Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England

Background: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. Aims: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. Methods: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. Results: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported – insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. Conclusion: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing professionspecific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status

Contemporary carbon fluxes do not reflect the long-term carbon balance for an Atlantic blanket bog

Peatlands are one of the largest terrestrial stores of carbon. Carbon exchange in peatlands is often assessed solely by measurement of contemporary fluxes; however, these fluxes frequently indicate a much stronger sink strength than that measured by the rate of C accumulation in the peat profile over longer timescales. Here we compare profile-based measurements of C accumulation with the published net ecosystem C balance for the largest peatland area in Britain, the Flow Country of northern Scotland. We estimate the long-term rate of C accumulation to be 15.4 g C m−2 yr−1 for a site where a recent eddy covariance study has suggested contemporary C uptake more than six times greater (99.37 g C m−2 yr−1). Our estimate is supported by two further long-term C accumulation records from nearby sites which give comparable results. We demonstrate that a strong contemporary C sink strength may not equate to a strong long-term sink and explore reasons for this disparity. We recommend that contemporary C sequestration should be viewed in the context of the long-term ecological drivers, such as fires, ecohydrological feedbacks and the changing quality of litter inputs

A review of trisomy X (47,XXX)

Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment

Carrion Beetles Visiting Pig Carcasses during Early Spring in Urban, Forest and Agricultural Biotopes of Western Europe

Carrion beetles are important in terrestrial ecosystems, consuming dead mammals and promoting the recycling of organic matter into ecosystems. Most forensic studies are focused on succession of Diptera while neglecting Coleoptera. So far, little information is available on carrion beetles postmortem colonization and decomposition process in temperate biogeoclimatic countries. These beetles are however part of the entomofaunal colonization of a dead body. Forensic entomologists need databases concerning the distribution, ecology and phenology of necrophagous insects, including silphids. Forensic entomology uses pig carcasses to surrogate human decomposition and to investigate entomofaunal succession. However, few studies have been conducted in Europe on large carcasses. The work reported here monitored the presence of the carrion beetles (Coleoptera: Silphidae) on decaying pig carcasses in three selected biotopes (forest, crop field, urban site) at the beginning of spring. Seven species of Silphidae were recorded: Nicrophorus humator (Gleditsch), Nicrophorus vespillo (L.), Nicrophorus vespilloides (Herbst), Necrodes littoralis L., Oiceoptoma thoracica L., Thanatophilus sinuatus (Fabricius), Thanatophilus rugosus (L.). All of these species were caught in the forest biotope, and all but O. thoracica were caught in the agricultural biotope. No silphids were caught in the urban site

ProCAID: a phase I clinical trial to combine the AKT inhibitor AZD5363 with docetaxel and prednisolone chemotherapy for metastatic castration resistant prostate cancer.

Background Docetaxel and prednisolone chemotherapy (DP) extends survival in metastatic castration resistant prostate cancer (mCRPC). However, emergent clinical resistance is almost inevitable. AKT pathway activation is highly prevalent in mCRPC contributing to disease progression and DP resistance. AZD5363 is a potent oral pan-AKT inhibitor with pre-clinical data indicating activity in mCRPC and synergy with docetaxel. Methods This phase I trial was to determine an AZD5363 recommended phase II dose (RP2D) for combination with DP. Eligibility criteria included chemotherapy naive mCRPC, PSA or radiographic disease progression and ECOG performance status 0 or 1. Treatment comprised DP (75 mg/m2, IV, day 1 and 5 mg BID, PO, day 1-21 respectively for ten cycles) and AZD5363 to disease progression for all patients. We utilised a 3 + 3 dose escalation design to determine a maximum tolerated dose according to defined dose limiting toxicity criteria assessed using CTCAE version 4.03. Planned AZD5363 dose levels were 320 mg (DL1), 400 mg (DL2) and 480 mg (DL3), BID, PO, 4 days on/3 days off, from day 2 of each cycle. Results 10 patients were treated. Dose limiting toxicities affected 2 patients (grade 3 rash ≥5 days; grade 3 diarrhoea) in DL2. The commonest grade 3 or 4, AZD5363 related, symptomatic adverse events were rash and diarrhoea. Hyperglycaemia affected all patients but was self-limiting. PSA reduction to <50% at 12 weeks occurred in 7 patients. Conclusions The RP2D for AZD5363 is 320 mg BID, 4 days on/3 days off, in combination with full dose DP for mCRPC

Domestic horses (Equus caballus) discriminate between negative and positive human nonverbal vocalisations

The ability to discriminate between emotion in vocal signals is highly adaptive in social species. It may also be adaptive for domestic species to distinguish such signals in humans. Here we present a playback study investigating whether horses spontaneously respond in a functionally relevant way towards positive and negative emotion in human nonverbal vocalisations. We presented horses with positively- and negatively-valenced human vocalisations (laughter and growling, respectively) in the absence of all other emotional cues. Horses were found to adopt a freeze posture for significantly longer immediately after hearing negative versus positive human vocalisations, suggesting that negative voices promote vigilance behaviours and may therefore be perceived as more threatening. In support of this interpretation, horses held their ears forwards for longer and performed fewer ear movements in response to negative voices, which further suggest increased vigilance. In addition, horses showed a right-ear/left-hemisphere bias when attending to positive compared with negative voices, suggesting that horses perceive laughter as more positive than growling. These findings raise interesting questions about the potential for universal discrimination of vocal affect and the role of lifetime learning versus other factors in interspecific communication

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

Fear of crime on the rail networks: Perceptions of the UK public and British Transport Police

Counter-terrorism on the rail network is vital to the security of the United Kingdom. The British Transport Police (BTP) employ covert and overt security measures to prevent crime, which includes: closed circuit television, armed police, unarmed polisce, police community support officers, police dogs, stops and searches and awareness campaigns. All security measures aim to deter crime while importantly reassuring the public. We surveyed both members of the public and BTP officers about the perceived effectiveness of current security measures, specifically with regards to fear of terrorism. Feelings of reassurance and the perceived effectiveness of security measures were positively related. The most effective and reassuring security measure was the use of armed police; whereas the least effective and reassuring was the use of awareness campaigns. However, interestingly, qualitative analyses suggested that an increase in armed police without informed awareness campaigns would have a negative impact on public reassurance by increasing fear

Laterality and Flight: Concurrent Tests of Side-Bias and Optimality in Flying Tree Swallows

Behavioural side-bias occurs in many vertebrates, including birds as a result of hemispheric specialization and can be advantageous by improving response times to sudden stimuli and efficiency in multi-tasking. However, behavioural side-bias can lead to morphological asymmetries resulting in reduced performance for specific activities. For flying animals, wing asymmetry is particularly costly and it is unclear if behavioural side-biases will be expressed in flight; the benefits of quick response time afforded by side-biases must be balanced against the costs of less efficient flight due to the morphological asymmetry side-biases may incur. Thus, competing constraints could lead to context-dependent expression or suppression of side-bias in flight. In repeated flight trials through an outdoor tunnel with obstacles, tree swallows (Tachycineta bicolor) preferred larger openings, but we did not detect either individual or population-level side-biases. Thus, while observed behavioural side-biases during substrate-foraging and copulation are common in birds, we did not see such side-bias expressed in obstacle avoidance behaviour in flight. This finding highlights the importance of behavioural context for investigations of side-bias and hemispheric laterality and suggests both proximate and ultimate trade-offs between species-specific cognitive ecology and flight biomechanics

Arabidopsis COMPASS-Like Complexes Mediate Histone H3 Lysine-4 Trimethylation to Control Floral Transition and Plant Development

Histone H3 lysine-4 (H3K4) methylation is associated with transcribed genes in eukaryotes. In Drosophila and mammals, both di- and tri-methylation of H3K4 are associated with gene activation. In contrast to animals, in Arabidopsis H3K4 trimethylation, but not mono- or di-methylation of H3K4, has been implicated in transcriptional activation. H3K4 methylation is catalyzed by the H3K4 methyltransferase complexes known as COMPASS or COMPASS-like in yeast and mammals. Here, we report that Arabidopsis homologs of the COMPASS and COMPASS-like complex core components known as Ash2, RbBP5, and WDR5 in humans form a nuclear subcomplex during vegetative and reproductive development, which can associate with multiple putative H3K4 methyltransferases. Loss of function of ARABIDOPSIS Ash2 RELATIVE (ASH2R) causes a great decrease in genome-wide H3K4 trimethylation, but not in di- or mono-methylation. Knockdown of ASH2R or the RbBP5 homolog suppresses the expression of a crucial Arabidopsis floral repressor, FLOWERING LOCUS C (FLC), and FLC homologs resulting in accelerated floral transition. ASH2R binds to the chromatin of FLC and FLC homologs in vivo and is required for H3K4 trimethylation, but not for H3K4 dimethylation in these loci; overexpression of ASH2R causes elevated H3K4 trimethylation, but not H3K4 dimethylation, in its target genes FLC and FLC homologs, resulting in activation of these gene expression and consequent late flowering. These results strongly suggest that H3K4 trimethylation in FLC and its homologs can activate their expression, providing concrete evidence that H3K4 trimethylation accumulation can activate eukaryotic gene expression. Furthermore, our findings suggest that there are multiple COMPASS-like complexes in Arabidopsis and that these complexes deposit trimethyl but not di- or mono-methyl H3K4 in target genes to promote their expression, providing a molecular explanation for the observed coupling of H3K4 trimethylation (but not H3K4 dimethylation) with active gene expression in Arabidopsis