Intersubject Regularity in the Intrinsic Shape of Human V1

Previous studies have reported considerable intersubject variability in the three-dimensional geometry of the human primary visual cortex (V1). Here we demonstrate that much of this variability is due to extrinsic geometric features of the cortical folds, and that the intrinsic shape of V1 is similar across individuals. V1 was imaged in ten ex vivo human hemispheres using high-resolution (200 μm) structural magnetic resonance imaging at high field strength (7 T). Manual tracings of the stria of Gennari were used to construct a surface representation, which was computationally flattened into the plane with minimal metric distortion. The instrinsic shape of V1 was determined from the boundary of the planar representation of the stria. An ellipse provided a simple parametric shape model that was a good approximation to the boundary of flattened V1. The aspect ration of the best-fitting ellipse was found to be consistent across subject, with a mean of 1.85 and standard deviation of 0.12. Optimal rigid alignment of size-normalized V1 produced greater overlap than that achieved by previous studies using different registration methods. A shape analysis of published macaque data indicated that the intrinsic shape of macaque V1 is also stereotyped, and similar to the human V1 shape. Previoud measurements of the functional boundary of V1 in human and macaque are in close agreement with these results

Phase curves of WASP-33b and HD 149026b and a New Correlation Between Phase Curve Offset and Irradiation Temperature

We present new 3.6 and 4.5 $\mu m$ Spitzer phase curves for the highly irradiated hot Jupiter WASP-33b and the unusually dense Saturn-mass planet HD 149026b. As part of this analysis, we develop a new variant of pixel level decorrelation that is effective at removing intrapixel sensitivity variations for long observations (>10 hours) where the position of the star can vary by a significant fraction of a pixel. Using this algorithm, we measure eclipse depths, phase amplitudes, and phase offsets for both planets at 3.6 $\mu m$ and 4.5 $\mu m$. We use a simple toy model to show that WASP-33b's phase offset, albedo, and heat recirculation efficiency are largely similar to those of other hot Jupiters despite its very high irradiation. On the other hand, our fits for HD 149026b prefer a very high albedo and an unusually high recirculation efficiency. We also compare our results to predictions from general circulation models, and find that while neither are a good match to the data, the discrepancies for HD 149026b are especially large. We speculate that this may be related to its high bulk metallicity, which could lead to enhanced atmospheric opacities and the formation of reflective cloud layers in localized regions of the atmosphere. We then place these two planets in a broader context by exploring relationships between the temperatures, albedos, heat transport efficiencies, and phase offsets of all planets with published thermal phase curves. We find a striking relationship between phase offset and irradiation temperature--the former drops with increasing temperature until around 3400 K, and rises thereafter. Although some aspects of this trend are mirrored in the circulation models, there are notable differences that provide important clues for future modeling efforts

3.6 and 4.5 μ\mum Spitzer{\it Spitzer} Phase Curves of the Highly-Irradiated Hot Jupiters WASP-19b and HAT-P-7b

We analyze full-orbit phase curve observations of the transiting hot Jupiters WASP-19b and HAT-P-7b at 3.6 and 4.5 $\mu$m obtained using the Spitzer Space Telescope. For WASP-19b, we measure secondary eclipse depths of $0.485\%\pm 0.024\%$ and $0.584\%\pm 0.029\%$ at 3.6 and 4.5 $\mu$m, which are consistent with a single blackbody with effective temperature $2372 \pm 60$ K. The measured 3.6 and 4.5 $\mu$m secondary eclipse depths for HAT-P-7b are $0.156\%\pm 0.009\%$ and $0.190\%\pm 0.006\%$, which are well-described by a single blackbody with effective temperature $2667\pm 57$ K. Comparing the phase curves to the predictions of one-dimensional and three-dimensional atmospheric models, we find that WASP-19b's dayside emission is consistent with a model atmosphere with no dayside thermal inversion and moderately efficient day-night circulation. We also detect an eastward-shifted hotspot, suggesting the presence of a superrotating equatorial jet. In contrast, HAT-P-7b's dayside emission suggests a dayside thermal inversion and relatively inefficient day-night circulation; no hotspot shift is detected. For both planets, these same models do not agree with the measured nightside emission. The discrepancies in the model-data comparisons for WASP-19b might be explained by high-altitude silicate clouds on the nightside and/or high atmospheric metallicity, while the very low 3.6 $\mu$m nightside planetary brightness for HAT-P-7b may be indicative of an enhanced global C/O ratio. We compute Bond albedos of 0 ($<0.08$ at $1\sigma$) and $0.38\pm 0.06$ for WASP-19b and HAT-P-7b, respectively. In the context of other planets with thermal phase curve measurements, we show that WASP-19b and HAT-P-7b fit the general trend of decreasing day-night heat recirculation with increasing irradiation.Comment: 22 pages, 29 figures, accepted by Ap

A pentapeptide as minimal antigenic determinant for MHC class I-restricted T lymphocytes

Peptides that are antigenic for T lymphocytes are ligands for two receptors, the class I or II glycoproteins that are encoded by genes in the major histocompatibility complex, and the idiotypic / chain T-cell antigen receptor1–9. That a peptide must bind to an MHC molecule to interact with a T-cell antigen receptor is the molecular basis of the MHC restriction of antigen-recognition by T lymphocytes10,11. In such a trimolecular interaction the amino-acid sequence of the peptide must specify the contact with both receptors: agretope residues bind to the MHC receptor and epitope residues bind to the T-cell antigen receptor12,13. From a compilation of known antigenic peptides, two algorithms have been proposed to predict antigenic sites in proteins. One algorithm uses linear motifs in the sequence14, whereas the other considers peptide conformation and predicts antigenicity for amphipathic -helices15,16. We report here that a systematic delimitation of an antigenic site precisely identifies a predicted pentapeptide motif as the minimal antigenic determinant presented by a class I MHC molecule and recognized by a cytolytic T lymphocyte clone

Household Disposal of Pharmaceuticals as a Pathway for Aquatic Contamination in the United Kingdom

Pharmaceuticals are produced and used in increasingly large volumes every year. With this growth comes concern about the fate and effects of these compounds in the environment. The discovery of pharmaceuticals in the aquatic environment has stimulated research in the last decade. A wide range of pharmaceuticals has been found in fresh and marine waters, and it has recently been shown that even in small quantities, some of these compounds have the potential to cause harm to aquatic life. The primary pathway into the environment is the use and disposal of medicines; although much of the research in the area currently focuses on the removal of pharmaceuticals during sewage treatment processes, disposal via household waste might be a significant pathway requiring further research. To investigate the household disposal of unused and expired pharmaceuticals as a source of pharmaceutical compounds in the environment, we carried out a survey and interviewed members of 400 households, predominantly from southeastern England. We used the information on when and how they disposed of unfinished pharmaceuticals to construct a conceptual model to assess the pathways of human pharmaceuticals into the environment. The model demonstrated that disposal of unused pharmaceuticals, either by household waste or via the sink or toilet, may be a prominent route that requires greater attention

Neoadjuvant chemoradiation compared to neoadjuvant radiation alone and surgery alone for Stage II and III soft tissue sarcoma of the extremities

<p>Abstract</p> <p>Background</p> <p>Neoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA).</p> <p>Methods</p> <p>We conducted a retrospective chart review of 112 cases.</p> <p>Results</p> <p>Treatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR.</p> <p>Conclusions</p> <p>NCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.</p

A Case-Control Study of Peripheral Blood Mitochondrial DNA Copy Number and Risk of Renal Cell Carcinoma

Background: Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results: from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S. population-based case-control study of RCC. Methodology/Principal Findings: Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1–2.2; Ptrend = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR Q1 = 1.4, 95% CI = 1.0–2.1) and to localized tumors (2.0, 1.3–2.8). Conclusions/Significance: Our findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies

Cost-effectiveness of self-management of blood pressure in hypertensive patients over 70 years with suboptimal control and established cardiovascular disease or additional cardiovascular risk diseases (TASMIN-SR).

BACKGROUND: A previous economic analysis of self-management, that is, self-monitoring with self-titration of antihypertensive medication evaluated cost-effectiveness among patients with uncomplicated hypertension. This study considered cost-effectiveness of self-management in those with raised blood pressure plus diabetes, chronic kidney disease and/or previous cardiovascular disease. DESIGN AND METHODS: A Markov model-based economic evaluation was undertaken to estimate the long-term cost-effectiveness of self-management of blood pressure in a cohort of 70-year-old 'high risk' patients, compared with usual care. The model used the results of the TASMIN-SR trial. A cost-utility analysis was undertaken from a UK health and social care perspective, taking into account lifetime costs of treatment, cardiovascular events and quality adjusted life years. A subgroup analysis ran the model separately for men and women. Deterministic sensitivity analyses examined the effect of different time horizons and reduced effectiveness of self-management. RESULTS: Base-case results indicated that self-management was cost-effective compared with usual care, resulting in more quality adjusted life years (0.21) and cost savings (-£830) per patient. There was a 99% chance of the intervention being cost-effective at a willingness to pay threshold of £20,000 per quality adjusted life year gained. Similar results were found for separate cohorts of men and women. The results were robust to sensitivity analyses, provided that the blood pressure lowering effect of self-management was maintained for more than a year. CONCLUSION: Self-management of blood pressure in high-risk people with poorly controlled hypertension not only reduces blood pressure, compared with usual care, but also represents a cost-effective use of healthcare resources.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG 0606-1153) and by the NIHR National School of Primary Care Research (NSPCR 16). The views expressed in this paper are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Service support costs were administered through the Primary Care Research Network and collaborating Comprehensive Local Research Networks. Prof McManus was supported by NIHR Career Development and Professional Fellowships, Professors Hobbs, Little and Williams are NIHR senior investigators. Professor McManus and Hobbs receive support from the NIHR CLAHRC Oxford. Professor Hobbs also receives support from the NIHR School for Primary Care Research and the NIHR Oxford BRC.This is the final version of the article. It first appeared from SAGE via https://doi.org/10.1177/204748731561878

3.6 and 4.5μm Phase Curves of the Highly Irradiated Eccentric Hot Jupiter WASP-14b

We present full-orbit phase curve observations of the eccentric (e ~ 0.08) transiting hot Jupiter WASP-14b obtained in the 3.6 and 4.5 μm bands using the Spitzer Space Telescope. We use two different methods for removing the intrapixel sensitivity effect and compare their efficacy in decoupling the instrumental noise. Our measured secondary eclipse depths of 0.1882% ± 0.0048% and 0.2247% ± 0.0086% at 3.6 and 4.5 μm, respectively, are both consistent with a blackbody temperature of 2402 ± 35 K. We place a 2σ upper limit on the nightside flux at 3.6 μm and find it to be 9% ± 1% of the dayside flux, corresponding to a brightness temperature of 1079 K. At 4.5 μm, the minimum planet flux is 30% ± 5% of the maximum flux, corresponding to a brightness temperature of 1380 ± 65 K. We compare our measured phase curves to the predictions of one-dimensional radiative transfer and three-dimensional general circulation models. We find that WASP-14b's measured dayside emission is consistent with a model atmosphere with equilibrium chemistry and a moderate temperature inversion. These same models tend to overpredict the nightside emission at 3.6 μm, while underpredicting the nightside emission at 4.5 μm. We propose that this discrepancy might be explained by an enhanced global C/O ratio. In addition, we find that the phase curves of WASP-14b (7.8 M_(Jup)) are consistent with a much lower albedo than those of other Jovian mass planets with thermal phase curve measurements, suggesting that it may be emitting detectable heat from the deep atmosphere or interior processes

Lynx X-Ray Observatory: An Overview

Lynx, one of the four strategic mission concepts under study for the 2020 Astrophysics Decadal Survey, provides leaps in capability over previous and planned x-ray missions and provides synergistic observations in the 2030s to a multitude of space- and ground-based observatories across all wavelengths. Lynx provides orders of magnitude improvement in sensitivity, on-axis subarcsecond imaging with arcsecond angular resolution over a large field of view, and high-resolution spectroscopy for point-like and extended sources in the 0.2- to 10-keV range. The Lynx architecture enables a broad range of unique and compelling science to be carried out mainly through a General Observer Program. This program is envisioned to include detecting the very first seed black holes, revealing the high-energy drivers of galaxy formation and evolution, and characterizing the mechanisms that govern stellar evolution and stellar ecosystems. The Lynx optics and science instruments are carefully designed to optimize the science capability and, when combined, form an exciting architecture that utilizes relatively mature technologies for a cost that is compatible with the projected NASA Astrophysics budget