Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

BackgroundNonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy.Hypothesis/objectivesThe primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine.AnimalsForty-seven client-owned dogs with measurable MCT.MethodsToceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone.ResultsThe MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy.Conclusions and clinical importanceCombined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT

The 2012 Olympic Learning Legacy Agenda – the intentionalities of mobility for a new London model

This paper investigates the emergence of a Learning Legacy Agenda (LLA) in the wake of the London 2012 Olympic Games as a governmental tool for the dissemination of urban development and infrastructure project delivery best practice. Focusing on the inception, coordination and implementation of the LLA we outline the intentionalities of mobility that underpin its formation and appropriation and suggest how this points to the emergence of a new ‘London model’ of development and governance. Three intentionalities of knowledge capture, public duty, and extra-local salience are unpacked to demonstrate the range of ways in which the bureaucratically-initiated LLA banner has been used by various development actors and organisations to validate their existing practices. The case study of the LLA as an institutionalised governance apparatus is used to analyse the impact of specific forms of social relations on the ways in which ‘models’ are produced, what their content consists of, how dominant agendas and narratives co-evolve with the priorities of an assemblage of actors, and the processes of selective abstraction used to curate particular messages and forms of fixed and potentially mobile knowledge, yet dubious claims of ‘learning’

Do pharmacy practice standards effectively describe behaviour? Reviewing practice standards using a behavioural specificity framework

BACKGROUND: Guidelines and practice standards exist to communicate the conduct and behaviour expected of health care professionals and ensure consistent quality practice. It is important that they describe behaviours explicitly so they can be interpreted, enacted and measured with ease. The AACTT framework specifies behaviour in terms of the: Action to be performed, Actor who performs the action, Context where the action occurs, Target who the action is performed with/for and Time when the action is performed (AACTT). It provides the most up to date framework for specifying behaviours and is particularly relevant to complex behavioural problems that involve sequences of behaviours performed by different people. Behavioural specificity within pharmacy practice standards has not been explored. AIM: To determine if behaviours described in the Professional Practice Standards for Australian Pharmacists specify Action, Actor, Context, Target and Time. METHODS: Two researchers independently reviewed the scope and structure of the practice standards and one extracted action statements (behaviours) verbatim. Through an iterative process, the researchers modified and developed the existing AACTT definitions to operationalise them for application to review of the action statements in the practice standards. The operational definitions, decision criteria and curated examples were combined in a codebook. The definitions were consistently applied through a directed content analysis approach to evaluate all extracted action statements by one researcher. For consistency 20% was independently checked for agreement by a second researcher. RESULTS: A novel codebook to apply AACTT criteria to evaluate practice standards was developed. Application of this codebook identified 768 independent behaviours. Of these, 300 (39%) described at least one discrete observable action, none specified an actor, 25 (3%) specified context, 131 (17%) specified target and 88 (11%) specified time. CONCLUSION(S): The behaviours detailed in practice standards for Australian pharmacists do not consistently specify behaviours in terms of Action, Actor, Context, Target and Time. Developers in the pharmacy profession, and beyond, should consider the behavioural specificity of their documents to improve interpretability, usability and adherence to the behaviours detailed. This also has implications for the development and evaluation of interventions to change such behaviours and improve quality of care

Use of professional practice guidance resources in pharmacy: a cross-sectional nationwide survey of pharmacists, intern pharmacists, and pharmacy students

BACKGROUND: Variations in practice are commonplace in healthcare where health professionals, such as pharmacists act as autonomous practitioners. This is evident in simulated patient studies, where pharmacists practice does not meet widely accepted standards for medicines supply or treatment of an ailment. To promote best pharmacy practice a myriad of guidance resources including practice guidelines, codes and standards are produced by professional organisations. These resources provide a framework for pharmacy practice and endeavour to facilitate consistency in provision of pharmacy-based services to consumers. Despite their role in specifying essential pharmacist behaviours, there is limited research exploring if and how these resources are used in practice. OBJECTIVE: To characterise Australian pharmacists' use of the Pharmaceutical Society of Australia's Code of Ethics, Professional Practice Guidelines and Professional Practice Standards. METHODS: A cross-sectional, self-administered, electronic survey of registered pharmacists, intern pharmacists and pharmacy students living in Australia was conducted in July 2020. Questions considered use of professional practice resources (by resource group) in the preceding 12 months. Data were analysed descriptively. RESULTS: Of 601 responses included in the analysis 462 (76.9%) of respondents were registered pharmacists, 88 (14.6%) pharmacy students and 51 (8.5%) intern pharmacists. Interns and students accessed overarching practice resources, such as the Professional Practice Standards, Code of Ethics and Dispensing Practice Guidelines more frequently than practising pharmacists. Pharmacists accessed professional practice guidelines, such as Practice Guidelines for the Provision of Immunisation Services Within Pharmacy, more often than students. More pharmacists than interns and students indicated that they would access guidelines to resolve practice and patient care issues. All resources except the Professional Practice Standards for Pharmacists (67.4%) were accessed by less than 50% of respondents in the preceding 12-month period. Reasons for not accessing resources varied between participant and resource groups, and generally were due to a lack of awareness of the resource or not considering them necessary for the individual's practice. CONCLUSION(S): Access and use patterns for professional practice guidance resources change with experience. Professional organisations responsible for developing resources should consider these patterns when designing and reviewing resources and related policies. To ensure resources are meeting the needs of the profession, students, interns, and pharmacists should be involved in the review of and design of further resources

