bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving outcomes from high-risk surgery: a multimethod evaluation of a patient-centred advanced care planning intervention
Authors: Selwood Amanda , Senthuran Siva , Blakely Brette , Lane Paul , North John , Clay-Williams Robyn 
Published: February 2017

IntroductionPatients who are frail, have multiple comorbidities or have a terminal illness often have poor outcomes from surgery. However, sole specialists may recommend surgery in these patients without consultation with other treating clinicians or allowing for patient goals. The Patient-Centred Advanced Care Planning (PC-ACP) model of care provides a framework in which a multidisciplinary advanced care plan is devised to incorporate high-risk patients' values and goals. Decision-making is performed collaboratively by patients, their family, surgeons, anaesthetists, intensivists and surgical case managers. This study aims to evaluate the feasibility of this new model of care, and to determine potential benefits to patients and clinicians.Methods and analysisAfter being assessed for frailty, patients will complete a patient–clinician information engagement survey pretreatment and at 6 months follow-up. Patients (and/or family members) will be interviewed about their experience of care pretreatment and at 3 and 6 months follow-ups. Clinicians will complete a survey on workplace attitudes and engagement both preimplementation and postimplementation of PC-ACP and be interviewed, following each survey, on the implementation of PC-ACP. We will use process mapping to map the patient journey through the surgical care pathway to determine areas of improvement and to identify variations in patient experience.Ethics and disseminationThis study has received ethical approval from Townsville Hospital and Health Service HREC (HREC/16/QTHS/100). Results will be communicated to the participating hospital, presented at conferences and submitted for publication in a peer-reviewed MEDLINE-indexed journal.
Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer
Authors: Mustachio Lisa Maria , Lu Yun , Tafe Laura J. , Memoli Vincent , Rodriguez-Canales Jaime , Mino Barbara , Villalobos Pamela Andrea , Wistuba Ignacio , Katayama Hiroyuki , Hanash Samir M. , Roszik Jason , Kawakami Masanori , Cho Kwang-jin , Hancock John F. , Chinyengetere Fadzai , Hu Shanhu , Liu Xi , Freemantle Sarah J. , Dmitrovsky Ethan 
Published: February 2017

Abstract
KRAS is frequently mutated in lung cancers and is associated with aggressive biology and chemotherapy resistance. Therefore, innovative approaches are needed to treat these lung cancers. Prior work implicated the IFN-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having antineoplastic activity by regulating lung cancer growth and oncoprotein stability. This study demonstrates that USP18 affects the stability of the KRAS oncoprotein. Interestingly, loss of USP18 reduced KRAS expression, and engineered gain of USP18 expression increased KRAS protein levels in lung cancer cells. Using the protein synthesis inhibitor cycloheximide, USP18 knockdown significantly reduced the half-life of KRAS, but gain of USP18 expression significantly increased its stability. Intriguingly, loss of USP18 altered KRAS subcellular localization by mislocalizing KRAS from the plasma membrane. To explore the biologic consequences, immunohistochemical (IHC) expression profiles of USP18 were compared in lung cancers of KrasLA2/+ versus cyclin E engineered mouse models. USP18 expression was higher in Kras-driven murine lung cancers, indicating a link between KRAS and USP18 expression in vivo. To solidify this association, loss of Usp18 in KrasLA2/+/Usp18−/− mice was found to significantly reduce lung cancers as compared with parental KrasLA2/+ mice. Finally, translational relevance was confirmed in a human lung cancer panel by showing that USP18 IHC expression was significantly higher in KRAS-mutant versus wild-type lung adenocarcinomas.
Implications: Taken together, this study highlights a new way to combat the oncogenic consequences of activated KRAS in lung cancer by inhibiting the DUB USP18. Mol Cancer Res; 15(7); 905–14. ©2017 AACR.
Phase I, Dose-Escalation, Two-Part Trial of the PARP Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected Sporadic Cancers
Authors: de Bono Johann , Ramanathan Ramesh K. , Mina Lida , Chugh Rashmi , Glaspy John , Rafii Saeed , Kaye Stan , Sachdev Jasgit , Heymach John , Smith David C. , Henshaw Joshua W. , Herriott Ashleigh , Patterson Miranda , Curtin Nicola J. , Byers Lauren Averett , Wainberg Zev A. 
Published: February 2017

Abstract
Talazoparib inhibits PARP catalytic activity, trapping PARP1 on damaged DNA and causing cell death in BRCA1/2-mutated cells. We evaluated talazoparib therapy in this two-part, phase I, first-in-human trial. Antitumor activity, MTD, pharmacokinetics, and pharmacodynamics of once-daily talazoparib were determined in an open-label, multicenter, dose-escalation study (NCT01286987). The MTD was 1.0 mg/day, with an elimination half-life of 50 hours. Treatment-related adverse events included fatigue (26/71 patients; 37%) and anemia (25/71 patients; 35%). Grade 3 to 4 adverse events included anemia (17/71 patients; 24%) and thrombocytopenia (13/71 patients; 18%). Sustained PARP inhibition was observed at doses ≥0.60 mg/day. At 1.0 mg/day, confirmed responses were observed in 7 of 14 (50%) and 5 of 12 (42%) patients with BRCA mutation–associated breast and ovarian cancers, respectively, and in patients with pancreatic and small cell lung cancer. Talazoparib demonstrated single-agent antitumor activity and was well tolerated in patients at the recommended dose of 1.0 mg/day.
Significance: In this clinical trial, we show that talazoparib has single-agent antitumor activity and a tolerable safety profile. At its recommended phase II dose of 1.0 mg/day, confirmed responses were observed in patients with BRCA mutation–associated breast and ovarian cancers and in patients with pancreatic and small cell lung cancer. Cancer Discov; 7(6); 620–9. ©2017 AACR.
This article is highlighted in the In This Issue feature, p. 539
Ketone Body Infusion With 3‐Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study
Authors: Gormsen Lars C. , Svart Mads , Thomsen Henrik Holm , Søndergaard Esben , Vendelbo Mikkel H. , Christensen Nana , Tolbod Lars Poulsen , Harms Hendrik Johannes , Nielsen Roni , Wiggers Henrik , Jessen Niels , Hansen Jakob , Bøtker Hans Erik , Møller Niels 
Published: February 2017

Background

High levels of ketone bodies are associated with improved survival as observed with regular exercise, caloric restriction, and—most recently—treatment with sodium–glucose linked transporter 2 inhibitor antidiabetic drugs. In heart failure, indices of ketone body metabolism are upregulated, which may improve energy efficiency and increase blood flow in skeletal muscle and the kidneys. Nevertheless, it is uncertain how ketone bodies affect myocardial glucose uptake and blood flow in humans. Our study was therefore designed to test whether ketone body administration in humans reduces myocardial glucose uptake (
MGU
) and increases myocardial blood flow.

Methods and Results

Eight healthy subjects, median aged 60 were randomly studied twice: (1) During 390 minutes infusion of Na‐3‐hydroxybutyrate (
KETONE
) or (2) during 390 minutes infusion of saline (
SALINE
), together with a concomitant low‐dose hyperinsulinemic–euglycemic clamp to inhibit endogenous ketogenesis. Myocardial blood flow was measured by
15
O‐H
2
O positron emission tomography/computed tomography, myocardial fatty acid metabolism by
11
C‐palmitate positron emission tomography/computed tomography and
MGU
by
18
F‐fluorodeoxyglucose positron emission tomography/computed tomography. Similar euglycemia, hyperinsulinemia, and suppressed free fatty acids levels were recorded on both study days; Na‐3‐hydroxybutyrate infusion increased circulating Na‐3‐hydroxybutyrate levels from zero to 3.8±0.5 mmol/L.
MGU
was halved by hyperketonemia (
MGU
[nmol/g per minute]: 304±97 [
SALINE
] versus 156±62 [
KETONE
],
P
<0.01), whereas no effects were observed on palmitate uptake oxidation or esterification. Hyperketonemia increased heart rate by ≈25% and myocardial blood flow by 75%.

Conclusions

Ketone bodies displace
MGU
and increase myocardial blood flow in healthy humans; these novel observations suggest that ketone bodies are important cardiac fuels and vasodilators, which may have therapeutic potentials.
Association Between Absolute Eosinophil Count and Complex Aortic Arch Plaque in Patients With Acute Ischemic Stroke
Authors: Kitano Takaya , Nezu Tomohisa , Shiromoto Takashi , Kubo Satoshi , Uemura Jyunichi , Wada Yuko , Yagita Yoshiki 
Published: February 2017

Background and Purpose—
Eosinophil counts are thought to be associated with atherosclerosis and aortic arch plaques. However, whether these associations exist among patients with acute ischemic stroke remains unclear. We aimed to evaluate the association between absolute eosinophil count (AEC) and aortic arch plaques among these patients.

