The relation of biotin to perosis in chicks

Publication authorized June 3, 1942.Digitized 2007 AES.Includes bibliographical references (page 10)

Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74

The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1

Implementation of routine outcome measurement in child and adolescent mental health services in the United Kingdom: a critical perspective

The aim of this commentary is to provide an overview of clinical outcome measures that are currently recommended for use in UK Child and Adolescent Mental Health Services (CAMHS), focusing on measures that are applicable across a wide range of conditions with established validity and reliability, or innovative in their design. We also provide an overview of the barriers and drivers to the use of Routine Outcome Measurement (ROM) in clinical practice

The use of routine outcome measures in two child and adolescent mental health services: a completed audit cycle

Background: Routine outcome measurement (ROM) is important for assessing the clinical effectiveness of health services and for monitoring patient outcomes. Within Child and Adolescent Mental Health Services (CAMHS) in the UK the adoption of ROM in CAMHS has been supported by both national and local initiatives (such as government strategies, local commissioning policy, and research). Methods: With the aim of assessing how these policies and initiatives may have influenced the uptake of ROM within two different CAMHS we report the findings of two case-note audits: a baseline audit conducted in January 2011 and a re-audit conducted two years later in December 2012-February 2013. Results: The findings show an increase in both the single and repeated use of outcome measures from the time of the original audit, with repeated use (baseline and follow-up) of the Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) scale increasing from 10% to 50% of cases. Re-audited case-notes contained more combined use of different outcome measures, with greater consensus on which measures to use. Outcome measures that were applicable across a wide range of clinical conditions were more likely to be used than symptom-specific measures, and measures that were completed by the clinician were found more often than measures completed by the service user. Conclusions: The findings show a substantial improvement in the use of outcome measures within CAMHS. These increases in use were found across different service organisations which were subject to different types of local service priorities and drivers

Enabling the classroom and the curriculum: higher education, literary studies and disability

In this article the tripartite model of disability is applied to the lived experience of twenty-first-century higher education. The tripartite model facilitates a complex understanding of disability that recognises assumptions and discrimination but not at the cost of valued identity. This being so, not only the normative positivisms and non-normative negativisms but also the non-normative positivisms of the classroom and the curriculum are explored. Inclusion is taken as the starting point and the argument progresses to a profound and innovational appreciation of disability. The problem addressed is that inclusion, as shown in The Biopolitics of Disability, constitutes little more than inclusion-ism until disability is recognised in the context of alternative lives and values that neither enforce nor reify normalcy. Informed by this understanding, the article adopts the disciplinary example of literary studies and refers to Brian Friel’s Molly Sweeney as a primary text. The conclusion is that, despite passive and active resistance, disability enters higher education in many ways, most of which are beneficial to students and educators alike

An exploration of the use of infant observation methods to research the identities of severely learning disabled adolescents and to enhance relationship-based practice for professional social work practice

This paper considers how infant observation methods may be adapted to explore and research the identities of severely learning disabled adolescents, a group of young people whose experiences are poorly represented in the literature. Through focusing on emotion and relationship, this ‘practice-near’ research method also offers a way for social workers to develop their reflective capacity in relation to the often hidden, uncomfortable emotions aroused by experiencing impairment and difference, but without the defences usually involved in assuming the professional role. The importance of taking time to get on a disabled child’s ‘wavelength’ is illustrated through extracts from the research which show how a young person’s agency and identity can be appreciated. The method also has the potential to develop social workers’ awareness of the powerful undercurrent of emotions apparent at times within families of severely disabled young people and tentative suggestions are made about the projective processes and hidden hostilities at work within one of the families observed as part of the research project. Professionals may be able to use this knowledge to become resilient and reflective practitioners and the observation method itself has something to offer by way of a containing experience for families

What are the experimentally observable effects of vertex corrections in superconductors?

We calculate the effects of vertex corrections, of non-constant density of states and of a (self-consistently determined) phonon self-energy for the Holstein model on a 3D cubic lattice. We replace vertex corrections with a Coulomb pseudopotential, mu*, adjusted to give the same Tc, and repeat the calculations, to see which effects are a distinct feature of vertex corrections. This allows us to determine directly observable effects ofvertex corrections on a variety of thermodynamic properties of superconductors. To this end, we employ conserving approximations (in the local approximation) to calculate the superconducting critical temperatures, isotope coefficients, superconducting gaps, free-energy differences and thermodynamic critical fields for a range of parameters. We find that the dressed value of lambda is significantly larger than the bare value. While vertex corrections can cause significant changes in all the above quantities (even whenthe bare electron-phonon coupling is small), the changes can usually be well-modeled by an appropriate Coulomb pseudopotential. The isotope coefficient proves to be the quantity that most clearly shows effects of vertex corrections that can not be mimicked by a mu*.Comment: 28 pages, 12 figure

‘It’s Kinda Punishment’: Tandem Logics and Penultimate Power in the Penal Voluntary Sector for Canadian Youth

This paper draws on original empirical research in Ontario, Canada which analyses penal voluntary sector practice with youth in conflict with the law. I illustrate how youth penal voluntary sector practice (YPVS) operates alongside, or in tandem with the statutory criminal justice system. I argue that examining the PVS and the statutory criminal justice system simultaneously, or in tandem, provides fuller understandings of PVS inclusionary (and exclusionary) control practices (Tomczak and Thompson 2017). I introduce the concept of penultimate power, which demonstrates the ability of PVS workers to trigger criminal justice system response toward a young person in conflict with the law. My novel concepts of tandem logics and penultimate power are useful for understanding PVS practice, explaining how seemingly contradictory approaches across state and ‘community’ organizations not only co-exist, but depend upon the tandem relationship between the PVS and the statutory criminal justice system

Sperm design and variation in the New World blackbirds (Icteridae)

Post-copulatory sexual selection (PCSS) is thought to be one of the evolutionary forces responsible for the rapid and divergent evolution of sperm design. However, whereas in some taxa particular sperm traits are positively associated with PCSS, in other taxa, these relationships are negative, and the causes of these different patterns across taxa are poorly understood. In a comparative study using New World blackbirds (Icteridae), we tested whether sperm design was influenced by the level of PCSS and found significant positive associations with the level of PCSS for all sperm components but head length. Additionally, whereas the absolute length of sperm components increased, their variation declined with the intensity of PCSS, indicating stabilizing selection around an optimal sperm design. Given the diversity of, and strong selection on, sperm design, it seems likely that sperm phenotype may influence sperm velocity within species. However, in contrast to other recent studies of passerine birds, but consistent with several other studies, we found no significant link between sperm design and velocity, using four different species that vary both in sperm design and PCSS. Potential reasons for this discrepancy between studies are discussed

Attribution of 12 high-risk human papillomavirus genotypes to infection and cervical disease

Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/ 16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions. Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine. Results: The cumulative incidence of persistent infection with?1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and6%forwomen ages 15 to 26, 24 to 34, and 35 to 45 years, respectively.Atotal of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, amongwomen ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively. Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58. Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1