Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH). METHODS: Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival. RESULTS: 124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m. CONCLUSION: These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Prioritisation of Clinical Research by the Example of Type 2 Diabetes: A Caregiver-Survey on Perceived Relevance and Need for Evidence

BACKGROUND: The Cochrane Collaboration aims at providing the best available evidence for interventions in health care. We wished to examine to which extent treatments considered relevant by caregivers in type 2 diabetes are covered by Cochrane systematic reviews. METHODOLOGY/PRINCIPAL FINDINGS: 130 different interventions in type 2 diabetes were identified based on a review of clinical practice guidelines and expert opinion (Table S1). 459 members of the German Diabetes Society (diabetologists, general practitioners, diabetic nurses, nutritionists, podologists, others) were surveyed via e-mail-list to rank a) the perceived clinical relevance and b) the perceived need for evidence of interventions, based on an internet survey. In the Cochrane Library, there were, at the time of this evaluation, 56 reviews on interventions in diabetes. Generally, coverage of topics by Cochrane reviews reflected the perceived clinical relevance and perceived need for evidence. As an example, highly ranked treatments such as lifestyle changes or oral antidiabetics were well covered, while low rank treatments such as complementary approaches were not covered. Discrepancies occurred with new treatments such as amylin-analogues (low relevance, high need for evidence, review not yet completed) and interventions with immediate and dramatic effects such as treating hypoglycemia (high relevance, low need for evidence, no review). Also, there was a relative scarcity of reviews concerning specific problems, in particular, treatment of late diabetic complications. CONCLUSIONS/SIGNIFICANCE: For most interventions, perceived relevance and perceived need for evidence are reflected by the evidence already available. Prioritizing should aim at improving immediacy and consideration of the treatment of complications

Bystander responses to a violent incident in an immersive virtual environment

Under what conditions will a bystander intervene to try to stop a violent attack by one person on another? It is generally believed that the greater the size of the crowd of bystanders, the less the chance that any of them will intervene. A complementary model is that social identity is critical as an explanatory variable. For example, when the bystander shares common social identity with the victim the probability of intervention is enhanced, other things being equal. However, it is generally not possible to study such hypotheses experimentally for practical and ethical reasons. Here we show that an experiment that depicts a violent incident at life-size in immersive virtual reality lends support to the social identity explanation. 40 male supporters of Arsenal Football Club in England were recruited for a two-factor between-groups experiment: the victim was either an Arsenal supporter or not (in-group/out-group), and looked towards the participant for help or not during the confrontation. The response variables were the numbers of verbal and physical interventions by the participant during the violent argument. The number of physical interventions had a significantly greater mean in the ingroup condition compared to the out-group. The more that participants perceived that the Victim was looking to them for help the greater the number of interventions in the in-group but not in the out-group. These results are supported by standard statistical analysis of variance, with more detailed findings obtained by a symbolic regression procedure based on genetic programming. Verbal interventions made during their experience, and analysis of post-experiment interview data suggest that in-group members were more prone to confrontational intervention compared to the out-group who were more prone to make statements to try to diffuse the situation

Shading by Napier Grass Reduces Malaria Vector Larvae in Natural Habitats in Western Kenya Highlands

Increased human population in the Western Kenya highlands has led to reclamation of natural swamps resulting in the creation of habitats suitable for the breeding of Anopheles gambiae, the major malaria vector in the region. Here we report on a study to restore the reclaimed swamp and reverse its suitability as a habitat for malaria vectors. Napier grass-shaded and non-shaded water channels in reclaimed sites in Western Kenya highlands were studied for the presence and density of mosquito larvae, mosquito species composition, and daily variation in water temperature. Shading was associated with 75.5% and 88.4% (P < 0.0001) reduction in anopheline larvae densities and 78.1% and 88% (P < 0.0001) reduction in Anopheles gambiae sensu lato (s.l.) densities in two sites, respectively. Shading was associated with a 5.7°C, 5.0°C, and 4.7°C, and 1.6°C, 3.9°C, and 2.8°C (for maximum, minimum, and average temperatures, respectively) reduction (P < 0.0001) in water temperatures in the two locations, respectively. An. gambiae s.l. was the dominant species, constituting 83.2% and 73.1%, and 44.5% and 42.3%, of anophelines in non-shaded and shaded channels, respectively, in the two sites, respectively. An. gambiae sensu stricto (s.s.) constituted the majority (97.4%) of An. gambiae s.l., while the rest (2.6%) comprised of Anopheles arabiensis. Minimum water temperature decreased with increasing grass height (P = 0.0039 and P = 0.0415 for Lunyerere and Emutete sites, respectively). The results demonstrate how simple environmental strategies can have a strong impact on vector densities

