bluuebunny/crossref_metadata_2025 huggingface dataset:
GABAergic Transmission during Brain Development: Multiple Effects at Multiple Stages
Authors: Kirmse Knut , Hübner Christian A. , Isbrandt Dirk , Witte Otto W. , Holthoff Knut
Published: April 2017

In recent years, considerable progress has been achieved in deciphering the cellular and network functions of GABAergic transmission in the intact developing brain. First, in vivo studies in non-mammalian and mammalian species confirmed the long-held assumption that GABA acts as a mainly depolarizing neurotransmitter at early developmental stages. At the same time, GABAergic transmission was shown to spatiotemporally constrain spontaneous cortical activity, whereas firm evidence for GABAergic excitation in vivo is currently missing. Second, there is a growing body of evidence indicating that depolarizing GABA may contribute to the activity-dependent refinement of neural circuits. Third, alterations in GABA actions have been causally linked to developmental brain disorders and identified as potential targets of timed prophylactic interventions. In this article, we review these major recent findings and argue that both depolarizing and inhibitory GABA actions may be crucial for physiological brain maturation.
Thinking Outside the Box
Authors: Ingles Judith , Kyathanahalli Chandrashekara N. , Jeyasuria Pancharatnam , Condon Jennifer C.
Published: April 2017

A broad definition of preconditioning is “the preparation for a subsequent action.” Mounting evidence demonstrates that novel remote preconditioning paradigms, in which protective stimuli experienced locally can capacitate systemic tolerance and enhanced cell viability upon exposure to ensuing cellular insults, have been largely successful in the field of cardiovascular ischemia/reperfusion injury. To ensure successful protective preconditioning, some models (including the uterus) have been demonstrated to activate the unfolded protein response (UPR), which is a cellular stress response controlled at the level of the endoplasmic reticulum. However, in the context of remote preconditioning, activation of these intracellular molecular pathways must result in the extracellular transmission of adaptive signals to remote targets. In our recently published manuscript, we have described the activation of the UPR in the pregnant uterine myocyte to be associated with increased uterine myocyte quiescence and normal gestational length. We hypothesize that ubiquitous uterine gestational stresses experienced in every pregnancy, which have been demonstrated in other systems to activate the UPR, may induce a robust paracrine dissemination of a uterine secretome, for example, glucose-regulated protein 78, with preconditioning-like properties. Furthermore, we speculate that the gestational stress-induced uterine secretome acts to promote both local and systemic tolerance to the ensuing gestational insults, allowing for the maintenance of uterine quiescence. In this context, preterm labor may be the result of a pregnant uterus experiencing a stress it cannot accommodate or when it is unable to host an appropriate UPR resulting in insufficient preconditioning and a diminished local and systemic capacity to tolerate pregnancy-dependent increases in normal gestational stress. This is highly attractive from a clinical viewpoint as we ultimately aim to identify local and systemic adaptations that may serve as preconditioning stimuli for use as a strategy to restore appropriate preconditioning profiles to prolong uterine quiescence in pregnancy.
Building a Novel Health Curriculum for Survivors of Intimate Partner Violence Residing at a Transitional Housing Program
Authors: Ragavan Maya , Bruce Janine , Bair-Merritt Megan , Lucha Sarah , Maya-Silva Jacqueline , Stebbins Emily , Chamberlain Lisa
Published: April 2017

We used a community-based participatory research approach to develop, implement, and evaluate one of the first health curricula for female intimate partner violence (IPV) survivors residing at a transitional housing program. The curriculum comprised 12 workshops that were developed based on the survivors’ experiences, needs, and interests. Evaluation participants included 20 of the 37 women who attended at least one workshop, 12 workshop facilitators, and two housing center staff. Participants found the curriculum to be engaging, interactive, and helpful in building a supportive community. Suggestions for curricular improvement as well as opportunities for further research and curricular development are discussed.
Effects of phosphorus-free antioxidants on oxidation stability and high-temperature tribological properties of lubricants
Authors: Liping Wang , Dongya Zhang , Hongxing Wu , Youbai Xie , Guangneng Dong
Published: April 2017

Oxidation stability plays an important role on the engine oil service performance. In this paper, the phosphorus-free antioxidants of diphenylamine, hindered phenol and dibutyldithiocarbamate, combined with zinc dialkyldithiophosphate were added as antioxidants in the base oil and the fully formulated 5W-30 oil, and the oxidation stabilities were evaluated by pressurized differential scanning calorimetry and Romaszewski oil bench oxidation standard tests. Meanwhile, the tribological properties of the fresh and aged oils were evaluated by a SRV tribo-meter. The results indicated that (i) an optimal ternary complex antioxidant of dibutyldithiocarbamate: diphenylamine: hindered phenol (ratio of 2:1:2) displayed good antioxidation property, and (ii) the fully formulated 5W-30 oil containing optimized ratio phosphorus-free antioxidants had better tribological properties than the commercial SN 5W-30 oil.
Investigation of the thermal property and tribological behavior of CaSO4 whisker-modified paper-based composite friction materials
Authors: Zhang Xiang , Li Ke-Zhi , Li He-Jun , Fu Ye-Wei
Published: April 2017

In this study, CaSO4 whisker was applied to the paper-based composite friction material as the friction layer (secondary layer) by the paper-making process. The tribological and thermal properties were analyzed. Three-dimensional surface profiles were observed to discuss the wear mechanism. The results showed that the samples with higher CaSO4 whisker contents owned better thermal resistance. The sample with 4% CaSO4 whisker content had the highest dynamic friction coefficient. As the CaSO4 whisker content increased from 0% to 16%, the wear rate decreased first and then increased, and the sample with 8% CaSO4 whisker content had the highest wear resistance.
Modeling average daily rate (ADR) volatility index and room price positioning matrix
Authors: Koh Yoon , DeFranco Agnes , Back Ki-Joon
Published: April 2017

Although strategic pricing literature identifies two key dimensions of relative price position and relative price fluctuation, only recently has relative price fluctuation started to gain attention in the hospitality and tourism literature. Given the theoretical and empirical support for considering both dimensions in strategic pricing positioning, this study developed a new index that calculates relative price fluctuation: the ADR volatility index. This new index provides a more complete picture of the pricing positioning of a lodging property. Together with a room price positioning matrix, these two new tools can assist hotels in maximizing their room revenues.
Patient safety in nursing homes in Sweden: nurses’ views on safety and their role
Authors: Andersson Frieda , Hjelm Katarina
Published: April 2017

Objective

Knowledge about patient safety in nursing homes is limited. The aim of this study was to describe what patient safety means to nurses working in nursing homes for the elderly and how these nurses address patient safety.

Method

Qualitative study of semi-structured interviews with 15 nurses aged 27–62 years. Qualitative content analysis was applied.

Results

Nurses describe the meaning of patient safety in terms of proper care and treatment, and a sense of security. Based on nurses’ description of patient safety, several factors were identified as prerequisites to achieve safe health care: competence; clear information transfer between health care organizations; continuity of care and appropriate environment. Barriers to patient safety were described as lack of sufficient resources; lack of communication and negative attitudes to incident reporting. To a great extent, nurses’ work for patient safety consists of efforts to compensate for defects and ensure good health care in their daily work, since work with patient safety is not a management priority.

Conclusion

Patient safety needs to be clarified and prioritized in nursing homes, and there is a need to understand nurses’ role among other care givers and the need for shared routines among care givers.
Analyzing the Effects of Psychotherapy on Weight Loss after Laparoscopic Gastric Bypass or Laparoscopic Adjustable Gastric Banding in Patients with Borderline Personality Disorder: A Prospective Study
Authors: Gallé F. , Cirella A. , Salzano A. M. , Onofrio V. Di , Belfiore P. , Liguori G.
Published: April 2017

Background and Aims:

Personality disorders are frequently associated with eating disorders in obese patients and may negatively affect weight loss and maintenance after bariatric surgery. This non-randomized study aimed to assess the effects of different psychotherapeutic interventions on weight loss in a sample of patients with borderline personality disorder who underwent laparoscopic gastric bypass or laparoscopic adjustable gastric banding.

Materials and Methods:

A total of 153 bariatric patients meeting borderline personality disorder criteria were chosen voluntarily and consecutively to undergo an interpersonal individual treatment (n = 50), a dialectical behavioral group treatment (n = 50), or treatment as usual (n = 53) for a year after surgery. Their body mass index was measured before and at the end of each treatment.

Results and Conclusion:

A total of 12 patients (7.8%) dropped out of the study. Significantly higher body mass index reductions were registered in both experimental groups (−14.2 and −9.4 kg/m2, respectively) compared with the treatment as usual group (−2.1 kg/m2; p < 0.01). Treated patients who underwent laparoscopic gastric bypass (total n = 94) showed better outcomes than those who underwent laparoscopic adjustable gastric banding (total n = 45), while no differences were observed in untreated patients. This study demonstrates the role of pre-operative psychological assessment and post-operative psychotherapeutic support in improving weight loss among bariatric patients with borderline personality disorder. A randomized controlled trial is needed to confirm these preliminary findings.
Symptomatic Delayed Aortic Dissection After Superior Mesenteric Artery Stenting for Chronic Mesenteric Ischemia
Authors: Huynh Cindy , Schwartz Robert
Published: April 2017

Chronic mesenteric ischemia most commonly occurs secondary to atherosclerotic disease of the mesenteric arteries. Patients are often older than 60 years and can present with postprandial abdominal pain, nausea, diarrhea, and significant weight loss. Symptomatic disease has traditionally been managed with open surgical repair, but endovascular strategies, such as percutaneous angioplasty and stenting, have emerged as the mainstays of therapy. Complications from stenting include plaque embolization, thrombosis, perforation, or dissection of the mesenteric arteries. We present a patient with symptomatic acute aortic dissection 18 months after celiac and superior mesenteric artery stent placement for chronic mesenteric ischemia.
Crashworthiness analysis and multiobjective optimization for circular tubes with functionally graded thickness under multiple loading angles
Authors: Yao Shuguang , Xing Yi , Zhao Kai
Published: April 2017

In this article, the nonlinear finite-element analysis software LS-DYNA is used to study the crashworthiness of functionally graded thickness circular tubes under multiple loading angles (0°, 10°, 20°, 30°, and 40°). The specific energy absorption (SEA) and maximum crashing force ([Formula: see text]) are used as evaluation indices with which to analyze the effect of the length-to-diameter ratio and thickness gradient index P on the crashworthiness characteristics of functionally graded thickness circular tubes. Taking the length-to-diameter ratio and thickness gradient as design variables, the full factorial experiment was designed. A surrogate model of the integrated specific energy absorption ([Formula: see text]) and maximum crashing force ([Formula: see text]) when the impact angle is 0° was constructed using the response surface method; the nondominated sorting genetic algorithm II was used to optimize the surrogate model, and the Pareto-front solution set was obtained. The results show that the thickness gradient index and the length-to-diameter ratio have a greater influence on the crashworthiness characteristics of functionally graded thickness circular tubes under oblique impact load, and the appropriate geometric parameters can improve the crashworthiness characteristics of functionally graded thickness circular tubes.
Dissent, Cultural Schizophrenia and Hong Kong Identity in David Lee’s Insanity
Authors: Wan Marco
Published: April 2017

How does film capture the zeitgeist of a time of cultural and political conflict? This article investigates the relationship between Hong Kong cinema, identity and dissent in David Lee’s Insanity (2015). Drawing on the notion of cultural schizophrenia as posited by Frederic Jameson and reworked by a number of Hong Kong scholars, it argues that Lee’s film about clinical schizophrenia can be interpreted as a representation of the cultural schizophrenia characteristic of Hong Kong identity at the current time.
Improving the foundation and practice of reliability engineering
Authors: Aven Terje
Published: April 2017

Reliability engineering is today a well-established field, accounting for many scientific journals and conferences, educational programmes and courses, academic positions and societies. There are also many standards which guide the practice of reliability engineering, and every year a number of scientific papers are published which address reliability engineering issues. Yet the area faces many challenges, in particular when addressing systems characterised by large uncertainties, and accurate prediction models are not easily established. We see alternative analysis perspectives being advocated, with varying degrees of theoretical justification. This article argues that there is potential for improvements to be made in terms of both theoretical frameworks and the practice of reliability engineering to meet these challenges and guide reliability engineers and decision-makers. Examples relate to the understanding and treatment of uncertainties, and the use of ideas and methods from risk management. Clear recommendations are provided on how to obtain such improvements.
Exploration of the functions of health impact assessment in real-world policymaking in the field of social health inequality: towards a conception of conceptual learning
Authors: Feyaerts Gille , Deguerry Murielle , Deboosere Patrick , De Spiegelaere Myriam
Published: April 2017

With the implementation of health impact assessment (HIA)’s conceptual model into real-world policymaking, a number of fundamental issues arise concerning its decision-support function. Rooted in a rational vision of the decision-making process, focus regarding both conceptualisation and evaluation has been mainly on the function of instrumental policy-learning. However, in the field of social health inequalities, this function is strongly limited by the intrinsic ‘wickedness’ of the policy issue. Focusing almost exclusively on this instrumental function, the real influence HIA can have on policymaking in the longer term is underestimated and remains largely unexploited. Drawing insights from theoretical models developed in the field of political science and sociology, we explore the different decision-support functions HIA can fulfill and identify conceptual learning as potentially the most important. Accordingly, dominant focus on the technical engineering function, where knowledge is provided in order to ‘rationalise’ the policy process and to tackle ‘tame’ problems, should be complemented with an analysis of the conditions for conceptual learning, where knowledge introduces new information and perspectives and, as such, contributes in the longer term to a paradigm change.
Why the Diabetes Technology Society Surveillance Protocol for Glucose Meters Needs to Be Revised
Authors: Krouwer Jan S.
Published: April 2017

The Diabetes Technology Society surveillance protocol provides a seal of approval for a glucose meter if a sufficient number of a candidate glucose meter’s results meet ISO 15197:2013 limits. The protocol provides clear details about how to conduct this study and analyze the data but has two flaws. There is no specification about the size of glucose meter errors that are outside of ISO limits. A meter that has a result in the E zone of a glucose meter error grid could receive the DTS seal of approval. In addition, the protocol uses the ISO standard, which could be considered a “state of the art” standard instead of an error grid, which is a clinical standard. Remedies for these problems are to replace the ISO standard with an error grid and to include requirements for errors found in C or higher zones of an error grid.
Performance of apparent diffusion coefficient of medial and lateral rectus muscles in Graves' orbitopathy
Authors: Abdel Razek Ahmed AK , El-Hadidy Mohamed , Moawad Mohamed E , El-Metwaly Nader , El-Said Amr A
Published: April 2017

Objective

The purpose of this study was to determine the performance of the apparent diffusion coefficient in the detection of involvement of the medial and lateral rectus muscles in patients with Graves' orbitopathy.

Methods and materials

This prospective study was conducted on 33 consecutive patients (16 males, 17 females with a mean age of 36 years) with Graves' orbitopathy and 18 age- and sex-matched volunteers. The patients and volunteers underwent diffusion-weighted magnetic resonance imaging of the orbit in the axial plane using echo-planar imaging. The apparent diffusion coefficient of the medial and lateral rectus muscles was calculated.

Results

The medial rectus muscle was more affected than the lateral rectus muscle. The mean apparent diffusion coefficient value of the medial and lateral rectus muscles was 1.81 ± 0.19 and 1.72 ± 0.07 × 10−3 mm2/s in patients with Graves' orbitopathy and 1.59 ± 0.06 and 1.51 ± 0.06 × 10−3 mm2/s in volunteers, respectively. There was a significant difference in apparent diffusion coefficient values of the medial and lateral rectus muscles between patients with Graves' orbitopathy and volunteers ( p = 0.001). The classification performance as measured with area under the receiver operator characteristic curve was 0.89 (95% confidence interval: 0.732–0.904). The best performing threshold of the apparent diffusion coefficient value of the medial rectus muscle was 1.69 × 10−3 mm2/s and associated efficiency was 86%, sensitivity was 97%, and specificity was 97%.

Conclusion

We concluded that the apparent diffusion coefficient of the medial rectus muscle can be used for diagnosis of Graves' orbitopathy.
The Silhouette Zoetrope: A New Blend of Motion, Mirroring, Depth, and Size Illusions
Authors: Veras Christine , Pham Quang-Cuong , Maus Gerrit W.
Published: April 2017

Here, we report a novel combination of visual illusions in one stimulus device, a contemporary innovation of the traditional zoetrope, called Silhouette Zoetrope. In this new device, an animation of moving silhouettes is created by sequential cutouts placed outside a rotating empty cylinder, with slits illuminating the cutouts successively from the back. This “inside-out” zoetrope incurs the following visual effects: the resulting animated figures are perceived (a) horizontally flipped, (b) inside the cylinder, and (c) appear to be of different size than the actual cutout object. Here, we explore the unique combination of illusions in this new device. We demonstrate how the geometry of the device leads to a retinal image consistent with a mirrored and distorted image and binocular disparities consistent with the perception of an object inside the cylinder.
Increasing physical activity in older adults using STARFISH, an interactive smartphone application (app); a pilot study
Authors: Paul Lorna , Brewster Stephen , Wyke Sally , McFadyen Angus K , Sattar Naveed , Gill Jason MR , Dybus Aleksandra , Gray Cindy M
Published: April 2017

Background

Increasing physical activity in older adults has preventative and therapeutic health benefits. We have developed STARFISH, a smartphone application, to increase physical activity. This paper describes the features of STARFISH, presents the views of older users on the acceptability and usability of the app and reports the results of a six week pilot study of the STARFISH app in older adults.

Methods

The operationalisation of the behaviour change techniques (BCTs) within the STARFISH app was mapped against the BCT Taxonomy of Michie et al. Sixteen healthy older adults (eight women and eight men; age 71.1 ± 5.2 years) used the app, in groups of four, for six weeks. Focus groups explored the user experience and objective measure of steps per day recorded.

Results

Participants were very positive about using the STARFISH app, in particular the embedded BCTs of self-monitoring, feedback and social support (in the form of group rewards). Objective step data, available for eight participants, showed that step counts increased by an average of 14% ( p = 0.077, d = 0.56).

Conclusion

The STARFISH app was acceptable and straightforward to use for older adults. STARFISH has potential to increase physical activity in older adults; however, a fully powered randomised controlled trial is required.
Simulating individual work trips for transit-facilitated accessibility study
Authors: Huang Ruihong
Published: April 2017

To measure job accessibility, person-based approaches have the advantage to capture all accessibility components: land use, transportation system, individual’s mobility and travel preference, as well as individual’s space and time constraints. This makes person-based approaches more favorable than traditional aggregated approaches in recent years. However, person-based accessibility measures require detailed individual trip data which are very difficult and expensive to acquire, especially at large scales. In addition, traveling by public transportation is a highly time sensitive activity, which can hardly be handled by traditional accessibility measures. This paper presents an agent-based model for simulating individual work trips in hoping to provide an alternative or supplementary solution to person-based accessibility study. In the model, population is simulated as three levels of agents: census tracts, households, and individual workers. And job opportunities (businesses) are simulated as employer agents. Census tract agents have the ability to generate household and worker agents based on their demographic profiles and a road network. Worker agents are the most active agents that can search jobs and find the best paths for commuting. Employer agents can estimate the number of transit-dependent employees, hire workers, and update vacancies. A case study is conducted in the Milwaukee metropolitan area in Wisconsin. Several person-based accessibility measures are computed based on simulated trips, which disclose low accessibility inner city neighborhoods well covered by a transit network.
Association of circulating transcriptomic profiles with mortality in sickle cell disease
Authors: Desai Ankit A. , Lei Zhengdeng , Bahroos Neil , Maienschein-Cline Mark , Saraf Santosh L. , Zhang Xu , Shah Binal N. , Nouraie Seyed M. , Abbasi Taimur , Patel Amit R. , Lang Roberto M. , Lussier Yves , Garcia Joe G. N. , Gordeuk Victor R. , Machado Roberto F.
Published: April 2017

Key Points

We validated the association of a circulating genome-wide gene expression profile with poor outcomes in 3 cohorts of SCD. A composite risk score using this genomic biomarker with clinical risk factors exhibited improved prediction than clinical factors alone.
Molecular convergence in ex vivo models of Diamond-Blackfan anemia
Authors: O'Brien Kelly A. , Farrar Jason E. , Vlachos Adrianna , Anderson Stacie M. , Tsujiura Crystiana A. , Lichtenberg Jens , Blanc Lionel , Atsidaftos Eva , Elkahloun Abdel , An Xiuli , Ellis Steven R. , Lipton Jeffrey M. , Bodine David M.
Published: April 2017

Key Points

Cultured erythroid cells from DBA patients show impaired growth kinetics and altered transcriptional profiles. Our data predict a link between GATA1 and RP mutations in the regulation of translation in erythroid differentiation.
Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus
Authors: Li Wei-Ping , Neradilek Moni B. , Gu Fu-Sheng , Isquith Daniel A. , Sun Zhi-Jun , Wu Xing , Li Hong-Wei , Zhao Xue-Qiao
Published: April 2017

Background

The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors.

Methods

PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events.

Results

ACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10(PAPP-A), 95% CI 2.11–4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27–4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model.

Conclusions

Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM.

Trial registrationISRCTN10805074. Registered on 20 January 2017, retrospectively registered.
Selecting image pairs for SfM by introducing Jaccard Similarity
Authors: Kato Takaharu , Shimizu Ikuko , Pajdla Tomas
Published: April 2017

We present a new approach for selecting image pairs that are more likely to match in Structure from Motion (SfM). We propose to use Jaccard Similarity (JacS) which shows how many different visual words is shared by an image pair. In our method, the similarity between images is evaluated using JacS of bag-of-visual-words in addition to tf-idf (term frequency-inverse document frequency), which is popular for this purpose. To evaluate the efficiency of our method, we carry out experiments on our original datasets as well as on “Pantheon” dataset, which is derived from Flickr. The result of our method using both JacS and tf-idf is better than the results of a standard method using tf-idf only.
IL-27 enhances LPS-induced IL-1β in human monocytes and murine macrophages
Authors: Petes Carlene , Wynick Christopher , Guzzo Christina , Mehta Divya , Logan Sarah , Banfield Bruce W , Basta Sameh , Cooper Andrea , Gee Katrina
Published: April 2017

IL-27 bridges innate and adaptive immunity by modulating cytokine production from myeloid cells and regulating Th cell differentiation. During bacterial infection, TLR4 triggering by LPS induces IL-27 production by monocytes and macrophages. We have previously shown that IL-27 can prime monocytes for LPS responsiveness by enhancing TLR4 expression and intracellular signaling. If unregulated, this could result in damaging inflammation, whereas on the other hand, this may also provide greater responses by inflammatory processes induced in response to bacterial pathogens. A key process in fine-tuning inflammatory responses is activation of the inflammasome, which ultimately results in IL-1β production. Herein, we investigated the molecular mechanisms by which IL-27 modulates LPS-induced IL-1β secretion in monocytes and macrophages. We found that when delivered simultaneously with LPS, IL-27 augments activation of caspase-1 and subsequent release of IL-1β. Furthermore, we determined that IL-27 primes cells for enhanced IL-1β production by up-regulating surface expression of TLR4 and P2X purinoceptor 7 (P2X7) for enhanced LPS and ATP signaling, respectively. These findings provide new evidence that IL-27 plays an important role in the proinflammatory capacity of monocytes and macrophages via enhancing IL-1β secretion levels triggered by dual LPS–ATP stimulation.
Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naïve Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial
Authors: Mason Malcolm D. , Clarke Noel W. , James Nicholas D. , Dearnaley David P. , Spears Melissa R. , Ritchie Alastair W.S. , Attard Gerhardt , Cross William , Jones Rob J. , Parker Christopher C. , Russell J. Martin , Thalmann George N. , Schiavone Francesca , Cassoly Estelle , Matheson David , Millman Robin , Rentsch Cyrill A. , Barber Jim , Gilson Clare , Ibrahim Azman , Logue John , Lydon Anna , Nikapota Ashok D. , O’Sullivan Joe M. , Porfiri Emilio , Protheroe Andrew , Srihari Narayanan Nair , Tsang David , Wagstaff John , Wallace Jan , Walmsley Catherine , Parmar Mahesh K.B. , Sydes Matthew R. ,   for the STAMPEDE Investigators
Published: April 2017

Purpose

Systemic Therapy for Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy is a randomized controlled trial using a multiarm, multistage, platform design. It recruits men with high-risk, locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy. We report survival data for two celecoxib (Cel)-containing comparisons, which stopped accrual early at interim analysis on the basis of failure-free survival.

Patients and Methods

Standard of care (SOC) was hormone therapy continuously (metastatic) or for ≥ 2 years (nonmetastatic); prostate (± pelvic node) radiotherapy was encouraged for men without metastases. Cel 400 mg was administered twice a day for 1 year. Zoledronic acid (ZA) 4 mg was administered for six 3-weekly cycles, then 4-weekly for 2 years. Stratified random assignment allocated patients 2:1:1 to SOC (control), SOC + Cel, or SOC + ZA + Cel. The primary outcome measure was all-cause mortality. Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors.

Results

A total of 1,245 men were randomly assigned (Oct 2005 to April 2011). Groups were balanced: median age, 65 years; 61% metastatic, 14% N+/X M0, 25% N0M0; 94% newly diagnosed; median prostate-specific antigen, 66 ng/mL. Median follow-up was 69 months. Grade 3 to 5 adverse events were seen in 36% SOC-only, 33% SOC + Cel, and 32% SOC + ZA + Cel patients. There were 303 control arm deaths (83% prostate cancer), and median survival was 66 months. Compared with SOC, the adjusted hazard ratio was 0.98 (95% CI, 0.80 to 1.20; P = .847; median survival, 70 months) for SOC + Cel and 0.86 (95% CI, 0.70 to 1.05; P =.130; median survival, 76 months) for SOC + ZA + Cel. Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 (95% CI, 0.62 to 0.98; P = .033) for SOC + ZA + Cel.

Conclusion

These data show no overall evidence of improved survival with Cel. Preplanned subgroup analyses provide hypotheses for future studies.
Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery
Authors: Meretoja Tuomo J. , Andersen Kenneth Geving , Bruce Julie , Haasio Lassi , Sipilä Reetta , Scott Neil W. , Ripatti Samuli , Kehlet Henrik , Kalso Eija
Published: April 2017

Purpose

Persistent pain after breast cancer surgery is a well-recognized problem, with moderate to severe pain affecting 15% to 20% of women at 1 year from surgery. Several risk factors for persistent pain have been recognized, but tools to identify high-risk patients and preventive interventions are missing. The aim was to develop a clinically applicable risk prediction tool.

Methods

The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity at 1 year postoperatively were developed by logistic regression analyses in the Finnish patient cohort. The models were tested in two independent cohorts from Denmark and Scotland by assessing the areas under the receiver operating characteristics curves (ROC-AUCs). The outcome variable was moderate to severe persistent pain at 1 year from surgery in the Finnish and Danish cohorts and at 9 months in the Scottish cohort.

Results

Moderate to severe persistent pain occurred in 13.5%, 13.9%, and 20.3% of the patients in the three studies, respectively. Preoperative pain in the operative area ( P < .001), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively.

Conclusion

Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen for patients at high risk of developing persistent pain after breast cancer surgery.
Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study
Authors: Kuijer Anne , Straver Marieke , den Dekker Bianca , van Bommel Annelotte C.M. , Elias Sjoerd G. , Smorenburg Carolien H. , Wesseling Jelle , Linn Sabine C. , Rutgers Emiel J.Th. , Siesling Sabine , van Dalen Thijs
Published: April 2017

Purpose

Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer.

Patients and Methods

In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available.

Results

Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients.

Conclusion

In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.
American Society of Clinical Oncology Position Statement: Strategies for Reducing Cancer Health Disparities Among Sexual and Gender Minority Populations
Authors: Griggs Jennifer , Maingi Shail , Blinder Victoria , Denduluri Neelima , Khorana Alok A. , Norton Larry , Francisco Michael , Wollins Dana S. , Rowland Julia H.
Published: April 2017

ASCO is committed to addressing the needs of sexual and gender minority (SGM) populations as a diverse group at risk for receiving disparate care and having suboptimal experiences, including discrimination, throughout the cancer care continuum. This position statement outlines five areas of recommendations to address the needs of both SGM populations affected by cancer and members of the oncology workforce who identify as SGM: (1) patient education and support; (2) workforce development and diversity; (3) quality improvement strategies; (4) policy solutions; and (5) research strategies. In making these recommendations, the Society calls for increased outreach and educational support for SGM patients; increased SGM cultural competency training for providers; improvement of quality-of-care metrics that include sexual orientation and gender information variables; and increased data collection to inform future work addressing the needs of SGM communities.
Systematically implementing an electronic platform to improve patient experience measurement in Ontario, Canada.
Authors: Moody Lesley , Dhanju Suman , Benn Sarah , Olaru Isabela , Sliz Nadia , Snow Amy , Khan Sara , Singh Simron
Published: April 2017

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Background: Cancer Care Ontario organizes and ensures quality cancer care for 13.5 million residents in Ontario, Canada and is systematically deploying a web-based tool, called Electronic Patient Reported Experience Measures (ePREM), through a touch-screen platform previously deployed within Regional Cancer Centres (RCCs). ePREM has been used to disseminate the first patient reported experience measure (PREM), called Your Voice Matters (YVM). YVM will be collected on all patients in Ontario undergoing cancer treatment in real time, creating the largest known, linkable patient experience dataset. Methods: Implementation feasibility and readiness was assessed across all 14 Regional Cancer Programs through a provincial assessment which informed the phased implementation. Implementation was rooted in a change management framework: clinical and administrative champions, available resources, existing technical environment and competing program priorities. In March 2016 a four-wave implementation was initiated controlling for readiness and centre volumes, with a focus on extensive stakeholder engagement, tool training, launch and operational support. To date, ePREM is fully operational in 10 of 15 RCCs. Results: Provincial deployment was 66% complete in October 2016. By March 2017 full provincial implementation will be complete. Successful implementation has been directly linked to an adaptive design within the implementation and change management framework as a four-wave roll out. Key factors included: multi-faceted communications with centre leadership, and implementation teams. During this initial data stabilization phase, there were 9,266 completed surveys submitted and 10,932 partial survey responses submitted. Conclusions: PREMs are appropriate quality improvement indicators for cancer patients within the treatment phase. ePREMs enables systematic, linkable collection of real time PREMs to improve the patient experience in Ontario and contribute to the planning of new initiatives. Upon full provincial implementation ePREMs will allow for the largest known dataset of PREMs. Successful implementation has been directly linked to an adaptive, four-wave approach.
Reviewing deaths within 30 days of systemic anti-cancer therapy: Driving quality in a regional chemotherapy service.
Authors: Forde Caroline , Scullin Paula , Edgar Lynne , McAleer James J , Coyle Victoria M
Published: April 2017

