Synthesis of substituted benzooxaborinin-1-ols via palladium-catalysed cyclisation of alkenyl- and alkynyl-boronic acids

Two new palladium-catalysed reactions have been developed for the synthesis of stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin-1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho-alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction to provide 4-allylbenzooxaborinin-1-ols

The course of mental health problems in children presenting with abdominal pain in general practice

Objective. To investigate the course of mental health problems in children presenting to general practice with abdominal pain and to evaluate the extent to which abdominal pain characteristics during follow-up predict the presence of mental health problems at 12 months' follow-up. Design. A prospective cohort study with one-year follow-up. Setting. 53 general practices in the Netherlands, between May 2004 and March 2006. Subjects. 281 children aged 4-17 years. Main outcome measures. The presence of a depressive problem, an anxiety problem, and multiple non-specific somatic symptoms at follow-up and odds ratios of duration, frequency, and severity of abdominal pain with these mental health problems at follow-up. Results. A depressive problem persisted in 24/74 children (32.9%; 95% CI 22.3-44.9%), an anxiety problem in 13/43 (30.2%; 95% CI 17.2-46.1%) and the presence of multiple non-specific somatic symptoms in 75/170 children (44.1%; 95% CI 36.7-51.6%). None of the abdominal pain characteristics predicted a depressive or an anxiety problem at 12 months' follow-up. More moments of moderate to severe abdominal pain predicted the presence of multiple nonspecific somatic symptoms at follow-up. Conclusions. In one-third of the children presenting to general practice for abdominal pain, anxiety and depressive problems persist during one year of follow-up. Characteristics of the abdominal pain during the follow-up period do not predict anxiety or depressive problems after one-year follow-up. We recommend following over time children seen in primary care with abdominal pain

Gender Discrimination and Ageist Perceptions:

This report presents the findings from an ESF Objective 3 Project “Gender Discrimination and Ageist Perceptions”. The project is based at Liverpool John Moores University, in the Faculty of Education, Community and Leisure. Context Older age groups have consistently been undervalued and often discarded by employers, for being too old. They are now being encouraged to re-enter the workplace through schemes such as New Deal 50 plus and Pathways to Work, or to take up volunteering through the promotion of “Active Citizenship”. In addition, the concept of lifelong learning has been advocated by New Labour as an attempt to move away from the traditional notions of education, towards a vision in which education forms a lifelong process, which can be accessed at any time during the life course. Yet, despite the lower labour market attachment of the over fifties, people of this age group in higher education account for only around 1% of the student population. There is a variety of ways in which people approaching their mid life would, on the face of it, be able to access work, education or volunteering experiences. However, past research and current data suggest that there appear to be barriers to the take up of such opportunities. The Aim This study set out to investigate the experiences and perceptions of women and men aged over fifty and the organisations which impact upon their lives, in an effort to understand more fully the potential barriers this age group may face when accessing opportunities, employment, training or education. Background Gender disadvantages in the world of work have been well documented. Increasingly, age perceptions are thought to be a factor in older peoples’ access to employment and training opportunities. Data shows that the and only a tenth of those are on employer and government training programmes (TAEN, 2006). The demographic change, with more people living longer, coupled with low birth rates, is creating an expanding older population and fuelling oncerns over labour shortages. There is, therefore, an economic imperative to draw workers back into work via a variety of avenues. Despite over 70% of women now participating in the workforce, the employment patterns of men and women show that only 21% of women over 40 are in full-time employment, compared with 46% of men. Women have not had the same opportunities as men to build a career or to earn the equivalent of males due to their child-rearing and caring responsibilities, with many continuing to be concentrated in traditionally low paid sectors. The pay gap between some men and women is widening,despite the long history of legislation on equal pay. To compound the situation, older women are now said to be facing a double jeopardy of age and gender discrimination. Tackling discrimination has been at the heart of equal opportunities legislation designed to prevent unequal treatment regardless of gender,race and disability. The Sex Discrimination Act (SDA) and Equal Pay Act (EPA) both came into force in 1975. Each Act attempted to redress the inequalities suffered by (mainly) women in terms of employment and education. The Bill to establish the Commission for Equality and Human Rights (CEHR) received Royal Assent on 16th February 2006 and will provide an integrated approach to all forms of discrimination including that on the grounds of age

Inhibition of interleukin 6 signalling and renal function: a Mendelian randomization study.

Inhibition of interleukin 6 (IL-6) signalling has been proposed as a potential cardioprotective strategy for patients with chronic kidney disease (CKD), but the direct effects of IL-6 inhibition on renal function are not known. A Mendelian randomization (MR) study was performed to investigate the association of genetically proxied inhibition of IL-6 signalling with estimated glomerular filtration rate (eGFR), CKD and blood urea nitrogen (BUN). Inverse-variance weighted MR was used as the main analysis, with sensitivity analyses performed using simple median, weighted median and MR-Egger methods. There was no evidence for an association of genetically proxied inhibition of IL-6 signalling (scaled per standard deviation unit decrease in C-reactive protein) with log eGFR (0.001, 95% confidence interval -0.004 - 0.007), BUN (0.009, 95% confidence interval -0.003 - 0.021) and CKD (odds ratio 0.948, 95% confidence interval 0.822 - 1.094). These findings do not raise concerns for IL-6 signalling having large adverse effects on renal function

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

An Extended Model for the Evolution of Prebiotic Homochirality: A Bottom-Up Approach to the Origin of Life

A generalized autocatalytic model for chiral polymerization is investigated in detail. Apart from enantiomeric cross-inhibition, the model allows for the autogenic (non-catalytic) formation of left and right-handed monomers from a substrate with reaction rates $\epsilon_L$ and $\epsilon_R$, respectively. The spatiotemporal evolution of the net chiral asymmetry is studied for models with several values of the maximum polymer length, N. For N=2, we study the validity of the adiabatic approximation often cited in the literature. We show that the approximation obtains the correct equilibrium values of the net chirality, but fails to reproduce the short time behavior. We show also that the autogenic term in the full N=2 model behaves as a control parameter in a chiral symmetry- breaking phase transition leading to full homochirality from racemic initial conditions. We study the dynamics of the N -> infinity model with symmetric ($\epsilon_L = \epsilon_R$) autogenic formation, showing that it only achieves homochirality for $\epsilon < \epsilon_c$, where $\epsilon_c$ is an N-dependent critical value. For $\epsilon \leq \epsilon_c$ we investigate the behavior of models with several values of N, showing that the net chiral asymmetry grows as tanh(N). We show that for a given symmetric autogenic reaction rate, the net chirality and the concentrations of chirally pure polymers increase with the maximum polymer length in the model. We briefly discuss the consequences of our results for the development of homochirality in prebiotic Earth and possible experimental verification of our findings

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.Comment: 15 pages, 6 figures, accepted for publication in Origins of Life and Evolution of Biosphere

A database of microRNA expression patterns in Xenopus laevis

MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

Recognizing detachment-mode seafloor spreading in the deep geological past.

Large-offset oceanic detachment faults are a characteristic of slow- and ultraslow-spreading ridges, leading to the formation of oceanic core complexes (OCCs) that expose upper mantle and lower crustal rocks on the seafloor. The lithospheric extension accommodated by these structures is now recognized as a fundamentally distinct “detachment-mode” of seafloor spreading compared to classical magmatic accretion. Here we demonstrate a paleomagnetic methodology that allows unequivocal recognition of detachment-mode seafloor spreading in ancient ophiolites and apply this to a potential Jurassic detachment fault system in the Mirdita ophiolite (Albania). We show that footwall and hanging wall blocks either side of an inferred detachment have significantly different magnetizations that can only be explained by relative rotation during seafloor spreading. The style of rotation is shown to be identical to rolling hinge footwall rotation documented recently in OCCs in the Atlantic, confirming that detachment-mode spreading operated at least as far back as the Jurassic

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions