Search

Background: This systematic review aimed to investigate the current state of risk prediction for abdominal aortic aneurysm in the literature, identifying and comparing published models and describing their performance and applicability to a population-based targeted screening strategy. Methods: Electronic databases MEDLINE (via Ovid), Embase (via Ovid), MedRxiv, Web of Science, and the Cochrane Library were searched for papers reporting or validating risk prediction models for abdominal aortic aneurysm. Studies were included only if they were developed on a cohort or study group derived from the general population and used multiple variables with at least one modifiable risk factor. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool. A synthesis and comparison of the identified models was undertaken. Results: The search identified 4813 articles. After full-text review, 37 prediction models were identified, of which 4 were unique predictive models that were reported in full. Applicability was poor when considering targeted screening strategies using electronic health record-based populations. Common risk factors used for the predictive models were explored across all 37 models; the most common risk factors in predictive models for abdominal aortic aneurysm were: age, sex, biometrics (such as height, weight, or BMI), smoking, hypertension, hypercholesterolaemia, and history of heart disease. Few models had undergone standardized model development, adequate external validation, or impact evaluation. Conclusion: This study identified four risk models that can be replicated and used to predict abdominal aortic aneurysm with acceptable levels of discrimination. None of the models have been validated externally. Lay Summary: Men in the UK are offered screening for abdominal aortic aneurysm (AAA) when they are 65 years old. Increasing costs in health services and the fact that AAA is becoming rarer mean that the future of screening is uncertain. One possible future of screening is to screen using a predictive model. This is called targeted screening. A predictive model can tell who is most likely to have an AAA. The aim of this study was to explore models in the literature and the main risk factors for AAA that these models identified. A systematic literature review was conducted to identify all relevant models. The initial search identified 4813 scientific articles. After title, abstract, and full-text screening, 37 models were found. The 37 models were analysed to identify the most common factors used to predict AAA. The factors age, sex, height and weight, smoking, high blood pressure, and heart disease were found to be the best predictors of developing an AAA. Only four of the studies reported the model in full, making them suitable for use in targeted screening. None of the four models had been tested based on data external to where they were developed, which limits their validity for use in screening programmes. This systematic review aimed to identify the current state and effectiveness of existing risk prediction models published for abdominal aortic aneurysm. The review identified 4 unique predictive models reported in full with acceptable levels of discrimination, and 33 additional predictive models not reported in full. None of the models had been validated externally. Common risk factors used across all models were identified, and applicability to targeted screening using electronic health records explored. [ABSTRACT FROM AUTHOR]

We tested an approach to estimate daily canopy net photosynthesis, A , based on estimates of transpiration, E , using measurements of sap flow and water-use efficiency, ω, by measuring δ13C in CO2 respired from shoots in the canopies of two conifers (Podocarpaceae) native to New Zealand. The trees were planted in adjacent 20-year-old stands with the same soil and environmental conditions. Leaf area index was lower for Dacrycarpus dacrydioides D.Don in Lamb (1.34 m2 m−2) than for Podocarpus totara G.Benn. ex D.Don var. totara (2.01 m2 m−2), but mean (± standard error) stem diameters were the same at 152 ± 21 mm for D. dacrydioides and 154 ± 25 mm for P. totara. Over a 28-day period, daily A (per unit ground area) ranged almost five-fold but there were no significant differences between species (mean 2.73 ± 1.02 gC m−2 day−1). This was attributable to higher daily values of E (2.63 ± 0.83 mm day−1) and lower ω (1.35 ± 0.53 gC kg H2O−1) for D. dacrydioides compared with lower E (1.82 ± 0.72 mm day−1) and higher ω (1.90 ± 0.77 gC kg H2O−1) for P. totara. We attributed this to higher nitrogen availability and nitrogen concentration per unit foliage area, N a, and greater exposure to irradiance in the D. dacrydioides canopy compared with P. totara. Our findings support earlier observations that D. dacrydioides is more adapted to sites with poor drainage. In contrast, the high retention of leaf area and maintaining low rates of transpiration by P. totara , resulting in higher water-use efficiency, is an adaptive response to survival in dry conditions. Our findings show that physiological adjustments for two species adapted to different environments led to similar canopy photosynthesis rates when the trees were grown in the same conditions. We demonstrated consistency between whole-tree and more intensive shoot-scale measurements, confirming that integrated approaches are appropriate for comparative estimates of carbon uptake in stands with different species. [ABSTRACT FROM AUTHOR]

Background: There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery. Methods: Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models. Results: A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) −0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) −0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) −0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) −0.307(0.09) mm/year, P = 0.00078). Conclusion: The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates. Abdominal aortic aneurysm growth rates were compared with smoking status, co-morbidities, and medication history in the UK Aneurysm Growth Study (UKAGS) prospective cohort. It was found that: smoking and antiplatelet use were associated with a more rapid abdominal aortic aneurysm growth rate; the drug metformin was strongly associated with a slower abdominal aortic aneurysm growth rate; and drugs in the angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist, and thiazide/related diuretic classes were also associated with a slower abdominal aortic aneurysm growth rate. These results suggest that common cardiometabolic medications may be useful therapeutic options to slow abdominal aortic aneurysm growth rates. [ABSTRACT FROM AUTHOR]

Cross-border supply chains and international trade enabled the manufacturing and delivery of billions of vaccine doses to inoculate the world against the Coronavirus disease (COVID-19). At the same time, the pandemic revealed how the World Trade Organization (WTO) must change to become more useful in the face of a public health emergency. This paper describes the market failures—especially on the supply side—justifying the domestic subsidies and contracting arrangements used to accelerate vaccine research and development and to increase the scale of vaccine production to save lives, livelihoods, and economic activity during a pandemic. It highlights the trade-offs associated with the US subsidies and the priority-rated contracts written for vaccines through the Defense Production Act under Operation Warp Speed. This case study reveals a rich environment in which cross-border supply chains exacerbate input shortages in ways that constrain vaccine production, highlighting the need for the WTO to embrace new forms of international policy coordination for pandemic preparedness and response. As part of a pandemic treaty, the paper proposes a plurilateral agreement on vaccine supply chain resilience that would include novel and enforceable disciplines for export restrictions, provisions to trigger coordinated subsidies across countries to jointly scale up vaccine output and input production capacity, and market surveillance initiatives on supply chain transparency. [ABSTRACT FROM AUTHOR]

