bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic determinants of risk of harmful alcohol drinking among people aged 50 or over in England
Authors: Iparraguirre José 
Published: July 2015

ObjectivesThis paper looks into the socioeconomic determinants of risk of harmful alcohol drinking and of the transitions between risk categories over time among the population aged 50 or over in England.SettingCommunity-dwellers across England.ParticipantsRespondents to the English Longitudinal Survey of Ageing, waves 4 and 5.Results(Confidence level at 95% or higher, except when stated):▸ Higher risk drinking falls with age and there is a non-linear association between age and risk for men, peaking in their mid-60s.▸ Retirement and income are positively associated with a higher risk for women but not for men.▸ Education and smoking are positively associated for both sexes.▸ Loneliness and depression are not associated.▸ Caring responsibilities reduce risk among women.▸ Single, separated or divorced men show a greater risk of harmful drinking (at 10% confidence level).▸ For women, being younger and having a higher income at baseline increase the probability of becoming a higher risk alcohol drinker over time.▸ For men, not eating healthily, being younger and having a higher income increase the probability of becoming a higher risk alcohol drinker. Furthermore, the presence of children living in the household, being lonely, being older and having a lower income are associated with ceasing to be a higher risk alcohol drinker over time.ConclusionsSeveral socioeconomic factors found to be associated with high-risk alcohol consumption behaviour among older people would align with those promoted by the ‘successful ageing’ policy framework.
‘Including health in systems responsible for urban planning’: a realist policy analysis research programme
Authors: Harris Patrick , Friel Sharon , Wilson Andrew 
Published: July 2015

IntroductionRealist methods are increasingly being used to investigate complex public health problems. Despite the extensive evidence base clarifying the built environment as a determinant of health, there is limited knowledge about how and why land-use planning systems take on health concerns. Further, the body of research related to the wider determinants of health suffers from not using political science knowledge to understand how to influence health policy development and systems. This 4-year funded programme of research investigates how the land-use planning system in New South Wales, Australia, incorporates health and health equity at multiple levels.Methods and analysisThe programme uses multiple qualitative methods to develop up to 15 case studies of different activities of the New South Wales land-use planning system. Comparison cases from other jurisdictions will be included where possible and useful.Data collectionincludes publicly available documentation and purposively sampled stakeholder interviews and focus groups of up to 100 participants across the cases. The units of analysis in each case are institutional structures (rules and mandates constraining and enabling actors), actors (the stakeholders, organisations and networks involved, including health-focused agencies), and ideas (policy content, information, and framing).Data analysiswill focus on and develop propositions concerning the mechanisms and conditions within and across each case leading to inclusion or non-inclusion of health. Data will be refined using additional political science and sociological theory. Qualitative comparative analysis will compare cases to develop policy-relevant propositions about the necessary and sufficient conditions needed to include health issues.Ethics and disseminationEthics has been approved by Sydney University Human Research Ethics Committee (2014/802 and 2015/178). Given the nature of this research we will incorporate stakeholders, often as collaborators, throughout. We outline our research translation strategies following best practice approaches.
ErbB3–ErbB2 Complexes as a Therapeutic Target in a Subset of Wild-type BRAF/NRAS Cutaneous Melanomas
Authors: Capparelli Claudia , Rosenbaum Sheera , Berman-Booty Lisa D. , Salhi Amel , Gaborit Nadège , Zhan Tingting , Chervoneva Inna , Roszik Jason , Woodman Scott E. , Davies Michael A. , Setiady Yulius Y. , Osman Iman , Yarden Yosef , Aplin Andrew E. 
Published: July 2015

Abstract
The treatment options remain limited for patients with melanoma who are wild-type for both BRAF and NRAS (WT/WT). We demonstrate that a subgroup of WT/WT melanomas display high basal phosphorylation of ErbB3 that is associated with autocrine production of the ErbB3 ligand neuregulin-1 (NRG1). In WT/WT melanoma cells displaying high levels of phospho-ErbB3, knockdown of NRG1 reduced cell viability and was associated with decreased phosphorylation of ErbB3, its coreceptor ErbB2, and its downstream target, AKT. Similar effects were observed by targeting ErbB3 with either siRNAs or the neutralizing ErbB3 monoclonal antibodies huHER3-8 and NG33. In addition, pertuzumab-mediated inhibition of ErbB2 heterodimerization decreased AKT phosphorylation, cell growth in vitro, and xenograft growth in vivo. Pertuzumab also potentiated the effects of MEK inhibitor on WT/WT melanoma growth in vitro and in vivo. These findings demonstrate that targeting ErbB3–ErbB2 signaling in a cohort of WT/WT melanomas leads to tumor growth reduction. Together, these studies support the rationale to target the NRG1–ErbB3–ErbB2 axis as a novel treatment strategy in a subset of cutaneous melanomas. Cancer Res; 75(17); 3554–67. ©2015 AACR.
Tumor-Promoting Effects of Myeloid-Derived Suppressor Cells Are Potentiated by Hypoxia-Induced Expression of miR-210
Authors: Noman Muhammad Zaeem , Janji Bassam , Hu Shijun , Wu Joseph C. , Martelli Fabio , Bronte Vincenzo , Chouaib Salem 
Published: July 2015

AbstractMyeloid-derived suppressor cells (MDSC) contribute significantly to the malignant characters conferred by hypoxic tumor microenvironments. However, selective biomarkers of MDSC function in this critical setting have not been defined. Here, we report that miR-210 expression is elevated by hypoxia-inducible factor-1α (HIF1α) in MDSC localized to tumors, compared with splenic MDSC from tumor-bearing mice. In tumor MDSC, we determined that HIF1α was bound directly to a transcriptionally active hypoxia-response element in the miR-210 proximal promoter. miR-210 overexpression was sufficient to enhance MDSC-mediated T-cell suppression under normoxic conditions, while targeting hypoxia-induced miR-210 was sufficient to decrease MDSC function against T cells. Mechanistic investigations revealed that miR-210 modulated MDSC function by increasing arginase activity and nitric oxide production, without affecting reactive oxygen species, IL6, or IL10 production or expression of PD-L1. In splenic MDSC, miR-210 regulated Arg1, Cxcl12, and IL16 at the levels of both mRNA and protein, the reversal of which under normoxic conditions decreased T-cell–suppressive effects and IFNγ production. Interestingly, miR-210 overexpression or targeting IL16 or CXCL12 enhanced the immunosuppressive activity of MDSC in vivo, resulting in increased tumor growth. Taken together, these results provide a preclinical rationale to explore miR-210 inhibitory oligonucleotides as adjuvants to boost immunotherapeutic responses in cancer patients. Cancer Res; 75(18); 3771–87. ©2015 AACR.
LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival
Authors: Torres Sofía , Garcia-Palmero Irene , Herrera Mercedes , Bartolomé Rubén A. , Peña Cristina , Fernandez-Aceñero M. Jesús , Padilla Guillermo , Peláez-García Alberto , Lopez-Lucendo María , Rodriguez-Merlo Rufo , de Herreros Antonio García , Bonilla Félix , Casal J. Ignacio 
Published: July 2015

Abstract
Purpose: Cancer-associated fibroblasts (CAF) are major mediators in tumor microenvironment. We investigated the changes in protein expression in colon cancer–associated fibroblasts compared with normal fibroblasts (NF) in the context of searching for prognostic biomarkers, particularly for stage II patients.
Experimental Design: CAFs and NFs isolated from colon cancer patients were used to identify differentially expressed proteins using quantitative proteomics. Stromal expression of deregulated proteins was analyzed by IHC. Prognostic impact was studied using external gene-expression datasets for training, then quantitative PCR and IHC for validation in different cohorts of patients. Combined datasets were used for prediction of risk assessment at stages II and III.
Results: A desmoplastic signature composed of 32 proteins, highly specific for stromal components in colon cancer, was identified. These proteins were enriched for extracellular matrix organization components, TGFβ signaling pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11 upregulated proteins and four downregulated proteins, selected for biomarker validation, was verified by orthogonal techniques. LOXL2 displayed a high prognostic impact by using external independent datasets and further validation in two different cohorts of patients. High expression of LOXL2 was associated with higher recurrence P = 0.001 HR, 5.38 [95% confidence interval (CI), 1.70–17.01] and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90–38.29). IHC analysis revealed a prognostic value for LOXL2 in stage II patients.
Conclusions: We identified LOXL2 to be associated with the outcome of colon cancer patients. Furthermore, it can be used to stratify patients at stages II and III for further therapeutic decisions. Clin Cancer Res; 21(21); 4892–902. ©2015 AACR.
Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations
Authors: Larrue Clément , Saland Estelle , Vergez François , Serhan Nizar , Delabesse Eric , Mansat-De Mas Véronique , Hospital Marie-Anne , Tamburini Jérôme , Manenti Stéphane , Sarry Jean Emmanuel , Récher Christian 
Published: July 2015

Abstract
We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in acute myeloid leukemia (AML). We used human leukemic cell lines cells, both in vitro and in vivo, as well as leukemic samples from AML patients to demonstrate the role of 2-DG in tumor cell growth inhibition. 2-DG, through N-linked glycosylation inhibition, affected the cell-surface expression and cellular signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death. Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1 c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with nonmutated cells. 2-DG activity was also demonstrated in leukemic cells harboring FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib. Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT–mutated cell lines and cell samples from core binding factor–AML patients. In these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3 and MAPK–ERK pathways, and strongly downregulated the expression of the receptor resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1 cells. Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl-2 and Bcl-w, ABT-737, and cytarabine. In conclusion, 2-DG displays a significant antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new therapeutic window in a subset of AML with mutated RTKs. Mol Cancer Ther; 14(10); 2364–73. ©2015 AACR.
Individual and Combined Risk Factors for Incident Atrial Fibrillation and Incident Stroke: An Analysis of 3 Million At‐Risk US Patients
Authors: Chyou Janice Y. , Hunter Tina D. , Mollenkopf Sarah A. , Turakhia Mintu P. , Reynolds Matthew R. 
Published: July 2015

Background

The incremental effects of risk factor combinations for atrial fibrillation (
AF
) and stroke are incompletely understood. We sought to quantify the risks of incident
AF
and stroke for combinations of established risk factors in a large
US
sample.

Methods and Results

Patients with no evidence of
AF
or stroke in 2007 were stratified by combinations of the following risk factors: heart failure, hypertension, diabetes, age 65 to 74, age ≥75, coronary artery disease, and chronic kidney disease. Patients with ≥2 of the first 5 or ≥3 of the first 7, classified as “high‐risk,” and an age‐matched sample of patients with fewer risk factors, classified as “low‐risk,” were followed over 2008–2010 for incident
AF
and stroke. Annualized incidence rates and risks were quantified for each combination of factors by using Cox regression. Annualized incidence rates for
AF
, stroke, and both were 3.59%, 3.27%, and 0.62% in 1 851 653 high‐risk patients and 1.32%, 1.48%, and 0.18% in 1 156 221 low‐risk patients, respectively. Among patients with 1 risk factor, those with age ≥75 had the highest hazards of incident
AF
and stroke (HR 9.2, 6.9). Among patients with 2 risk factors, those with age ≥75 and heart failure had the highest annualized incidence rates of
AF
and stroke (10.2%, 5.9%). The combination of age ≥75 and hypertension was prevalent and had the highest incidences of
AF
and stroke.

Conclusions

Adults with combinations of known risk factors are at increased risk of incident
AF
and stroke, but combinations of risk factors are not always additive.
Very Low Ventricular Pacing Rates Can Be Achieved Safely in a Heterogeneous Pacemaker Population and Provide Clinical Benefits: The CANadian Multi‐Centre Randomised Study‐Spontaneous AtrioVEntricular Conduction pReservation (CAN‐SAVE R) Trial
Authors: Thibault Bernard , Ducharme Anique , Baranchuk Adrian , Dubuc Marc , Dyrda Katia , Guerra Peter G. , Macle Laurent , Mondésert Blandine , Rivard Léna , Roy Denis , Talajic Mario , Andrade Jason , Nitzsché Rémi , Khairy Paul ,   the CAN‐SAVE R Study Investigators
Published: July 2015

Background

It is well recognized that right ventricular apical pacing can have deleterious effects on ventricular function. We performed a head‐to‐head comparison of the SafeR pacing algorithm versus
DDD
pacing with a long atrioventricular delay in a heterogeneous population of patients with dual‐chamber pacemakers.

Methods and Results

In a multicenter prospective double‐blinded randomized trial conducted at 10 centers in Canada, 373 patients, age 71±11 years, with indications for dual chamber
DC
pacemakers were randomized 1:1 to SafeR or
DDD
pacing with a long atrioventricular delay (250 ms). The primary objective was twofold: (1) reduction in the proportion of ventricular paced beats at 1 year; and (2) impact on atrial fibrillation burden at 3 years, defined as the ratio between cumulative duration of mode‐switches divided by follow‐up time. Statistical significance of both co‐primary end points was required for the trial to be considered positive. At 1 year of follow‐up, the median proportion of ventricular‐paced beats was 4.0% with
DDD
versus 0% with SafeR (
P
<0.001). At 3 years of follow‐up, the atrial fibrillation burden was not significantly reduced with SafeR versus
DDD
(median 0.00%, interquartile range [0.00% to 0.23%] versus median 0.01%, interquartile range [0.00% to 0.44%], respectively,
P
=0.178]), despite a persistent reduction in the median proportion of ventricular‐paced beats (10% with
DDD
compared to 0% with SafeR).

Conclusions
A ventricular‐paced rate <1% was safely achieved with SafeR in a population with a wide spectrum of indications for dual‐chamber pacing. However, the lower percentage of ventricular pacing did not translate into a significant reduction in atrial fibrillation burden.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov/
Unique identifier:
NCT
01219621.
Fourth eu aml Directive: What is Missing? Section 319 patriot Act and the New eu aml Directive
Authors: Canestri Daniele 
Published: July 2015

eu Member States are updating their anti-money laundering (aml) regimes by implementing a fourth anti money laundering directive (4th amld). However, an assessment of various aml enforcement regimes reveals that not European, but usa regulations are the most effective. The usa’s aml legislation grants the usa authorities extraterritorial power, which allows them to impose usa requirements on any foreign financial institution that has a correspondent relationship with a usa bank. This long-arm approach is mainly based on Section 319 of the patriot Act. Despite the clear success of Section 319, eu legislators have avoided introducing a similar norm into the latest eu directive. The author analyses why the usa’ effective extraterritorial practice has not been introduced into the 4th amld. Arguing for the adoption of extraterritorial aml practice by the eu, the author then goes on to outline which reforms the eu should introduce if it wishes to follow the path already taken by the usa.
A Three-Dimensional Multivariate Modal Analysis of Atmospheric Predictability with Application to the ECMWF Ensemble
Authors: Žagar Nedjeljka , Buizza Roberto , Tribbia Joseph 
Published: July 2015

