Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila.

Tissue-specific mRNA stability is important for cell fate and physiology, but the mechanisms involved are not fully understood. We found that zygotic mRNA stability in Drosophila correlates with codon content: optimal codons are enriched in stable transcripts associated with metabolic functions like translation, while non-optimal codons are enriched in unstable transcripts, including those associated with neural development. Bioinformatic analyses and reporter assays revealed that similar codons stabilize or destabilize mRNAs in the nervous system and other tissues, but the link between codon content and stability is attenuated in the nervous system. We confirmed that optimal codons are decoded by abundant tRNAs while non-optimal codons are decoded by less abundant tRNAs in embryos and in the nervous system. We conclude that codon optimality is a general determinant of zygotic mRNA stability, and attenuation of codon optimality allows trans-acting factors to exert greater influence over mRNA decay in the nervous system

Male Pattern Baldness in Relation to Prostate Cancer–Specific Mortality: A Prospective Analysis in the NHANES I Epidemiologic Follow-up Study

We used male pattern baldness as a proxy for long-term androgen exposure and investigated the association of dermatologist-assessed hair loss with prostate cancer–specific mortality in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. From the baseline survey (1971–1974), we included 4,316 men who were 25–74 years of age and had no prior cancer diagnosis. We estimated hazard ratios and used Cox proportional hazards regressions with age as the time metric and baseline hazard stratified by baseline age. A hybrid framework was used to account for stratification and clustering of the sample design, with adjustment for the variables used to calculate sample weights. During follow-up (median, 21 years), 3,284 deaths occurred; prostate cancer was the underlying cause of 107. In multivariable models, compared with no balding, any baldness was associated with a 56% higher risk of fatal prostate cancer (hazard ratio = 1.56; 95% confidence interval: 1.02, 2.37), and moderate balding specifically was associated with an 83% higher risk (hazard ratio = 1.83; 95% confidence interval: 1.15, 2.92). Conversely, patterned hair loss was not statistically significantly associated with all-cause mortality. Our analysis suggests that patterned hair loss is associated with a higher risk of fatal prostate cancer and supports the hypothesis of overlapping pathophysiological mechanisms

Medical Students\u27 Experiences and Outcomes Using a Virtual Human Simulation to Improve Communication Skills: Mixed Methods Study

Background: Attending to the wide range of communication behaviors that convey empathy is an important but often underemphasized concept to reduce errors in care, improve patient satisfaction, and improve cancer patient outcomes. A virtual human (VH)–based simulation, MPathic-VR, was developed to train health care providers in empathic communication with patients and in interprofessional settings and evaluated through a randomized controlled trial. Objective: This mixed methods study aimed to investigate the differential effects of a VH-based simulation developed to train health care providers in empathic patient-provider and interprofessional communication. Methods: We employed a mixed methods intervention design, involving a comparison of 2 quantitative measures—MPathic-VR–calculated scores and the objective structured clinical exam (OSCE) scores—with qualitative reflections by medical students about their experiences. This paper is a secondary, focused analysis of intervention arm data from the larger trial. Students at 3 medical schools in the United States (n=206) received simulation to improve empathic communication skills. We conducted analysis of variance, thematic text analysis, and merging mixed methods analysis. Results: OSCE scores were significantly improved for learners in the intervention group (mean 0.806, SD 0.201) compared with the control group (mean 0.752, SD 0.198; F1,414=6.09; P=.01). Qualitative analysis revealed 3 major positive themes for the MPathic-VR group learners: gaining useful communication skills, learning awareness of nonverbal skills in addition to verbal skills, and feeling motivated to learn more about communication. Finally, the results of the mixed methods analysis indicated that most of the variation between high, middle, and lower performers was noted about nonverbal behaviors. Medium and high OSCE scorers most often commented on the importance of nonverbal communication. Themes of motivation to learn about communication were only present in middle and high scorers. Conclusions: VHs are a promising strategy for improving empathic communication in health care. Higher performers seemed most engaged to learn, particularly nonverbal skills