In response to the Covid-19 pandemic, the US government used novel policies to accelerate research, development, and production of a diversified portfolio of new vaccines. This article begins by describing the Defense Production Act (DPA) of 1950 and the initial 'priority-rated' contracts agreed to under Operation Warp Speed in 2020 to expedite manufacturing and achieve scale, which succeeded in producing hundreds of millions of doses of Covid-19 vaccines by early 2021. However, a puzzle soon emerged, as the scale of US vaccine production was shortly thereafter overtaken by plants in the European Union and India. The paper investigates the trade-offs US policy-makers faced in early 2021—once much of the initial uncertainty about the safety and effectiveness of many Covid-19 vaccines had been resolved—about whether to recalibrate contracts to expand production capacity to help meet global, instead of US, vaccine demand. It also examines the emergence of input shortages and assesses whether both the price constraints implicit in the 2020 DPA contracts and business decisions made to quicken the process of bringing new vaccine plants online globally inadvertently exacerbated them. It also explores the potential need for complementary, input capacity-enhancing policies in the face of highly fragmented, cross-border Covid-19 vaccine supply chains. [ABSTRACT FROM AUTHOR]

This is Part II of a novel 'epistemic' theory of the criminal process. Part I, a formal treatment of how poor measurements degrade control over systems of classification, was published in the last issue. This distinguished four distinct realms of control a policymaker may inhabit and established that the criminal process in the USA is trapped in the third best of these, routinely unable to establish that any policy is better than any other. Here, I first use the new epistemic concepts to mathematize Packer's influential 'two models' theory, both a validation of the formal work and a way of giving it traction in the real world. I then use the new techniques to critique Posner's law and economics and reject it on methodological grounds. I then argue that the activity of making policy for the criminal process, including any quantativity, is largely a form of ritual. The function of this has been to keep at bay an enduring pressure for rationality, as in Weber's rationalization thesis, that could not be satisfied. Now that we have the capacity for better measurements, a rational approach is for the first time attainable, and I contemplate the end of the old order. [ABSTRACT FROM AUTHOR]

The criminal process can be seen as a system of classification, akin to a search engine. I consider the impact on it of poor measurements of the rates of false positives and false negatives. With ordinal rather than interval measurements, we lose some but not all control. I identify a novel form of indeterminacy, 'directional aimlessness', that leads to a behaviour of 'shoving'. This can take a form, 'naked shoving', that looks purposeful but isn't. I empirically establish the presence of naked shoving in the USA. This methodological work comprises Part I of a novel theory of the criminal process. In Part II, I use it to mathematize Herbert Packer's influential 'two models' theory in criminology, both a form of validation and a way of giving an abstract theory traction in the real world. We acquire a general 'epistemic' alternative to economic, organizational, legal or political forms of analysis and I use it to critique Richard Posner's law and economics. Given the lack of purpose, I conclude that policymaking in the criminal process is usually a form of ritual and, now that we have the capacity for interval measurements, contemplate the end of the old order. [ABSTRACT FROM AUTHOR]

Background: Population-wide ultrasound screening programmes for abdominal aortic aneurysm (AAA) for men have already been established in some countries. Women account for one third of aneurysm-related mortality and are four times more likely to experience an AAA rupture than men. Whole-population screening for AAA in women is unlikely to be clinically or economically effective. The aim of this study was to determine the outcomes of a targeted AAA screening programme for women at high risk of AAA. Method: Women aged 65-74 years deemed at high risk of having an AAA (current smokers, ex-smokers, or with a history of coronary artery disease) were invited to attend ultrasound screening (July 2016 to March 2019) for AAA in the Female Aneurysm screening STudy (FAST). Primary outcomes were attendance for screening and prevalence of AAA. Biometric data, medical history, quality of life (QoL) and aortic diameter on ultrasound imaging were recorded prospectively. Results: Some 6037 women were invited and 5200 attended screening (86.7 per cent). Fifteen AAAs larger than 29mm were detected (prevalence 0.29 (95 per cent c.i. 0.18 to 0.48) per cent). Current smokers had the highest prevalence (0.83 (95 per cent c.i. 0.34 to 1.89) per cent) but lowest attendance (75.2 per cent). Three AAAs greater than 5.5cm were identified and referred for consideration of surgical repair; one woman underwent repair. There was a significant reduction in patient-reported QoL scores following screening. Conclusion: A low prevalence of AAA was detected in high-risk women, with lowest screening uptake in those at highest risk. Screening for AAA in high-risk women may not be beneficial. [ABSTRACT FROM AUTHOR]

Background: The incidence of, and risk factors for, acute kidney injury (AKI) after endovascular intervention for peripheral artery disease (PAD) remain unknown. The aim of this study was to assess the proportion of patients who develop AKI and explore the risk factors. Methods: Prospectively collected data on patients undergoing femoropopliteal endovascular intervention for symptomatic PAD across three vascular centres were analysed. The proportion of patients developing AKI (according to the Kidney Disease Improving Global Outcomes definition) within 48 h, and the proportion developing the composite Major Adverse Kidney Events (MAKE) endpoints (death, dialysis, drop in estimated glomerular filtration rate at least 25 per cent) at 30 days (MAKE30) and remains 90 days (MAKE90) were calculated. Multivariable regression analysis was used to assess predictors of AKI, and the association between AKI and death. Results: Some 2041 patients were included in the analysis. AKI developed in 239 patients (11.7 per cent), with 47 (2.3 per cent) requiring dialysis within 30 days, and 18 (0.9 per cent) requiring ongoing dialysis. The MAKE30 and MAKE90 composite endpoints were reached in 358 (17.5 per cent) and 449 (22.0 per cent) patients respectively. Risk factors for AKI were age, sex, congestive heart failure, chronic limb-threatening ischaemia, emergency procedure, and pre-existing chronic kidney disease. AKI, dementia, congestive heart failure, and major amputation were risk factors for medium-term mortality. Conclusion: AKI is a common complication after intervention for PAD and is associated with medium-term mortality. [ABSTRACT FROM AUTHOR]

An introduction is presented in which editor discusses various articles within the issue on topics including use of national security as a policy argument, model of political economy of trade to explain trade and investment policy and transfer of technology.

