Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient’s clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.

Comparing open-source DEM frameworks for simulations of common bulk processes

Multiple software frameworks based on the Discrete Element Method (DEM) are available for simulating granular materials. All of them employ the same principles of explicit time integration, with each time step consisting of three main steps: contact detection, calculation of interactions, and integration of the equations of motion. However, there exist significant algorithmic differences, such as the choice of contact models, particle and wall shapes, and data analysis methods. Further differences can be observed in the practical implementation, including data structures, architecture, parallelization and domain decomposition techniques, user interaction, and the documentation of resources. This study compares, verifies, and benchmarks nine widely-used software frameworks. Only open-source packages were considered, as these are freely available and their underlying algorithms can be reviewed, edited, and tested. The benchmark consists of three common bulk processes: silo emptying, drum mixing, and particle impact. To keep it simple and comparable, only standard features were used, such as spherical particles and the Hertz-Mindlin model for dry contacts. Scripts for running the benchmarks in each software are provided as a dataset.</p

Velocity-Metallicity Correlation for high-z DLA Galaxies: Evidence for a Mass-Metallicity Relation?

We used our database of VLT-UVES quasar spectra to build up a sample of 70 Damped Lyman-alpha (DLA) or strong sub-DLA systems with total neutral hydrogen column densities of log N(HI)>20 and redshifts in the range 1.7<z_abs<4.3. For each of the systems, we measured in an homogeneous manner the metallicities relative to Solar, [X/H] (with X=Zn, or S or Si), and the velocity widths of low-ionization line profiles, Delta V. We provide for the first time evidence for a correlation between DLA metallicity and line profile velocity width, which is detected at the 6.1sigma significance level. This confirms the trend previously observed in a much smaller sample by Wolfe & Prochaska (1998). The best-fit linear relation is [X/H]=1.55(\pm 0.12) log Delta V -4.33(\pm 0.23) with Delta V expressed in km/s. The slope of the DLA velocity-metallicity relation is the same within uncertainties between the higher (z_abs>2.43) and the lower (z_abs<2.43) redshift halves of our sample. However, the two populations of systems are statistically different. There is a strong redshift evolution in the sense that the mean metallicity and mean velocity width increase with decreasing redshift. We argue that the existence of a DLA velocity-metallicity correlation, over more than a factor of 100 spread in metallicity, is probably the consequence of an underlying mass-metallicity relation for the galaxies responsible for DLA absorption lines. Assuming a simple linear scaling of the galaxy luminosity with the mass of the dark-matter halo, we find that the slope of the DLA velocity-metallicity relation is consistent with that of the luminosity-metallicity relation derived for local galaxies. [...] abridged.Comment: 10 pages, 4 figures, A&A in pres

Comparing open-source DEM frameworks for simulations of common bulk processes

Multiple software frameworks based on the Discrete Element Method (DEM) are available for simulating granular materials. All of them employ the same principles of explicit time integration, with each time step consisting of three main steps: contact detection, calculation of interactions, and integration of the equations of motion. However, there exist significant algorithmic differences, such as the choice of contact models, particle and wall shapes, and data analysis methods. Further differences can be observed in the practical implementation, including data structures, architecture, parallelization and domain decomposition techniques, user interaction, and the documentation of resources.This study compares, verifies, and benchmarks nine widely-used software frameworks. Only open-source packages were considered, as these are freely available and their underlying algorithms can be reviewed, edited, and tested. The benchmark consists of three common bulk processes: silo emptying, drum mixing, and particle impact. To keep it simple and comparable, only standard features were used, such as spherical particles and the Hertz-Mindlin model for dry contacts. Scripts for running the benchmarks in each software are provided as a dataset

Explanations for the Lower Rates of Diabetic Neuropathy in Indian Asians Versus Europeans

OBJECTIVE - Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS - This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS - Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (-0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO2) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO2 (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS - Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk. © 2010 by the American Diabetes Association

Discovery of a compact gas-rich DLA galaxy at z = 2.2: evidences for a starburst-driven outflow

We present the detection of Ly-alpha, [OIII] and H-alpha emission associated with an extremely strong DLA system (N(HI) = 10^22.10 cm^-2) at z=2.207 towards the quasar SDSS J113520-001053. This is the largest HI column density ever measured along a QSO line of sight, though typical of what is seen in GRB-DLAs. This absorption system also classifies as ultrastrong MgII system with W2796_r=3.6 A. The mean metallicity of the gas ([Zn/H]=-1.1) and dust depletion factors ([Zn/Fe]=0.72, [Zn/Cr]=0.49) are consistent with (and only marginally larger than) the mean values found in the general QSO-DLA population. The [OIII]-Ha emitting region has a very small impact parameter with respect to the QSO line of sight, b=0.1", and is unresolved. From the Ha line, we measure SFR=25 Msun/yr. The Ly-a line is double-peaked and is spatially extended. More strikingly, the blue and red Ly-a peaks arise from distinct regions extended over a few kpc on either side of the star-forming region. We propose that this is the consequence of Ly-a transfer in outflowing gas. The presence of starburst-driven outflows is also in agreement with the large SFR together with a small size and low mass of the galaxy (Mvir~10^10 Msun). From the stellar UV continuum luminosity of the galaxy, we estimate an age of at most a few 10^7 yr, again consistent with a recent starburst scenario. We interpret the data as the observation of a young, gas rich, compact starburst galaxy, from which material is expelled through collimated winds powered by the vigorous star formation activity. We substantiate this picture by modelling the radiative transfer of Ly-a photons in the galactic counterpart. Though our model (a spherical galaxy with bipolar outflowing jets) is a simplistic representation of the true gas distribution and velocity field, the agreement between the observed and simulated properties is particularly good. [abridged]Comment: 15 pages, 18 figures, 4 tables, accepted for publication in Astronomy and Astrophysic

A protocol for a trial of homeopathic treatment for irritable bowel syndrome

Background Irritable bowel syndrome is a chronic condition with no known cure. Many sufferers seek complementary and alternative medicine including homeopathic treatment. However there is much controversy as to the effectiveness of homeopathic treatment. This three-armed study seeks to explore the effectiveness of individualised homeopathic treatment plus usual care compared to both an attention control plus usual care and usual care alone, for patients with irritable bowel syndrome. Methods/design This is a three-armed pragmatic randomised controlled trial using the cohort multiple randomised trial methodology. Patients are recruited to an irritable bowel syndrome cohort from primary and secondary care using GP databases and consultants lists respectively. From this cohort patients are randomly selected to be offered, 5 sessions of homeopathic treatment plus usual care, 5 sessions of supportive listening plus usual care or usual care alone. The primary clinical outcome is the Irritable Bowel Syndrome Symptom Severity at 26 weeks. From a power calculation, it is estimated that 33 people will be needed for the homeopathic treatment arm and 132 for the usual care arm, to detect a minimal clinical difference at 80 percent power and 5 percent significance allowing for loss to follow up. An unequal group size has been used for reasons of cost. Analysis will be by intention to treat and will compare homeopathic treatment with usual care at 26 weeks as the primary analysis, and homeopathic treatment with supportive listening as an additional analysis. Discussion This trial has received NHS approval and results are expected in 2013. Trial registration Current Controlled Trials ISRCTN9065114

Clinical improvement and radiological progression in a girl with early onset scoliosis (EOS) treated conservatively – a case report

BACKGROUND: Chêneau-Brace treatment of a certain standard reduces the rate of surgery, prevents progression and in a certain patient population leads to marked improvement of Cobb angle and cosmetic appearance. During the last two years a patient refusing surgery with a double major curvature of initially 60° showed a clear cosmetic improvement and a clear radiological progression at the same time. The findings of this patient have been reviewed in order to find out how cosmetic appearance and Cobb angle can develop differently. METHODS: The patient entered conservative treatment at the age of 13 years, premenarchial with Tanner II and a Cobb angle of 60° thoracic and 59° lumbar. The angle of trunk rotation (ATR; Scoliometer) was 13° thoracic and 13° lumbar. We have documented the findings of this patient (Surface topography, ATR, Cobb angles and angles of vertebral rotation (according to Raimondi) during the treatment period (27 Month) until 2 years after the onset of menarche. RESULTS: After a treatment time of 27 Month the Cobb angle increased to 74° thoracic and 65° lumbar. The angles of vertebral rotation according to Raimondi increased slightly from 26° thoracic and 28° lumbar to 30° thoracic and 28° lumbar. The ATR improved to 12° thoracic and 5° lumbar while Lateral deviation improved from 22,4 mm to 4,6 mm and average surface rotation improved from 10,6° to 6°. In the X-rays a reduction of decompensation was visible. The patient felt comfortable with the cosmetic result. CONCLUSION: Conservative treatment may improve cosmetic appearance while the curve progresses radiologically. This could be explained by assuming that (1) the Rigo Chêneau brace is able to improve cosmetic appearance by changing the shape of the thorax when the curve itself is too stiff to be corrected by a brace, that (2) reduction of decompensation leads to significant cosmetical improvements or (3) that the patient gained weight and therefore the deformation is masked. However, the weight the patient gained cannot explain the cosmetical improvement in this case. Conservative treatment with a certain standard of quality seems a viable alternative for patients with Cobb angles of > 60° when surgical treatment is refused. Specialists in scoliosis management should be aware of the fact that curve progression can occur even if the clinical measurements show an improvement

Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review

<p>Abstract</p> <p>Background</p> <p>Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population.</p> <p>Methods</p> <p>Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded.</p> <p>Results</p> <p>A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.</p> <p>Conclusions</p> <p>The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.</p