Methods—
Consecutive acute ischemic stroke patients undergoing transesophageal echocardiography were retrospectively analyzed. Complex aortic arch plaques (CAPs) were defined as plaques ≥4 mm in thickness, with ulcer, or with mobile component.

Results—

A total of 430 patients (289 male, mean age 69.8±11.4 years) were enrolled. Patients with CAPs (n=169) showed higher mean AEC than those without (167±174/µL versus 127±127/µL;
P
=0.007). Multivariate analysis showed that increased AEC was independently associated with the presence of CAPs (odds ratio, 2.09; 95% confidence interval, 1.21–3.65).

Conclusions—
Among patients with acute ischemic stroke, increased AEC was independently associated with the presence of CAPs. Our results suggest that AEC may be a useful predictor for the presence of CAPs in these patients.
Allyl isothiocyanate shows promise as a naturally produced suppressant of the potato cyst nematode, Globodera pallida, in biofumigation systems
Authors: Wood Claire , Kenyon David M. , Cooper Julia M. 
Published: February 2017

The ability of isothiocyanates to suppressGlobodera pallidawas evaluated throughin vitroassays. Several isothiocyanates increased juvenile mortality, the most effective being allyl isothiocyanate, which caused 100% mortality at both 25 and 50 ppm after 72 and 24 h exposure, respectively. In a hatching assay, allyl isothiocyanate was able to suppress hatch; in addition, replenishing allyl isothiocyanate every 3 days increased hatch suppression, and viability staining indicated that egg mortality was increased. Allyl isothiocyanate above concentrations of 50 ppm significantly affected both hatch suppression and mortality. Differing effects of isothiocyanates onG. pallidasuggest that their toxicity depends on the pest of interest and this study shows that allyl isothiocyanate is a good candidate for the control of potato cyst nematodes using biofumigation.
Equivocations of Gender: Feminist Storytelling and Women’s Studies in the Contemporary
Authors: Sreekumar Sharmila 
Published: February 2017

This article seeks to explore the stories that women’s studies in India tells about itself—its beginnings, trajectories and situations in the contemporary. Deploying the term ‘feminist storytelling’, the article focuses particularly on the origin stories that it diligently narrates. Feminist storytelling is to be understood here as a certain account-taking, a certain history-telling. It necessarily entails that we choose from a multitude of details; that we select and omit. It means that we plot different elements in terms of causality, sequence, consequence that we frame a beginning, middle and culmination. In other words, storytelling demands that we configure and construct—a temporal range, definite perspectives, priorities, order, conflicts, tempo, significations and resolutions. This article zeroes in on two stories that are repeatedly called upon to mark the beginnings of women’s studies: (i) the long fertile 19th century with its clamour over the ‘women’s question’ and (ii) the tumultuous decade of the 1970s which witnessed twinned events—the publication of the Towards Equality report and the emergence of the autonomous women’s movement. The particular manner in which women’s studies claim these histories, the article argues, mediates present dispositions and the modes by which women’s studies orients itself in the world. It conditions the responses we formulate under the sign of gender and in the name of woman. After analysing a few key renderings of ‘feminist storytelling’, this article quickly sketches a cartography of impasses confronting contemporary women’s studies. Several of these, it proposes, can be traced back to the origin stories propounded by feminist storytelling.
Data monitoring committees: Promoting best practices to address emerging challenges
Authors: Fleming Thomas R , DeMets David L , Roe Matthew T , Wittes Janet , Calis Karim A , Vora Amit N , Meisel Alan , Bain Raymond P , Konstam Marvin A , Pencina Michael J , Gordon David J , Mahaffey Kenneth W , Hennekens Charles H , Neaton James D , Pearson Gail D , Andersson Tomas LG , Pfeffer Marc A , Ellenberg Susan S 
Published: February 2017