The USA, European Union, and Japan have begun a trilateral process to confront the Chinese economic model, including its use of industrial subsidies and deployment of state-owned enterprises. This paper seeks to identify the main areas of tension and to assess the legal-economic challenges to constructing new rules to address the underlying conflict. It begins by providing a brief history of subsidy disciplines in the General Agreement on Tariffs and Trade and World Trade Organization predating any concerns introduced by China. It then describes contemporary economic problems with China's approach to subsidies, their impact, and the apparent ineffectiveness of the World Trade Organization's Agreement on Subsidies and Countervailing Measures to address them. Finally, it calls for increased efforts to measure and pinpoint the source of the problems—in a manner analogous to how the Organization for Economic Cooperation and Development took on agricultural subsidies in the 1980s—before providing a legal-economic assessment of proposals for reforms to notifications, evidence, remedies, enforcement, and the definition of a subsidy. [ABSTRACT FROM AUTHOR]

Background: Screening for abdominal aortic aneurysm (AAA) is known to reduce AAA‐related mortality; however, the psychological impact of population AAA screening is unclear. The aim was to assess the impact of AAA diagnosis on quality of life (QoL) using data from an established AAA screening programme. Methods: Mental and physical QoL scores for men diagnosed with AAA through participation in the English and Welsh AAA screening programmes were compared with no‐AAA controls. Participants were identified through the United Kingdom Aneurysm Growth Study (UKAGS), a nationwide prospective cohort study of men with an AAA of less than 55 mm diagnosed through voluntary participation in screening. The UKAGS participants completed QoL questionnaires at the time of screening and annually thereafter. Results: A transient reduction in mental QoL scores was observed following the diagnosis of AAA, returning to baseline levels after 12 months. Physical QoL remained consistently lower in the AAA cohort. Participants thought about their AAA and the AAA growth progressively less 12 months after the initial screening diagnosis. AAA growth rate had no influence over QoL parameters. Discussion: This study suggests that screening for AAA does reduce mental QoL; however, this effect is transient (less than 12 months). Men diagnosed with AAA have a consistently worse physical QoL compared with controls. [ABSTRACT FROM AUTHOR]

Background The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK. Methods Anonymized data from the UK National Vascular Registry (NVR) for patients undergoing AAA repair (January 2010 to December 2014) were analysed. Co-variables were extracted for analysis by sex. The primary outcome measure was in-hospital mortality. Secondary outcome measures included mortality by 5-year age groups and duration of hospital stay. Logistic regression was performed to adjust for age, calendar time, AAA diameter and smoking status. NVR-based outcomes were checked against Hospital Episode Statistics (HES) data. Results A total of 23 245 patients were included (13·0 per cent women). Proportionally, more women than men underwent open repair. For elective open AAA repair, the in-hospital mortality rate was 6·9 per cent in women and 4·0 per cent in men (odds ratio (OR) 1·48, 95 per cent c.i. 1·08 to 2·02; P = 0·014), whereas for elective endovascular AAA repair it was 1·8 per cent in women and 0·7 per cent in men (OR 2·86, 1·72 to 4·74; P < 0·001); the results in HES were similar. For ruptured AAA, there was no sex difference in mortality within the NVR; however, in HES, for ruptured open AAA repair, the in-hospital mortality rate was higher in women (33·6 versus 27·1 per cent; OR 1·36, 1·16 to 1·59; P < 0·001). Conclusion Women have a higher in-hospital mortality rate than men after elective AAA repair even after adjustment. This higher mortality may have an impact on the benefit offered by any screening programme offered to women. [ABSTRACT FROM AUTHOR]

Aims To quantify the difference in long-term survival and cardiovascular morbidity between women and men undergoing elective abdominal aortic aneurysm (AAA) repair at National Health Service hospitals in England. Methods and results Patients having elective repair of AAA were reviewed using the Hospital Episode Statistics and Office for National Statistics (ONS) datasets. The primary outcome measure was 30-day mortality and the secondary outcomes were 1-year, 5-year, and aortic-related mortality and post-operative complication rates. We used logistic regression and survival models to assess risk factors on the primary and secondary outcomes. Between 1 April 2002 and 31 March 2013, a total of 31 090 patients (4795 women and 26 295 men) underwent open AAA repair. Between 1 January 2006 and 31 March 2013, a total of 16 777 patients (2036 women and 14 741 men) underwent endovascular aneurysm repair (EVAR). All-cause and aortic-related mortalities at 30 days, 1 year, and 5 years were all higher in women, despite a lower prevalence of pre-operative cardiovascular risk factors. Female sex was a significant independent risk factor for 30-day mortality in both open repair [odds ratio (OR) 1.39; 95% confidence interval (CI) 1.25-1.56; P<0.001] and EVAR (OR 1.57; 95% CI 1.23-2.00; P<0.001) groups. Based on an all-cause long-term survival model, conditional on 30-day survival, the estimated hazard for women in the open repair group was significantly (P = 0.006) higher than men, but the sex difference was not significant in the EVAR group (P = 0.356). In the open repair group, women had significantly (P<0.001) higher cumulative incidence probabilities for both aortic-related mortality and other-cause mortality. In the EVAR group, women had significantly (P<0.001) higher mean cumulative incidence probabilities for the aortic-related mortality compared with men, but not for the other-cause mortality (P = 0.235). Conclusion Women undergoing elective AAA repair at National Health Service hospitals in England had increased short- and long-term mortality and post-operative morbidity compared with men. These findings can be used to improve preoperative counselling for women undergoing AAA repair, and highlight the need for female-specific pre-, peri-, and post-operative management strategies. [ABSTRACT FROM AUTHOR]

Background Vascular surgical care has changed dramatically in recent years with little knowledge of the impact of system failures on patient safety. The primary aim of this multicentre observational study was to define the landscape of surgical system failures, errors and inefficiency (collectively termed failures) in aortic surgery. Secondary aims were to investigate determinants of these failures and their relationship with patient outcomes. Methods Twenty vascular teams at ten English hospitals trained in structured self-reporting of intraoperative failures (phase I). Failures occurring in open and endovascular aortic procedures were reported in phase II. Failure details (category, delay, consequence), demographic information (patient, procedure, team experience) and outcomes were reported. Results There were strong correlations between the trainer and teams for the number and type of failures recorded during 88 procedures in phase I. In 185 aortic procedures, teams reported a median of 3 (i.q.r. 2-6) failures per procedure. Most frequent failures related to equipment (unavailability, failure, configuration, desterilization). Most major failures related to communication. Fourteen failures directly harmed 12 patients. Significant predictors of an increased failure rate were: endovascular compared with open repair (incidence rate ratio ( IRR) for open repair 0·71, 95 per cent c.i. 0·57 to 0·88; P = 0·002), thoracic aneurysms compared with other aortic pathologies ( IRR 2·07, 1·39 to 3·08; P < 0·001) and unfamiliarity with equipment ( IRR 1·52, 1·20 to 1·91; P < 0·001). The major failure total was associated with reoperation ( P = 0·011), major complications ( P = 0·029) and death ( P = 0·027). Conclusion Failure in aortic procedures is frequently caused by issues with team-working and equipment, and is associated with patient harm. Multidisciplinary team training, effective use of technology and new-device accreditation may improve patient outcomes. [ABSTRACT FROM AUTHOR]

