Reduction in Drinking was Associated With Improved Clinical Outcomes in Women With HIV Infection and Unhealthy Alcohol Use: Results From a Randomized Clinical Trial of Oral Naltrexone Versus Placebo

Background Alcohol consumption is associated with poor health outcomes in women living with HIV (WLWH), but whether medication can help to reduce drinking in non–treatment‐seeking women or whether reduction in drinking improves HIV outcomes is unclear. We conducted a randomized clinical trial (RCT) of daily oral naltrexone (50 mg) versus placebo in WLWH who met criteria for current unhealthy alcohol use. Methods WLWH with current unhealthy alcohol use (\u3e7 drinks/wk or \u3e3 drinks/occasion) were randomly assigned to daily oral naltrexone 50 mg (n = 96) or placebo (n = 98) for 4 months. Drinking outcomes, including the proportion of women who reduced ( Results The participants’ mean age was 48 years, 86% were African American, and 94% were receiving HIV antiretroviral therapy. Among all participants, 89% and 85% completed the 4‐month and 7‐month follow‐ups, respectively. Participants in both groups substantially reduced drinking over time. At 1 and 3 months, naltrexone was associated with a greater reduction in drinking (p \u3c 0.05), but the proportion who reduced/quit drinking at 4 months (52% vs. 45%, p = 0.36) or 7 months (64% in both groups) was not different. HIV viral suppression at follow‐up was significantly better in participants who reduced/quit drinking versus those continuing unhealthy alcohol use at 4 months (72% vs. 53%, p = 0.02) and 7 months (74% vs. 54%, p = 0.02). Conclusions Participating in an RCT to reduce drinking was associated with significant drinking reduction regardless of medication assignment, suggesting that nonmedication aspects of research study participation (e.g., repeated assessments and support from research staff) could be important interventions to help reduce drinking outside of research studies. Drinking reduction was associated with improved HIV viral suppression, providing evidence to support recommendations to avoid unhealthy alcohol use among WLWH

Investigating the physical properties of transiting hot Jupiters with the 1.5-m Kuiper Telescope

We present new photometric data of 11 hot Jupiter transiting exoplanets (CoRoT-12b, HAT-P-5b, HAT-P-12b, HAT-P-33b, HAT-P-37b, WASP-2b, WASP-24b, WASP-60b, WASP-80b, WASP-103b, XO-3b) in order to update their planetary parameters and to constrain information about their atmospheres. These observations of CoRoT-12b, HAT-P-37b and WASP-60b are the first follow-up data since their discovery. Additionally, the first near-UV transits of WASP-80b and WASP-103b are presented. We compare the results of our analysis with previous work to search for transit timing variations (TTVs) and a wavelength dependence in the transit depth. TTVs may be evidence of a third body in the system and variations in planetary radius with wavelength can help constrain the properties of the exoplanet's atmosphere. For WASP-103b and XO-3b, we find a possible variation in the transit depths that may be evidence of scattering in their atmospheres. The B-band transit depth of HAT-P-37b is found to be smaller than its near-IR transit depth and such a variation may indicate TiO/VO absorption. These variations are detected from 2-4.6$\sigma$, so follow-up observations are needed to confirm these results. Additionally, a flat spectrum across optical wavelengths is found for 5 of the planets (HAT-P-5b, HAT-P-12b, WASP-2b, WASP-24b, WASP-80b), suggestive that clouds may be present in their atmospheres. We calculate a refined orbital period and ephemeris for all the targets, which will help with future observations. No TTVs are seen in our analysis with the exception of WASP-80b and follow-up observations are needed to confirm this possible detection.Comment: 18 pages, 7 figures, 9 Tables. Light Curves available online. Accepted to MNRAS (2017 August 25

A prospective, multicentre, observational cohort study of analgesia and outcome after pneumonectomy

