NICMOS Observations of the Transiting Hot Jupiter XO-1b

We refine the physical parameters of the transiting hot Jupiter planet XO-1b and its stellar host XO-1 using HST NICMOS observations. XO-1b has a radius Rp=1.21+/-0.03 RJup, and XO-1 has a radius Rs=0.94+/-0.02 RSun, where the uncertainty in the mass of XO-1 dominates the uncertainty of Rp and Rs. There are no significant differences in the XO-1 system properties between these broad-band NIR observations and previous determinations based upon ground-based optical observations. We measure two transit timings from these observations with 9 s and 15 s precision. As a residual to a linear ephemeris model, there is a 2.0 sigma timing difference between the two HST visits that are separated by 3 transit events (11.8 days). These two transit timings and additional timings from the literature are sufficient to rule out the presence of an Earth mass planet orbiting in 2:1 mean motion resonance coplanar with XO-1b. We identify and correct for poorly understood gain-like variations present in NICMOS time series data. This correction reduces the effective noise in time series photometry by a factor of two, for the case of XO-1.Comment: 13 pages, 8 figures, submitted to Ap

Averaged Energy Inequalities for the Non-Minimally Coupled Classical Scalar Field

The stress energy tensor for the classical non-minimally coupled scalar field is known not to satisfy the point-wise energy conditions of general relativity. In this paper we show, however, that local averages of the classical stress energy tensor satisfy certain inequalities. We give bounds for averages along causal geodesics and show, e.g., that in Ricci-flat background spacetimes, ANEC and AWEC are satisfied. Furthermore we use our result to show that in the classical situation we have an analogue to the phenomenon of quantum interest. These results lay the foundations for analogous energy inequalities for the quantised non-minimally coupled fields, which will be discussed elsewhere.Comment: 8 pages, RevTeX4. Minor typos corrected; version to appear in Phys Rev

Improving Effective Surgical Delivery in Humanitarian Disasters: Lessons from Haiti

Kathryn Chu and colleagues describe the experiences of Médecins sans Frontières after the 2010 Haiti earthquake, and discuss how to improve delivery of surgery in humanitarian disasters

A Search for Exozodiacal Clouds with Kepler

Planets embedded within dust disks may drive the formation of large scale clumpy dust structures by trapping dust into resonant orbits. Detection and subsequent modeling of the dust structures would help constrain the mass and orbit of the planet and the disk architecture, give clues to the history of the planetary system, and provide a statistical estimate of disk asymmetry for future exoEarth-imaging missions. Here we present the first search for these resonant structures in the inner regions of planetary systems by analyzing the light curves of hot Jupiter planetary candidates identified by the Kepler mission. We detect only one candidate disk structure associated with KOI 838.01 at the 3-sigma confidence level, but subsequent radial velocity measurements reveal that KOI 838.01 is a grazing eclipsing binary and the candidate disk structure is a false positive. Using our null result, we place an upper limit on the frequency of dense exozodi structures created by hot Jupiters. We find that at the 90% confidence level, less than 21% of Kepler hot Jupiters create resonant dust clumps that lead and trail the planet by ~90 degrees with optical depths >~5*10^-6, which corresponds to the resonant structure expected for a lone hot Jupiter perturbing a dynamically cold dust disk 50 times as dense as the zodiacal cloud.Comment: 22 pages, 6 figures, Accepted for publication in Ap

Homocysteine, grey matter and cognitive function in adults with cardiovascular disease

Background: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. Methods: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. Results: Participants with high tHcy (≥15 μmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. Conclusions: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that the relationship is not causal

Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84-17.0] and UC (OR 10.8; 95% CI 1.8-64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49-5.39; and OR 0.21; 95% CI 0.21-1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84-34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46-6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47-43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28-14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD

A Multidimensional Analytical Comparison of Remicade and the Biosimilar Remsima

In April 2016, the Food and Drug Administration approved the first biosimilar monoclonal antibody (mAb) – Inflectra/Remsima (Celltrion) based off the original product Remicade (infliximab, Janssen). Biosimilars promise significant cost savings for patients, but the unavoidable differences between innovator and copycat biologics raise questions regarding product interchangeability. In this study, Remicade and Remsima were examined by native mass spectrometry, ion mobility and quantitative peptide mapping. The levels of oxidation, deamidation and mutation of individual amino acids were remarkably similar. We found different levels of C-terminal truncation, soluble protein aggregates and glycation that all likely have a limited clinical impact. Importantly, we identified over 25 glycoforms for each product and observed glycoform population differences, with afucosylated glycans accounting for 19.7% of Remicade and 13,2% of Remsima glycoforms, which translated into a 2-fold reduction in FcγRIIIa binding for Remsima. While this difference was acknowledged in Remsima regulatory filings, our glycoform analysis and receptor binding results appear to be somewhat different from the published values, likely due to methodological differences between laboratories and improved glycoform identification by our laboratory using a peptide map-based method. Our mass spectrometry based analysis provides rapid and robust analytical information vital for biosimilar development. We have demonstrated the utility of our multiple attribute monitoring workflow using the model mAbs Remicade and Remsima, and have provided a template for analysis of future mAb biosimilars

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects