bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective Diaphragm Area Test Program for Air-Operated Valve Actuators
Authors: Leutwyler Zachary , Thidavanh Lisa , Estep Neal 
Published: May 2019

Kalsi Engineering, Inc. (KEI), initiated an independent test program that includes a number of actuator manufacturers, models, and sizes based on a survey of United States (U.S.) nuclear power plants. The test matrix includes evaluation of the effect of the key parameters on the effective diaphragm area (EDA) throughout the stroke. These parameters include stroke position, pressure, materials, measurement uncertainty, and manufacturing tolerances. Because of differences in the test data obtained by different sources for the same actuator type and size, systematic test procedures have been developed by KEI to address differences in the testing methods and test configurations, including testing of a balanced actuator (no spring in the actuator) vs. a spring-return actuator of the same diaphragm size. The effect of elevated temperature and aging may also be included later by testing a selected number of actuators based on industry input. The benefit of this program is to provide reliable data for air-operated valve (AOV) design-basis evaluations as required by U.S. Nuclear Regulatory Commission (NRC) Regulatory Issue Summary (RIS) 2000–03. This paper presents the results for the Masoneilan Model 38 Size 18 diaphragm actuator, which show that EDA is both position- and pressure-dependent.
Paper published with permission.
AOV Quarter-Turn Efficiency Models and Validation
Authors: Leutwyler Zachary , Leutwyler Emil , Estep Neal 
Published: May 2019

Common quarter-turn (QT) mechanisms used in nuclear plant air-operated valves (AOVs) include scotch yoke, lever, and link-and-lever mechanisms coupled to diaphragms and pistons. QT mechanism efficiency varies as a function of valve position and is a critical design input used to determine AOV margin. Because of the lack of publicly available data of a quality commensurate with “nuclear QA [quality assurance],” Kalsi Engineering, Inc. (KEI), initiated an independent QT-mechanism efficiency test program that includes a number of commonly used actuator manufacturers, models, and sizes based on a survey of U.S. nuclear power plants.
The first test specimen was a diaphragm actuator with a lever QT mechanism. The diaphragm rod of the test specimen was instrumented with strain gauges so that a direct measurement of the net actuator force transmitted to the QT mechanism could be measured. In addition to the net thrust, the output torque, diaphragm pressure, and actuator position were measured. Measuring the net thrust, diaphragm pressure, and position allowed the spring rate, spring preload, and effective diaphragm area to be quantified.
This test specimen was tested using two different types of bearings at the actuator shaft-to-lever connection. Needle bearings were used to provide torque results for a nearly frictionless QT mechanism, and bronze bearings were used to simulate a more realistic QT-mechanism configuration. Predictions made using the first-principles efficiency model are compared to efficiencies extracted from test. The predicted efficiency using a realistic range for the friction coefficient of the bronze bearings is in good agreement with the extracted efficiencies.
Paper published with permission.
Experiences of support garments following bowel stoma formation: analysis of free-text responses in a cross-sectional survey
Authors: Hubbard Gill , Taylor Claire , Munro Julie , Dames Nicola , Goodman William , Oliphant Raymond , Beeken Rebecca 
Published: May 2019

AimTo explore the experiences of support garments when adjusting to bodily change following bowel stoma formation.DesignThematic analyses of free-text responses in a cross-sectional survey of the stoma population in 2018.MethodsFree-text responses were invited so that respondents could describe their experiences in more detail. A process of induction was chosen to allow for themes to emerge directly from the data. The concept ‘embodiment’ was used as a theoretical framework during interpretation.Results1425 people with a bowel stoma responded to the survey, of whom 598 provided free-text responses. Four themes about experiences of support garments in the context of changed bodily experiences following stoma formation were identified:body complications, which is about experiences of using support garments to prevent or self-manage parastomal hernia;body appearance, which is about hiding the stoma and stoma appliance;body function, which is about managing stoma appliance complications; andbody sensation, which is mainly about negative experiences of ill-fitting garments.ConclusionSupport garments can be understood as items that are used by people during an ongoing process of adjusting to bodily changes following stoma formation and as part of an ongoing process of reconstructing new embodied selves.ImpactThis is the first study to explore people’s experiences of support garments following bowel stoma formation. Support garments are used in the self-management of body complications, appearance, function and sensations. Stoma nurses may draw on the findings of this study to advise patients about the benefits of garments for adjusting to bodily change, and garment suppliers should address people’s negative experiences by improving garments.
Association between spatial accessibility to fire protection services and unintentional residential fire injuries or deaths: a cross-sectional study in Dallas, Texas
Authors: Min Soojin , Kim Dohyeong , Lee Chang Kil 
Published: May 2019

ObjectivesIn addition to neighbourhood characteristics encompassing racial composition, socioeconomic status and housing environments, it was unclear if location characteristics relating to the accessibility of fire protection services were risk factors for unintentional residential fire-related injuries in urban areas. This study was aimed to measure spatial accessibility to fire protection services at the census block group level, and examine whether it is associated with unintentional residential fire-related injuries.DesignA cross-sectional study.SettingUnintentional residential fire incidents between 2012 and 2015 in Dallas City, Texas, USA.Main outcome measuresUsing multiple logistic regression, the study analysed association between unintentional residential fire incidents in the city and risk factors, including spatial accessibility to fire protection services, measured by the two-step floating catchment area method.ResultsCompared with incidents without any injuries, fire incidents involving injuries were significantly more likely to include unconfined fire, fire originating in a cooking area, a bedroom for less than five people or a common family area, census block groups with >75% African American residents, >25% elderly single-person households and positive population growth rates <25% or >25%. Incidents involving injuries were significantly less likely to occur in areas with high spatial accessibility, as measured by spatial accessibility score.ConclusionsIn addition to fire characteristics and neighbourhood demographics, spatial accessibility to fire protection services was significantly associated with unintentional residential fire-related injuries. The findings can be used to help select locations of additional fire stations.
Willingness of patients to use unused medication returned to the pharmacy by another patient: a cross-sectional survey
Authors: Bekker Charlotte , van den Bemt Bart , Egberts Toine CG , Bouvy Marcel , Gardarsdottir Helga 
Published: May 2019

ObjectivesRedispensing by pharmacies of medication unused by another patient could contribute to optimal use of healthcare resources. This study aimed to assess patient willingness to use medication returned by another patient and patient characteristics associated with this willingness.DesignCross-sectional survey.SettingA total of 41 community and 5 outpatient pharmacies in the Netherlands.ParticipantsTotal of 2215 pharmacy visitors.Primary and secondary outcome measuresPatients completed a questionnaire regarding their willingness to use medication returned unused to the pharmacy by another patient, assuming quality was guaranteed. Secondary outcome measures included patient sociodemographic characteristics that were associated with patient willingness, analysed using logistic regression analysis and reported as ORs with 95% CIs.ResultsOf the 2215 patients (mean (SD) age 50.6(18.0) years; 61.4% female), 61.2% were willing to use medication returned unused to the pharmacy by another patient. Patients who were unwilling mostly found it risky. Men were more willing to use returned medication (OR 1.3 95% CI 1.1 to 1.6), as did patients with a high educational level (OR 1.8 95% CI 1.3 to 2.5), those who regularly use 1–3 medications (OR 1.3 95% CI 1.1 to 1.7), those who returned medication to the pharmacy for disposal (OR 1.5 95% CI 1.0 to 2.3) and those who ever had unused medication themselves (OR 1.3 95% CI 1.1 to 1.6)). Patients with non-Dutch cultural background were less willing to use returned medication (OR 0.395% CI 0.3 to 0.4)).ConclusionsWhen quality is guaranteed, a substantial proportion of patients are willing to use medication returned unused to the pharmacy by another patient. This suggests that implementation of redispensing may be supported by patients.
Systematic client feedback to brief therapy in basic mental healthcare: study protocol for a four-centre clinical trial
Authors: Bovendeerd Bram , de Jong Kim , Colijn Sjoerd , de Groot Erik , Hafkenscheid Anton , Moerbeek Mirjam , de Keijser Jos 
Published: May 2019

IntroductionThe Partners for Change Outcome Management System (PCOMS) is a client feedback-system built on two brief visual analogue self-report scales. Prior studies of PCOMS have found effects varying from significant positive to negative. Aims of present study are; to test the predicted beneficial impact of PCOMS, while accounting for methodological flaws in prior studies and to clarify under which circumstances the addition of PCOMS to therapy has a beneficial effect.Methods and analysisThis study focuses on patients applying for brief, time-limited treatments. Four centres will be randomised to either treatment as usual (TAU) or TAU with PCOMS. All participating patients will be assessed four times. The full staff in the experimental condition will be trained in PCOMS. In the second part of this study, all therapists in the PCOMS condition will fill in a questionnaire concerning the influence of regulatory focus, self-efficacy, external or internal feedback orientation and perceived feedback validity of PCOMS. Finally, patients in the PCOMS condition will be asked to give feedback through a structured interview.The primary outcome measure is the Outcome Questionnaire over the period from beginning to end of therapy. The Mental Health Continuum-Short Form and Consumer Quality Index are also completed. In the primary analysis, outcomes of the two treatment conditions on treatment outcome, patient satisfaction, costs, drop-out and duration will be examined with a three-level (within patient, between patients and between therapists) multilevel analysis. The DSM-classification, sex, education level, age of each patient and therapist factors will be included as covariates.Ethics and disseminationThe Medical Ethics Committee of the University of Twente approved this study (K15-11, METC Twente). Data will be included from 1 January 2016 to 1 July 2019. Study results will be disseminated through peer-reviewed journals and conferences.Trial registration numberNTR5466; Pre-results.
Evaluating antibiotic stewardship in a tertiary care hospital in Kerala, India: a qualitative interview study
Authors: Baubie Kelsey , Shaughnessy Catherine , Kostiuk Lia , Varsha Joseph Mariam , Safdar Nasia , Singh Sanjeev K , Siraj Dawd , Sethi Ajay , Keating Julie 
Published: May 2019

ObjectivesTo determine what barriers and facilitators to antibiotic stewardship exist within a healthcare facility.Setting1300-bed tertiary care private hospital located in the state of Kerala, India.Participants31 semistructured interviews and 4 focus groups with hospital staff ranging from physicians, nurses, pharmacists and a clinical microbiologist.ResultsKey facilitators of antibiotic stewardship (AS) at the hospital included a dedicated committee overseeing appropriate inpatient antibiotic use, a prompt microbiology laboratory, a high level of AS understanding among staff, established guidelines for empiric prescribing and an easily accessible antibiogram. We identified the following barriers: limited access to clinical pharmacists, physician immunity to change regarding stewardship policies, infrequent antibiotic de-escalation, high physician workload, an incomplete electronic medical record (EMR), inadequate AS programme (ASP) physical visibility and high antibiotic use in the community.ConclusionsOpportunities for improvement at this institution include increasing accessibility to clinical pharmacists, implementing strategies to overcome physician immunity to change and establishing a more accessible and complete EMR. Our findings are likely to be of use to institutions developing ASPs in lower resource settings.
Multinational comparison of new antidepressant use in older adults: a cohort study
Authors: Tamblyn Robyn , Bates David Westfall , Buckeridge David L , Dixon Will , Forster Alan J , Girard Nadyne , Haas Jennifer , Habib Bettina , Kurteva Siyana , Li Jack , Sheppard Therese 
Published: May 2019

ObjectivesWe used an international pharmacosurveillance network to estimate the rate and characteristics of antidepressant use in older adults in countries with more conservative (UK) and liberal depression guidelines (Canada, USA).SettingElectronic health records and population-based administrative data from six jurisdictions in four countries (UK, Taiwan, USA and Canada).ParticipantsA historical cohort of older adults (≥65 years) who had a new episode of antidepressant use between 2009 and 2014.Outcome measuresThe age and sex-standardised cumulative incidence of new episodes of antidepressant use in older adults was measured. Descriptive statistics were used to compare the proportion of new users by the antidepressant prescribed, therapeutic class, potential treatment indication and country, as well as the characteristics of the first treatment episode (standardised daily doses, duration and changes).ResultsThe incidence of antidepressant use between 2009 and 2014 varied from 4.7% (Montreal and Quebec City) to 18.6% (Taiwan). Tricyclic antidepressants (TCAs) were the most commonly used class in the UK (48.8%) and Taiwan (52.4%) compared with selective serotonin reuptake inhibitors (SSRIs) in North American jurisdictions (42.3%–53.3%). Chronic pain was the most common potential treatment indication (41.2%–68.2%). Among users with chronic pain, TCAs were used most frequently in the UK and Taiwan (55.2%–60.4%), whereas SSRIs were used most frequently in North America (33.5%–46.4%). Treatment was longer (252–525 vs 169–437 days), standardised doses were higher (0.7–1.3 vs 0.5–1.0) and treatment was more likely to be changed (31%–46% vs 21%–34%) among patients with depression (9.1%–43%) than those with chronic pain.ConclusionAntidepressant use in older adults varied 24-fold by country, with the UK, which has the most conservative treatment guidelines, being among the lowest. Chronic pain was the most common potential treatment indication. Evaluation of real-world risks of TCAs is a priority for future research, given high rates of use and the potential for increased toxicity in older adults because of potent anticholinergic effects.
Novel swine model of colonic diverticulosis
Authors: Guo Xiaomei , Patel Bhavesh , Han Ling , Al-Dulaimi Hiba , Van Alstine William G. , Noblet Jillian N. , Chambers Sean , Kassab Ghassan S 
Published: May 2019

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 ( n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 ( n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 ( n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30–75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis.NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.
Inhibition of Pyruvate Dehydrogenase Kinase Enhances the Antitumor Efficacy of Oncolytic Reovirus
Authors: Kennedy Barry E. , Murphy John Patrick , Clements Derek R. , Konda Prathyusha , Holay Namit , Kim Youra , Pathak Gopal P. , Giacomantonio Michael A. , Hiani Yassine El , Gujar Shashi 
Published: May 2019

Abstract

Oncolytic viruses (OV) such as reovirus preferentially infect and kill cancer cells. Thus, the mechanisms that dictate the susceptibility of cancer cells to OV-induced cytotoxicity hold the key to their success in clinics. Here, we investigated whether cancer cell metabolism defines its susceptibility to OV and if OV-induced metabolic perturbations can be therapeutically targeted. Using mass spectrometry–based metabolomics and extracellular flux analysis on a panel of cancer cell lines with varying degrees of susceptibility to reovirus, we found that OV-induced changes in central energy metabolism, pyruvate metabolism, and oxidative stress correlate with their susceptibility to reovirus. In particular, reovirus infection accentuated Warburg-like metabolic perturbations in cell lines relatively resistant to oncolysis. These metabolic changes were facilitated by oxidative stress–induced inhibitory phosphorylation of pyruvate dehydrogenase (PDH) that impaired the routing of pyruvate into the tricarboxylic acid cycle and established a metabolic state unsupportive of OV replication. From the therapeutic perspective, reactivation of PDH in cancer cells that were weakly sensitive for reovirus, either through PDH kinase (PDK) inhibitors dichloroacetate and AZD7545 or short hairpin RNA–specific depletion of PDK1, enhanced the efficacy of reovirus-induced oncolysis in vitro and in vivo. These findings identify targeted metabolic reprogramming as a possible combination strategy to enhance the antitumor effects of OV in clinics.

Significance:
This study proposes targeted metabolic reprogramming as a valid combinatorial strategy to enhance the translational efficacy of oncolytic virus–based cancer therapies.
Magnetic Resonance Imaging Is More Sensitive Than PET for Detecting Treatment-Induced Cell Death–Dependent Changes in Glycolysis
Authors: Hesketh Richard L. , Wang Jiazheng , Wright Alan J. , Lewis David Y. , Denton Alice E. , Grenfell Richard , Miller Jodi L. , Bielik Robert , Gehrung Marcel , Fala Maria , Ros Susana , Xie Bangwen , Hu De-en , Brindle Kevin M. 
Published: May 2019

AbstractMetabolic imaging has been widely used to measure the early responses of tumors to treatment. Here, we assess the abilities of PET measurement of [18F]FDG uptake and MRI measurement of hyperpolarized [1-13C]pyruvate metabolism to detect early changes in glycolysis following treatment-induced cell death in human colorectal (Colo205) and breast adenocarcinoma (MDA-MB-231) xenografts in mice. A TRAIL agonist that binds to human but not mouse cells induced tumor-selective cell death. Tumor glycolysis was assessed by injecting [1,6-13C2]glucose and measuring 13C-labeled metabolites in tumor extracts. Injection of hyperpolarized [1-13C]pyruvate induced rapid reduction in lactate labeling. This decrease, which correlated with an increase in histologic markers of cell death and preceded decrease in tumor volume, reflected reduced flux from glucose to lactate and decreased lactate concentration. However, [18F]FDG uptake and phosphorylation were maintained following treatment, which has been attributed previously to increased [18F]FDG uptake by infiltrating immune cells. Quantification of [18F]FDG uptake in flow-sorted tumor and immune cells from disaggregated tumors identified CD11b+/CD45+ macrophages as the most [18F]FDG-avid cell type present, yet they represented &lt;5% of the cells present in the tumors and could not explain the failure of [18F]FDG-PET to detect treatment response. MRI measurement of hyperpolarized [1-13C]pyruvate metabolism is therefore a more sensitive marker of the early decreases in glycolytic flux that occur following cell death than PET measurements of [18F]FDG uptake.Significance:These findings demonstrate superior sensitivity of MRI measurement of hyperpolarized [1-13C]pyruvate metabolism versus PET measurement of 18F-FDG uptake for detecting early changes in glycolysis following treatment-induced tumor cell death.
Progress in Understanding Complexity and Determinants of Immune-Related Prognostic Subsets in Primary Melanoma
Authors: Anichini Andrea 
Published: May 2019

Abstract
Gene signatures are increasingly being used to infer the immune composition of the tumor microenvironment. This strategy holds the promise for earlier detection, identification of patients at higher risk of progression, and for understanding therapeutic response and resistance to immunotherapy. This gene signature approach is now being integrated with information from genomic changes, gene networks, and master immunoregulatory genes, and this development can lead to identify the main determinants shaping the tumor immune landscape. A study in this issue of Cancer Research indicates a way forward to discover prognostic immune-related subsets in primary melanoma and to understand major determinants impairing protective immunity in early stage of disease.
See related article by Poźniak et al., p. 2684
Phosphatase 1 Nuclear Targeting Subunit, a Novel DNA Repair Partner of PARP1
Authors: Murai Junko , Pommier Yves 
Published: May 2019

Abstract
There is extensive literature on PARP1, owing to the multiple functions of PARP1 for DNA repair, aging, chromatin remodeling and transcription, and to the successful clinical development of four PARP inhibitors. In this issue of Cancer Research, Wang and colleagues identified phosphatase 1 nuclear targeting subunit (PNUTS, also referred to as PP1R10) as a partner of PARP1 and demonstrated that PNUTS and PARP1 are interdependent for their recruitment to DNA damage sites. As PARP1 is a prominent target for cancer therapy and PNUTS has PARP-dependent as well as PARP1-independent activities, the findings of Wang and colleagues add insight into DNA repair mechanisms with potential application to drug targeting and precision therapy.
See related article by Wang et al., p. 2526