Debilitating consequences of drooling

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Ices in the edge-on disk CRBR 2422.8-3423: Spitzer spectroscopy and Monte Carlo radiative transfer modeling

We present 5.2-37.2 micron spectroscopy of the edge-on circumstellar disk CRBR 2422.8-3423 obtained using the InfraRed Spectrograph (IRS) of the Spitzer Space Telescope. The IRS spectrum is combined with ground-based 3-5 micron spectroscopy to obtain a complete inventory of solid state material present along the line of sight toward the source. We model the object with a 2D axisymmetric (effectively 3D) Monte Carlo radiative transfer code. It is found that the model disk, assuming a standard flaring structure, is too warm to contain the very large observed column density of pure CO ice, but is possibly responsible for up to 50% of the water, CO2 and minor ice species. In particular the 6.85 micron band, tentatively due to NH4+, exhibits a prominent red wing, indicating a significant contribution from warm ice in the disk. It is argued that the pure CO ice is located in the dense core Oph-F in front of the source seen in the submillimeter imaging, with the CO gas in the core highly depleted. The model is used to predict which circumstances are most favourable for direct observations of ices in edge-on circumstellar disks. Ice bands will in general be deepest for inclinations similar to the disk opening angle, i.e. ~70 degrees. Due to the high optical depths of typical disk mid-planes, ice absorption bands will often probe warmer ice located in the upper layers of nearly edge-on disks. The ratios between different ice bands are found to vary by up to an order of magnitude depending on disk inclination due to radiative transfer effects caused by the 2D structure of the disk. Ratios between ice bands of the same species can therefore be used to constrain the location of the ices in a circumstellar disk. [Abstract abridged]Comment: 49 pages, accepted for publication in Ap

DNA Nucleobase Synthesis at Titan Atmosphere Analog by Soft X-rays

Titan, the largest satellite of Saturn, has an atmosphere chiefly made up of N2 and CH4 and includes traces of many simple organic compounds. This atmosphere also partly consists of haze and aerosol particles which during the last 4.5 gigayears have been processed by electric discharges, ions, and ionizing photons, being slowly deposited over the Titan surface. In this work, we investigate the possible effects produced by soft X-rays (and secondary electrons) on Titan aerosol analogs in an attempt to simulate some prebiotic photochemistry. The experiments have been performed inside a high vacuum chamber coupled to the soft X-ray spectroscopy beamline at the Brazilian Synchrotron Light Source, Campinas, Brazil. In-situ sample analyses were performed by a Fourier transform infrared spectrometer. The infrared spectra have presented several organic molecules, including nitriles and aromatic CN compounds. After the irradiation, the brownish-orange organic residue (tholin) was analyzed ex-situ by gas chromatographic (GC/MS) and nuclear magnetic resonance (1H NMR) techniques, revealing the presence of adenine (C5H5N5), one of the constituents of the DNA molecule. This confirms previous results which showed that the organic chemistry on the Titan surface can be very complex and extremely rich in prebiotic compounds. Molecules like these on the early Earth have found a place to allow life (as we know) to flourish.Comment: To appear in Journal of Physical Chemistry A.; Number of pages: 6; Number of Figures: 5; Number of Tables: 1; Number of references:49; Full paper at http://pubs.acs.org/doi/abs/10.1021/jp902824

Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study

Effisayil 1 was a multicentre, randomized, double‐blind, placebo‐controlled study of the anti‐interleukin (IL)‐36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre‐specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline

EQ-5D in skin conditions: an assessment of validity and responsiveness

Aims and objectives This systematic literature review aims to assess the reliability, validity and responsiveness of three widely used generic preference-based measures of health-related quality of life (HRQL), i.e., EQ-5D, Health Utility Index 3 (HUI3) and SF-6D in patients with skin conditions. Methods A systematic search was conducted to identify studies reporting health state utility values obtained using EQ-5D, SF-6D, or HUI3 alongside other HRQL measures or clinical indices for patients with skin conditions. Data on test-retest analysis for reliability, known group differences or correlation and regression analyses for validity, and change over time or responsiveness indices analysis were extracted and reviewed. Results A total of 16 papers reporting EQ-5D utilities in people with skin conditions were included in the final review. No papers for SF-6D and HUI3 were found. Evidence of reliability was not found for any of these measures. The majority of studies included in the review (12 out of 16) examined patients with plaque psoriasis or psoriatic arthritis and the remaining four studies examined patients with either acne, hidradenitis suppurativa, hand eczema, or venous leg ulcers. The findings were generally positive in terms of performance of EQ-5D. Six studies showed that EQ-5D was able to reflect differences between severity groups and only one reported differences that were not statistically significant. Four studies found that EQ-5D detected differences between patients and the general population, and differences were statistically different for three of them. Further, moderate-to-strong correlation coefficients were found between EQ-5D and other skin-specific HRQL measures in four studies. Eight studies showed that EQ-5D was able to detect change in HRQL appropriately over time and the changes were statistically significant in seven studies. Conclusions Overall, the validity and responsiveness of the EQ-5D was found to be good in people with skin diseases, especially plaque psoriasis or psoriatic arthritis. No evidence on SF-6D and HUI3 was available to enable any judgments to be made on their performance

Can we <i>S</i>ave the rectum by watchful waiting or <i>T</i>rans<i>A</i>nal microsurgery following (chemo) <i>R</i>adiotherapy versus total mesorectal excision for early <i>RE</i>ctal <i>C</i>ancer (STAR-TREC study)?::protocol for a multicentre, randomised feasibility study

Introduction Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. Methods and analysis STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2

Hysterectomy Does Not Cause Constipation

PURPOSE: This study was designed to evaluate the risk on development and persistence of constipation after hysterectomy. METHODS: We conducted a prospective, observational, multicenter study with three-year follow-up in 13 teaching and nonteaching hospitals in the Netherlands. A total of 413 females who underwent hysterectomy for benign disease other than symptomatic uterine prolapse were included. All patients underwent vaginal hysterectomy, subtotal abdominal hysterectomy, or total abdominal hysterectomy. A validated disease-specific quality-of-life questionnaire was completed before and three years after surgery to assess the presence of constipation. RESULTS: Of the 413 included patients, 344 (83 percent) responded at three-year follow-up. Constipation had developed in 7 of 309 patients (2 percent) without constipation before surgery and persisted in 16 of 35 patients (46 percent) with constipation before surgery. Preservation of the cervix seemed to be associated with an increased risk of the development of constipation (relative risk, 6.6; 95 percent confidence interval, 1.3-33.3; P=0.02). Statistically significant risk factors for the persistence of constipation could not be identified. CONCLUSIONS: Hysterectomy does not seem to cause constipation. In nearly half of the patients reporting constipation before hysterectomy, this symptom will disappear

Problem solving ability and repetition of deliberate self-harm: a multicentre study.

Background. While recent studies have found problem-solving impairments in individuals who engage in deliberate self-harm (DSH), few studies have examined repeaters and non-repeaters separately. The aim of the present study was to investigate whether specific types of problem-solving are associated with repeated DSH. Method. As part of the WHO/EURO Multicentre Study on Suicidal Behaviour, 836 medically treated DSH patients (59% repeaters) from 12 European regions were interviewed using the European Parasuicide Study Interview Schedule (EPSIS II) approximately 1 year after their index episode. The Utrecht Coping List (UCL) assessed habitual responses to problems. Results. Factor analysis identified five dimensions – Active Handling, Passive-Avoidance, Problem Sharing, Palliative Reactions and Negative Expression. Passive-Avoidance – characterized by a pre-occupation with problems, feeling unable to do anything, worrying about the past and taking a gloomy view of the situation, a greater likelihood of giving in so as to avoid difficult situations, the tendency to resign oneself to the situation, and to try to avoid problems – was the problem-solving dimension most strongly associated with repetition, although this association was attenuated by self-esteem. Conclusions. The outcomes of the study indicate that treatments for DSH patients with repeated episodes should include problem-solving interventions. The observed passivity and avoidance of problems (coupled with low self-esteem) associated with repetition suggests that intensive therapeutic input and follow-up are required for those with repeated DSH