Gene transfer agents (GTAs) are phage-like particles that can package and transfer a random piece of the producing cell's genome, but are unable to transfer all the genes required for their own production. As such, GTAs represent an evolutionary conundrum: are they selfish genetic elements propagating through an unknown mechanism, defective viruses, or viral structures "repurposed" by cells for gene exchange, as their name implies? In Rhodobacter capsulatus, production of the R. capsulatus GTA (RcGTA) particles is associated with a cluster of genes resembling a small prophage. Utilizing transcriptomic, genetic and biochemical approaches, we report that the RcGTA "genome" consists of at least 24 genes distributed across five distinct loci. We demonstrate that, of these additional loci, two are involved in cell recognition and binding and one in the production and maturation of RcGTA particles. The five RcGTA "genome" loci are widespread within Rhodobacterales, but not all loci have the same evolutionary histories. Specifically, two of the loci have been subject to frequent, probably virus-mediated, gene transfer events. We argue that it is unlikely that RcGTA is a selfish genetic element. Instead, our findings are compatible with the scenario that RcGTA is a virus-derived element maintained by the producing organism due to a selective advantage of within-population gene exchange. The modularity of the RcGTA "genome" is presumably a result of selection on the host organism to retain GTA functionality. [ABSTRACT FROM AUTHOR]

Background Although women represent an increasing proportion of those presenting with abdominal aortic aneurysm ( AAA) rupture, the current prevalence of AAA in women is unknown. The contemporary population prevalence of screen-detected AAA in women was investigated by both age and smoking status. Methods A systematic review was undertaken of studies screening for AAA, including over 1000 women, aged at least 60 years, done since the year 2000. Studies were identified by searching MEDLINE, Embase and CENTRAL databases until 13 January 2016. Study quality was assessed using the Newcastle-Ottawa scoring system. Results Eight studies were identified, including only three based on population registers. The largest studies were based on self-purchase of screening. Altogether 1 537 633 women were screened. Overall AAA prevalence rates were very heterogeneous, ranging from 0·37 to 1·53 per cent: pooled prevalence 0·74 (95 per cent c.i. 0·53 to 1·03) per cent. The pooled prevalence increased with both age (more than 1 per cent for women aged over 70 years) and smoking (more than 1 per cent for ever smokers and over 2 per cent in current smokers). Conclusion The current population prevalence of screen-detected AAA in older women is subject to wide demographic variation. However, in ever smokers and those over 70 years of age, the prevalence is over 1 per cent. [ABSTRACT FROM AUTHOR]

Background: Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle-brachial pressure index (ABPI) is the recommended diagnostic tool for PAD.Purpose: We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice.Methods: GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle-brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study.Results: All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use.Conclusions: Targeted training of nursing staff may improve ABPI usage, although a less time-consuming test for PAD may be another option. [ABSTRACT FROM AUTHOR]

Background Screening for abdominal aortic aneurysm ( AAA) has reduced the rate of AAA rupture. However, cardiovascular disease is still a major cause of death in men with an AAA. The aim of this study was to assess cardiovascular risk in patients with a small AAA. Methods Standard PRISMA guidelines were followed. Analysis was performed of studies reporting cardiovascular outcomes in patients with a small AAA (30-54 mm). Weighted metaregression was performed for cardiovascular death in patients with a small AAA, and the prevalence of cardiovascular disease was reviewed. Results Twenty-one articles were identified describing patients with an AAA, and the prevalence of, and death from, cardiovascular disease. Ten of these reported cardiovascular death rates in patients with a small AAA. Some 2323 patients with a small AAA were identified; 335 cardiovascular deaths occurred, of which 37 were due to AAA rupture. Metaregression demonstrated that the risk of cardiovascular death was 3·0 (95 per cent c.i. 1·7 to 4·3) per cent per year in patients with a small AAA ( R2 = 0·902, P < 0·001). The prevalence of ischaemic heart disease (44·9 per cent), myocardial infarction (26·8 per cent), heart failure (4·4 per cent) and stroke (14·0 per cent) was also high in these patients. Conclusion The risk of cardiovascular death in patients with a small AAA is high and increases by approximately 3 per cent each year after diagnosis. Patients with a small AAA have a high prevalence of cardiovascular disease. Patients a small AAA should be considered for lifestyle modifications and secondary cardiovascular protection. [ABSTRACT FROM AUTHOR]

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Background Many studies have investigated the systemic and local expression of biomarkers in patients with abdominal aortic aneurysm ( AAA). The natural history of AAA varies between patients, and predictors of the presence and diameter of AAA have not been determined consistently . The aim of this study was to perform a systematic review, meta-analysis and meta-regression of studies comparing biomarkers in patients with and without AAA, with the aim of summarizing the association of identified markers with both AAA presence and size. Methods and results Literature review identified 106 studies suitable for inclusion. Meta-analysis demonstrated a significant difference between matrix metalloproteinase ( MMP) 9, tissue inhibitor of matrix metalloproteinase 1, interleukin ( IL) 6, C-reactive protein ( CRP), α1-antitrypsin, triglycerides, lipoprotein(a), apolipoprotein A and high-density lipoprotein in patients with and without AAA. Although meta-analysis was not possible for MMP-2 in aortic tissue, tumour necrosis factor α, osteoprotegerin, osteopontin, interferon γ, intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1, systematic review suggested an increase in these biomarkers in patients with AAA. Meta-regression analysis identified a significant positive linear correlation between aortic diameter and CRP level. Conclusion A wide variety of biomarkers are dysregulated in patients with AAA, but their clinical value is yet to be established. Future research should focus on the most relevant biomarkers of AAA, and how they could be used clinically. [ABSTRACT FROM AUTHOR]

Background The National Vascular Registry Report on Surgical Outcomes ( NVSRO) coincided with the update of the National Health Service Standard Contract for Specialized Vascular Services in Adults ( NHSSCSVS). The latter promises patients minimum standards for vascular centres. The present study aimed to determine whether current data support the standards proposed in the NHSSCSVS. Methods Numbers of abdominal aortic aneurysm ( AAA) repairs and carotid endarterectomies ( CEAs) performed by hospital Trust and surgeon, and their outcomes were obtained from the NVRSO. These were assessed against NHSSCSVS recommendations that included: more than 60 AAA repairs per year per Trust, over 50 CEAs per year per Trust and at least six vascular surgeons per Trust. Results Based on NVRSO data, 107 hospital Trusts (92·2 per cent) would fail to meet the minimum standards required to achieve vascular centre status. Outcomes were poorer in these hospitals (overall mortality rate after AAA: 2·7 versus 1·3 per cent; P = 0·007). There were strong associations between number of AAA repairs or CEAs per Trust and better outcomes ( AAA repair, P < 0·001; CEA, P = 0·004). These remained significant when analysed by individual surgeon ( AAA repair, P < 0·001; CEA, P < 0·001). Trusts undertaking 60 or fewer elective AAA repairs per year had significantly higher elective AAA mortality rates (2·7 versus 1·7 per cent; P = 0·010). Trusts performing a minimum of 50 CEAs per year had significantly lower perioperative mortality/morbidity rates (1·9 versus 3·0 per cent; P = 0·032). Trusts with seven or more surgeons demonstrated lower AAA-related mortality rates (1·7 versus 2·7 per cent; P = 0·018). Conclusion Data from the NVRSO suggest that the majority of hospital Trusts presently fail to meet the standards for vascular centre status. NVRSO data support a standard of more than 60 elective AAA repairs and 50 CEAs per Trust per year. A minimum of seven vascular surgeons per unit was associated with better outcomes. These data support the ongoing remodelling of vascular services in the UK. [ABSTRACT FROM AUTHOR]

Methods We conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo. Results Up to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25–0.66, I2 = 70%, P = 1.1 × 10–5 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80–0.89, I2 = 0%, P = 2.7 × 10–11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers. Conclusions A Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management. [ABSTRACT FROM PUBLISHER]

Background Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm ( EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance. Methods Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan-Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre. Results Some 761 patients, with a median age of 75 (interquartile range 70-80) years, underwent EVAR. Median follow-up was 36 (range 11-94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter ( P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002). Conclusion The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits. [ABSTRACT FROM AUTHOR]

Background The aim was to assess the risk of rupture, and determine the benefits of intervention for the treatment of type II endoleak after endovascular abdominal aortic aneurysm repair ( EVAR). Methods This systematic review was done according to PRISMA guidelines. Outcome data included incidence, spontaneous resolution, sac expansion, interventions, clinical success, and complications including conversion to open repair, and rupture. Results Thirty-two non-randomized retrospective studies were included, totalling 21 744 patients who underwent EVAR. There were 1515 type II endoleaks and 393 interventions. Type II endoleak was seen in 10·2 per cent of patients after EVAR; 35·4 per cent resolved spontaneously. Fourteen patients (0·9 per cent) with isolated type II endoleak had ruptured abdominal aortic aneurysm; six of these did not have known aneurysm sac expansion. Of 393 interventions for type II endoleak, 28·5 per cent were unsuccessful. Translumbar embolization had a higher clinical success rate than transarterial embolization (81 versus 62·5 per cent respectively; P = 0·024) and fewer recurrent endoleaks were reported (19 versus 35·8 per cent; P = 0·036). Transarterial embolization also had a higher rate of complications (9·2 per cent versus none; P = 0·043). Conclusion Aortic aneurysm rupture after EVAR secondary to an isolated type II endoleak is rare (less than 1 per cent), but over a third occur in the absence of sac expansion. Translumbar embolization had a higher success rate with a lower risk of complications. [ABSTRACT FROM AUTHOR]

Background Any possible long-term benefit from endovascular ( EVAR) versus open surgical repair for abdominal aortic aneurysm ( AAA) remains unproven. Long-term data from the Open Versus Endovascular Repair ( OVER) trial add to the debate regarding long-term all-cause and aneurysm-related mortality. The aim of this study was to investigate 30-day and long-term mortality, reintervention, rupture and morbidity after EVAR and open repair for AAA in a systematic review. Methods Standard PRISMA guidelines were followed. Random-effects Mantel-Haenszel meta-analysis was performed to evaluate mortality and morbidity outcomes. Results The existing published randomized trials, together with information from Medicare and SwedVasc databases, were included in a meta-analysis. This included 25 078 patients undergoing EVAR and 27 142 undergoing open repair for AAA. Patients who had EVAR had a significantly lower 30-day or in-hospital mortality rate (1·3 per cent versus 4·7 per cent for open repair; odds ratio ( OR) 0·36, 95 per cent confidence interval 0·21 to 0·61; P < 0·001). By 2-year follow-up there was no difference in all-cause mortality (14·3 versus 15·2 per cent; OR 0·87, 0·72 to 1·06; P = 0·17), which was maintained after at least 4 years of follow-up (34·7 versus 33·8 per cent; OR 1·11, 0·91 to 1·35; P = 0·30). There was no significant difference in aneurysm-related mortality by 2 years or longer follow-up. A significantly higher proportion of patients undergoing EVAR required reintervention ( P = 0·003) and suffered aneurysm rupture ( P < 0·001). Conclusion There is no long-term survival benefit for patients who have EVAR compared with open repair for AAA. There are also significantly higher risks of reintervention and aneurysm rupture after EVAR. [ABSTRACT FROM AUTHOR]

One of the most enduring critical legacies of modernism has been the condemnation of the sentimentality of Victorian art. This essay argues that recent art historical attempts to discuss Victorian sentimentality are condemned to repeat modernist critical judgements about sentimental art because of their espousal of historicist methodologies which produce historical distance between artwork and the critical viewer in the present. Instead, I argue, our own emotional involvement with Victorian paintings should form part of our scholarly accounts of their meanings, because their affective power is central to their aesthetic qualities. To look properly, I argue, is also to feel. To exemplify this I discuss Augustus Mulready's Remembering the Joys that Have Passed Away (1873), in order to show how a sentimental look at this painting undermines approaches that absorb sentimentality into historicist, social-constructionist and ideological accounts of such a picture. [ABSTRACT FROM AUTHOR]

Six clones of radiata pine with known differences in growth rate were examined for clonal nutritional characteristics and for physiological determinants of clonal growth rate. We compared growth, foliar characteristics and nutrient, 13C and 15N concentration data for the six clones in 4- to 6-year-old field trials planted over a range of nutritionally contrasting sites. These data were also compared with growth, nutrient uptake and remobilization, foliar characteristic and gas exchange data from intensive physiological glasshouse experiments using 1- and 2-year-old plants of the same clones. Significant genotype × environment interactions in our field experiments conducted over strong nutritional gradients allowed us to identify radiata pine clones with consistent, superior growth and nutritional characteristics and clones that may be suited to particular site conditions. Our results suggest that the opportunity exists to exploit clone × site variation for site-specific clonal deployment and planting of fast-growing clones could be accompanied by planting of clones able to take relative advantage of site nutritional characteristics. Faster tree growth was not strongly related to any physiological characteristic, and the factors influencing growth rate differed among clones. The fastest-growing clone had consistent, high uptake of all nutrients, high fascicle weights and high water-use efficiency. [ABSTRACT FROM PUBLISHER]

The article presents a study which investigates the efficiency of optical scanning for rapid intraoperative diagnosis of breast cancer with sentinel node metastases. The study used elastic scattering spectroscopy (ESS) and developed an optical scanner as part of the procedure of the investigation. It was concluded that the results of ESS were observed to be comparable with intraoperative diagnostic techniques of lymph node assessment.

Mesophyll conductance, gm, may pose significant limitations to photosynthesis and may be differentially affected by nutrition and genotype in Pinus radiata D. Don. Simultaneous measurements of gas exchange and chlorophyll fluorescence were made to determine gm, using the constant J method (Harley, P.C., F. Loreto, G. Di Marco and T.D. Sharkey. 1992. Theoretical considerations when estimating the mesophyll conductance to CO2 flux by analysis of the response of photosynthesis to CO2. Plant Physiol. 98:1429–1436), in a fast- and a slow-growing clone of P. radiata grown in a greenhouse with a factorial combination of nitrogen (N) and phosphorus (P) supply. Values of gm increased linearly with the rate of photosynthesis at saturating irradiance and ambient CO2 concentration, Asat (gm = 0.020Asat, r2 = 0.25, P < 0.001) and with stomatal conductance to CO2 transfer, gs (gm = 1.16gs, r2 = 0.14, P < 0.001). Values of gm were greater than those of stomatal conductance, gs, and the ratio (gm/gs) was not influenced by single or combined N and P additions or clone with a mean (±SE) value of 1.22 ± 0.06. Relative limitations to mesophyll conductance, Lm (16%) to photosynthesis, were generally greater than those imposed by stomata, Ls (13%). The mean (±SE) CO2 concentration in the intercellular air spaces (Ci) was 53 ± 3 μmol mol−1 lower than that in the atmosphere (Ca). Mean (±SE) CO2 concentration in the chloroplasts (Cc) was 48 ± 2 μmol mol−1 lower than Ci. Values of Ls, Lm and CO2 diffusion gradients posed by gs (Ca − Ci) and gm (Ci − Cc) did not significantly differ with nutrient supply or clone. Mean values of Vcmax and Jmax calculated on a Cc basis were 15.4% and 3.1% greater than those calculated on a Ci basis, which translated into different slopes of the Jmax/Vcmax relationship (Cc basis: Jmax = 2.11Vcmax, r2 = 0.88, P < 0.001; Ci basis: Jmax = 2.43Vcmax, r2 = 0.86, P < 0.001). These results will be useful for correcting estimates of Vcmax and Jmax used to characterize the biochemical properties of photosynthesis for P. radiata. [ABSTRACT FROM PUBLISHER]

For countries to engage successfully in the international trading system, their industries, firms, and workers must respond continually to new conditions of competition. The continuing need to adjust arises both from policy changes approved in multilateral negotiations--e.g, implementation of trade liberalization commitments, preference erosion, or adverse terms-of-trade consequences of export subsidy elimination--and from ongoing changes in competitive pressures inherent in a liberal trading system--e.g. effects on comparative advantage of changes in technology or factor supplies. But the political response to a situation calling for adjustment is often a call for 'safeguards'--whether as an ex ante provision in negotiated agreements or as an ex post measure once the agreement has been signed and the reality of new conditions takes shape. This paper examines the range of adjustment problems confronting the current and future international trading system, the economic arguments for intervention to deal with these problems, the adjustment environment as set out in the current World Trade Organization (WTO) Agreements, and proposals for reform. While the adjustment problems we discuss apply to both rich and poor WTO member countries, we highlight the issues of adjustment especially relevant for developing countries. [ABSTRACT FROM AUTHOR]

The ECTOPICALLY PARTING CELLS 1 (EPC1) gene encodes a putative retaining glycosyltransferase of the GT64 family, and epc1-1 mutant plants have a severely dwarfed phenotype. A new mutant allele of this gene, epc1-2, has been isolated. Reduced cell adhesion that has previously been reported for the epc1-1 mutant was not observed for either the epc1-1 or epc1-2 mutants grown in our conditions, suggesting that EPC1 does not affect cell adhesion but is involved in some other process affecting plant growth and development. It is shown that the epc1-2 mutant exhibits hypersensitivity to the phytohormone abscisic acid in germination and root elongation assays, however it shows an unaltered response to gibberellin, epi-brassinosteroid, auxin, or ethylene. An EPC1:YFP fusion protein is localized to small motile structures within the cytosol that are similar in size and number to the Golgi apparatus. Analysis of cell wall pectins revealed that levels of β-(1,4)-galactan in the epc1-2 mutant are reduced by 50%, whilst other pectic polysaccharides (homogalacturonan, arabinan, and rhamnogalacturonan II) are unchanged. [ABSTRACT FROM PUBLISHER]

Responses of photosynthesis (A) to intercellular CO2 concentration (Ci) were measured in a fast- and a slow-growing clone of Pinus radiata D. Don cultivated in a greenhouse with a factorial combination of nitrogen and phosphorus supply. Stomatal limitations scaled with nitrogen and phosphorus supply as a fixed proportion of the light-saturated photosynthetic rate (18.5%) independent of clone. Photosynthetic rates at ambient CO2 concentration were mainly in the portion of the CO2 response rate that is limited by maximal carboxylation rate (Vcmax) at low-nitrogen supply and at the transition between Vcmax and Jmax at high-nitrogen supply. Nutrient limitations to photosynthesis were partitioned based on the ratio of foliage nitrogen to phosphorus expressed on a leaf area basis (Na/Pa), by minimizing the mean square error of segmented linear models relating photosynthetic parameters (Vcmax, Jmax, Tp) to foliar nitrogen and phosphorus concentrations. A value of Na/Pa equal to 23 (mole basis) was identified as the threshold separating nitrogen (Na/Pa ≤ 23) from phosphorus (NNa/Pa > 23) limitations independent of clones. On an area basis, there were significant positive linear relationships between the parameters, Vcmax, Jmax, Tp and Na and Pa, but only the relationships between Tp and Na and Pa differed significantly between clones. These findings suggest that, in genotypes with contrasting growth, the responses of Vcmax and Jmax to nutrient limitation are equivalent. The relationships between the parameters Vcmax, Jmax, Tp and foliage nutrient concentration on a mass basis were unaffected by clone, because the slow-growing clone had a significantly greater leaf area to mass ratio than the fast-growing clone. These results may be useful in discriminating nitrogen-limited photosynthesis from phosphorus-limited photosynthesis. [ABSTRACT FROM AUTHOR]

• Background and Aims Although density-specific stiffness, E/ρ, (where E is Young's modulus and ρ is wood density) is often assumed constant by the elastic similarity model, and in determination of critical buckling height (Hcrit), few studies have tested this assumption within species. Here this assumption is tested for Pinus radiata growing across an environmental gradient, and theory is combined with data to develop a model of Young's modulus.• Methods Analyses use an extensive series of environmental plots covering the range of climatic and edaphic conditions over which P. radiata is grown in New Zealand. Reduced major axis regression was used to determine scaling exponents between log–log plots of Hcrit vs. groundline diameter (D), and E/ρ vs. D. Path analysis was used to identify significant direct and indirect (through stem slenderness) edaphic and climatic influences on E.• Key Results Density-specific stiffness exhibited 3-fold variation. As E/ρ scaled positively with D, the exponent of 0·95 between Hcrit and D exceeded the assumed value of 0·67 under constant E/ρ. The final path analysis model included mean air temperature in early autumn (Taut) and slenderness as significant (P < 0·05) positive direct influences on E. Tree leaf area index and Taut were indirectly associated with E through their significant (P < 0·05) positive direct relationship with stem slenderness. Young's modulus was most sensitive to Taut, followed by stem slenderness then leaf area index, and the final model explained 76 % of the variance in E.• Conclusions The findings suggest that within species E/ρ variation may influence Hcrit and the scaling exponent between D and Hcrit so important in assumptions regarding allometric relationships. The model presented may provide a useful means of determining variation in E, E/ρ and Hcrit across environmental gradients. [ABSTRACT FROM AUTHOR]

The poorest WTO member countries almost universally fail to engage as either complainants or interested third parties in formal dispute settlement activity related to their market access interests. This paper focuses on costs of the WTO’s extended litigation process as an explanation for the potential but ‘missing’ developing country engagement. We provide a positive examination of the current system, and we catalogue and analyze a set of proposals encouraging the private sector to provide DSU-specific legal assistance to poor countries. We investigate the role of legal service centres, non-governmental organizations, development organizations, international trade litigators, economists, consumer organizations, and law schools to provide poor countries with the services needed at critical stages of the WTO’s extended litigation process. In the absence of systemic rules reform, the public-private partnership model imposes a substantial cooperation burden on such groups as they organize export interests, estimate the size of improved market access payoffs, prioritize across potential cases, engage domestic governments, prepare legal briefs, assist in evidentiary discovery, and pursue the public relations effort required to induce foreign political compliance. [ABSTRACT FROM AUTHOR]

What affects a country's decision of whether to formally engage in a trade dispute directly related to its exporting interests? This article empirically examines determinants of affected country participation decisions in formal trade litigation arising under the World Trade Organization (wto) between 1995 and 2000. It investigates determinants of nonparticipation and examines whether the incentives generated by the system's rules and procedures discourage active engagement in dispute settlement by developing country members in particular. Though the size of exports at stake is found to be an important economic determinant affecting the decision to participate in challenges to a wto-inconsistent policy, the evidence also shows that measures of a country's retaliatory and legal capacity as well as its international political economy relationships matter. These results are consistent with the hypothesis of an implicit "institutional bias" generated by the system's rules and incentives that particularly affects developing economy participation in dispute settlement. [ABSTRACT FROM AUTHOR]

Examines whether the legs or gastrointestinal tract provide the greater contribution to the inflammatory response during abdominal aortic aneurysm repair. Measurement of interleukin 6 using a commercially available enzyme-linked immunosorbent assay kit.

This article describes the creation of an assessment team, the Countywide Assessment Team , in Gloucestershire, England as a result of the desire to maximize the institutionalization of older people in the county, and to ensure that care appropriate to the needs of the client was provided. The primary purpose of the team was to ensure that multidisciplinary assessment, and adequate rehabilitation, had been carried out before funded care was granted by social services, and to audit the quality of those assessments. The introduction of an independent multidisciplinary assessment panel has brought a consistency to the decisions and categorization of care for state-funded entrants to institutional care across the county. The importance of consistency was emphasized in a previous report of a specialist team in implementing continuing health care guidelines. In addition to ensuring consistent categorization of care, the team has frequently intervened to request further specialist assessments. While the growing emphasis on intermediate care, it was also interesting that, for at least 34 cases, a review following admission to care was recommended, with the expectation that a lower level of care would be satisfactory.

Background: Operative repair of ruptured abdominal aortic aneurysm (RAAA) is associated with a high mortality rate but reported figures vary widely. The aim of this study was to estimate the operative mortality of RAAA repair and determine how it has changed over time. Methods: A meta-analysis of all English language literature quoting figures for operative mortality of RAAA repair. Results: The pooled estimate for the overall operative mortality rate of RAAA repair from 1955 to 1998 was 48 (95 per cent confidence interval 46 to 50) per cent. Meta-regression analysis of operative mortality over time demonstrated a constant reduction of approximately 3·5 per cent per decade (1954–1997) with an operative mortality rate estimate for the year 2000 of 41 per cent. Seventy-seven studies reported intraoperative mortality but, while this appears to have remained constant over time, there was evidence of the presence of publication bias in the subgroup of papers reporting this outcome. There was no evidence of publication bias for the overall operative mortality outcome. Conclusion: Contrary to the conclusion of recent studies, this paper demonstrates a gradual reduction with time in the operative mortality rate of RAAA repair. [ABSTRACT FROM AUTHOR]

Consequences of initial spatial organisation of model fungal communities upon their spatio-temporal development were investigated. Dynamics of prescribed two- and three-species ‘communities’ developing on tessellated agar tile model systems were analysed in terms of literal maps, principal component analyses, or as the proportion of species extant within tiles. It was established that for two-species interactions of equal patch size, large-scale (i.e. many constituent tiles) behaviour could be extrapolated from the relevant small-scale (i.e. pairs of tiles) interactions. However, relative patch sizes (scale) of species within tessellations influenced the times taken by individuals to colonise tiles and, hence, temporal behaviour of the system. Outcome of arrangements involving three species of equal patch size and inoculum potential, and prescribed with different mixing patterns, could not be directly extrapolated by reference to the outcome of pair-wise interactions between constituent species. Three-species arrangements attempt to limit assembly of lateral aggregates of individuals (patch size) and hence any effects of tile colonisation times, so as to reveal effects of nearest neighbour context within the complex community. Such arrangements indicate that spatial configuration of inoculum influences community development and reproducibility. They also suggest that spatial distribution of species affects persistence of individuals, which would otherwise be expected to be eliminated from the system. Two-species interactions appeared generally more reproducible than those comprising three species, and the sensitivity of fungal community development to temperature was not solely associated with influence on colony extension rate. [Copyright &y& Elsevier]

Discusses the contemporary significance of the paintings of 19th century English artist John Anster Fitzgerald. Focus on the painting 'Cock Robin'; Paintings of fairies hunting, capturing and killing robins; Influence of Fitzgerald's employment as a theatrical scene painter; Speculation on what Fitzgerald's visual and other sources might have been.

