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Background The relationship between indices of mechanical ventilation and pulmonary artery pressures remains ill-defined in ARDS. As our understanding of mechanical ventilation has progressed, there is now a greater appreciation of the impact of high driving pressures and mechanical power in perpetuating lung injury. However, the relationship between the newer derived indices of mechanical ventilation and pulmonary artery pressure is unclear. We performed a post hoc analysis of the Fluid and Catheters Treatment Trial (FACTT) trial to investigate the associations between mechanical ventilation indices in ARDS patients and the prevalence of pulmonary hypertension. This may help elucidate future clinical targets for more, right ventricular protective, mechanical ventilation strategies. Methods We performed a post hoc analysis of the FACTT database to identify ARDS patients who had a pulmonary artery catheter (PAC) inserted and pulmonary artery pressure readings recorded. We excluded any patient with a PAC inserted who was spontaneously breathing, as driving pressure and mechanical power are not validated in this cohort. Three independent analyses were performed: a univariate analysis, to assess for associations between mPAP and mechanical ventilation parameters using Pearson correlation coefficients, a multivariate analysis, to assess for independent associations with mPAP using a multiple regression model according to Akaike’s information criteria and finally an analysis for nonlinearity, using the best-fitting model according to the Bayesian information criterion (BIC) from linear, quadratic, fractional polynomial and restricted cubic spline models. Results All the ventilation parameters demonstrated a significant correlation with mPAP, except tidal volume (once adjusted for respiratory rate) in the univariate analysis. The multivariate analysis demonstrated that the blood pH level, P/F ratio, PaCO2 level, mean airway pressure and the mechanical power indexed to compliance were independently associated with mPAP. In the final nonlinear analysis, associations did not differ from linearity except for 4 variables for which the fractional polynomial was the best-fitting model. These were mechanical power (p = 0.01 compared to the linear model), respiratory rate (p = 0.04), peak pressure (p = 0.03) and mean airway pressure (p = 0.01). Two nonlinear variables associated with mPAP were assessed in more detail, respiratory rate and mechanical power. Inflexion points at a respiratory rate of 16.8 cycles per minute and a mechanical power of 8.8 J/min were demonstrated. Conclusions The associations identified between mPAP and mechanical ventilation variables in this analysis would suggest that classical ARDS lung protective strategies, including low tidal volume ventilation and permissive hypercapnia, may negatively impact the management of the subset of ARDS patients with associated right ventricular dysfunction or ACP. Additionally, respiratory rates above 17 cycles per minute show an incremental increase in mPAP. Therefore, increases in tidal volume (within the limitation of driving pressure

Background Pre-operative anaemia is associated with mortality and red blood cell (RBC) transfusion requirement after cardiac surgery. However, the effect on post-operative total morbidity burden (TMB) is unknown. We explored the effect of pre-operative anaemia on post-operative TMB. Methods Data were drawn from the Cardiac Post-Operative Morbidity Score (C-POMS) development study (n = 442). C-POMS describes and quantifies (0–13) TMB after cardiac surgery by noting the presence/absence of 13 morbidity domains on days 3 (D3), 5 (D5), 8 (D8) and 15 (D15). Anaemia was defined as a haemoglobin concentration below 130 g/l for men and 120 g/l for women. Results Most patients were White British (86.1%) and male (79.2%) and underwent coronary artery bypass surgery (67.4%). Participants with pre-operative anaemia (n = 137, 31.5%) were over three times more likely to receive RBC transfusion (OR 3.08, 95%CI 1.88–5.06, p

Background Many SNPs have been identified in genes regulating LDL-C metabolism, but whether their influence is similar in subjects from different ethnicities is unclear. Effect of 4 such SNPs on LDL-C and coronary heart disease (CHD) was examined in Pakistani subjects and was compared with middle aged UK men from Northwick Park Heart Study II (NPHSII). Methods One thousand nine hundred sixty-five (1770 non CHD, 195 CHD) UK and 623 (219 non CHD, 404 CHD) Pakistani subjects were enrolled in the study. The SNPs SORT1 rs646776, APOB rs1042031 and APOE rs429358, rs7412 were genotyped by TaqMan/KASPar technique and their gene score was calculated. LDL-C was calculated by Friedewald equation, results were analyzed using SPSS. Results Allele frequencies were significantly different (p =

Abdominal aortic aneurysm (AAA) is among a number of vascular disorders to be recently associated with a common allelic variant situated on chromosome 9p21. To further assess the significance of this region of the genome in AAA development, we genotyped the sequence variation tagged by rs10757278 in two geographically independent cohorts of patients and compared them to matched controls. We also assessed the impact of this variant on AAA growth rate in cohorts with a median surveillance period of 3.2 and 4.5 years. Using meta-analysis to combine the findings of both cohorts, we found a significant association between rs10757278-G and the presence of AAA (OR (95%CI) 1.38 (1.04–1.82) P=0.03), an effect size completely consistent with that originally reported. rs10757278 was not significantly associated with altered AAA growth rate in either cohort.

We have performed a series of three-dimensional simulations of a starburst-driven wind in an inhomogeneous interstellar medium. The introduction of an inhomogeneous disk leads to differences in the formation of a wind, most noticeably the absence of the ``blow-out'' effect seen in homogeneous models. A wind forms from a series of small bubbles that propagate into the tenuous gas between dense clouds in the disk. These bubbles merge and follow the path of least resistance out of the disk, before flowing freely into the halo. Filaments are formed from disk gas that is broken up and accelerated into the outflow. These filaments are distributed throughout a biconical structure within a more spherically distributed hot wind. The distribution of the inhomogeneous interstellar medium in the disk is important in determining the morphology of this wind, as well as the distribution of the filaments. While higher resolution simulations are required in order to ascertain the importance of mixing processes, we find that soft X-ray emission arises from gas that has been mass-loaded from clouds in the disk, as well as from bow shocks upstream of clouds, driven into the flow by the ram pressure of the wind, and the interaction between these shocks.

In 1474 healthy Caucasoid men aged 45-65 y, insulin-like growth factor II (IGF2) Apal AA homozygotes showed a mean body weight 4 kg lower than Apal GG homozygotes (77.6 +/- 10.9 kg vs 81.6 +/- 11.5 kg, P = 0.003) with heterozygotes (GA) intermediate (80.1 +/- 11.9 kg). The mean serum IGF-II concentration in 44 Apal AA individuals was significantly higher than in 48 Apal GG individuals (683.3 +/- 146.9 ng/ml vs 614.0 +/- 124.0 ng/ml, P = 0.01). An INS Pstl polymorphism showed no association with weight and it was also found to be in minimal linkage disequilibrium with the IGF2 Apal site (coefficient 0.016). The IGF2 Apal AA genotype is therefore associated with lower mean body weight but higher serum IGF-II concentrations than the GG genotype. Apal GG homozygotes incur a 1.67-fold risk of pathological Body Mass index (BMI) (> 30 kg/m2) compared with AA homozygotes.

Background Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been associated with more modest effects on triglyceride metabolism. The objective of this study was to determine whether ANGPTL4 E40K and T266M are associated with triglyceride levels in the setting of obesity and T2D, and whether modification of triglyceride levels by these genetic variants is altered by a lifestyle intervention designed to treat T2D. Methods The association of ANGPTL4 E40K and T266M with fasting triglyceride levels was investigated in 2,601 participants from the Look AHEAD Clinical Trial, all of whom had T2D and were at least overweight. Further, we tested for an interaction between genotype and treatment effects on triglyceride levels. Results Among non-Hispanic White Look AHEAD participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 ± 0.62 mmol/L, 0.33 mmol/L lower than E40 homozygotes (p = 0.001). Individuals homozygous for the minor M266 allele (MAF 30%) had triglyceride levels of 1.75 ± 0.58 mmol/L, 0.24 mmol/L lower than T266 homozygotes (p = 0.002). The association of the M266 with triglycerides remained significant even after removing K40 carriers from the analysis (p = 0.002). There was no interaction between the weight loss intervention and genotype on triglyceride levels. Conclusions This is the first study to demonstrate that the ANGPTL4 E40K and T266M variants are associated with lower triglyceride levels in the setting of T2D. In addition, our findings demonstrate that ANGPTL4 genotype status does not alter triglyceride response to a lifestyle intervention in the Look AHEAD study.