Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

Tooling design and microwave curing technologies for the manufacturing of fiber-reinforced polymer composites in aerospace applications

The increasing demand for high-performance and quality polymer composite materials has led to international research effort on pursuing advanced tooling design and new processing technologies to satisfy the highly specialized requirements of composite components used in the aerospace industry. This paper reports the problems in the fabrication of advanced composite materials identified through literature survey, and an investigation carried out by the authors about the composite manufacturing status in China’s aerospace industry. Current tooling design technologies use tooling materials which cannot match the thermal expansion coefficient of composite parts, and hardly consider the calibration of tooling surface. Current autoclave curing technologies cannot ensure high accuracy of large composite materials because of the wide range of temperature gradients and long curing cycles. It has been identified that microwave curing has the potential to solve those problems. The proposed technologies for the manufacturing of fiber-reinforced polymer composite materials include the design of tooling using anisotropy composite materials with characteristics for compensating part deformation during forming process, and vacuum-pressure microwave curing technology. Those technologies are mainly for ensuring the high accuracy of anisotropic composite parts in aerospace applications with large size (both in length and thickness) and complex shapes. Experiments have been carried out in this on-going research project and the results have been verified with engineering applications in one of the project collaborating companies

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Acupuncture or low frequency infrared treatment for low back pain in Chinese patients: a discrete choice experiment

Acupuncture is a popular but controversial treatment option for low back pain. In China, it is practised as traditional Chinese medicine; other treatment strategies for low back pain are commonly practised as Western medicine. Research on patient preference for low back-pain treatment options has been mainly conducted in Western countries and is limited to a willingness-to-pay approach. A stated-preference, discrete choice experiment was conducted to determine Chinese patient preferences and trade-offs for acupuncture and low frequency infrared treatment in low back pain from September 2011 to August 2012 after approval from the Department of Scientific Research in the study settings. Eight-six adult outpatients who visited the ‘traditional medicine department’ at a traditional Chinese medicine hospital and the ‘rehabilitation department’ at a Western medicine hospital in Guangdong Province of China for chronic low back pain during study period participated in an interview survey. A questionnaire containing 10 scenarios (5 attributes in each scenario) was used to ask participants' preference for acupuncture, low frequency infrared treatment or neither option. Validated responses were analysed using a nested-logit model. The decision on whether to receive a therapy was not associated with the expected utility of receiving therapy, female gender and higher out-of-pocket payment significantly decreased chance to receive treatments. Of the utility of receiving either acupuncture or low frequency infrared treatment, the treatment sensation was the most important attribute as an indicator of treatment efficacy, followed by the maximum efficacy, maintenance duration and onset of efficacy, and the out-of-pocket payment. The willingness-to-pay for acupuncture and low frequency infrared treatment were about $618.6 and$592.4 USD per course respectively, demonstrated patients' demand of pain management. The treatment sensation was regarded as an indicator of treatment efficacy and the most important attribute for choosing acupuncture or low frequency infrared treatment. The high willingness-to-pay demonstrated patients' demand of pain management. However, there may be other factors influencing patients' preference to receive treatments

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

Aims To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. Methods and results The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Conclusion Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. Clinical trial registration: ISRCTN 48334791

Substrate parameters affecting propagation of juvenile freshwater pearl mussels margaritifera margaritifera (bivalvia: margaritiferidae)

Interstitial habitat conditions are of critical importance to species inhabiting the hyporheic zone, particularly for moderately immobile species incapable of escaping poor habitat conditions. The critically endangered freshwater pearl mussel (Margaritifera margaritifera Linnaeus, 1758) has seen increasing propagation effort over the last three decades, often with mixed success. This study aimed to investigate parameters with the potential to affect juvenile survival in captivity by considering a range of habitat conditions within the substrate of a previously described propagation system using different substrate size classes (0.25–1 and 1–2mm) and cleaning regimes (weekly and monthly). Juvenile survival was highest in larger substrates, likely because of higher flow through larger pore spaces. This provided higher dissolved oxygen delivery in 1–2mm substrates cleaned weekly (8.26 ± 0.19 mg/L) and monthly (8.24 ± 0.44 mg/L), compared with 0.25–1mm substrates cleaned weekly (7.98 ± 0.44 mg/L) and monthly (6.78 ± 1.27 mg/L). The amount of organic material trapped in the substrate did not differ between treatments but the high concentrations of inorganic phosphorus liberated from ashed organic matter indicated phosphorus storage in phytoplankton. High dissolved oxygen concentrations and good water replacement between the water column and the substrate are crucial for survival in captive freshwater pearl mussels.N/

Effects of substrate size and cleaning regime on growth and survival of captive-bred juvenile freshwater pearl mussels, Margaritifera margaritifera (Linnaeus, 1758)

This study tested a culture system for rearing Margaritifera margaritifera at the Freshwater Pearl Mussel Ark in Windermere and investigated the effects of substrate size (0.25-1 mm and 1-2 mm) and cleaning regime (weekly and monthly) on survival and growth. At 362 days (12 months) and 758 days (25 months), a total of 1207 and 518 juveniles were reared successfully in the system described here. After 362 days, survival was significantly higher in 1-2 mm substrate treatments cleaned monthly (55 ± 6%) and lowest in 0.25-1 mm substrate cleaned weekly (14 ± 3%). Growth was significantly higher in 1-2 mm substrates cleaned weekly (length = 1.15 ± 0.21 mm) and lowest in 0.25-1 mm substrates cleaned monthly (length = 0.83 ± 0.23 mm). Survival rates in this investigation were comparable to, if not better than, other published studies culturing M. margaritifera of this age. Juveniles from most treatments did not display size-dependent over-winter survival, but a significant correlation was found between shell length and survival in the 0.25-1 mm weekly treatment which was the least suitable treatment. Additionally we examined the effects of flow rate, dissolved oxygen concentration, ammonia concentration and biofilm as factors which may affect growth and survival of juveniles between July - September 2015. These results provide an insight into findings from the initial work and discussion is offered on the challenges for practically applying this method to captive rearing at the Ark in future