Background and Purpose: Data monitoring committees are responsible for safeguarding the interests of study participants and assuring the integrity and credibility of clinical trials. The independence of data monitoring committees from sponsors and investigators is essential in achieving this mission. Creative approaches are needed to address ongoing and emerging challenges that potentially threaten data monitoring committees’ independence and effectiveness. Methods: An expert panel of representatives from academia, industry and government sponsors, and regulatory agencies discussed these challenges and proposed best practices and operating principles for effective functioning of contemporary data monitoring committees. Results and Conclusions: Prospective data monitoring committee members need better training. Options could include didactic instruction as well as apprenticeships to provide real-world experience. Data monitoring committee members should be protected against legal liability arising from their service. While avoiding breaches in confidentiality of interim data remains a high priority, data monitoring committees should have access to unblinded efficacy and safety data throughout the trial to enable informed judgments about risks and benefits. Because overly rigid procedures can compromise their independence, data monitoring committees should have the flexibility necessary to best fulfill their responsibilities. Data monitoring committee charters should articulate principles that guide the data monitoring committee process rather than list a rigid set of requirements. Data monitoring committees should develop their recommendations by consensus rather than through voting processes. The format for the meetings of the data monitoring committee should maintain the committee’s independence and clearly establish the leadership of the data monitoring committee chair. The independent statistical group at the Statistical Data Analysis Center should have sufficient depth of knowledge about the study at hand and experience with trials in general to ensure that the data monitoring committee has access to timely, reliable, and readily interpretable insights about emerging evidence in the clinical trial. Contracts engaging data monitoring committee members for industry-sponsored trials should have language customized to the unique responsibilities of data monitoring committee members rather than use language appropriate to consultants for product development. Regulatory scientists would benefit from experiencing data monitoring committee service that does not conflict with their regulatory responsibilities.
Accuracy and User Performance Evaluation of a New, Wireless-enabled Blood Glucose Monitoring System That Links to a Smart Mobile Device
Authors: Bailey Timothy S. , Wallace Jane F. , Pardo Scott , Warchal-Windham Mary Ellen , Harrison Bern , Morin Robert , Christiansen Mark 
Published: February 2017

Background: The new Contour®Plus ONE blood glucose monitoring system (BGMS) features an easy-to-use, wireless-enabled blood glucose meter that links to a smart mobile device via Bluetooth® connectivity and can sync with the Contour™ Diabetes app on a smartphone or tablet. Methods: The accuracy of the new BGMS was assessed in 2 studies according to ISO 15197:2013 criteria. In Study 1 (laboratory study), fingertip capillary blood samples from 100 subjects were tested in duplicate using 3 test strip lots. In Study 2 (clinical study), 134 subjects with type 1 or type 2 diabetes enrolled at 2 clinical sites. BGMS results and YSI analyzer (YSI) reference results were compared for fingertip blood obtained by untrained subjects’ self-testing and for study staff–obtained fingertip, subject palm, and venous results. Results: In Study 1, 99.0% (594/600) of combined results for all 3 test strip lots fulfilled ISO 15197:2013 Section 6.3 accuracy criteria. In Study 2, 99.2% (133/134) of subject-obtained capillary fingertip results, 99.2% (133/134) of study staff–obtained fingertip results, 99.2% (125/126) of subject-obtained palm results, and 100% (132/132) of study staff–obtained venous results met ISO 15197:2013 Section 8 accuracy criteria. Moreover, 95.5% (128/134) of subject-obtained fingertip self-test results were within ±10 mg/dl (±0.6 mmol/L) or ±10% of the YSI reference result. Questionnaire results showed that most subjects found the BGMS easy to use. Conclusions: The BGMS exceeded ISO 15197:2013 accuracy criteria both in the laboratory and in a clinical setting when used by untrained subjects with diabetes.
Cardiac and renal complications of carfilzomib in patients with multiple myeloma
Authors: Dimopoulos Meletios A. , Roussou Maria , Gavriatopoulou Maria , Psimenou Erasmia , Ziogas Dimitrios , Eleutherakis-Papaiakovou Evangelos , Fotiou Despina , Migkou Magdalini , Kanellias Nikolaos , Panagiotidis Ioannis , Ntalianis Argyrios , Papadopoulou Elektra , Stamatelopoulos Kimon , Manios Efstathios , Pamboukas Constantinos , Kontogiannis Sofoklis , Terpos Evangelos , Kastritis Efstathios 
Published: February 2017

Key PointsCarfilzomib is associated with reversible cardiotoxicity in 12% of consecutive myeloma patients. Transient renal toxicity is common, but carfilzomib may improve renal function in myeloma-related renal impairment.
Intermediate-Acting Nondepolarizing Neuromuscular Blocking Agents and Risk of Postoperative 30-Day Morbidity and Mortality, and Long-term Survival
Authors: Bronsert Michael R. , Henderson William G. , Monk Terri G. , Richman Joshua S. , Nguyen Jennifer D. , Sum-Ping John T. , Mangione Michael P. , Higley Binh , Hammermeister Karl E. 
Published: February 2017