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Background: Systemic anti-cancer therapy (SACT) administration rate at the end of life has been deemed a key metric for assessing quality of cancer care. A structured peer review process has been developed within the Cancer Centre, Belfast City Hospital, to discuss all patient deaths occurring within 30 days of SACT across Northern Ireland at a monthly, multidisciplinary, educational mortality meeting. We aimed to review cases discussed, characterising patients, causes of death and the role of SACT in patients’ deaths. Methods: A retrospective analysis was undertaken of 282 solid tumour patients, whose deaths were discussed at the mortality meetings from January 2013 to August 2016. Results: The 30-day mortality rate for the Cancer Centre was 4.5%. Most commonly represented tumour sites were gastrointestinal (39%), lung (22%) and breast (17%) with 96% receiving palliative treatments. WHO Performance Status (PS) was 0-2 at final SACT cycle in 83% (8% PS 3, unknown 9%). 43% of patients were receiving their first cycle and 56% receiving first line treatment for advanced disease. 77% of deaths occurred in hospital with 57% attributed to progressive disease. Other causes of death included infection (7% neutropenic, 11% non-neutropenic) and thromboembolism (12%). In 10% SACT was deemed to have caused or hastened death whereas in 65% SACT was non-contributory. In 25% SACT did not play a major role, but a contributory role could not be confidently excluded. Conclusions: SACT related death rate appears comparable to other institutions’ published routine outcomes. Robust review of SACT mortality encourages service improvement and individual reflection. Prescribers are reminded of the critical importance of carefully balancing patients’ needs and concerns with realistic outcomes and treatment risks, particularly in heavily pretreated or poor PS patients. Case discussions have generated service improvements including site and regimen specific prepopulated consent forms, a standardised SACT assessment proforma and mandatory response assessments as part of SACT protocols. Neutropenic sepsis remains the leading cause of SACT related mortality and further innovative improvements in care are required.
Hard-wiring survivorship care plan delivery.
Authors: Barbarotta Lisa , Jauk Mae Anne , Chiang Anne C. , Sanft Tara Beth
Published: April 2017

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Background: As outlined by the Institute of Medicine (IOM) report, ASCO, the Commission on Cancer, survivorship care planning is an essential part of quality cancer care. Meeting SCP delivery standards is a challenge due to complex systems, difficulty identifying eligible patients, lack of clarity around roles and responsibilities, and time required to complete the care plans. Yale Cancer Center/Smilow Cancer Hospital is a NCI-designated comprehensive cancer center with 12 multidisciplinary cancer programs, a large cancer hospital and 10 care centers in the community. We have approximately 4000 early stage analytic cases per year. We set out to standardize SCP delivery. Methods: A group of multidisciplinary stakeholders convened to outline goals and identify needs. Based on gap analysis and review of national standards, a standard operating procedure for the creation and delivery of SCPs was developed. Models of care were outlined in the policy. Disease specific treatment summary and care plan templates for the most common cancer types were developed within our electronic medical record (EMR) based on ASCO standards and were vetted by disease team experts. The templates were built to minimize the need for manual entry of content. Automated alerts were developed within the EMR to trigger identification of eligible patients. An operational plan was developed for each clinical area to outline responsibilities for care plan creation and delivery. Results: Implementation of model survivorship care within each disease team and community site was performed over a period of one year. The number of care plans delivered has already increased by 20%. At least 10% of early stage analytic cases received SCPs in 2015. Conclusions: Meeting SCP standards in a large, single institution can be challenging. With a standard operating procedure, clear delineation of responsibility within teams, disease specific templates, and EMR tools to trigger visits, meeting these standards becomes an achievable goal. A systematic approach to developing comprehensive survivorship care in a large academic center can hardwire high quality patient care and compliance with standards.
Creating an educational quality improvement program for radiation oncology residents in McGill University.
Authors: Pembroke Catherine Anne , Biron Alain , Alfieri Joanne
Published: April 2017

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Background: Quality insurance (QI) is a pillar of good clinical governance and is at the centre of modern health care. The Royal College of Physicians and Surgeons of Canada CanMeds 2015 have now mandated that QI should be taught and the competencies assessed in all post-graduate residency programs. To our knowledge, this is the first attempt to create a post-graduate QI curriculum amongst radiation oncology trainees. We aim to describe the feasibility of introducing these professional skills which should be integral to every training program. Methods: A QI team has been created within the department of Radiation Oncology at McGill University consisting of a clinical fellow and 3 staff physicians. QI teaching will take place in a longitudinal manner with the mandatory curriculum divided into foundation, intermediate and advanced competencies depending on years of seniority. Teaching is delivered by a combination of two academic half days, consisting of didactic lectures and practical workshops, and self-directed online modules. Each resident during the intermediate years (PGY2-4) will complete a QI project in 9 months under the supervision of an attending physician. The resident will become well versed with QI tools and techniques by presenting their project at specific 3-monthly time points to their supervisor and QI team. In June we will host a QI day where a QI scholar will be invited to teach, each resident will present their project and merit prizes will be awarded. Formal mandatory assessments will take place with a combination of self-assessment, QI- knowledge based assessments (QI-KATs) and balanced score cards. Results: The curriculum has been developed with input from McGill University curriculum and assessment experts. This is a pilot program for the academic 2016/17 year. We are currently meeting our pre-defined milestones. The program will be formally evaluated and adapted to ensure sustainability. Conclusions: The QI skills gained will enable the individual to maintain the highest standards throughout their subsequent careers. A robust, interactive, sustainable curriculum will ensure that this is delivered effectively within radiation oncology and act as a model for all residency programmes.