Objective: Photodynamic therapy (PDT) uses red light (non-thermal, non-ionising) to activate a previously administered photosensitising drug. This inhibits neointimal hyperplasia in injured arteries in small animals where it appears safe and well tolerated. Our aim was to develop a method for percutaneous application of PDT to iliac and coronary arteries in a large animal model and investigate its influence on the remodeling and intimal hyperplastic response to balloon injury. Methods: Studies were undertaken on 13 juvenile Large White–Landrace crossbred pigs (15–20 kg). After intravenous administration of the photosensitising agent 5-amino laevulinic acid (ALA), the arterial tree was accessed via the left common carotid artery and balloon injuries made by overdistension in both common iliacs (thirteen animals) and one or two main coronary arteries (eight animals). Half the injured sites were then illuminated with red laser light transmitted via the catheter. Animals were culled 28 days later and tissue harvested for histomorphometry. Results: Compared with control injured vessels, PDT treated, balloon injured coronary arteries had a larger lumen (1.4 vs. 0.8 mm2, P=0.002), larger area within the external elastic lamina (2.8 vs. 2.2 mm2, P=0.006) and smaller area of neointimal hyperplasia (0.4 vs. 0.7 mm2, P=0.06), 28 days after intervention. Less neointimal hyperplasia and the absence of negative remodeling resulted in the lumen of PDT-treated, injured segments being the same as that of adjacent reference segments (1.5 vs. 1.6 mm2). Similar trends, but with smaller differences, were seen in the iliac vessels. Conclusions: Intra-arterial, trans-catheter PDT favourably influences the arterial response to balloon injury in both the coronary and peripheral circulations. This technique offers a promising new approach to restenosis after endovascular procedures. [ABSTRACT FROM PUBLISHER]

Objective Neurogranin is a postsynaptic protein associated with declining memory and executive functioning in Alzheimer's disease (ad). While previous research suggests neurogranin concentrations in ad are higher in women, it is unclear whether sex differences exist in earlier disease stages or predict different cognitive outcomes. This study investigates cerebrospinal fluid (CSF) neurogranin in relation to longitudinal cognitive decline in older adults ranging from normal cognition to mild cognitive impairment, assessing for interactions by sex. Method Vanderbilt Memory & Aging Project participants completed baseline fasting lumbar puncture (n = 155, 73 ± 8 years) for neurogranin quantification and serial neuropsychological assessments at 18-month intervals. Linear mixed effect regression adjusting for age, sex (for main effect models), race/ethnicity, education, cognitive diagnosis, depressed mood, and APOE-ε4 carrier status. Results CSF neurogranin predicted worse cognitive decline across multiple domains (p-values <0.05). Sex interactions existed for Boston Naming Test (β = −0.007, p = 0.001), WAIS-IV Coding (β = −0.01, p = 0.02), Hooper Visual Orientation Test (β = −0.005, p = 0.02), and Category (animals) Fluency (β = −0.005, p = 0.048) wherein CSF neurogranin predicted worse decline among women (p-values≤0.03) but not men (p-values≥0.36). Conclusion Results suggest that among nondemented older adults, CSF neurogranin predicts worse longitudinal cognitive decline in women but not in men. Further research is needed to elucidate underlying mechanisms that may account for these differences, such as possible sex hormone factors. These findings highlight the importance of pursuing individualized prevention and treatment approaches to combat accelerated cognitive aging that take into account the possibility of multiple, divergent disease pathways preceding ad and dementia among various demographic groups. [ABSTRACT FROM AUTHOR]

Objective Cerebrospinal fluid (CSF) and plasma neurofilament light (NFL) concentrations were assessed in relation to longitudinal objective and subjective cognitive outcomes in older adults ranging from normal cognition to mild cognitive impairment. Interactive effects were assessed for apolipoprotein E ϵ4 (APOE4) carriership, a strong genetic risk factor for Alzheimer's disease and molecular moderator of vascular disease. Method Vanderbilt Memory & Aging Project participants (CSF n = 149, 72 ± 6 years; plasma n = 333, 73 ± 7 years) underwent fasting blood draw and lumbar puncture at baseline for NFL quantification. Serial neuropsychological assessments and subjective cognitive decline (SCD) questionnaires were completed at 18-month increments. Linear mixed effects regression models adjusted for age, sex, race/ethnicity, education, APOE4 carriership (for main effect models), and depressed mood. NFL x APOE4 interaction terms were used as predictors in follow-up models. Results CSF NFL predicted steeper declines in an executive functioning composite score (β = −0.0001, p = 0.001) and WAIS-IV Coding (β = −0.001, p = 0.001). An APOE4 interaction was present for executive functioning (β = −0.0002, p = 0.005) such that CSF NFL associations with longitudinal decline were stronger among APOE4+ participants. Plasma NFL predicted worsening SCD (β = 0.27, p = 0.002) and objective cognitive decline across all domains (p-values <0.05), with multiple APOE4 interactions (p-values <0.05) suggesting stronger associations with objective cognitive decline among APOE4+ participants. Conclusions Both CSF and plasma NFL detect neuropathology associated with cognitive decline among non-demented older adults, especially among APOE4 carriers. Findings further support the value of SCD as reflecting neurodegenerative changes associated with accelerated cognitive aging. [ABSTRACT FROM AUTHOR]

Objective Subjective cognitive decline (SCD), a potential precursor to Alzheimer's disease (ad), has been associated with increased neurodegeneration and cerebrovascular disease longitudinally. However, the impact of amyloid status, an early pathological marker of Alzheimer's disease (ad) on these longitudinal associations is less clear. Here, we related baseline SCD to longitudinal biomarkers of brain health in the context of amyloid status. Method Participants included 139 non-demented older adults (72 ± 7 years) from the Vanderbilt Memory & Aging Project who completed a SCD questionnaire and fasting lumbar-puncture to quantify amyloid status (defined using published cutoffs of amyloid-beta42 levels) at baseline. 3 T brain-MRI to measure gray and white matter hyperintensity (WMH) volumes was collected at baseline, 18-months, 3-years, and 5-years. Linear mixed effects models assessed if baseline SCD X amyloid status was associated with longitudinal total and lobar grey and white matter volumes, covarying for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein-Ee4 status. Models were also stratified by baseline amyloid status. Results Baseline SCD score and amyloid status interacted with total gray (p = 0.02) and WMH volume (p < 0.05). In stratified models, higher total SCD predicted increased inferior lateral ventricular volume (p < 0.001) among amyloid positive individuals. Conversely, in amyloid negative, greater baseline SCD was associated with increased WMH volumes globally (p = 0.03) and in the frontal and parietal lobes (p-values <0.035). Conclusion In the presence of amyloid, the presence of SCD is predictive of neurodegeneration in ad -specific regions. Conversely, SCD without amyloidosis may reflect a cerebrovascular disease, indicated by WMHs. Results highlight how amyloid status may help delineate etiologies of SCD. [ABSTRACT FROM AUTHOR]