Plasma ferritin concentrations are not associated with abdominal aortic aneurysm diagnosis, size or growth

Background and aims: Experimental studies using a rodent model have suggested that iron overload may contribute to abdominal aortic aneurysm (AAA) pathogenesis. Methods: We assessed the association of total body iron, as measured by plasma ferritin, with AAA diagnosis, size and growth in 4024 community-dwelling older men screened for AAA, using logistic regression and linear mixed effects models. Results: Plasma ferritin concentrations were similar in men who did (n = 293) and did not (n = 3731) have an AAA (median [inter-quartile range] concentrations 115.4 [63.0–203.1] and 128.5 [66.1–229.1] ng/mL respectively, p = 0.124). There was no association between plasma ferritin concentration and AAA diagnosis in unadjusted logistic regression (odds ratio (OR) for a 1 standard deviation increase: 0.880 [95%CI: 0.764–1.015]; p = 0.078), or when adjusting for AAA risk factors and factors known to influence circulating ferritin (OR for a 1 standard deviation increase: 0.898 [95% CI: 0.778–1.035]; p = 0.138). Iron overload prevalence (plasma ferritin concentrations >200 ng/mL) was lower in men with an AAA (25.3%) than those without (30.8%; p = 0.048), but was not associated with AAA diagnosis after adjusting as above (OR: 0.781 [95% CI:0.589–1.035]; p = 0.086). The association of iron overload with AAA growth was investigated in 265 men with small AAAs who received at least 1 repeat ultrasound scan in the 3 years following screening. We saw no difference in AAA growth between men who did and did not have iron overload (n = 65 and 185 respectively, p = 0.164). Conclusions: Our data suggest that iron overload is unlikely to be important in AAA pathogenesis

Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): Study protocol for a randomised controlled trial

Background: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. Methods/design: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair. A total of 42 participants scheduled for an elective open AAA repair will be randomly assigned to either 145 mg of fenofibrate per day or identical placebo for a minimum period of 2 weeks prior to surgery. Primary outcome measures will be macrophage number and osteopontin (OPN) concentration within the AAA wall as well as serum concentrations of OPN. Secondary outcome measures will include levels of matrix metalloproteinases and proinflammatory cytokines within the AAA wall, periaortic fat and intramural thrombus and circulating concentrations of AAA biomarkers. Discussion: At present, there is no recognised medical therapy to limit AAA progression. The FAME trial aims to assess the ability of fenofibrate to alter tissue markers of AAA pathology. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12612001226897. Registered on 20 November 2012. © 2017 The Author(s)

Nearly Perfect Fluidity: From Cold Atomic Gases to Hot Quark Gluon Plasmas

Shear viscosity is a measure of the amount of dissipation in a simple fluid. In kinetic theory shear viscosity is related to the rate of momentum transport by quasi-particles, and the uncertainty relation suggests that the ratio of shear viscosity eta to entropy density s in units of hbar/k_B is bounded by a constant. Here, hbar is Planck's constant and k_B is Boltzmann's constant. A specific bound has been proposed on the basis of string theory where, for a large class of theories, one can show that eta/s is greater or equal to hbar/(4 pi k_B). We will refer to a fluid that saturates the string theory bound as a perfect fluid. In this review we summarize theoretical and experimental information on the properties of the three main classes of quantum fluids that are known to have values of eta/s that are smaller than hbar/k_B. These fluids are strongly coupled Bose fluids, in particular liquid helium, strongly correlated ultracold Fermi gases, and the quark gluon plasma. We discuss the main theoretical approaches to transport properties of these fluids: kinetic theory, numerical simulations based on linear response theory, and holographic dualities. We also summarize the experimental situation, in particular with regard to the observation of hydrodynamic behavior in ultracold Fermi gases and the quark gluon plasma.Comment: 76 pages, 11 figures, review article, extensive revision

Thermodynamic Measurements in a Strongly Interacting Fermi Gas

We conduct a series of measurements on the thermodynamic properties of an optically-trapped strongly interacting Fermi gas, including the energy $E$, entropy $S$, and sound velocity $c$. Our model-independent measurements of $E$ and $S$ enable a precision study of the finite temperature thermodynamics. The $E(S)$ data are directly compared to several recent predictions. The temperature in both the superfluid and normal fluid regime is obtained from the fundamental thermodynamic relation $T=\partial E/\partial S$ by parameterizing the $E(S)$ data. Our $E(S)$ data are also used to experimentally calibrate the endpoint temperatures obtained for adiabatic sweeps of the magnetic field between the ideal and strongly interacting regimes. This enables the first experimental calibration of the temperature scale used in experiments on fermionic pair condensation. Our calibration shows that the ideal gas temperature measured for the onset of pair condensation corresponds closely to the critical temperature estimated in the strongly interacting regime from the fits to our $E(S)$ data. The results are in very good agreement with recent predictions. Finally, using universal thermodynamic relations, we estimate the chemical potential and heat capacity of the trapped gas from the $E(S)$ data.Comment: 29 pages, 12 figures. To appear in JLTP online, and in the January, 2009 volum