Physical activity, obesity and cardiometabolic risk factors in 9- to 10-year-old UK children of white European, South Asian and black African-Caribbean origin: the Child Heart And health Study in England (CHASE)

Physical inactivity is implicated in unfavourable patterns of obesity and cardiometabolic risk in childhood. However, few studies have quantified these associations using objective physical activity measurements in children from different ethnic groups. We examined these associations in UK children of South Asian, black African-Caribbean and white European origin. This was a cross-sectional study of 2,049 primary school children in three UK cities, who had standardised anthropometric measurements, provided fasting blood samples and wore activity monitors for up to 7 days. Data were analysed using multilevel linear regression and allowing for measurement error. Overall physical activity levels showed strong inverse graded associations with adiposity markers (particularly sum of skinfold thicknesses), fasting insulin, HOMA insulin resistance, triacylglycerol and C-reactive protein; for an increase of 100 counts of physical activity per min of registered time, levels of these factors were 12.2% (95% CI 10.2-14.1%), 10.2% (95% CI 7.5-12.8%), 10.2% (95% CI 7.5-12.8%), 5.8% (95% CI 4.0-7.5%) and 19.2% (95% CI 13.9-24.2%) lower, respectively. Similar increments in physical activity levels were associated with lower diastolic blood pressure (1.0 mmHg, 95% CI 0.6-1.5 mmHg) and LDL-cholesterol (0.04 mmol/l, 95% CI 0.01-0.07 mmol/l), and higher HDL-cholesterol (0.02 mmol/l, 95% CI 0.01-0.04 mmol/l). Moreover, associations were broadly similar in strength in all ethnic groups. All associations between physical activity and cardiometabolic risk factors were reduced (albeit variably) after adjustment for adiposity. Objectively measured physical activity correlates at least as well with obesity and cardiometabolic risk factors in South Asian and African-Caribbean children as in white European children, suggesting that efforts to increase activity levels in such groups would have equally beneficial effect

Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Diabetes mellitus, as well as subsequent ocular complications such as cystoid macular edema (CME), are of fundametal socio-economic relevance. Therefore, we evaluated the influence of internal limiting membrane (ILM) removal on longterm morphological and functional outcome in patients with diabetes mellitus (DM) type 2 and chronic CME without evident vitreomacular traction. METHOD: Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively. Prior focal (n = 31) or panretinal (n = 25) laser coagulation was permitted. Group I (n = 19 patients) underwent surgical induction of posterior vitreous detachment (PVD), group II (n = 20 patients) PVD and removal of the ILM. Eleven patients with detached posterior hyaloid (group III) were not randomized, and ILM removal was performed. One eye had to be excluded from further analysis. Examinations included ETDRS best-corrected visual acuity (BCVA), fluorescein angiography (FLA) and OCT at baseline, 3 and 6 months postoperatively. Main outcome measure was BCVA at 6 months, secondary was foveal thickness. RESULTS: Mean BCVA over 6 months remained unchanged in 85% of patients of group II, and decreased in 53% of patients of group I. Results were not statistically significant different [group I: mean decrease log MAR 95% CI (0.06; 0.32), group II: (-0.02; 0.11)]. OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [group I: mean change: 95% CI (-208.95 μm; -78.05 μm), group II: (-80.90 μm: +59.17 μm)]. CONCLUSION: Vitrectomy, PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction. ILM delamination shows improved morphological results, and appears to be beneficial in eyes with preexisting PVD