Intractable policy failure: the case of bovine TB and badgers

The failure to eliminate bovine TB from the English and Welsh cattle herd represents a long-term intractable policy failure. Cattle-to-cattle transmission of the disease has been underemphasised in the debate compared with transmission from badgers despite a contested evidence base. Archival evidence shows that mythical constructions of the badger have shaped the policy debate. Relevant evidence was incomplete and contested; alternative framings of the policy problem were polarised and difficult to reconcile; and this rendered normal techniques of stakeholder management through co-option and mediation of little assistance

Masses, Radii, and Cloud Properties of the HR 8799 Planets

The near-infrared colors of the planets directly imaged around the A star HR 8799 are much redder than most field brown dwarfs of the same effective temperature. Previous theoretical studies of these objects have concluded that the atmospheres of planets b, c, and d are unusually cloudy or have unusual cloud properties. Some studies have also found that the inferred radii of some or all of the planets disagree with expectations of standard giant planet evolution models. Here we compare the available data to the predictions of our own set of atmospheric and evolution models that have been extensively tested against observations of field L and T dwarfs, including the reddest L dwarfs. Unlike some previous studies we require mutually consistent choices for effective temperature, gravity, cloud properties, and planetary radius. This procedure thus yields plausible values for the masses, effective temperatures, and cloud properties of all three planets. We find that the cloud properties of the HR 8799 planets are not unusual but rather follow previously recognized trends, including a gravity dependence on the temperature of the L to T spectral transition--some reasons for which we discuss. We find the inferred mass of planet b is highly sensitive to whether or not we include the H and K band spectrum in our analysis. Solutions for planets c and d are consistent with the generally accepted constraints on the age of the primary star and orbital dynamics. We also confirm that, like in L and T dwarfs and solar system giant planets, non-equilibrium chemistry driven by atmospheric mixing is also important for these objects. Given the preponderance of data suggesting that the L to T spectral type transition is gravity dependent, we present an exploratory evolution calculation that accounts for this effect. Finally we recompute the the bolometric luminosity of all three planets.Comment: 52 pages, 12 figures, Astrophysical Journal, in press. v2 features minor editorial updates and correction

Improving risk management for violence in mental health services: a multimethods approach

contractual_start_date: 07-2008 editorial_review_begun: 07-2014 accepted_for_publication: 06-2015contractual_start_date: 07-2008 editorial_review_begun: 07-2014 accepted_for_publication: 06-2015contractual_start_date: 07-2008 editorial_review_begun: 07-2014 accepted_for_publication: 06-2015contractual_start_date: 07-2008 editorial_review_begun: 07-2014 accepted_for_publication: 06-201

CM363, a novel naphthoquinone derivative which acts as multikinase modulator and overcomes imatinib resistance in chronic myelogenous leukemia

Human Chronic Myelogenous Leukemia (CML) is a hematological stem cell disorder which is associated with activation of Bcr-Abl-Stat5 oncogenic pathway. Direct Bcr-Abl inhibitors are initially successful for the treatment of CML but over time many patients develop drug resistance. In the present study, the effects of CM363, a novel naphthoquinone (NPQ) derivative, were evaluated on human CML-derived K562 cells. CM363 revealed an effective cell growth inhibition (IC50 = 0.7 ± 0.5 μM) by inducing cancer cells to undergo cell cycle arrest and apoptosis. CM363 caused a dose- and time-dependent reduction of cells in G0/G1 and G2/M phases. This cell cycle arrest was associated with increased levels of cyclin E, pChk1 and pChk2 whereas CM363 downregulated cyclin B, cyclin D3, p27, pRB, Wee1, and BUBR1. CM363 increased the double-strand DNA break marker γH2AX. CM363 caused a time-dependent increase of annexin V-positive cells, DNA fragmentation and increased number of apoptotic nuclei. CM363 triggered the mitochondrial apoptotic pathway as reflected by a release of cytochrome C from mitochondria and induction of the cleavage of caspase-3 and -9, and PARP. CM363 showed multikinase modulatory effects through an early increased JNK phosphorylation followed by inhibition of pY-Bcrl-Abl and pY-Stat5. CM363 worked synergistically with imatinib to inhibit cell viability and maintained its activity in imatinib-resistant cells. Finally, CM363 (10 mg/Kg) suppressed the growth of K562 xenograft tumors in athymic mice. In summary, CM363 is a novel multikinase modulator that offers advantages to circumvent imanitib resistance and might be therapeutically effective in Bcrl-Abl-Stat5 related malignancies

Associations between DSM-IV diagnosis, psychiatric symptoms and morning cortisol levels in a community sample of adolescents

Purpose. Dysfunction of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) is implicated in a variety of psychiatric and emotional disorders. In this study, we explore the association between HPA-axis functioning, as measured by morning cortisol, and common psychiatric disorders and symptoms among a community sample of adolescents. Method. Data from a cross-sectional school-based survey of 501 school pupils, aged 15, were used to establish the strength of association between salivary morning cortisol and both diagnosis of psychiatric disorders and a number of psychiatric symptoms, as measured via a computerised psychiatric interview. Analysis, conducted separately by gender, used multiple regressions, adjusting for relevant confounders. Results-á-áWith one exception (a positive association between conduct disorder symptoms and cortisol among females) there was no association between morning cortisol and psychiatric diagnosis or symptoms. However, there was a significant two-way interaction between gender and conduct symptoms, with females showing a positive and males a negative association between cortisol and conduct symptoms. A further three-way interaction showed that while the association between cortisol and conduct symptoms was negative among males with a few mood disorder symptoms, among females with many mood symptoms it was positive. Conclusions. Except in relation to conduct symptoms, dysregulation of morning cortisol levels seems unrelated to any psychiatric disorder or symptoms. However, the relationship between cortisol and conduct symptoms is moderated by both gender and mood symptoms. Findings are compatible with the recent work suggesting research should concentrate on the moderated associations between gender, internalising and externalising symptoms and cortisol, rather than any simple relationship

Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., autism and attention-deficit hyperactivity disorder). This phenotype may reflect gonadal steroid deficiency, haploinsufficiency of X chromosome genes, failure to express parentally imprinted genes, and the uncovering of X chromosome mutations. Understanding the contribution of these different mechanisms to outcome has the potential to improve clinical care for individuals with TS and to better our understanding of the differential vulnerability to and expression of neurodevelopmental disorders in males and females. In this paper, we review what is currently known about cognition and brain development in individuals with TS, discuss underlying mechanisms and their relevance to understanding male-biased neurodevelopmental conditions, and suggest directions for future research