Smoking behaviour predicts tobacco control attitudes in a high smoking prevalence hospital: A cross-sectional study in a Portuguese teaching hospital prior to the national smoking ban

<p>Abstract</p> <p>Background</p> <p>Several studies have investigated attitudes to and compliance with smoking bans, but few have been conducted in healthcare settings and none in such a setting in Portugal. Portugal is of particular interest because the current ban is not in line with World Health Organization recommendations for a "100% smoke-free" policy. In November 2007, a Portuguese teaching-hospital surveyed smoking behaviour and tobacco control (TC) attitudes before the national ban came into force in January 2008.</p> <p>Methods</p> <p>Questionnaire-based cross-sectional study, including all eligible staff. Sample: 52.9% of the 1, 112 staff; mean age 38.3 ± 9.9 years; 65.9% females. Smoking behaviour and TC attitudes and beliefs were the main outcomes. Bivariable analyses were conducted using chi-squared and MacNemar tests to compare categorical variables and Mann-Whitney tests to compare medians. Multilogistic regression (MLR) was performed to identify factors associated with smoking status and TC attitudes.</p> <p>Results</p> <p>Smoking prevalence was 40.5% (95% CI: 33.6-47.4) in males, 23.5% (95% CI: 19.2-27.8) in females (p < 0.001); 43.2% in auxiliaries, 26.1% in nurses, 18.9% among physicians, and 34.7% among other non-health professionals (p = 0.024). The findings showed a very high level of agreement with smoking bans, even among smokers, despite the fact that 70.3% of the smokers smoked on the premises and 76% of staff reported being frequently exposed to second-hand smoke (SHS). In addition 42.8% reported that SHS was unpleasant and 28.3% admitted complaining. MLR showed that smoking behaviour was the most important predictor of TC attitudes.</p> <p>Conclusions</p> <p>Smoking prevalence was high, especially among the lower socio-economic groups. The findings showed a very high level of support for smoking bans, despite the pro-smoking environment. Most staff reported passive behaviour, despite high SHS exposure. This and the high smoking prevalence may contribute to low compliance with the ban and low participation on smoking cessation activities. Smoking behaviour had greater influence in TC attitudes than health professionals' education. Our study is the first in Portugal to identify potential predictors of non-compliance with the partial smoking ban, further emphasising the need for a 100% smoke-free policy, effective enforcement and public health education to ensure compliance and promote social norm change.</p

Liver-Derived IGF-I Regulates Mean Life Span in Mice

Background: Transgenic mice with low levels of global insulin-like growth factor-I (IGF-I) throughout their life span, including pre- and postnatal development, have increased longevity. This study investigated whether specific deficiency of liver-derived, endocrine IGF-I is of importance for life span. Methods and Findings: Serum IGF-I was reduced by approximately 80 % in mice with adult, liver-specific IGF-I inactivation (LI-IGF-I-/- mice), and body weight decreased due to reduced body fat. The mean life span of LI-IGF-I-/- mice (n = 84) increased 10 % vs. control mice (n = 137) (Cox’s test, p,0.01), mainly due to increased life span (16%) of female mice [LI-IGF-I-/- mice (n = 31): 26.761.1 vs. control (n = 67): 23.060.7 months, p,0.001]. Male LI-IGF-I-/- mice showed only a tendency for increased longevity (p = 0.10). Energy expenditure, measured as oxygen consumption during and after submaximal exercise, was increased in the LI-IGF-I-/- mice. Moreover, microarray and RT-PCR analyses showed consistent regulation of three genes (heat shock protein 1A and 1B and connective tissue growth factor) in several body organs in the LI-IGF-I-/- mice. Conclusions: Adult inactivation of liver-derived, endocrine IGF-I resulted in moderately increased mean life span. Body weight and body fat decreased in LI-IGF-I-/- mice, possibly due to increased energy expenditure during exercise. Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms tha

Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required

Effect of VX-770 in Persons with Cystic Fibrosis and the G551D- CFTR Mutation

A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk