Implementation of influenza point-of-care-testing and patient-cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes.

BACKGROUND: During high-incidence influenza seasons, a robust infection prevention and control policy is imperative to reduce nosocomial transmission of influenza. AIM: To assess the impact of Emergency Department (ED) influenza point-of-care-testing (POCT) and influenza-ward patient-cohorting on infection prevention and control and clinical outcomes. METHODS: Influenza POCT was operational in our adult ED from 21st January 2018 and an influenza-ward from 25th January 2018. A retrospective 'before-after' analysis was performed with pre-intervention defined as 1st November 2017-20th January 2018 and post-intervention 21st January-30th April 2018. Primary outcome was rate of hospital-acquired influenza (HAI). Secondary outcomes included antiviral prescription and length of stay. The length of time inpatients remain influenza RNA detected by polymerase chain reaction (PCR) was also analysed

Assessing the impact of care farms on quality of life and offending: a pilot study among probation service users in England

OBJECTIVES: To assess the feasibility of conducting a cost-effectiveness study of using care farms (CFs) to improve quality of life and reduce reoffending among offenders undertaking community orders (COs). To pilot questionnaires to assess quality of life, connection to nature, lifestyle behaviours, health and social-care use. To assess recruitment and retention at 6 months and feasibility of data linkage to Police National Computer (PNC) reconvictions data and data held by probation services. DESIGN: Pilot study using questionnaires to assess quality of life, individually linked to police and probation data. SETTING: The pilot study was conducted in three probation service regions in England. Each site included a CF and at least one comparator CO project. CFs are working farms used with a range of clients, including offenders, for therapeutic purposes. The three CFs included one aquaponics and horticulture social enterprise, a religious charity focusing on horticulture and a family-run cattle farm. Comparator projects included sorting secondhand clothes and activities to address alcohol misuse and anger management. PARTICIPANTS: We recruited 134 adults (over 18) serving COs in England, 29% female. RESULTS: 52% of participants completed follow-up questionnaires. Privatisation of UK probation trusts in 2014 negatively impacted on recruitment and retention. Linkage to PNC data was a more successful means of follow-up, with 90% consenting to access their probation and PNC data. Collection of health and social-care costs and quality-adjusted life year derivation were feasible. Propensity score adjustment provided a viable comparison method despite differences between comparators. We found worse health and higher reoffending risk among CF participants due to allocation of challenging offenders to CFs, making risk of reoffending a confounder. CONCLUSIONS: Recruitment would be feasible in a more stable probation environment. Follow-up was challenging; however, assessing reconvictions from PNC data is feasible and a potential primary outcome for future studies

Impact and cost-effectiveness of care farms on health and well-being of offenders on probation: a pilot study

Background Care farms (CFs), in which all or part of the farm is used for therapeutic purposes, show potential for improving well-being for disadvantaged groups. We assessed the feasibility of determining the cost-effectiveness of CFs in improving quality of life compared with comparator sites among probationers undertaking community orders (COs). Objectives (1) To conduct a systematic review of CF impacts and mechanisms in improving health and logic model development; (2) to inform future studies by estimating differences in quality of life and other outcomes, identifying factors driving CO allocation and ways to maximise recruitment and follow-up; and (3) to assess feasibility of cost-effectiveness analysis. Review methods A mixed-methods synthesis following Campbell Collaboration guidelines. Pilot study: three probation service regions in England, each with a CF and a comparator CO site. Participants were adult offenders (aged ≥ 18 years) serving COs. The primary outcome was quality of life [as measured via the Clinical Outcome in Routine Evaluation–Outcome Measure (CORE-OM)]. Other outcomes were health behaviours, mental well-being, connectedness to nature and reconvictions. Data sources In November 2014, we searched 22 health, education, environmental, criminal justice and social science electronic databases, databases of grey literature and care farming websites across Europe. There were no language restrictions. A full list of databases searched is given in Appendix 1; some examples include Web of Science, Cumulative Index to Nursing and Allied Health Literature (via EBSCOhost), The Campbell Library, Criminal Justice Abstracts (via EBSCOhost), MEDLINE (via Ovid) and Scopus (Elsevier B.V., Amsterdam, the Netherlands). Results Our systematic review identified 1659 articles: 14 qualitative, 12 quantitative and one mixed-methods study. Small sample sizes and poor design meant that all were rated as being at a high risk of bias. Components of CFs that potentially improve health are being in a group, the role of the farmer and meaningful work, and interaction with animals. There was a lack of quantitative evidence indicating that CFs improve quality of life and there was weak evidence of improved mental health, self-efficacy, self-esteem, affect and mood. In the pilot study we recruited 134 respondents, and only 21 declined; 37% were allocated to three CFs and the remainder to comparators. This was below our recruitment target of 300. Recruitment proved challenging as a result of the changes in probation (probation trusts were disbanded in 2014) and closure of one CF. We found significant differences between CFs and comparator users: those at CFs were more likely to be male, smokers, substance users, at higher risk of reoffending (a confounder) and have more missing CORE-OM questions. Despite these differences, the use of propensity analysis facilitated comparison. Participants consented to our team accessing, and we were able to link, probation and police reconviction data for 90% of respondents. We gained follow-up questionnaire data from 52% of respondents, including health and social care use cost data. We transformed CORE-OM into CORE-6D, allowing derivation of quality-adjusted life-years. As a pilot, our study was not powered to identify significant differences in outcomes. Qualitatively, we observed that within COs, CFs can be formally recognised as rehabilitative but in practice can be seen as punitive. Limitations Changes in probation presented many challenges that limited recruitment and collection of cost data. Conclusions Recruitment is likely to be feasible in a more stable probation environment. Retention among probationers is challenging but assessing reconvictions from existing data is feasible. We found worse health and risk of reoffending among offenders at CFs, reflecting the use of CFs by probation to manage challenging offenders. Future work A sufficiently powered natural experiment is feasible and of value. Using reconvictions (from police data) as a primary outcome is one solution to challenges with retention. Propensity analysis provides a viable method for comparison despite differences in participants at CFs and comparator sites. However, future work is dependent on stability and support for CFs within probation services. Study registration This study is registered as PROSPERO CRD42014013892 and SW2013–04 (the Campbell Collaboration). Funding details The National Institute for Health Research Public Health Research programme

Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation

<p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K⁺channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K⁺(K_Ca++) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K⁺(K_ATP) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca⁺⁺channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca⁺⁺channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca⁺⁺channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca⁺⁺channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K_Ca++and K_ATPchannels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K⁺channels. Blockade of the voltage-operated Ca⁺⁺channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca⁺⁺channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K_Ca++and K_ATPchannels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens

Abstract Background The ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue processing can cause fragmentation and chemical modifications of the RNA. A number of recent technical advances have been reported to overcome these issues. Our current study evaluates whether or not the technology is ready for clinical applications. Methods A modified RNA extraction method and a recent DNA microarray technique, cDNA-mediated annealing, selection, extension and ligation (DASL, Illumina Inc) were evaluated. The gene profiles generated from FFPE specimens were compared to those obtained from paired fresh fine needle aspiration biopsies (FNAB) of 25 breast cancers of different clinical subtypes (based on ER and Her2/neu status). Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens. Results Compared to FNAB, RNA isolated from FFPE samples was relatively more degraded, nonetheless, over 80% of the RNA samples were deemed suitable for subsequent DASL assay. Despite a higher noise level, a set of genes from FFPE specimens correlated very well with the gene profiles obtained from FNAB, and could differentiate breast cancer subtypes. Expression levels of these genes were validated using RT-qPCR. Finally, for the first time we correlated gene expression profiles from FFPE samples to survival using two independent microarray databases. Specifically, over-expression of ANLN and KIF2C, and under-expression of MAPT strongly correlated with poor outcomes in breast cancer patients. Conclusion We demonstrated that FFPE specimens retained important prognostic information that could be identified using a recent gene profiling technology. Our study supports the use of FFPE specimens for the development and refinement of prognostic gene signatures for breast cancer. Clinical applications of such prognostic gene profiles await future large-scale validation studies

A Reliable Method for the Selection of Exploitable Melanoma Archival Paraffin Embedded Tissues for Transcript Biomarker Profiling

The source tissue for biomarkers mRNA expression profiling of tumors has traditionally been fresh-frozen tissue. The adaptation of formalin-fixed, paraffin-embedded (FFPE) tissues for routine mRNA profiling would however be invaluable in view of their abundance and the clinical information related to them. However, their use in the clinic remains a challenge due to the poor quality of RNA extracted from such tissues. Here, we developed a method for the selection of melanoma archival paraffin-embedded tissues that can be reliably used for transcript biomarker profiling. For that, we used qRT-PCR to conduct a comparative study in matched pairs of frozen and FFPE melanoma tissues of the expression of 25 genes involved in angiogenesis/tumor invasion and 15 housekeeping genes. A classification method was developed that can select the samples with a good frozen/FFPE correlation and identify those that should be discarded on the basis of paraffin data for four reference genes only. We propose therefore a simple and inexpensive assay which improves reliability of mRNA profiling in FFPE samples by allowing the identification and analysis of “good” samples only. This assay which can be extended to other genes would however need validation at the clinical level and on independent tumor series

Making Connections - Envisioning Springfield\u27s North End

This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio: 1. Input and interaction – Visioning workshops connect campus and community 2. Community-building art - Expression of place and people 3. Healthy living - Urban agriculture and education 4. Urban greenways – Abandoned railways and urban rivers and streams 5. Green infrastructure - Green streets as networks and structural framework 6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood

Clinicopathologic and gene expression parameters predict liver cancer prognosis

<p>Abstract</p> <p>Background</p> <p>The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.</p> <p>Methods</p> <p>Tumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.</p> <p>Results</p> <p>HCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.</p> <p>Conclusion</p> <p>When applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.</p

Genome-wide expression assay comparison across frozen and fixed postmortem brain tissue samples

<p>Abstract</p> <p>Background</p> <p>Gene expression assays have been shown to yield high quality genome-wide data from partially degraded RNA samples. However, these methods have not yet been applied to postmortem human brain tissue, despite their potential to overcome poor RNA quality and other technical limitations inherent in many assays. We compared cDNA-mediated annealing, selection, and ligation (DASL)- and <it>in vitro </it>transcription (IVT)-based genome-wide expression profiling assays on RNA samples from artificially degraded reference pools, frozen brain tissue, and formalin-fixed brain tissue.</p> <p>Results</p> <p>The DASL-based platform produced expression results of greater reliability than the IVT-based platform in artificially degraded reference brain RNA and RNA from frozen tissue-based samples. Although data associated with a small sample of formalin-fixed RNA samples were poor when obtained from both assays, the DASL-based platform exhibited greater reliability in a subset of probes and samples.</p> <p>Conclusions</p> <p>Our results suggest that the DASL-based gene expression-profiling platform may confer some advantages on mRNA assays of the brain over traditional IVT-based methods. We ultimately consider the implications of these results on investigations of neuropsychiatric disorders.</p