Lateral grating DFB AlGaInN laser diodes for optical communications and atomic clocks

AlGaInN laser diode technology is of considerable interest for telecom applications and next generation atomic optical clocks based on Sr (by using 422nm & 461nm) and Rb at 420.2nm.Very narrow linewidths (<1MHz) are required for such applications. We report lateral gratings on AlGaInN ridge waveguide laser diodes to achieve a single wavelength device with a good side mode suppression ratio (SMSR) that is suitable for atomic clock and telecom applications

The causes of prescribing errors in English general practices: a qualitative study

Background: Few detailed studies exist of the underlying causes of prescribing errors in the UK. Aim: To examine the causes of prescribing and monitoring errors in general practice and provide recommendations for how they may be overcome. Design and setting: Qualitative interview and focus group study with purposive sampling of English general practices. Method: General practice staff from 15 general practices across three PCTs in England participated in a combination of semi-structured interviews (n = 34) and six focus groups (n = 46). Thematic analysis informed by Reason’s Accident Causation Model was used. Results: Seven categories of high-level error-producing conditions were identified: the prescriber, the patient, the team, the working environment, the task, the computer system, and the primary–secondary care interface. These were broken down to reveal various error-producing conditions: the prescriber’s therapeutic training, drug knowledge and experience, knowledge of the patient, perception of risk, and their physical and emotional health; the patient’s characteristics and the complexity of the individual clinical case; the importance of feeling comfortable within the practice team was highlighted, as well as the safety implications of GPs signing prescriptions generated by nurses when they had not seen the patient for themselves; the working environment with its extensive workload, time pressures, and interruptions; and computer-related issues associated with mis-selecting drugs from electronic pick-lists and overriding alerts were all highlighted as possible causes of prescribing errors and were often interconnected. Conclusion: Complex underlying causes of prescribing and monitoring errors in general practices were highlighted, several of which are amenable to intervention

Eliciting willingness-to-pay to prevent hospital medication administration errors in the UK: a contingent valuation survey.

Medication errors are common in hospitals. These errors can result in adverse drug events (ADEs), which can reduce the health and well-being of patients', and their relatives and caregivers. Interventions have been developed to reduce medication errors, including those that occur at the administration stage. OBJECTIVE: We aimed to elicit willingness-to-pay (WTP) values to prevent hospital medication administration errors. DESIGN AND SETTING: An online, contingent valuation (CV) survey was conducted, using the random card-sort elicitation method, to elicit WTP to prevent medication errors. PARTICIPANTS: A representative sample of the UK public. METHODS: Seven medication error scenarios, varying in the potential for harm and the severity of harm, were valued. Scenarios were developed with input from: clinical experts, focus groups with members of the public and piloting. Mean and median WTP values were calculated, excluding protest responses or those that failed a logic test. A two-part model (logit, generalised linear model) regression analysis was conducted to explore predictive characteristics of WTP. RESULTS: Responses were collected from 1001 individuals. The proportion of respondents willing to pay to prevent a medication error increased as the severity of the ADE increased and was highest for scenarios that described actual harm occurring. Mean WTP across the scenarios ranged from £45 (95% CI £36 to £54) to £278 (95% CI £200 to £355). Several factors influenced both the value and likelihood of WTP, such as: income, known experience of medication errors, sex, field of work, marriage status, education level and employment status. Predictors of WTP were not, however, consistent across scenarios. CONCLUSIONS: This CV study highlights how the UK public value preventing medication errors. The findings from this study could be used to carry out a cost-benefit analysis which could inform implementation decisions on the use of technology to reduce medication administration errors in UK hospitals

WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel

WT1 is a transcription factor which regulates the epithelial-mesenchymal balance during embryonic development and, if mutated, can lead to the formation of Wilms' tumour, the most common paediatric kidney cancer. Its expression has also been reported in several adult tumour types, including breast cancer, and usually correlates with poor outcome. However, published data is inconsistent and the role of WT1 in this malignancy remains unclear. Here we provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis. Using in vitro cell lines, clinical samples and publicly available gene expression datasets, we demonstrate that WT1 plays a role in regulating the epithelial-mesenchymal balance of breast cancer cells and that WT1-expressing tumours are mainly associated with a mesenchymal phenotype. WT1 gene expression also correlates with CYP3A4 levels and is associated with poorer response to taxane treatment. Our work is the first to demonstrate that the known association between WT1 expression in breast cancer and poor prognosis is potentially due to cancer-related epithelial-to-mesenchymal transition (EMT) and poor chemotherapy response

Structure of the mirror nuclei 9^9Be and 9^9B in a microscopic cluster model

The structure of the mirror nuclei $^9$Be and $^9$B is studied in a microscopic $\alpha+ \alpha+ n$ and $\alpha+ \alpha+ p$ three-cluster model using a fully antisymmetrized 9-nucleon wave function. The two-nucleon interaction includes central and spin-orbit components and the Coulomb potential. The ground state of $^9$Be is obtained accurately with the stochastic variational method, while several particle-unbound states of both $^9$Be and $^9$B are investigated with the complex scaling method.The calculation for $^9$Be supports the recent identification for the existence of two broad states around 6.5 MeV, and predicts the $\frac{3}{2}^{-}_2$ and $\frac{5}{2}^{-}_2$ states at about 4.5 MeV and 8 MeV, respectively. The similarity of the calculated spectra of $^9$Be and $^9$B enables one to identify unknown spins and parities of the $^9$B states. Available data on electromagnetic moments and elastic electron scatterings are reproduced very well. The enhancement of the $E$1 transition of the first excited state in $^9$Be is well accounted for. The calculated density of $^9$Be is found to reproduce the reaction cross section on a Carbon target. The analysis of the beta decay of $^9$Li to $^9$Be clearly shows that the wave function of $^9$Be must contain a small component that cannot be described by the simple $\alpha+ \alpha+ n$ model. This small component can be well accounted for by extending a configuration space to include the distortion of the $\alpha$-particle to $t+p$ and $h+n$ partitions.Comment: 24 page

Attachment and Entry of Chlamydia Have Distinct Requirements for Host Protein Disulfide Isomerase

Chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans. Attachment and entry are key processes in infectivity and subsequent pathogenesis of Chlamydia, yet the mechanisms governing these interactions are unknown. It was recently shown that a cell line, CHO6, that is resistant to attachment, and thus infectivity, of multiple Chlamydia species has a defect in protein disulfide isomerase (PDI) N–terminal signal sequence processing. Ectopic expression of PDI in CHO6 cells led to restoration of Chlamydia attachment and infectivity; however, the mechanism leading to this recovery was not ascertained. To advance our understanding of the role of PDI in Chlamydia infection, we used RNA interference to establish that cellular PDI is essential for bacterial attachment to cells, making PDI the only host protein identified as necessary for attachment of multiple species of Chlamydia. Genetic complementation and PDI-specific inhibitors were used to determine that cell surface PDI enzymatic activity is required for bacterial entry into cells, but enzymatic function was not required for bacterial attachment. We further determined that it is a PDI-mediated reduction at the cell surface that triggers bacterial uptake. While PDI is necessary for Chlamydia attachment to cells, the bacteria do not appear to utilize plasma membrane–associated PDI as a receptor, suggesting that Chlamydia binds a cell surface protein that requires structural association with PDI. Our findings demonstrate that PDI has two essential and independent roles in the process of chlamydial infectivity: it is structurally required for chlamydial attachment, and the thiol-mediated oxido-reductive function of PDI is necessary for entry

A bacterial glycan core linked to surface (S)-layer proteins modulates host immunity through Th17 suppression

Tannerella forsythia is a pathogen implicated in periodontitis, an inflammatory disease of the tooth-supporting tissues often leading to tooth loss. This key periodontal pathogen is decorated with a unique glycan core O-glycosidically linked to the bacterium's proteinaceous surface (S)-layer lattice and other glycoproteins. Herein, we show that the terminal motif of this glycan core acts to modulate dendritic cell effector functions to suppress T-helper (Th)17 responses. In contrast to the wild-type bacterial strain, infection with a mutant strain lacking the complete S-layer glycan core induced robust Th17 and reduced periodontal bone loss in mice. Our findings demonstrate that surface glycosylation of this pathogen may act to ensure its persistence in the host likely through suppression of Th17 responses. In addition, our data suggest that the bacterium then induces the Toll-like receptor 2–Th2 inflammatory axis that has previously been shown to cause bone destruction. Our study provides a biological basis for pathogenesis and opens opportunities in exploiting bacterial glycans as therapeutic targets against periodontitis and a range of other infectious diseases

Understanding the impact of the Hajj: explaining experiences of self-change at a religious mass gathering

Previous research has shown that participation in the Hajj pilgrimage to Mecca can lead to both more positive outgroup attitudes and increased commitment to Muslim identity. We describe a survey of pilgrims (N = 1176) carried out at Mecca, during the Hajj, which tested explanations for these experiences of self‐change at the time of their occurrence. In line with contact theory, perceived cooperation among pilgrims indirectly predicted more positive outgroup attitudes (as well as enhanced Muslim identification), via identification with the crowd. In line with social identity and identity congruence explanations, positive emotional experience and the perception that the crowd embodied the Muslim value of unity predicted self‐change variables through identification with the crowd. The finding that participation in an all‐Muslim gathering increases positive views of other groups (including non‐Muslims) through identification with the crowd offers an alternative perspective to suggestions that such gatherings might encourage intolerance