Ordered exponential random walks

We study a $d$-dimensional random walk with exponentially distributed increments conditioned so that the components stay ordered (in the sense of Doob). We find explicitly a positive harmonic function $h$ for the killed process and then construct an ordered process using Doob's $h$-transform. Since these random walks are not nearest-neighbour, the harmonic function is not the Vandermonde determinant. The ordered process is related to the departure process of M/M/1 queues in tandem. We find asymptotics for the tail probabilities of the time until the components in exponential random walks become disordered and a local limit theorem. We find the distribution of the processes of smallest and largest particles as Fredholm determinants.Comment: 43 pages. The second version of the paper has been restructured, errors/typos corrected and further details added. To appear in ALE

2003 Canadian Asthma Consensus Guidelines Executive Summary

<p>Abstract</p> <p>Background</p> <p>Guidelines for the diagnosis and management of asthma have been published over the last 15 years; however, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies, particularly in children, have highlighted the need to incorporate new information into the asthma guidelines. The objectives of this article are to review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Report and its 2001 update, with a major focus on pediatric issues.</p> <p>Methods</p> <p>The diagnosis of asthma in young children and prevention strategies, pharmacotherapy, inhalation devices, immunotherapy, and asthma education were selected for review by small expert resource groups. The reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published through December 2004 were subsequently reviewed by the individual expert resource groups.</p> <p>Results</p> <p>This report evaluates early-life prevention strategies and focuses on treatment of asthma in children, emphasizing the importance of early diagnosis and preventive therapy, the benefits of additional therapy, and the essential role of asthma education.</p> <p>Conclusion</p> <p>We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This document is a guide for asthma management based on the best available published data and the opinion of health care professionals, including asthma experts and educators.</p

The medium-term sustainability of organisational innovations in the national health service

Background: There is a growing recognition of the importance of introducing new ways of working into the UK's National Health Service (NHS) and other health systems, in order to ensure that patient care is provided as effectively and efficiently as possible. Researchers have examined the challenges of introducing new ways of working-'organisational innovations'-into complex organisations such as the NHS, and this has given rise to a much better understanding of how this takes place-and why seemingly good ideas do not always result in changes in practice. However, there has been less research on the medium-and longer-term outcomes for organisational innovations and on the question of how new ways of working, introduced by frontline clinicians and managers, are sustained and become established in day-to-day practice. Clearly, this question of sustainability is crucial if the gains in patient care that derive from organisational innovations are to be maintained, rather than lost to what the NHS Institute has called the 'improvement-evaporation effect'. Methods: The study will involve research in four case-study sites around England, each of which was successful in sustaining its new model of service provision beyond an initial period of pilot funding for new genetics services provided by the Department of Health. Building on findings relating to the introduction and sustainability of these services already gained from an earlier study, the research will use qualitative methods-in-depth interviews, observation of key meetings, and analysis of relevant documents-to understand the longer-term challenges involved in each case and how these were surmounted. The research will provide lessons for those seeking to sustain their own organisational innovations in wide-ranging clinical areas and for those designing the systems and organisations that make up the NHS, to make them more receptive contexts for the sustainment of innovation. Discussion: Through comparison and contrast across four sites, each involving different organisational innovations, different forms of leadership, and different organisational contexts to contend with, the findings of the study will have wide relevance. The research will produce outputs that are useful for managers and clinicians responsible for organisational innovation, policy makers and senior managers, and academics

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

Clinical leadership in service redesign using Clinical Commissioning Groups: a mixed-methods study

Background: A core component of the Health and Social Care Act 2012 (Great Britain. Health and Social Care Act 2012. London: HMSO; 2012) was the idea of devolving to general practitioners (GPs) a health service leadership role for service redesign. For this purpose, new Clinical Commissioning Groups (CCGs) were formed in the English NHS.Objectives: This research examined the extent to which, and the methods by which, clinicians stepped forward to take up a leadership role in service redesign using CCGs as a platform.Design: The project proceeded in five phases: (1) a scoping study across 15 CCGs, (2) the design and administration of a national survey of all members of CCG governing bodies in 2014, (3) six main in-depth case studies, (4) a second national survey of governing body members in 2016, which allowed longitudinal comparisons, and (5) international comparisons.Participants: In addition to GPs serving in clinical lead roles for CCGs, the research included insights from accountable officers and other managers and perspectives from secondary care and other provider organisations (local authority councillors and staff, patients and the public, and other relevant bodies).Results: Instances of the exercise of clinical leadership utilising the mechanism of the CCGs were strikingly varied. Some CCG teams had made little of the opportunity. However, we found other examples of clinicians stepping forward to bring about meaningful improvements in services. The most notable cases involved the design of integrated care for frail elderly patients and others with long-term conditions. The leadership of these service redesigns required cross-boundary working with primary care, secondary care, community care and social work. The processes enabling such breakthroughs required interlocking processes of leadership across three arenas: (1) strategy-level work at CCG board level, (2) mid-range operational planning and negotiation at programme board level and (3) the arena of practical implementation leadership at the point of delivery. The arena of the CCG board provided the legitimacy for strategic change; the programme boards worked through the competing logics of markets, hierarchy and networks; and the practice arena allowed the exercise of clinical leadership in practical problemsolving, detailed learning and routinisation of new ways of working at a common-sense everyday level.Limitations: Although the research was conducted over a 3-year period, it could be argued that a much longer period is required for CCGs to mature and realise their potential.Conclusions: Despite the variation in practice, we found significant examples of clinical leaders forging new modes of service design and delivery. A great deal of the service redesign effort was directed at compensating for the fragmented nature of the NHS – part of which had been created by the 2012 reforms. This is the first study to reveal details of such work in a systematic way

Inhibition of dipeptidyl peptidase IV and xanthine oxidase by amino acids and dipeptides

peer-reviewedXanthine oxidase (XO) and dipeptidyl peptidase IV (DPP-IV) inhibition by amino acids and dipeptides was studied. Trp and Trp-containing dipeptides (Arg-Trp, Trp-Val, Val-Trp, Lys-Trp and Ile-Trp) inhibited XO. Three amino acids (Met, Leu and Trp) and eight dipeptides (Phe-Leu, Trp-Val, His-Leu, Glu-Lys, Ala-Leu, Val-Ala, Ser-Leu and Gly-Leu) inhibited DPP-IV. Trp and Trp-Val were multifunctional inhibitors of XO and DPP-IV. Lineweaver and Burk analysis showed that Trp was a non-competitive inhibitor of XO and a competitive inhibitor of DPP-IV. Molecular docking with Autodock Vina was used to better understand the interaction of the peptides with the active site of the enzyme. Because of the non-competitive inhibition observed, docking of Trp-Val to the secondary binding sites of XO and DPP-IV is required. Trp-Val was predicted to be intestinally neutral (between 25% and 75% peptide remaining after 60 min simulated intestinal digestion). These results are of significance for the reduction of reactive oxygen species (ROS) and the increase of the half-life of incretins by food-derived peptides. (C) 2013 Elsevier Ltd. All rights reserved.ACCEPTEDpeer-reviewe

Outcomes of the 2019 GRAPPA workshop on continuous composite indices for the assessment of psoriatic arthritis and membership-recommended next steps

OBJECTIVE: Improving the assessment of psoriatic arthritis (PsA) is a key purpose of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA). Herein, we report the proceedings of the GRAPPA composites workshop at the 2019 GRAPPA annual meeting and the membership\u27s recommended next steps. METHODS: A review of continuous composite measures was conducted in an introductory workshop, followed by 10 breakout group sessions and a final plenary session for feedback and voting. RESULTS: Participants included 154 members: 87 rheumatologists, 18 dermatologists, 2 rheumatologist/dermatologists, 12 patient research partners, 14 academics, 1 methodologist, and 20 industry members. Of voting members, 88.8% agreed a need exists for a continuous composite measure for routine practice, but only 62% were currently using a composite measure. Of these, 27% were using the 28-joint count Disease Activity Score (DAS), which is not a PsA-specific measure; 20% were using a PsA-specific measure such as PsA DAS (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), or Disease Activity Index for PsA (DAPSA). Members agreed that the existing measures were not feasible in their current forms (CPDAI 83%, PASDAS 82%, and DAPSA 47%) and that modification should be tested. The majority (76%) agreed that disease effect should be measured separately from disease activity. CONCLUSION: The GRAPPA membership supports the need for a continuous composite measure of disease activity for use in routine clinical care, the separate measurement of disease effect and activity, and the testing of modifications to candidate instruments rather than the development of new measures