bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a systematic review of preference-based instruments for measuring care-related outcomes and their suitability for the palliative care setting
Authors: McCaffrey Nikki , Al-Janabi Hareth , Currow David , Hoefman Renske , Ratcliffe Julie 
Published: September 2016

IntroductionDespite informal caregivers' integral role in supporting people affected by disease or disability, economic evaluations often ignore the costs and benefits experienced by this group, especially in the palliative setting. The purpose of this systematic review is to identify preference-based instruments for measuring care-related outcomes and provide guidance on the selection of instrument in palliative care economic evaluations.Methods and analysisA comprehensive search of the literature will be conducted from database inception (ASSIA; CINAHL; Cochrane library including DARE, NHS EED, HTA; Econlit; Embase; PsychINFO; PubMed). Published peer-reviewed, English-language articles reporting preference-based instruments for measuring care-related outcomes in any clinical area will be included. One researcher will complete the searches and screen the results for potentially eligible studies. A randomly selected subset of 10% citations will be independently screened by two researchers. Any disagreement will be resolved by consensus among the research team. Subsequently, a supplementary search will identify studies detailing the development, valuation, validation and application of the identified instruments. The degree of suitability of the instruments for palliative economic evaluations will be assessed using criteria in the International Society for Quality of Life Research minimum standards for patient-reported outcome measures, the checklist for reporting valuation studies of multiattribute utility-based instruments and information on the development of the instrument in the palliative setting. A narrative summary of the included studies and instruments will be provided; similarities and differences will be described and possible reasons for variations explored. Recommendations for practice on selection of instruments in palliative care economic analyses will be provided.Ethics and disseminationThis is a planned systematic review of published literature. Therefore, ethics approval to conduct this research is not required. Findings will be presented at leading palliative care and health economic conferences and published in a peer-reviewed journal.Trial registration numberCRD42016034188.
Effect of exercise-based management on multidirectional instability of the glenohumeral joint: a pilot randomised controlled trial protocol
Authors: Warby Sarah A , Ford Jon J , Hahne Andrew J , Watson Lyn , Balster Simon , Lenssen Ross , Pizzari Tania 
Published: September 2016

IntroductionThe most commonly recommended treatment for multidirectional instability (MDI) of the shoulder is exercise. Despite this recommendation, there is limited evidence to support the effectiveness of exercise. The aim of this paper is to describe a pilot randomised controlled trial comparing the effectiveness of 2 exercise programmes on outcomes of participants with MDI.Methods and analysisConsenting participants between 12 and 35 years, with non-traumatic MDI will be randomly allocated to participate in either the Rockwood Instability programme or the Watson MDI programme. Both programmes involve 1 consultation per week for 12 weeks with a physiotherapist to prescribe and progress a home exercise programme. Outcomes will be assessed at baseline, 6, 12, 24 and 52 weeks. Primary outcome measures include the Melbourne Instability Shoulder Score and Western Ontario Shoulder Index. Secondary outcomes include scapular coordinates, scapular upward rotation angles, muscle strength, symptomatic onset, limiting factor and angle of limiting factor in abduction range, incidence of complete glenohumeral joint dislocation, global rating of change, satisfaction scores, the Orebro Musculoskeletal Pain Questionnaire, adverse events and compliance with the home exercise programme. Data will be analysed on intention-to-treat principles and a per protocol basis.DiscussionThis trial will evaluate whether there are differences in outcomes between the Rockwood and the Watson MDI programmes for participants with MDI.Ethics and disseminationParticipant confidentiality will be maintained with publication of results. Ethics approval: Faculty of Health Sciences (FHEC12/201).Trial registration numberACTRN12613001240730; Pre-results.
RK-33 Radiosensitizes Prostate Cancer Cells by Blocking the RNA Helicase DDX3
Authors: Xie Min , Vesuna Farhad , Tantravedi Saritha , Bol Guus M. , Heerma van Voss Marise R. , Nugent Katriana , Malek Reem , Gabrielson Kathleen , van Diest Paul J. , Tran Phuoc T. , Raman Venu 
Published: September 2016

Abstract
Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second highest cause of cancer-related mortality. We identified an RNA helicase gene, DDX3 (DDX3X), which is overexpressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in the aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3. Functional studies indicated that RK-33 preferentially bound to DDX3 and perturbed its activity. RK-33 treatment of prostate cancer cell lines DU145, 22Rv1, and LNCaP (which have high DDX3 levels) decreased proliferation and induced a G1 phase cell-cycle arrest. Conversely, the low DDX3–expressing cell line, PC3, exhibited few changes following RK-33 treatment. Importantly, combination studies using RK-33 and radiation exhibited synergistic effects both in vitro and in a xenograft model of prostate cancer demonstrating the role of RK-33 as a radiosensitizer. Taken together, these results indicate that blocking DDX3 by RK-33 in combination with radiation treatment is a viable option for treating locally advanced prostate cancer. Cancer Res; 76(21); 6340–50. ©2016 AACR.
Molecular Pathways: Targeting CD96 and TIGIT for Cancer Immunotherapy
Authors: Blake Stephen J. , Dougall William C. , Miles John J. , Teng Michele W.L. , Smyth Mark J. 
Published: September 2016

AbstractThe receptors CD96 and TIGIT are expressed on the surface of T and natural killer (NK) cells, and recent studies suggest both play important inhibitory roles in immune function. CD96 has been shown to modulate immune cell activity in mice, with Cd96−/− mice displaying hypersensitive NK-cell responses to immune challenge and significant tumor resistance. TIGIT overexpression has been shown to reduce NK-cell–mediated cytotoxicity. TIGIT is also upregulated on T cells during cancer and chronic viral infection, with expression associated with effector T-cell exhaustion and increased regulatory T-cell suppression. The counterbalance between the putative inhibitory CD96 and TIGIT receptors and the activating receptor, CD226, offers unique strategies for immuno-oncology drug development. Blocking CD96 or TIGIT with mAbs has been shown to improve tumor control in mice, in particular when used in combination with PD-1/PD-L1 blockade. These results have highlighted these pathways as promising new targets for immune modulation. This review will examine the rationale behind targeting CD96 and TIGIT, and discuss the potential approaches in translating these preclinical findings into novel clinical agents. Clin Cancer Res; 22(21); 5183–8. ©2016 AACR.
Adipose-Induced Retroperitoneal Soft Tissue Sarcoma Tumorigenesis: A Potential Crosstalk between Sarcoma and Fat Cells
Authors: Loewenstein Shelly , Lubezky Nir , Nizri Eran , Zemel Meir , Levin Yishai , Savidor Alon , Sher Osnat , Klausner Joseph M. , Lahat Guy 
Published: September 2016

Abstract
Previous data demonstrated that high retroperitoneal visceral fat content increases retroperitoneal soft-tissue sarcoma (RSTS) local recurrence and patients' mortality. Most RSTS tumors initiate and recur within visceral fat. The objective of the current study was to evaluate potential paracrine effects of visceral fat on RSTS. A xenograft model was used to evaluate in vivo effects of human visceral fat on STS growth. Tissue explants were prepared from visceral fat, and their conditioned medium (CM) was utilized for various in vitro experiments designed to evaluate growth, survival, migration, and invasion of STS and endothelial cells. Visceral fat–secreted protumorigenic factors were identified by mass spectrometry. The in vivo experiments demonstrated a significant increase in STS tumor growth rate when SK-LMS-1 leiomyosarcoma cells were colocalized with human visceral fat compared with subcutaneous injection of cancer cells only. The in vitro model demonstrated that visceral fat CM increased STS cellular growth and reduced doxorubicin-induced apoptosis. Visceral fat also enhanced STS cellular migration and invasion. In addition, visceral fat CM significantly increased endothelial cell tube formation, suggesting its role as a proangiogenic factor in the STS tumor microenvironment (TME). Using a robust proteomic approach, liquid chromatography and tandem mass spectrometry resolved various molecules within the visceral fat CM, of which a subset was associated with protumorigenic biologic processes. These results suggest that visceral fat directly interacts with STS cells by secreting specific adipokines into the TME, thus augmenting STS tumor cell proliferation and invasiveness. Fat-induced STS molecular deregulations should be studied to identify new potential prognostic and therapeutic targets.
Implications: Visceral fat induces protumorigenic effects, in STS, through various secreted factors that should be investigated to improve our understanding of adipose–cancer cell interactions. Mol Cancer Res; 14(12); 1254–65. ©2016 AACR.
Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis
Authors: Hulten Edward , Agarwal Vikram , Cahill Michael , Cole Geoff , Vita Tomas , Parrish Scott , Bittencourt Marcio Sommer , Murthy Venkatesh L. , Kwong Raymond , Di Carli Marcelo F. , Blankstein Ron 
Published: September 2016

Background—
Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis.

Methods and Results—

We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men).One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7;
P
=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34–86.3];
P
=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68–143];
P
=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47–15.6];
P
<0.001). There was no significant heterogeneity for any outcomes.

Conclusions—
LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis.
Collaborative Efforts between the United States and United Kingdom to Advance Prediction of High-Impact Weather
Authors: Willington Steve , Clark Adam J. , Weiss Steven J. , Weeks Mark , Jirak Israel L. , Coniglio Michael C. , Roberts Nigel M. , Karstens Christopher D. , Wilkinson Jonathan M. , Knopfmeier Kent H. , Lean Humphrey W. , Ellam Laura , Hanley Kirsty , North Rachel , Suri Dan 
Published: September 2016

AbstractIn recent years, a growing partnership has emerged between the Met Office and the designated U.S. national centers for expertise in severe weather research and forecasting, that is, the National Oceanic and Atmospheric Administration (NOAA) National Severe Storms Laboratory (NSSL) and the NOAA Storm Prediction Center (SPC). The driving force behind this partnership is a compelling set of mutual interests related to predicting and understanding high-impact weather and using high-resolution numerical weather prediction models as foundational tools to explore these interests.The forum for this collaborative activity is the NOAA Hazardous Weather Testbed, where annual Spring Forecasting Experiments (SFEs) are conducted by NSSL and SPC. For the last decade, NSSL and SPC have used these experiments to find ways that high-resolution models can help achieve greater success in the prediction of tornadoes, large hail, and damaging winds. Beginning in 2012, the Met Office became a contributing partner in annual SFEs, bringing complementary expertise in the use of convection-allowing models, derived in their case from a parallel decadelong effort to use these models to advance prediction of flash floods associated with heavy thunderstorms.The collaboration between NSSL, SPC, and the Met Office has been enthusiastic and productive, driven by strong mutual interests at a grassroots level and generous institutional support from the parent government agencies. In this article, a historical background is provided, motivations for collaborative activities are emphasized, and preliminary results are highlighted.
Modeling the Mechanisms of Linear and Nonlinear ENSO Responses to the Pacific Meridional Mode
Authors: Thomas Erin E. , Vimont Daniel J. 
Published: September 2016

Abstract
Interactions between the Pacific meridional mode (PMM) and El Niño–Southern Oscillation (ENSO) are investigated using the National Center for Atmospheric Research (NCAR) Community Earth System Model (CESM) and an intermediate coupled model (ICM). The two models are configured so that the CESM simulates the PMM but not ENSO, and the ICM simulates ENSO but not the PMM, allowing for a clean separation between the PMM evolution and the subsequent ENSO response. An ensemble of CESM simulations is run with an imposed surface heat flux associated with the North Pacific Oscillation (NPO) generating a sea surface temperature (SST) and wind response representative of the PMM. The PMM wind is then applied as a forcing to the ICM to simulate the ENSO response. The positive (negative) ensemble-mean PMM wind forcing results in a warm (cold) ENSO event although the responses are not symmetric (warm ENSO events are larger in amplitude than cold ENSO events), and large variability between ensemble members suggests that any individual ENSO event is strongly influenced by natural variability contained within the CESM simulations. Sensitivity experiments show that 1) direct forcing of Kelvin waves by PMM winds dominates the ENSO response, 2) seasonality of PMM forcing and ENSO growth rates influences the resulting ENSO amplitude, 3) ocean dynamics within the ICM dominate the ENSO asymmetry, and 4) the nonlinear relationship between PMM wind anomalies and surface wind stress may enhance the La Niña response to negative PMM variations. Implications for ENSO variability are discussed.
On the Controls of Daytime Precipitation in the Amazonian Dry Season
Authors: Ghate Virendra P. , Kollias Pavlos 
Published: September 2016

Abstract
The Amazon plays an important role in the global energy and hydrological budgets. The precipitation during the dry season (June–September) plays a critical role in maintaining the extent of the rain forest. The deployment of the first Atmospheric Radiation Measurement (ARM) Mobile Facility (AMF-1) in the context of the Green Ocean Amazon (GOAmazon) field campaign at Manacapuru, Brazil, provided comprehensive measurements of surface, cloud, precipitation, radiation, and thermodynamic properties for two complete dry seasons (2014 and 2015). The precipitation events occurring during the nighttime were associated with propagating storm systems (nonlocal effects), while the daytime precipitation events were primarily a result of local land–atmosphere interactions. During the two dry seasons, precipitation was recorded at the surface on 106 days (43%) from 158 rain events with 82 daytime precipitation events occurring on 64 days (60.37%). Detailed comparisons between the diurnal cycles of surface and profile properties between days with and without daytime precipitation suggested the increased moisture at low and midlevels to be responsible for lowering the lifting condensation level, reducing convective inhibition and entrainment, and thus triggering the transition from shallow to deep convection. Although the monthly accumulated rainfall decreased during the progression of the dry season, the contribution of daytime precipitation to it increased, suggesting the decrease to be mainly due to reduction in propagating squall lines. The control of daytime precipitation during the dry season on large-scale moisture advection above the boundary layer and the total rainfall on propagating squall lines suggests that coarse-resolution models should be able to accurately simulate the dry season precipitation over the Amazon basin.
Investigation of Near-Storm Environments for Tornado Events and Warnings
Authors: Anderson-Frey Alexandra K. , Richardson Yvette P. , Dean Andrew R. , Thompson Richard L. , Smith Bryan T. 
Published: September 2016