BACKGROUND:Nondepolarizing neuromuscular blocking drugs (NNMBDs) are commonly used as an adjunct to general anesthesia. Residual blockade is common, but its potential adverse effects are incompletely known. This study was designed to assess the association between NNMBD use with or without neostigmine reversal and postoperative morbidity and mortality.METHODS:This is a retrospective observational study of 11,355 adult patients undergoing general anesthesia for noncardiac surgery at 5 Veterans Health Administration (VA) hospitals. Of those, 8984 received NNMBDs, and 7047 received reversal with neostigmine. The primary outcome was a composite of respiratory complications (failure to wean from the ventilator, reintubation, or pneumonia), which was “yes” if a patient had any of the 3 component events and “no” if they had none. Secondary outcomes were nonrespiratory complications, 30-day and long-term all-cause mortality. We adjusted for differences in patient risk using propensity matched (PM) followed by assessment of the association of interest by logistic regression between the matched pairs as our primary analysis and multivariable logistic regression (MLR) as a sensitivity analysis.RESULTS:Our primary aim was to assess the adverse outcomes in the patients who had received NNMBDs with and without neostigmine. Administration of an NNMBD without neostigmine reversal compared with NNMBD with neostigmine reversal was associated with increased odds of respiratory complications (PM odds ratio [OR], 1.75 [95% confidence interval [CI], 1.23–2.50]; MLR OR, 1.71 [CI, 1.24–2.37]) and a marginal increase in 30-day mortality (PM OR, 1.83 [CI, 0.99–3.37]; MLR OR, 1.78 [CI, 1.02–3.13]). However, there were no statistically significant associations with nonrespiratory complications or long-term mortality. Patients who were administered an NNMBD followed by neostigmine had no differences in outcomes compared with patients who had general anesthesia without an NNMBD.CONCLUSIONS:The use of NNMBDs without neostigmine reversal was associated with increased odds of our composite respiratory outcome compared with patients reversed with neostigmine. Based on these data, we conclude that reversal of NNMBDs should become a standard practice if extubation is planned.
Cross-Disciplinary Perceptions of Structured Interprofessional Rounds in Promoting Teamwork Within an Academic Tertiary Care Obstetric Unit
Authors: Chau Anthony , Vijjeswarapu Mary A. , Hickey Margaret , Acker David , Huang Chuan-Chin , Tsen Lawrence C. 
Published: February 2017

BACKGROUND:
In 2005, physician and nursing leaders at Brigham and Women’s Hospital initiated structured interprofessional rounds (SIPRs) on the labor and delivery (L&D) suite to improve team communication. We performed a cross-sectional analysis of providers’ perceptions of SIPRs and their effectiveness in improving teamwork. We hypothesized that on average, providers would perceive SIPRs as being effective in promoting teamwork, but ratings would differ among professional groups.

METHODS:
After a factor analysis and internal consistency assessment, a 19-item paper-based questionnaire was used to evaluate providers’ perceptions using a 5-point Likert scale. Respondents included L&D nurses, midwives, obstetricians, and anesthesiologists who participate in SIPRs. The primary aim was to evaluate the providers’ perceptions of SIPRs and their association with professional roles. The outcome was total response score for each provider, ranging from 19 to 95; perception of SIPRs as being effective in promoting teamwork was defined as having a total response score of >66.5 (mean score, >3.5 per question). A univariable linear regression model was performed, followed by a multivariable analysis adjusting for predictors that modified the outcome; predictors included years of professional practice, years of experience on the L&D suite, number of clinical work hours worked weekly, and principal shift assignment among nurses. The associations between these predictors and providers’ perceptions were assessed as a secondary aim.

RESULTS:
A total of 234 practitioners responded (100% response rate). The mean total response score (SD) for all providers was 73.3 (9.5). After multivariable adjustment, the mean total response scores were significantly higher for obstetric providers than for anesthesia (Δ mean, 6.5, 95% CI, 0.3, 12.7 P = .036) and midwifery (Δ mean, 12.5, 95% CI, 2.0, 23.0, P = .009) providers. Providers scored significantly lower if they worked >60 clinical hours per week compared with ≤20 (Δ mean, −13.7, 95% CI, −25.3, −2.1, P = .009), 21–40 (Δ mean, −8.0, 95% CI, −15.8, −0.09, P = .049), or 41–60 hours (Δ mean, −8.1, 95% CI, −14.5, −1.7, P = .004). Duration of practice in professional role and experience on the L&D suite were not predictive of SIPRs ratings.

CONCLUSIONS:
On average, providers on the L&D suite perceive SIPRs as being effective in promoting teamwork. Perception ratings were significantly influenced by professional role and number of clinical hours worked weekly, suggesting that these factors should be explored in future research to minimize perception gaps and support a dynamic culture of interprofessional collaboration.