Search for Exotic Strange Quark Matter in High Energy Nuclear Reactions

We report on a search for metastable positively and negatively charged states of strange quark matter in Au+Pb reactions at 11.6 A GeV/c in experiment E864. We have sampled approximately six billion 10% most central Au+Pb interactions and have observed no strangelet states (baryon number A < 100 droplets of strange quark matter). We thus set upper limits on the production of these exotic states at the level of 1-6 x 10^{-8} per central collision. These limits are the best and most model independent for this colliding system. We discuss the implications of our results on strangelet production mechanisms, and also on the stability question of strange quark matter.Comment: 21 pages, 9 figures, to be published in Nuclear Physics A (Carl Dover memorial edition

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

<p>Abstract</p> <p>Background</p> <p>Continuing challenges to timely adoption of evidence-based clinical practices in healthcare have generated intense interest in the development and application of new implementation methods and frameworks. These challenges led the United States (U.S.) Department of Veterans Affairs (VA) to create the Quality Enhancement Research Initiative (QUERI) in the late 1990s. QUERI's purpose was to harness VA's health services research expertise and resources in an ongoing system-wide effort to improve the performance of the VA healthcare system and, thus, quality of care for veterans. QUERI in turn created a systematic means of involving VA researchers both in enhancing VA healthcare quality, by implementing evidence-based practices, and in contributing to the continuing development of implementation science.</p> <p>The efforts of VA researchers to improve healthcare delivery practices through QUERI and related initiatives are documented in a growing body of literature. The scientific frameworks and methodological approaches developed and employed by QUERI are less well described. A QUERI Series of articles in <it>Implementation Science </it>will illustrate many of these QUERI tools. This <it>Overview </it>article introduces both QUERI and the Series.</p> <p>Methods</p> <p>The <it>Overview </it>briefly explains the purpose and context of the QUERI Program. It then describes the following: the key operational structure of QUERI Centers, guiding frameworks designed to enhance implementation and related research, QUERI's progress and promise to date, and the Series' general content. QUERI's frameworks include a core set of steps for diagnosing and closing quality gaps and, simultaneously, advancing implementation science. Throughout the paper, the envisioned involvement and activities of VA researchers within QUERI Centers also are highlighted. The Series is then described, illustrating the use of QUERI frameworks and other tools designed to respond to implementation challenges.</p> <p>Conclusion</p> <p>QUERI's simultaneous pursuit of improvement and research goals within a large healthcare system may be unique. However, descriptions of this still-evolving effort, including its conceptual frameworks, methodological approaches, and enabling processes, should have applicability to implementation researchers in a range of health care settings. Thus, the <it>Series </it>is offered as a resource for other implementation research programs and researchers pursuing common goals in improving care and developing the field of implementation science.</p

Effects of Human Respiratory Syncytial Virus, Metapneumovirus, Parainfluenza Virus 3 and Influenza Virus on CD4+ T Cell Activation by Dendritic Cells

BACKGROUND: Human respiratory syncytial virus (HRSV), and to a lesser extent human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought to be viral interference with dendritic cell (DC)-mediated stimulation of CD4+ T cells. METHODOLOGY, PRINCIPAL FINDINGS: We infected human monocyte-derived DC with purified HRSV, HMPV, HPIV3, or influenza A virus (IAV) and compared their ability to induce activation and proliferation of autologous CD4+ T cells in vitro. IAV was included because symptomatic re-infection without antigenic change is less frequent, suggesting that immune protection is more complete and durable. We examined virus-specific memory responses and superantigen-induced responses by multiparameter flow cytometry. Live virus was more stimulatory than inactivated virus in inducing DC-mediated proliferation of virus-specific memory CD4+ T cells, suggesting a lack of strong suppression by live virus. There were trends of increasing proliferation in the order: HMPV<HRSV<HPIV3<IAV, and greater production of interferon-γ and tumor necrosis factor-α by proliferating cells in response to IAV, but differences were not significant. Exposure of DC to HRSV, HPIV3, or IAV reduced CD4+ T cell proliferation in response to secondary stimulus with superantigen, but the effect was transitory and greatest for IAV. T cell cytokine production was similar, with no evidence of Th2 or Th17 skewing. CONCLUSIONS, SIGNIFICANCE: Understanding the basis for the ability of HRSV in particular to symptomatically re-infect without significant antigenic change is of considerable interest. The present results show that these common respiratory viruses are similar in their ability to induce DC to activate CD4+ T cells. Thus, the results do not support the common model in which viral suppression of CD4+ T cell activation and proliferation by HRSV, HMPV, and HPIV3 is a major factor in the difference in re-infectability compared to IAV

Low CCR7-Mediated Migration of Human Monocyte Derived Dendritic Cells in Response to Human Respiratory Syncytial Virus and Human Metapneumovirus

Human respiratory syncytial virus (HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC) is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to lymphatic tissue contributes to reduced adaptive responses to these viruses

Human bipedal instability in tree canopy environments is reduced by “light touch” fingertip support

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However “light touch”, a sensorimotor feedback strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor’s ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use

Search for Strange Quark Matter Produced in Relativistic Heavy Ion Collisions

We present the final results from Experiment 864 of a search for charged and neutral strange quark matter produced in interactions of 11.5 GeV/c per nucleon Au beams with Pt or Pb targets. Searches were made for strange quark matter with A>4. Approximately 30 billion 10% most central collisions were sampled and no strangelet states with A<100 were observed. We find 90% confidence level upper limits of approximately 10^{-8} per central collision for both charged and neutral strangelets. These limits are for strangelets with proper lifetimes greater than 50 ns. Also limits for H^{0}-d and pineut production are given. The above limits are compared with the predictions of various models. The yields of light nuclei from coalescence are measured and a penalty factor for the addition of one nucleon to the coalescing nucleus is determined. This is useful in gauging the significance of our upper limits and also in planning future searches for strange quark matter.Comment: 35 pages, 18 figures, submitted to Phys. Rev.

Practice change in chronic conditions care: an appraisal of theories

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Management of chronic conditions can be complex and burdensome for patients and complex and costly for health systems. Outcomes could be improved and costs reduced if proven clinical interventions were better implemented, but the complexity of chronic care services appears to make clinical change particularly challenging. Explicit use of theories may improve the success of clinical change in this area of care provision. Whilst theories to support implementation of practice change are apparent in the broad healthcare arena, the most applicable theories for the complexities of practice change in chronic care have not yet been identified. Methods We developed criteria to review the usefulness of change implementation theories for informing chronic care management and applied them to an existing list of theories used more widely in healthcare. Results Criteria related to the following characteristics of chronic care: breadth of the field; multi-disciplinarity; micro, meso and macro program levels; need for field-specific research on implementation requirements; and need for measurement. Six theories met the criteria to the greatest extent: the Consolidate Framework for Implementation Research; Normalization Process Theory and its extension General Theory of Implementation; two versions of the Promoting Action on Research Implementation in Health Services framework and Sticky Knowledge. None fully met all criteria. Involvement of several care provision organizations and groups, involvement of patients and carers, and policy level change are not well covered by most theories. However, adaptation may be possible to include multiple groups including patients and carers, and separate theories may be needed on policy change. Ways of qualitatively assessing theory constructs are available but quantitative measures are currently partial and under development for all theories. Conclusions Theoretical bases are available to structure clinical change research in chronic condition care. Theories will however need to be adapted and supplemented to account for the particular features of care in this field, particularly in relation to involvement of multiple organizations and groups, including patients, and in relation to policy influence. Quantitative measurement of theory constructs may present difficulties

Digital health behaviour change interventions targeting physical activity and diet in cancer survivors: a systematic review and meta-analysis

Purpose: The number of cancer survivors has risen substantially due to improvements in early diagnosis and treatment. Health behaviours such as physical activity (PA) and diet can reduce recurrence and mortality, and alleviate negative consequences of cancer and treatments. Digital behaviour change interventions (DBCIs) have the potential to reach large numbers of cancer survivors. Methods: We conducted a systematic review and meta-analyses of relevant studies identified by a search of Medline, EMBASE, PubMed and CINAHL. Studies which assessed a DBCI with measures of PA, diet and/or sedentary behaviour were included. Results: 15 studies were identified. Random effects meta-analyses showed significant improvements in moderate-vigorous PA (7 studies; mean difference (MD) = 41 minutes per week; 95% CI: 12, 71) and body mass index (BMI)/weight (standardised mean difference (SMD) = -0.23; 95% CI: -0.41, -0.05). There was a trend toward significance for reduced fatigue and no significant change in cancer-specific quality of life (QoL). Narrative synthesis revealed mixed evidence for effects on diet, generic QoL and self-efficacy and no evidence of an effect on mental health. Two studies suggested improved sleep quality. Conclusions: DBCIs may improve PA and BMI among cancer survivors and there is mixed evidence for diet. The number of included studies is small and risk of bias and heterogeneity was high. Future research should address these limitations with large, high-quality RCTs, with objective measures of PA and sedentary time. Implications for cancer survivors: Digital technologies offer a promising approach to encourage health behaviour change among cancer survivors

Qualitative study on the implementation of professional pharmacy services in Australian community pharmacies using framework analysis

Abbreviations: BCT, Behavioural change techniques taxonomy; BCW, Behavioural change wheel; CFIR, Consolidated framework for implementation research; EPOC, Cochrane effective practice and organisation of care; FISpH, Framework for the implementation of services in pharmacy; GIF, Generic implementation framework; KPI, Key performance indicator; TDF, Theoretical domains frameworkBackground: Multiple studies have explored the implementation process and influences, however it appears there is no study investigating these influences across the stages of implementation. Community pharmacy is attempting to implement professional services (pharmaceutical care and other health services). The use of implementation theory may assist the achievement of widespread provision, support and integration. The objective was to investigate professional service implementation in community pharmacy to contextualise and advance the concepts of a generic implementation framework previously published. Methods: Purposeful sampling was used to investigate implementation across a range of levels of implementation in community pharmacies in Australia. Twenty-five semi-structured interviews were conducted and analysed using a framework methodology. Data was charted using implementation stages as overarching themes and each stage was thematically analysed, to investigate the implementation process, the influences and their relationships. Secondary analyses were performed of the factors (barriers and facilitators) using an adapted version of the Consolidated Framework for Implementation Research (CFIR), and implementation strategies and interventions, using the Expert Recommendations for Implementing Change (ERIC) discrete implementation strategy compilation. Results: Six stages emerged, labelled as development or discovery, exploration, preparation, testing, operation and sustainability. Within the stages, a range of implementation activities/steps and five overarching influences (pharmacys' direction and impetus, internal communication, staffing, community fit and support) were identified. The stages and activities were not applied strictly in a linear fashion. There was a trend towards the greater the number of activities considered, the greater the apparent integration into the pharmacy organization. Implementation factors varied over the implementation stages, and additional factors were added to the CFIR list and definitions modified/contextualised for pharmacy. Implementation strategies employed by pharmacies varied widely. Evaluations were lacking. Conclusions: The process of implementation and five overarching influences of professional services implementation in community pharmacy have been outlined. Framework analysis revealed, outside of the five overarching influences, factors influencing implementation varied across the implementation stages. It is proposed at each stage, for each domain, the factors, strategies and evaluations should be considered. The Framework for the Implementation of Services in Pharmacy incorporates the contextualisation of implementation science for pharmacy.The study was funded as part of a University of Technology Sydney (UTS) Research Excellence Scholarship (RES), comprising of an Australian Postgraduate Award (APA) Scholarship funded by the Australian Government, plus a Top-up funded by the University of Technology Sydney, received from the primary author (JCM)