A VSA search for the extended Sunyaev-Zel'dovich Effect in the Corona Borealis Supercluster

We present interferometric imaging at 33 GHz of the Corona Borealis supercluster, using the extended configuration of the Very Small Array. A total area of 24 deg^2 has been imaged, with an angular resolution of 11 arcmin and a sensitivity of 12 mJy/beam. The aim of these observations is to search for Sunyaev-Zel'dovich (SZ) detections from known clusters of galaxies in this supercluster and for a possible extended SZ decrement due to diffuse warm/hot gas in the intercluster medium. We measure negative flux values in the positions of the ten richest clusters in the region. Collectively, this implies a 3.0-sigma detection of the SZ effect. In the clusters A2061 and A2065 we find decrements of approximately 2-sigma. Our main result is the detection of two strong and resolved negative features at -70+-12 mJy/beam (-157+-27 microK) and -103+-10 mJy/beam (-230+-23 microK), respectively, located in a region with no known clusters, near the centre of the supercluster. We discuss their possible origins in terms of primordial CMB anisotropies and/or SZ signals related to either unknown clusters or to a diffuse extended warm/hot gas distribution. Our analyses have revealed that a primordial CMB fluctuation is a plausible explanation for the weaker feature (probability of 37.82%). For the stronger one, neither primordial CMB (probability of 0.33%) nor SZ can account alone for its size and total intensity. The most reasonable explanation, then, is a combination of both primordial CMB and SZ signal. Finally, we explore what characteristics would be required for a filamentary structure consisting of warm/hot diffuse gas in order to produce a significant contribution to such a spot taking into account the constraints set by X-ray data.Comment: 16 pages, 10 figures. Accepted in MNRA

Initial Construct Validity Evidence of a Virtual Human Application for Competency Assessment in Breaking Bad News to a Cancer Patient

Background: Despite interest in using virtual humans (VHs) for assessing health care communication, evidence of validity is limited. We evaluated the validity of a VH application, MPathic-VR, for assessing performance-based competence in breaking bad news (BBN) to a VH patient. Methods: We used a two-group quasi-experimental design, with residents participating in a 3-hour seminar on BBN. Group A (n=15) completed the VH simulation before and after the seminar, and Group B (n=12) completed the VH simulation only after the BBN seminar to avoid the possibility that testing alone affected performance. Pre-and postseminar differences for Group A were analyzed with a paired t-test, and comparisons between Groups A and B were analyzed with an independent t-test. Results: Compared to the preseminar result, Group A\u27s postseminar scores improved significantly, indicating that the VH program was sensitive to differences in assessing performance-based competence in BBN. Postseminar scores of Group A and Group B were not significantly different, indicating that both groups performed similarly on the VH program. Conclusion: Improved pre-post scores demonstrate acquisition of skills in BBN to a VH patient. Pretest sensitization did not appear to influence posttest assessment. These results provide initial construct validity evidence that the VH program is effective for assessing BBN performance-based communication competence

First results from the Very Small Array -- I. Observational methods

The Very Small Array (VSA) is a synthesis telescope designed to image faint structures in the cosmic microwave background on degree and sub-degree angular scales. The VSA has key differences from other CMB interferometers with the result that different systematic errors are expected. We have tested the operation of the VSA with a variety of blank-field and calibrator observations and cross-checked its calibration scale against independent measurements. We find that systematic effects can be suppressed below the thermal noise level in long observations; the overall calibration accuracy of the flux density scale is 3.5 percent and is limited by the external absolute calibration scale.Comment: 9 pages, 10 figures, MNRAS in press (Minor revisions

Observations of Galactic star-forming regions with the Cosmic Background Imager at 31 GHz

Studies of the diffuse Galactic radio emission are interesting both for better understanding the physical conditions in our Galaxy and for minimizing the contamination in cosmological measurements. Motivated by this, we present Cosmic Background Imager 31 GHz observations of the Galactic regions NGC 6357, NGC 6334, W51 and W40 at ∼4.5 arcmin resolution and conduct an investigation of the spectral emission process in the regions at 4.5 arcmin and 1° resolution. We find that most of the emission in the regions is due to optically thin free–free. For two sub-regions of NGC 6334 and for a sub-region of W51 though, at 4.5 arcmin resolution and at 31 GHz we detect less emission than expected from extrapolation of radio data at lower frequencies assuming a spectral index of −0.12 for optically thin free–free emission, at 3.3σ, 3.7σ and 6.5σ, respectively. We also detect excess emission in a sub-region of NCG 6334 at 6.4σ, after ruling out any possible contribution from ultra-compact H II regions. At 1° resolution, we detect a spinning dust component in the spectral energy distribution of W40 that accounts for 18 ± 7 per cent of the total flux density in the region at the peak frequency of 37 GHz. Comparison with 100 μm data indicates an average dust emissivity for the sub-regions of 0.5 ± 4.4 μK(MJy sr^(−1))^(−1). Finally, we translate the excess emission in the regions to an anomalous microwave emission (AME) emissivity relative to the optical depth at 250 μm. We find that this form of emissivity is independent of the AME significance and has a value somewhere in the order of 10^4 Jy

Lymphoblastoid Cell Lines as a Tool to Study Inter-Individual Differences in the Response to Glucose

Background: White blood cells have been shown in animal studies to play a central role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are immortalized EBV-transformed primary B-cell leukocytes that have been extensively used as a model for conditions in which white blood cells play a primary role. The purpose of this study was to investigate whether lymphoblastoid cell lines, by retaining many of the key features of primary leukocytes, can be induced with glucose to demonstrate relevant biological responses to those found in diabetic retinopathy. Methods: Lymphoblastoid cell lines were obtained from twenty-three human subjects. Differences between high and standard glucose conditions were assessed for expression, endothelial adhesion, and reactive oxygen species. Results: Collectively, stimulation of the lymphoblastoid cell lines with high glucose demonstrated corresponding changes on molecular, cellular and functional levels. Lymphoblastoid cell lines up-regulated expression of a panel of genes associated with the leukocyte-mediated inflammation found in diabetic retinopathy that include: a cytokine (IL-1B fold change = 2.11, p-value = 0.02), an enzyme (PKCB fold change = 2.30, p-value = 0.01), transcription factors (NFKB-p50 fold change = 2.05, p-value = 0.01), (NFKB-p65 fold change = 2.82, p-value = 0.003), and an adhesion molecule (CD18 fold change = 2.59, 0.02). Protein expression of CD18 was also increased (p-value = 2.14x10-5). The lymphoblastoid cell lines demonstrated increased adhesiveness to endothelial cells (p = 1.28x10-5). Reactive oxygen species were increased (p = 2.56x10-6). Significant inter-individual variation among the lymphoblastoid cell lines in these responses was evident (F = 18.70, p Conclusions: Exposure of lymphoblastoid cell lines derived from different human subjects to high glucose demonstrated differential and heterogeneous gene expression, adhesion, and cellular effects that recapitulated features found in the diabetic state. Lymphoblastoid cells may represent a useful tool to guide an individualized understanding of the development and potential treatment of diabetic complications like retinopathy.</p

CMB observations from the CBI and VSA: A comparison of coincident maps and parameter estimation methods

We present coincident observations of the Cosmic Microwave Background (CMB) from the Very Small Array (VSA) and Cosmic Background Imager (CBI) telescopes. The consistency of the full datasets is tested in the map plane and the Fourier plane, prior to the usual compression of CMB data into flat bandpowers. Of the three mosaics observed by each group, two are found to be in excellent agreement. In the third mosaic, there is a 2 sigma discrepancy between the correlation of the data and the level expected from Monte Carlo simulations. This is shown to be consistent with increased phase calibration errors on VSA data during summer observations. We also consider the parameter estimation method of each group. The key difference is the use of the variance window function in place of the bandpower window function, an approximation used by the VSA group. A re-evaluation of the VSA parameter estimates, using bandpower windows, shows that the two methods yield consistent results.Comment: 10 pages, 6 figures. Final version. Accepted for publication in MNRA