331 research outputs found

    On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

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    © 2017, Springer Science+Business Media, LLC, part of Springer Nature. One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment

    Healthcare Co-production and the Indirect Government Paradigm: addressing the managerial challenges

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    This qualitative study focuses on the relevant organizational challenges of co-production for the public healthcare system at the micro-level, that of the providers: the hospitals, trust, local health communities, etc. To build this complex picture the authors use a framework developed in the field of policy studies. An analysis and discussion of the scientific literature on the implications of the co-production options highlights the implementation gaps and the as-yet unsolved organizational puzzles and how they are managed in actual practice. The study considers co-production as an indirect tool of government and maps a research agenda of the knowledge gaps and open issues in extant literature

    Co-production in healthcare: moving patient engagement towards a managerial approach

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    The pressure toward co-produced health services is increasing as an answer to quality improvement and system sustainability. However, the reflection and the empirical knowledge on the nature of co-production and on how healthcare practices change in order to manage effective partnerships between clients and professionals remain scant. The chapter addresses this gap by analysing how the concept of co-production is used and investigated in the healthcare literature. Specifically, it focuses on two key perspectives that vary significantly on the issues of who the co-producing health authors are; what the domains of co-production are; and how to stimulate and support patients in their role of co-producers. The first perspective frames co-production as focusing on individual patient engagement and on the bilateral clinical dimension of relations with the medical staff. The second recognises co-production as a complex system of multiple relations between a cast of both single (patients, informal caregivers, clinical staff) and collective actors (the healthcare providers such as hospitals, trusts, local health communities), that involves patients in different service delivery phases and focuses on the change in the production processes when value is co-produced

    Healthcare Co-production and the indirect governance toolkit: demystifying the organizational puzzle

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    Background The economic meltdown, coupled with the public-sector legitimacy crisis, forced public services to reconcile increasing demand with decreasing resources and, at the same time, unleashed a wave of criticism on traditional service delivery patterns. One remedy to this challenge that is gaining an increasing attention is co-production - defined as engaging citizens and, more generally, voluntary and non-profit organizations in the production of public services (Alford, 2009; Pestoff, Osborne, & Brandsen, 2006; Thomas, 2013; van Eijk & Steen, 2013). Social and health services are the most elective co-production practices in the public sector, but set the healthcare providers two major challenges. The first is to engage the patient, an ongoing process that calls for this latter to actively participate in their healthcare plan (Coulter, Parsons, & Askham, 2008). The second is to ensure that the patient engages with both their therapy and the hospital organizational system by managing the interdependency within and between \u2018organizational production and client co-production\u2019 (Alford & O'Flynn, 2012, p. 182) in order to govern the healthcare organization\u2019s interactions (Alford, 2009; Brandsen & van Hout, 2008). Aim This qualitative study analyses and discusses the relevant organizational challenges of co-production for the public healthcare system at the micro-level, that of the providers \u2013 hospitals, trust, local health communities, etc. The paper highlights the implementation gaps and the as-yet unsolved organizational puzzles through an analysis and discussion of the scientific literature on the implications of co-production practices and on how they are managed in actual practice. Theoretical framework The co-production analysis is informed by the \u201cindirect government\u201d conceptual framework to gain access to the set of tools that \u2018rely heavily on a wide assortment of \u201cthird parties\u201d to deliver publicly financed services and pursue publicly authorized purposes\u2019 (Salamon, 2002, p. 2). Unlike traditional direct-government methods, this approach to public problem-solving sets fresh, sometimes unprecedented challenges and brings into play new capabilities and tools. It is not, therefore, something that \u2018self-implements\u2019. On the whole, co-production is a form of indirect government requiring \u201cconcerted action across multiple sectors\u201d (Kettl, 2006, p. 14) and actors and the taking on of new responsibilities. Kettl (2002) calls for a management approach that encompasses three key components: process (managing programs by structuring contracts and by tracking money); people (addressing people problems and the indirect government skill set); and performance (reinventing government and the performance puzzle). Research method The study was conducted in two phases. Phase one entailed an systematic interdisciplinary review of the public administration, management, and public policy literatures, mostly by trawling the main electronic databases to find scholarly articles on co-production in healthcare services. This first step enabled us to identify the theoretical and empirical contributions that investigate co-production from the specific viewpoint of the service providers. Phase two inventoried the themes, approaches and key findings of this subset of articles to draw a fairly clear picture of the conditions and capabilities needed by the healthcare providers to manage the organizational implications of co-production. Kettl\u2019s conceptual framework is the basis on which the results are then discussed and compared. Contribution 1) Up-to-date overview of the research on co-production in healthcare services. 2) Analysis of the co-production organizational challenges and how these are addressed in the practice. 3) Insights and policy indications for public managers on how government can play a supportive role in the delivery of co-produced healthcare services. References Alford, J. (2009). Engaging Public Sector Clients. From Service-Delivery to Co-production. Basingstoke: Palgrave Macmillan. Alford, J., & O'Flynn, J. (2012). Rethinking Public Service Delivery. Basingstoke: Palgrave Macmillan. Brandsen, T., & van Hout, E. (2008). Co-Management in Public Service Networks. The organizational effects. In V. Pestoff & T. Brandsen (Eds.), Co-Production. The Third Sector and the Delivery of Public Services (pp. 45-58). London: Routledge Taylor & Francis Group. Coulter, A., Parsons, S., & Askham, J. (2008). Where are the patients in decision-making about their own care? Kettl, D. F. (2002). Managing indirect government. In L. M. Salamon (Ed.), The tools of government. A Guide to the New Governance (pp. 490-510). Oxford: Oxford University Press. Kettl, D. F. (2006). Managing Boundaries in American Administration: the Collaboration Imperative. Public Administration Review, 66(Special Issue), 10-19. Pestoff, V., Osborne, S. P., & Brandsen, T. (2006). Patterns of co-production in public services. Public Management Review, 8(4), 591-595. Salamon, L. M. (Ed.). (2002). The tools of government. A Guide to the New Governance. Oxford: Oxford University Press. Thomas, J. C. (2013). Citizen, Customer, Partner: Rethinking the Place of the Public in Public Management. Public Administration Review, 73(6), 786-796. van Eijk, C. J. A., & Steen, T. P. S. (2013). Why People Co-Produce: Analysing citizens\u2019 perceptions on co-planning engagement in health care services. Public Management Review, 16(3), 358-382

    Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid

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    In this work a novel self-powered microneedle-based transdermal biosensor for pain-free high-accuracy real-time measurement of glycaemia in interstitial fluid (ISF) is reported. The proposed transdermal biosensor makes use of an array of silicon-dioxide hollow microneedles that are about one order of magnitude both smaller (borehole down to 4 µm) and more densely-packed (up to 1×106 needles/cm2) than state-of-the-art microneedles used for biosensing so far. This allows self-powered (i.e. pump-free) uptake of ISF to be carried out with high efficacy and reliability in a few seconds (uptake rate up to 1 µl/s) by exploiting capillarity in the microneedles. By coupling the microneedles operating under capillary-action with an enzymatic glucose biosensor integrated on the back-side of the needle-chip, glucose measurements are performed with high accuracy (±20% of the actual glucose level for 96% of measures) and reproducibility (coefficient of variation 8.56%) in real-time (30 s) over the range 0–630 mg/dl, thus significantly improving microneedle-based biosensor performance with respect to the state-of-the-art

    Co-production in healthcare services: What we know, how we can evaluate it

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    Purpose The implementation of co-production in healthcare provision is not only spreading rapidly but also being increasingly appraised as a more sustainable model for the future. Despite this widespread acceptance, minimal consensus exists, however, on the co-production\u2019s definition and on the mechanisms for evaluating the actual impacts of the implementation of co-production in healthcare. This study aims to define the current state of art of the healthcare service co-production research field with a specific focus on evaluation issues. Methodolody First of all, a quantitative bibliometric analysis, using Bibliometrix software (Aria and Cuccurullo, 2017), was carried. The reference database chosen is WoS and the inclusion criterion was \u201cco-production AND heath* OR coproduction AND health*\u201d in topic. As second stage, a qualitative content analysis based on PRISMA protocol is developed, focusing on those papers targeting evaluation issues. Results The bibliometric analysis shows an annual percentage growth rate of about 26% with the biggest increase in the last 5 years in number of publications. The co-citation analysis highlights two main intellectual areas: a public administration and management cluster and a service management cluster. Nonetheless, only few studies focus on the evaluation of outcomes. Among them, the content analysis has revealed a predominantly mono-dimensional and mono-stakeholder approach. Specifically, clinical, economic or psychological-social - mainly in terms of patient satisfaction \u2013 impacts are assessed. Practical implications The study offers the base to develop a systematic analytical framework for the evaluation of co-production of healthcare. Originality The study represents the first bibliometric analysis on co-production in healthcare

    Aetiology of canine infectious respiratory disease complex and prevalence of its pathogens in Europe

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    The canine infectious respiratory disease complex (CIRDC) is an endemic worldwide syndrome involving multiple viral and bacterial pathogens. Traditionally, Bordetella bronchiseptica (Bb), canine adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine herpesvirus (CHV) and canine parainfluenza virus (CPiV) were considered the major causative agents. Lately, new pathogens have been implicated in the development of CIRDC, namely canine influenza virus (CIV), canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), Mycoplasma cynos and Streptococcus equi subspecies zooepidemicus. To better understand the role of the different pathogens in the development of CIRDC and their epidemiological relevance in Europe, prevalence data were collected from peer-reviewed publications and summarized. Evidence of exposure to Bb is frequently found in healthy and diseased dogs and client-owned dogs are as likely to be infected as kennelled dogs. Co-infections with viral pathogens are common. The findings confirm that Bb is an important cause of CIRDC in Europe. CAV-2 and CDV recovery rates from healthy and diseased dogs are low and the most likely explanation for this is control through vaccination. Seroconversion to CHV can be demonstrated following CIRDC outbreaks and CHV has been detected in the lower respiratory tract of diseased dogs. There is some evidence that CHV is not a primary cause of CIRDC, but opportunistically re-activates at the time of infection and exacerbates the disease. The currently available data suggest that CIV is, at present, neither a prevalent nor a significant pathogen in Europe. CPiV remains an important pathogen in CIRDC and facilitates co-infection with other viral and bacterial pathogens. CnPnV and CRCoV are important new elements in the aetiology of CIRDC and spread particularly well in multi-dog establishments. M. cynos is common in Europe and is more likely to occur in younger and kennelled dogs. This organism is frequently found together with other CIRDC pathogens and is significantly associated with more severe respiratory signs. S. zooepidemicus infection is not common and appears to be a particular problem in kennels. Protective immunity against respiratory diseases is rarely complete, and generally only a reduction in clinical signs and excretion of pathogen can be achieved through vaccination. However, even vaccines that only reduce and do not prevent infection carry epidemiological advantages. They reduce spread, increase herd immunity and decrease usage of antimicrobials. Recommending vaccination of dogs against pathogens of CIRDC will directly provide epidemiological advantages to the population and the individual dog

    Cost-benefit analysis of applied research infrastructure : Evidence from health care

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    The present study aims at offering empirical evidence to improve existing knowledge and theory building on research infrastructure evaluation. Through an inductive case study research strategy, an innovative cost-benefit analysis framework has been used to assess the impact of an applied research infrastructure. The case study is the National Hadrontherapy Centre for Cancer Treatment (CNAO) located in Pavia (Italy). CNAO is an applied research facility specialised in hadrontherapy, an advanced oncological treatment showing clinical advantages as compared to traditional radiotherapy, at the same time being more expensive as it exploits non-commercial accelerators technology and sophisticated control and dose delivery systems. The analysis shows that with a fairly high probability the Centre provides a positive net contribution to society's welfare. Source of benefits are mainly health treatments to patients, for whom gains in terms of longer or better lives are guaranteed as compared to a counterfactual situation where they are treated with conventional therapies or they have no alternatives. Such benefits are the direct consequences of the application to end users of the knowledge developed in the Centre with research activities and are quantified and assessed on the basis of conventional cost-benefit analysis (CBA) approaches for health benefits. Additional benefits generated by the Centre are typical of research infrastructures in different scientific domains and refer to technological spillovers (namely creation of spin-offs, technological transfer to companies in the supply chain and to other similar facilities), knowledge creation (production of scientific outputs), human capital formation (training of doctoral students, technicians and professionals in the field of hadrontherapy) and cultural outreach (students, researchers and wider public visiting the facilities). Evidences show that the adopted CBA framework is a promising avenue as compared to existing alternative methodologies informing decision-making. Further research is however needed to fine tune the methodology, in particular for what concerns technological spillovers and knowledge creation benefits

    Co-production in healthcare services: the evaluation of economic and organizational impacts

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    In times of increasing population aging, higher incidence of chronic diseases and higher expectations regarding public service provision, healthcare services are under increasing strain to cut costs while keeping quality. In this context, debates on the importance of promoting systems of co-produced health between stakeholders have gained considerable traction both in the literature and in policy debates of the public sector. (Gilardi et al. 2016; European Commission 2010; UK Department of Health 2006) The implementation of co-production in healthcare provision is not only spreading rapidly but also being increasingly appraised as a more sustainable model for the future. Despite this widespread acceptance, minimal consensus exists, however, on the mechanisms for evaluating the actual impacts of the implementation of co-production in healthcare provision. More specifically, little has been produced on how the results of these changing structures, practices and goals in healthcare management and provision can be monitored and evaluated. Aiming at the reduction of this gap, this article proposes a discussion on the challenges and limitations of assessing co-production\u2019s impacts going beyond more traditionally used clinical criteria (that currently dominate evaluation activities in the field) towards analyses that take into consideration broader organizational and economic aspects of co-production activities. Finally, the article sketches the initial contours of an original and alternative evaluation model which highlights the importance of organizational and economic aspects for the effective implementation of co-production in healthcare
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