Facilitating personal development for public involvement in health-care education and research: a co-produced pilot study in one UK higher education institute

BACKGROUND: Public involvement in the education of students enrolled on higher education programmes has gained impetus. For students enrolled on professional health-care programmes and health-related modules in the UK, there is also a requirement by professional bodies to include "service user" involvement in preparation for entry to a professional health-care register and continuing professional development. Actively involving patients and members of the public in research is also a requirement by many research funders. In this article, the term Patient and Public Involvement (PPI) will be used throughout to include lay members, volunteers, user and carers. OBJECTIVES: A unique pilot study was introduced across a health faculty to integrate PPI in a deliberate way. It aimed to provide an educational, focused programme of events that was meaningful to develop and inform peoples' knowledge, skills and confidence for their involvement in the health faculty. DESIGN: PPI members volunteered to sit on a steering group to determine the educational journey; the outcomes of three focus groups with PPI members (N = 32) and academics informed the programme content which included a range of workshops covering the exploration of public roles and barriers to involvement, introduction to research and interviewing skills. RESULTS: The workshops were well attended, and outcomes indicated the importance of co-production when designing, delivering and evaluating programmes. DISCUSSION: Co-production underpinned this pilot study, resulting in a programme which was meaningfully received by public contributors. RECOMMENDATIONS: Co-production was seen as integral to this research to ensure that outcomes were indeed "fit for purpose"

Axion Protection from Flavor

The QCD axion fails to solve the strong CP problem unless all explicit PQ violating, Planck-suppressed, dimension n<10 operators are forbidden or have exponentially small coefficients. We show that all theories with a QCD axion contain an irreducible source of explicit PQ violation which is proportional to the determinant of the Yukawa interaction matrix of colored fermions. Generically, this contribution is of low operator dimension and will drastically destabilize the axion potential, so its suppression is a necessary condition for solving the strong CP problem. We propose a mechanism whereby the PQ symmetry is kept exact up to n=12 with the help of the very same flavor symmetries which generate the hierarchical quark masses and mixings of the SM. This "axion flavor protection" is straightforwardly realized in theories which employ radiative fermion mass generation and grand unification. A universal feature of this construction is that the heavy quark Yukawa couplings are generated at the PQ breaking scale.Comment: 16 pages, 2 figure

Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model

The value of including boys in an HPV vaccination programme: a cost-effectiveness analysis in a low-resource setting

We assessed the cost-effectiveness of including boys vs girls alone in a pre-adolescent vaccination programme against human papillomavirus (HPV) types 16 and 18 in Brazil. Using demographic, epidemiological, and cancer data from Brazil, we developed a dynamic transmission model of HPV infection between males and females. Model-projected reductions in HPV incidence under different vaccination scenarios were applied to a stochastic model of cervical carcinogenesis to project lifetime costs and benefits. We assumed vaccination prevented HPV-16 and -18 infections in individuals not previously infected, and protection was lifelong. Coverage was varied from 0-90% in both genders, and cost per-vaccinated individual was varied from I$25 to 400. At 90$50, vaccinating girls alone was <$200 per year of life saved (YLS), while including boys ranged from$810–18 650 per YLS depending on coverage. For all coverage levels, increasing coverage in girls was more effective and less costly than including boys in the vaccination programme. In a resource-constrained setting such as Brazil, our results support that the first priority in reducing cervical cancer mortality should be to vaccinate pre-adolescent girls

The potential of trading activity income to fund third sector organisations operating in deprived areas

In the United Kingdom, as in other countries, Third Sector Organisations (TSOs) have been drawn towards income sources associated with trading activities (Teasdale, 2010), but many remain reliant on grant funding to support such activities (Chell, 2007). Using a multivariate analysis approach and data from the National Survey of Charities and Social Enterprises (NSCSE), it is found that trading activities are used relatively commonly in deprived areas. These organisations are also more likely to attempt to access public sector funds. This suggests policy-makers need to consider the impact of funding cuts on TSOs in the most deprived areas as TSOs are unlikely achieve their objectives without continuing support