ITO-free top emitting organic light emitting diodes with enhanced light out-coupling

Bottom emitting organic light emitting diodes (OLEDs) can suffer from lower external quantum efficiencies (EQE) due to inefficient out-coupling of the generated light. Herein, it is demonstrated that the current efficiency and EQE of red, yellow, and blue fluorescent single layer polymer OLEDs is significantly enhanced when a MoOx(5 nm)/Ag(10 nm)/MoOx(40 nm) stack is used as the transparent anode in a top emitting OLED structure. A maximum current efficiency and EQE of 21.2 cd/A and 6.7%, respectively, was achieved for a yellow OLED, while a blue OLED achieved a maximum of 16.5 cd/A and 10.1%, respectively. The increase in light out-coupling from the top-emitting OLEDs led to increase in efficiency by a factor of up to 2.2 relative to the optimised bottom emitting devices, which is the best out-coupling reported using solution processed polymers in a simple architecture and a significant step forward for their use in large area lighting and displays.

Peer mentoring for radiotherapy planning skills development: A pilot study

Introduction: This study aimed to determine the potential role and guidelines for implementation of skill-based peer mentoring for radiotherapy planning education. Methods: After four weekly mentoring sessions, both Year 3 mentors (n=9) and Year 2 mentees (n=9) were invited to complete a short online questionnaire relating to the impact of the initiative. The tool contained a mixture of Likert-style questions concerning student enjoyment and perceived usefulness of the initiative as well as more qualitative open questions that gathered perceptions of the peer mentoring process, implementation methods and potential future scope. Results: Several key discussion themes related to benefits to each stakeholder group, challenges arising, improvements and potential future directions. There were high levels of enjoyment and perceived value of the mentoring from both sides with 100% of the 18 respondents enjoying the experience. The informal format encouraged further learning, while mentors reported acquisition of valuable skills and gains in knowledge. Conclusions: Peer mentoring has a valuable and enjoyable role to play in radiotherapy planning training and helps consolidate theoretical understanding for experienced students. An informal approach allows for students to adopt the most appropriate mentoring model for their needs while providing them with a free space to engender additional discussion.

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom

Objective - To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods - HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. Results - The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10-99). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10-5), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HkA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. Conclusion - HLA-B27 and -B60 are associated with susceptibility to AS, but differences in BLA-B27 subtype do not affect susceptibility to AS in this white population.

Crystal structure of ammonium (3,5-dichlorophenoxy)acetate hemihydrate

In the structure of the title hydrated salt, NH4+·C8H5Cl2O3-·0.5H2O, where the anion derives from (3,5-di­chloro­phen­oxy)acetic acid, the ammonium cation is involved in extensive N-H...O hydrogen bonding with both carboxyl­ate and ether O-atom acceptors giving sheet structures lying parallel to (100). The water mol­ecule of solvation lies on a crystallographic twofold rotation axis and is involved in intra-sheet O-H...Ocarboxyl­ate hydrogen-bonding inter­actions. In the anion, the oxoacetate side chain assumes an antiperiplanar conformation with the defining C-O-C-C torsion angle = -171.33 (15)°.

A comprehensive ovine model of blood transfusion

Background The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. Results Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline–adenine–glucose–mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. Methods. One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data Results. We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). Conclusion. A role for HLA NIMA in RA is suggested by these results.

Cost effectiveness of bone density measurements

Objective. To assess the cost-effectiveness of bone density screening programmes for osteoporosis. Study design. Using published and locally available data regarding fracture rates and treatment costs, the overall costs per fracture prevented, cost per quality of life year (QALY) saved and cost per year of life gained were estimated for different bone density screening and osteoporosis treatment programmes. Main outcome measures. Cost per fracture prevented, cost per QALY saved, and cost per year of life gained. Results. In women over the age of 50 years, the costs per fracture prevented of treating all women with hormone replacement therapy, or treating only if osteoporosis is demonstrated on bone density screening were £32,594 or £23,867 respectively. For alendronate therapy for the same groups, the costs were £171,067 and £14,067 respectively. Once the background rate of treatment with alendronate reaches 18%, bone density screening becomes cost-saving. Costs estimates per QALY saved ranged from £1,514 to £39,076 for osteoporosis treatment with alendronate following bone density screening. Conclusions. For relatively expensive medications such as alendronate, treatment programmes with prior bone density screening are far more cost effective than those without, and in some circumstances become cost-saving. Costs per QALY of life saved and per year of life gained for osteoporosis treatment with prior bone density screening compare favourably with treatment of hypertension and hypercholesterolemia.

Saussure, science and structuralism

This paper investigates the influence of an extensive family tradition in science-based interdisciplinary research on the origins and development of Ferdinand de Saussure's 'structuralism', or his 'scientization' of linguistic study.

Utility of magnetic resonance imaging-based finite element analysis for the biomechanical stress analysis of hemorrhagic and non-hemorrhagic carotid plaques

Background: Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Methods and Results: Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-CstressSL) for each slice was determined. Within a plaque, the maximum M-CstressSL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-CstressPL) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-CstressPL) than plaques without PH (median [interquartile range]: 315 kPa [247-434] vs. 200 kPa [171-282], P=0.003). Conclusions: Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability.

Rank regression for analysis of clustered data: A natural induced smoothing approach

We consider rank regression for clustered data analysis and investigate the induced smoothing method for obtaining the asymptotic covariance matrices of the parameter estimators. We prove that the induced estimating functions are asymptotically unbiased and the resulting estimators are strongly consistent and asymptotically normal. The induced smoothing approach provides an effective way for obtaining asymptotic covariance matrices for between- and within-cluster estimators and for a combined estimator to take account of within-cluster correlations. We also carry out extensive simulation studies to assess the performance of different estimators. The proposed methodology is substantially Much faster in computation and more stable in numerical results than the existing methods. We apply the proposed methodology to a dataset from a randomized clinical trial.

Optimal designs for evaluating a series of treatments

Several articles in this journal have studied optimal designs for testing a series of treatments to identify promising ones for further study. These designs formulate testing as an ongoing process until a promising treatment is identified. This formulation is considered to be more realistic but substantially increases the computational complexity. In this article, we show that these new designs, which control the error rates for a series of treatments, can be reformulated as conventional designs that control the error rates for each individual treatment. This reformulation leads to a more meaningful interpretation of the error rates and hence easier specification of the error rates in practice. The reformulation also allows us to use conventional designs from published tables or standard computer programs to design trials for a series of treatments. We illustrate these using a study in soft tissue sarcoma.

The designed environment and how it affects brain morphology and mental health

Background The environment is inextricably related to mental health. Recent research replicates findings of a significant, linear correlation between a childhood exposure to the urban environment and psychosis. Related studies also correlate the urban environment and aberrant brain morphologies. These findings challenge common beliefs that the mind and brain remain neutral in the face of worldly experience. Aim There is a signature within these neurological findings that suggests that specific features of design cause and trigger mental illness. The objective in this article is to work backward from the molecular dynamics to identify features of the designed environment that may either trigger mental illness or protect against it. Method This review analyzes the discrete functions putatively assigned to the affected brain areas and a neurotransmitter called dopamine, which is the primary target of most antipsychotic medications. The intention is to establish what the correlations mean in functional terms, and more specifically, how this relates to the phenomenology of urban experience. In doing so, environmental mental illness risk factors are identified. Conclusions Having established these relationships, the review makes practical recommendations for those in public health who wish to use the environment itself as a tool to improve the mental health of a community through design.

The missing link of crime analysis: A systematic approach to testing competing hypotheses

Crime analysts have traditionally received little guidance from academic researchers in key tasks in the analysis process, specifically the testing of multiple hypotheses and evaluating evidence in a scientific fashion. This article attempts to fill this gap by outlining a method (the Analysis of Competing Hypotheses) of systematically analysing multiple explanations for crime problems. The method is systematic, avoids many cognitive errors common in analysis, and is explicit. It is argued that the implementation of this approach makes analytic products audit-able, the reasoning underpinning them transparent, and provides intelligence managers a rational professional development tool for individual analysts.

Leaders' personal wisdom and leader-member exchange quality: The role of individualized consideration

Business scholars have recently proposed that the virtue of personal wisdom may predict leadership behaviors and the quality of leader–follower relationships. This study investigated relationships among leaders’ personal wisdom—defined as the integration of advanced cognitive, reflective, and affective personality characteristics (Ardelt, Hum Dev 47:257–285, 2004)—transformational leadership behaviors, and leader–member exchange (LMX) quality. It was hypothesized that leaders’ personal wisdom positively predicts LMX quality and that intellectual stimulation and individualized consideration, two dimensions of transformational leadership, mediate this relationship. Data came from 75 religious leaders and 1–3 employees of each leader (N = 158). Results showed that leaders’ personal wisdom had a positive indirect effect on follower ratings of LMX quality through individualized consideration, even after controlling for Big Five personality traits, emotional intelligence, and narcissism. In contrast, intellectual stimulation and the other two dimensions of transformational leadership (idealized influence and inspirational motivation) did not mediate the positive relationship between leaders’ personal wisdom and LMX quality. Implications for future research on personal wisdom and leadership are discussed, and some tentative suggestions for leadership development are outlined.