The non-absoluteness of model existence in uncountable cardinals for Lw1,w

"Vegeu el resum a l'inici del document del fitxer adjunt"

Non-characteristic half-lives in radioactive decay

Half-lives of radionuclides span more than 50 orders of magnitude. We characterize the probability distribution of this broad-range data set at the same time that explore a method for fitting power-laws and testing goodness-of-fit. It is found that the procedure proposed recently by Clauset et al. [SIAM Rev. 51, 661 (2009)] does not perform well as it rejects the power-law hypothesis even for power-law synthetic data. In contrast, we establish the existence of a power-law exponent with a value around 1.1 for the half-life density, which can be explained by the sharp relationship between decay rate and released energy, for different disintegration types. For the case of alpha emission, this relationship constitutes an original mechanism of power-law generation.

Caffeine intake and CYP1A2 variants associated with high caffeine intake protect non-smokers from hypertension.

The 15q24.1 locus, including CYP1A2, is associated with blood pressure (BP). The CYP1A2 rs762551 C allele is associated with lower CYP1A2 enzyme activity. CYP1A2 metabolizes caffeine and is induced by smoking. The association of caffeine consumption with hypertension remains controversial. We explored the effects of CYP1A2 variants and CYP1A2 enzyme activity on BP, focusing on caffeine as the potential mediator of CYP1A2 effects. Four observational (n = 16 719) and one quasi-experimental studies (n = 106) including European adults were conducted. Outcome measures were BP, caffeine intake, CYP1A2 activity and polymorphisms rs762551, rs1133323 and rs1378942. CYP1A2 variants were associated with hypertension in non-smokers, but not in smokers (CYP1A2-smoking interaction P = 0.01). Odds ratios (95% CIs) for hypertension for rs762551 CC, CA and AA genotypes were 1 (reference), 0.78 (0.59-1.02) and 0.66 (0.50-0.86), respectively, P = 0.004. Results were similar for the other variants. Higher CYP1A2 activity was linearly associated with lower BP after quitting smoking (P = 0.049 and P = 0.02 for systolic and diastolic BP, respectively), but not while smoking. In non-smokers, the CYP1A2 variants were associated with higher reported caffeine intake, which in turn was associated with lower odds of hypertension and lower BP (P = 0.01). In Mendelian randomization analyses using rs1133323 as instrument, each cup of caffeinated beverage was negatively associated with systolic BP [-9.57 (-16.22, -2.91) mmHg]. The associations of CYP1A2 variants with BP were modified by reported caffeine intake. These observational and quasi-experimental results strongly support a causal role of CYP1A2 in BP control via caffeine intake.

SwissSidechain: a molecular and structural database of non-natural sidechains.

Amino acids form the building blocks of all proteins. Naturally occurring amino acids are restricted to a few tens of sidechains, even when considering post-translational modifications and rare amino acids such as selenocysteine and pyrrolysine. However, the potential chemical diversity of amino acid sidechains is nearly infinite. Exploiting this diversity by using non-natural sidechains to expand the building blocks of proteins and peptides has recently found widespread applications in biochemistry, protein engineering and drug design. Despite these applications, there is currently no unified online bioinformatics resource for non-natural sidechains. With the SwissSidechain database (http://www.swisssidechain.ch), we offer a central and curated platform about non-natural sidechains for researchers in biochemistry, medicinal chemistry, protein engineering and molecular modeling. SwissSidechain provides biophysical, structural and molecular data for hundreds of commercially available non-natural amino acid sidechains, both in l- and d-configurations. The database can be easily browsed by sidechain names, families or physico-chemical properties. We also provide plugins to seamlessly insert non-natural sidechains into peptides and proteins using molecular visualization software, as well as topologies and parameters compatible with molecular mechanics software.

An audit of diagnostic reference levels in interventional cardiology and radiology: are there differences between academic and non-academic centres?

A wide variation in patient exposure has been observed in interventional radiology and cardiology. The purpose of this study was to investigate the patient dose from fluoroscopy-guided procedures performed in non-academic centres when compared with academic centres. Four procedures (coronary angiography, percutaneous coronary intervention, angiography of the lower limbs and percutaneous transluminal angioplasty of the lower limbs) were evaluated. Data on the dose-area product, fluoroscopy time and number of images for 1000 procedures were obtained from 23 non-academic centres and compared with data from 5 academic centres. No differences were found for cardiology procedures performed in non-academic centres versus academic ones. However, significantly lower doses were delivered to patients for procedures of the lower limbs when they were performed in non-academic centres. This may be due to more complex procedures performed in the academic centres. Comparison between the centres showed a great variation in the patient dose for these lower limb procedures.

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10-3 to 0.76×10-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

Prolonged antiretroviral therapy initiated at seroconversion is associated with a polyfunctional HIV-1-specific T-cell profile comparable to that of long-term non-progressors (LTNPs)

Background: Early initiation of antiretroviral therapy (ART) may dramatically curtail cumulative immunological damage allowing maximal levels of immune preservation/reconstitution and induce an immunovirological status similar to that of HIV-1 LTNPs with low viral reservoirs and polyfunctional HIV-1 specific T cell responses.Methods: We performed a cross-sectional study of an HIV-1 seroconverter cohort on long-term ART (LTTS) and compared it to one of LTNPs. Inclusion criteria for 20 LTTS were: (a) ?4 years ART; (b) long-term aviremia and (c) absence of treatment failure and for 15 LTNPs: (a) ?7 years of documented HIV-1 infection; (b) <1000 HIV-1 RNA copies/mL and ?500 CD4+ T-cells/mm3 in >90% of measurements; (d) absence of AIDS-defining conditions; (e) ART-naı¨ve except for temporary ART for prevention of MTCT. In both cohorts, we analysed residual viral replication and reservoirs in peripheral blood, as measured by cellassociated HIV-1 RNA and DNA in PBMCs, respectively and used polychromatic flow cytometry to analyse HIV-1-specific CD4+ and CD8+ T-cell functional profile in terms of cytokine production using IFN-c, IL-2, TNF-a production.Results: Cell-associated DNA [47.7 (4.8-583.2) in LTTS and 19.7 (0.5-295.5) in LTNPS, p=0.10], and RNA [3.9 (0-36) and 5.8 (0-10.3), respectively] were shown to be similarly low in both cohorts. We identified 103 CD8 T cell epitope-specific responses, all subjects responding to ?1 epitope. Mean responding number of responding epitopes per patient was 2 and 4 in LTTS and LTNPS, respectively. Mean% of cytokine-secreting CD8 T cells was 0.37% and 0.50% (p=0.06), of these 43% and 39% (p=0.12) were secreting simultaneously IFN-c, IL-2 and TNF-a. Respective values for CD4 T cells were 0.28% and 0.33% (p=0.28) of which 33% and 30% (0.32) were secreting these 3 cytokines simultaneously.Conclusions: Long-term aviremia after very early ART initiation is associated with low levels of reservoirs saturation ad residual replication. Although less broad CD8 T cell responses were found in LTTS, HIV-1 specific CD4 and CD8 T cell responses showed similar magnitude and functional profile in the 2 cohorts. Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs. (BHIVA Research Award Winner 2008: Anna Garcia-Diaz.)

The Office International des Epizooties ad hoc Group on Non Tsetse Animal Trypanosomoses: Its Origin, Scope and Perspectives

A summary of the goals and activities of the ad hoc group on Non Tsetse Transmitted Animal Trypanosomosis belonging to the Office International des Epizooties is presented.

Distribution of Sandflies (Diptera:Psychodidae) on Tree-trunks in a Non-flooded Area of the Ducke Forest Reserve, Manaus, AM, Brazil

Sandflies were collected in the base of tree-trunks in the seasons of high and least rainfall in the Ducke Forest Reserve, near Manaus in the State of Amazonas. Lutzomyia umbratilis was the most abundant sandfly species. Caryocar villosum, Chrysophyllum amazonicum, Dinizia excelsa, Eschweilera atropetiolata and Parkia multijuga were the tree species on which most sandflies were collected and relative abundance were related to trunk characteristics. Seasonal patterns of sandfly distribution in the forest were observed.

Life-threatening versus non-life-threatening manual strangulation: are there appropriate criteria for MR imaging of the neck?

The aim of the study was to determine objective radiological signs of danger to life in survivors of manual strangulation and to establish a radiological scoring system for the differentiation between life-threatening and non-life-threatening strangulation by dividing the cross section of the neck into three zones (superficial, middle and deep zone). Forensic pathologists classified 56 survivors of strangulation into life-threatening and non-life-threatening cases by history and clinical examination alone, and two blinded radiologists evaluated the MRIs of the neck. In 15 cases, strangulation was life-threatening (27%), compared with 41 cases in which strangulation was non-life-threatening (73%). The best radiological signs on MRI to differentiate between the two groups were intramuscular haemorrhage/oedema, swelling of platysma and intracutaneous bleeding (all p = 0.02) followed by subcutaneous bleeding (p = 0.034) and haemorrhagic lymph nodes (p = 0.04), all indicating life-threatening strangulation. The radiological scoring system showed a sensitivity and specificity of approximately 70% for life-threatening strangulation, when at least two neck zones were affected. MRI is not only helpful in assessing the severity of strangulation, but is also an excellent documentation tool that is even admissible in court.

Patient-ventilator asynchrony during non-invasive ventilation for acute respiratory failure: a multicenter study.

OBJECTIVE : To determine the prevalence of patient-ventilator asynchrony in patients receiving non-invasive ventilation (NIV) for acute respiratory failure. DESIGN : Prospective multicenter observation study. SETTING : Intensive care units in three university hospitals. METHODS: Patients consecutively admitted to ICU were included. NIV, performed with an ICU ventilator, was set by the clinician. Airway pressure, flow, and surface diaphragmatic electromyography were recorded continuously for 30 min. Asynchrony events and the asynchrony index (AI) were determined from visual inspection of the recordings and clinical observation. RESULTS: A total of 60 patients were included, 55% of whom were hypercapnic. Auto-triggering was present in 8 (13%) patients, double triggering in 9 (15%), ineffective breaths in 8 (13%), premature cycling 7 (12%) and late cycling in 14 (23%). An AI > 10%, indicating severe asynchrony, was present in 26 patients (43%), whose median (25-75 IQR) AI was 26 (15-54%). A significant correlation was found between the magnitude of leaks and the number of ineffective breaths and severity of delayed cycling. Multivariate analysis indicated that the level of pressure support and the magnitude of leaks were weakly, albeit significantly, associated with an AI > 10%. Patient comfort scale was higher in pts with an AI < 10%. CONCLUSION: Patient-ventilator asynchrony is common in patients receiving NIV for acute respiratory failure. Our results suggest that leaks play a major role in generating patient-ventilator asynchrony and discomfort, and point the way to further research to determine if ventilator functions designed to cope with leaks can reduce asynchrony in the clinical setting.

Effects of Non-Susceptible Hosts on the Infection with Trypanosoma cruzi of the Vector Triatoma infestans: an Experimental Model

We tested experimentally the effects of the presence of non-susceptible hosts on the infection with Trypanosoma cruzi of the vector Triatoma infestans. The experiment consisted in two treatments: with chickens, including two chickens (non-susceptible hosts) and two infected guinea pigs (susceptible hosts), and without chickens, including only two infected guinea pigs. The hosts were held unrestrained in individual metal cages inside a closed tulle chamber. A total of 200 uninfected T. infestans third instar nymphs were liberated in each replica, collected on day 14, and examined for infection and blood meal sources on day 32-36. The additional presence of chickens relative to infected guinea pigs: (a) significantly modified the spatial distribution of bugs; (b) increased significantly the likelihoods of having a detectable blood meal on any host and molting to the next instar; (c) did not affect the bugs' probability of death by predation; and (d) decreased significantly the overall percentage of T. infestans infected with T. cruzi. The bugs collected from inside or close to the guinea pigs' cages showed a higher infection rate (71-88%) than those collected from the chickens' cages (22-32%). Mixed blood meals on chickens and guinea pigs were detected in 12-21% of bugs. Although the presence of chickens would decrease the overall percentage of infected bugs in short term experiments, the high rate of host change of T. infestans would make this difference fade out if longer exposure times had been provided.