Abstract
In this study, a 13-yr climatology of tornado event and warning environments, including metrics of tornado intensity and storm morphology, is investigated with particular focus on the environments of tornadoes associated with quasi-linear convective systems and right-moving supercells. The regions of the environmental parameter space having poor warning performance in various geographical locations, as well as during different times of the day and year, are highlighted. Kernel density estimations of the tornado report and warning environments are produced for two parameter spaces: mixed-layer convective available potential energy (MLCAPE) versus 0–6-km vector shear magnitude (SHR6), and mixed-layer lifting condensation level (MLLCL) versus 0–1-km storm-relative helicity (SRH1). The warning performance is best in environments characteristic of severe convection (i.e., environments featuring large values of MLCAPE and SHR6). For tornadoes occurring during the early evening transition period, MLCAPE is maximized, MLLCL heights decrease, SHR6 and SRH1 increase, tornadoes rated as 2 or greater on the enhanced Fujita scale (EF2+) are most common, the probability of detection is relatively high, and false alarm ratios are relatively low. Overall, the parameter-space distributions of warnings and events are similar; at least in a broad sense, there is no systematic problem with forecasting that explains the high overall false alarm ratio, which instead seems to stem from the inability to know which storms in a given environment will be tornadic.
Patient Perceptions About Prediabetes and Preferences for Diabetes Prevention
Authors: O’Brien Matthew J. , Moran Margaret R. , Tang Joyce W. , Vargas Maria C. , Talen Mary , Zimmermann Laura J. , Ackermann Ronald T. , Kandula Namratha R. 
Published: September 2016

Purpose The purpose of this study was to explore how adults with prediabetes perceive their risk of developing diabetes and examine their preferences for evidence-based treatment options to prevent diabetes. Methods A qualitative study was conducted in 2 large Midwest primary care practices, involving in-depth semistructured interviews with 35 adult patients with prediabetes. Results This ethnically diverse (77% nonwhite) sample of middle-aged primary care patients exhibited multiple diabetes risk factors. Knowledge gaps about prediabetes and its medical management were pervasive. Most patients overestimated the risk of developing diabetes and were not familiar with evidence-based treatment options for prediabetes. They suggested that receiving brief, yet specific information about these topics during the study interview motivated them to act. The majority of participants considered both intensive lifestyle intervention and metformin acceptable treatment options. Many preferred initial treatment with intensive lifestyle intervention but would take metformin if their efforts at lifestyle change failed and their primary care physician recommended it. Some participants expressed wanting to combine both treatments. Conclusions This qualitative study highlights potential opportunities to promote patient-centered dialogue about prediabetes in primary care settings. Providing patients specific information about the risk of developing diabetes and evidence-based treatment options to prevent or delay its onset may encourage action. Physicians’ prediabetes counseling efforts should be informed by the finding that most patients consider both intensive lifestyle intervention and metformin acceptable treatment options.
A Comparison of the Use of Clinical-Guideline–Recommended Antihypertensive Regimens in Mexican American, Non-Hispanic Black, and Non-Hispanic White Adults With Type 2 Diabetes and Hypertension in the United States
Authors: Perez Alexandra , Levin Andrea , Alam Nowrin 
Published: September 2016

Purpose The purpose of this study was to determine the use of clinical-guideline–recommended antihypertensive regimens among Mexican Americans (MAs) and non-Hispanic blacks and whites with type 2 diabetes and hypertension. Methods A secondary data analysis based on National Health and Nutrition Examination Survey 2003-2012 cohort data included 1857 noninstitutionalized civilian MA, black, and white adults with type 2 diabetes and hypertension. Unadjusted and adjusted 2-way analysis of variance models evaluated whether there was a difference in the use of recommended antihypertensive regimens across race/ethnic group. Results There was no difference in the use of recommended regimens across race/ethnic group (MAs, 79.1%; blacks, 81.7%; whites, 82.3%). Similarly, there was no difference between blood pressure goal levels and the use of recommended therapies across race/ethnicity ( P = .632). Mexican Americans were least likely and blacks most likely to be on 3 or more antihypertensive drug classes (16.8% vs 28%). Furthermore, MAs were least likely to be on recommended add-on therapies such as calcium channel blockers and diuretics. Conclusion Racial/ethnic medication use disparities were observed when looking at the number of antihypertensive drug classes per patient regimen, and add-on therapy use was evaluated. Along with lifestyle modifications, frequent antihypertensive regimen reassessment is necessary.