiscent of a reactive lesion or another lymphoma subtype. In addition, clonality assessment may establish the clonal relationship of composite or subsequent lymphoma presentations within one patient. During the last few decades, more insight has been obtained on the molecular mechanisms that drive cHL development, including recurrently affected signaling pathways (e.g., NF-κB and JAK/STAT) and immune evasion. We provide an overview of the different approaches to characterize the molecular composition of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.
We present the measurements of Faraday rotation for 477 pulsars observed by the Parkes 64 m radio telescope and the Green Bank 100 m radio telescope. Using these results, along with previous ...measurements for pulsars and extragalactic sources, we analyze the structure of the large-scale magnetic field in the Galactic disk. Comparisons of rotation measures of pulsars in the disk at different distances, as well as with rotation measures of background radio sources beyond the disk, reveal large-scale reversals of the field directions between the spiral arms and interarm regions. We develop a model for the disk magnetic field, which can reproduce not only these reversals but also the distribution of the observed rotation measures of background sources.
In AURA3 (NCT02151981), osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), significantly prolonged progression-free survival and improved ...response in patients with EGFR T790M advanced non-small-cell lung cancer (NSCLC) and progression on prior EGFR-TKI treatment. We report the final AURA3 overall survival (OS) analysis.
Adult patients were randomized 2 : 1 to osimertinib (80 mg orally, once daily) or pemetrexed plus carboplatin/cisplatin (platinum–pemetrexed) intravenously, every 3 weeks (≤6 cycles). Patients could crossover to osimertinib on progression confirmed by blinded independent central review. OS and safety were secondary end points.
A total of 279 patients were randomly assigned to receive osimertinib and 140 to platinum–pemetrexed (136 received treatment). At data cut-off (DCO; 15 March 2019), 188 patients (67%) receiving osimertinib versus 93 (66%) receiving platinum–pemetrexed had died. The hazard ratio (HR) for OS was 0.87 95% confidence interval (CI) 0.67–1.12; P = 0.277; the median OS was 26.8 months (95% CI 23.5–31.5) versus 22.5 months (95% CI 20.2–28.8) for osimertinib and platinum–pemetrexed, respectively. The estimated 24- and 36-month survival was 55% versus 43% and 37% versus 30%, respectively. After crossover adjustment, there was an HR of 0.54 (95% CI 0.18–1.6). Time to first subsequent therapy or death showed a clinically meaningful advantage toward osimertinib (HR 0.21, 95% CI 0.16–0.28; P < 0.001). At DCO, 99/136 (73%) patients in the platinum–pemetrexed arm had crossed over to osimertinib, 66/99 (67%) of whom had died. The most common adverse events possibly related to study treatment were diarrhea (32%; grade ≥3, 1%) and rash (grouped term; 32%; grade ≥3, <1%) in the osimertinib arm, versus nausea (47%; grade ≥3, 3%) in the platinum–pemetrexed arm.
In patients with T790M advanced NSCLC, no statistically significant benefit in OS was observed for osimertinib versus platinum–pemetrexed, which possibly reflects the high crossover rate of patients from platinum–pemetrexed to osimertinib.
ClinicalTrials.gov NCT02151981; https://clinicaltrials.gov/ct2/show/NCT02151981.
•Median OS with osimertinib was 26.8 months versus 22.5 months with platinum–pemetrexed (HR 0.87, 95% CI 0.67–1.12; P = 0.277).•The lack of a significant survival benefit could reflect high percentage (73%) of platinum–pemetrexed to osimertinib crossover.•Analysis of OS adjusted for crossover showed an HR of 0.54 (95% CI 0.18–1.60).•Among patients receiving subsequent anticancer therapy, platinum chemotherapy was the most common after osimertinib (65%).•Grade ≥3 (possibly treatment-related) adverse events were observed less frequently with osimertinib (9% versus 34% with platinum–pemetrexed).
Mechanical cues can influence the manner in which cells generate traction forces and form focal adhesions. The stiffness of a cell’s substrate and the available area on which it can spread can ...influence its generation of traction forces, but to what extent these factors are intertwined is unclear. In this study, we used microcontact printing and micropost arrays to control cell spreading, substrate stiffness, and post density to assess their effect on traction forces and focal adhesions. We find that both the spread area and the substrate stiffness influence traction forces in an independent manner, but these factors have opposite effects: cells on stiffer substrates produce higher average forces, whereas cells with larger spread areas generate lower average forces. We show that post density influences the generation of traction forces in a manner that is more dominant than the effect of spread area. Additionally, we observe that focal adhesions respond to spread area, substrate stiffness, and post density in a manner that closely matches the trends seen for traction forces. This work supports the notion that traction forces and focal adhesions have a close relationship in their response to mechanical cues.
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