Background Meta-analysis and systematic reviews of epidural compared with paravertebral blockade analgesia techniques for thoracotomy conclude that although the analgesia is comparable, paravertebral blockade has a better short-term side-effect profile. However, reduction in major complications including mortality has not been proven. Methods The UK pneumonectomy study was a prospective observational cohort study in which all UK thoracic surgical centres were invited to participate. Data presented here relate to the mode of analgesia and outcome. Data were analysed for 312 patients having pneumonectomy at 24 UK thoracic surgical centres in 2005. The primary endpoint was a major complication. Results The most common type of analgesia used was epidural (61.1%) followed by paravertebral infusion (31%). Epidural catheter use was associated with major complications (odds ratio 2.2, 95% confidence interval 1.1–3.8; P=0.02) by stepwise logistic regression analysis. Conclusions An increased incidence of clinically important major post-pneumonectomy complications was associated with thoracic epidural compared with paravertebral blockade analgesia. However, this study is unable to provide robust evidence to change clinical practice for a better clinical outcome. A large multicentre randomized controlled trial is now needed to compare the efficacy, complications, and cost-effectiveness of epidural and paravertebral blockade analgesia after major lung resection with the primary outcome of clinically important major morbidity

Inferring tumor progression from genomic heterogeneity

Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth. © 2010 by Cold Spring Harbor Laboratory Press

Reliability of upright posture measurements in primary school children

BACKGROUND: Correct upright posture is considered to be a measure of good musculoskeletal health. Little is known about the usual variability of children's upright standing posture. The aim of this study was to assess differences between repeated measures of upright posture in a group of primary school children. METHODS: Sagittal plane photographs of usual, relaxed upright standing posture of 38 boys and girls aged 5–12 years were taken twice within an hour. Reflective markers were placed over the canthus, tragus, C7 spinous process, greater trochanter and lateral malleolus. Digitising software was used to calculate the x,y plane coordinates, from which five postural angles were calculated (trunk, neck, gaze, head on neck, lower limb). Height, weight, motor control estimates (as measured by the Brace Tests) and presence of recent pain were recorded for each child, and the association between the first test measure of posture angles and these factors was assessed using linear regression and ANOVA models. Multiple ANOVA models were applied to analyse the effect of repeated testing, and significant predictors on the angles. RESULTS: Four of the five postural angles (trunk, neck, head on neck, lower limb) were significantly influenced by age. As age was strongly associated with height (r(2 )= 0.84) and moderately associated with weight and motor control (r(2 )= 0.67, 0.56 respectively), these developmental parameters may well explain the age effect on angles. There was no relationship between age and pain reported on either the testing day, or recently, and there was no gender influence on any angle. There was no significant effect of repeated testing on any angle (ICC>0.93). None of the hypothesized predictors were associated with differences in angles from repeated testing. CONCLUSION: This study outlined the variability of relaxed upright standing posture of children aged 5–12 years, when measured twice in an hour. Age influenced the size of the angles but not the variability. While the subject numbers in this study are small, the findings provide useful information on which further studies in posture and its development in pre-adolescent children can be based

Subclonal TP53 copy number is associated with prognosis in multiple myeloma

Multiple myeloma (MM) is a genetically heterogeneous cancer of bone marrow plasma cells with variable outcome. To assess the prognostic relevance of clonal heterogeneity of TP53 copy number, we profiled tumors from 1777 newly diagnosed Myeloma XI trial patients with multiplex ligation-dependent probe amplification (MLPA). Subclonal TP53 deletions were independently associated with shorter overall survival, with a hazard ratio of 1.8 (95% confidence interval, 1.2-2.8; P = .01). Clonal, but not subclonal, TP53 deletions were associated with clinical markers of advanced disease, specifically lower platelet counts (P < .001) and increased lactate dehydrogenase (P < .001), as well as a higher frequency of features indicative of genomic instability, del(13q) (P = .002) or del(1p) (P = .006). Biallelic TP53 loss-of-function by mutation and deletion was rare (2.4%) and associated with advanced disease. We present a framework for identifying subclonal TP53 deletions by MLPA, to improve patient stratification in MM and tailor therapy, enabling management strategies