Abstract
A new methodology for the analysis of ensemble prediction systems (ENSs) is presented and applied to 1 month (December 2014) of ECMWF operational ensemble forecasts. The method relies on the decomposition of the global three-dimensional wind and geopotential fields onto the normal-mode functions. The ensemble properties are quantified in terms of the 50-member ensemble spread associated with the balanced and inertio-gravity (IG) modes for forecast ranges every 12 h up to 7 days. Ensemble reliability is defined for the balanced and IG modes comparing the ensemble spread with the control analysis in each scale.
Modal analysis shows that initial uncertainties in the ECMWF ENS are largest in the tropical large-scale modes and their spatial distribution is similar to the distribution of the short-range forecast errors. Initially the ensemble spread grows most in the smallest scales and in the synoptic range of the IG modes but the overall growth is dominated by the increase of spread in balanced modes in synoptic and planetary scales in the midlatitudes. During the forecasts, the distribution of spread in the balanced and IG modes grows toward the climatological spread distribution characteristic of the analyses. In the 2-day forecast range, the global IG spread reaches 60% of its asymptotic value while the same percentage of the global balanced spread is reached after 5 days of forecasts. An underdispersiveness of the system is suggested to be associated with the lack of tropical variability, primarily the Kelvin waves.
The Dynamical Influence of Separate Teleconnections from the Pacific and Indian Oceans on the Northern Annular Mode
Authors: Fletcher Christopher G. , Cassou Christophe 
Published: July 2015

Abstract
The northern annular mode (NAM) influences wintertime climate variability in the Northern Hemisphere, and understanding the processes controlling its sign and amplitude is of critical importance. Mounting evidence supports a robust teleconnection between the El Niño–Southern Oscillation (ENSO) and the NAM, while internal variability generated in the tropical Indian Ocean (TIO) may be associated with a NAM response of the opposite sign. This study uses a coupled ocean–atmosphere model to separate the influence on the NAM from teleconnections driven by ENSO and the TIO. In composites constructed using a long preindustrial control integration, increased December–February precipitation in the central/eastern Pacific drives a negative late-winter NAM response. When isolated from ENSO variability, increased precipitation over the western-central TIO drives a strong and persistent positive NAM response throughout the winter. Opposite linear interference of the anomalous wave teleconnections explains most of the opposite-signed planetary wavedriving of the NAM responses. The case with combined ENSO and TIO variability yields cancellation of the wave interference and a weak NAM response. This mechanism is confirmed using experiments where the tropical ocean is nudged separately over the Pacific and TIO to the large-amplitude 1997/98–1998/99 ENSO cycle. The phases of the Rossby wave and NAM responses in these two cases are of opposite sign, providing strong evidence that internal variability over the TIO can induce teleconnections independent of—and with opposite sign to—those associated with ENSO.
Development of a Four-Dimensional Variational Assimilation System for Coastal Data Assimilation around Japan
Authors: Usui Norihisa , Fujii Yosuke , Sakamoto Kei , Kamachi Masafumi 
Published: July 2015

Abstract
The authors have developed an assimilation system toward coastal data assimilation around Japan, which consists of a four-dimensional variational (4DVAR) assimilation scheme with an eddy-resolving model in the western North Pacific (MOVE-4DVAR-WNP) and a fine-resolution coastal model covering the western part of the Japanese coastal region around the Seto Inland Sea (MOVE-Seto). The 4DVAR scheme is developed as a natural extension of the 3DVAR scheme used in the Meteorological Research Institute Multivariate Ocean Variational Estimation (MOVE) system. An initialization scheme of incremental analysis update (IAU) is incorporated into MOVE-4DVAR-WNP to filter out high-frequency noises. During the backward integration of the adjoint model, it works as an incremental digital filtering. MOVE-Seto, which is nested within MOVE-4DVAR-WNP, also employs IAU to initialize the interior of the coastal model using MOVE-4DVAR-WNP analysis fields. The authors conducted an assimilation experiment using MOVE-4DVAR-WNP, and results were compared with an additional experiment using the 3DVAR scheme. The comparison reveals that MOVE-4DVAR-WNP improves mesoscale variability. In particular, short-term variability such as small-scale Kuroshio fluctuations is much enhanced. Using MOVE-Seto and MOVE-4DVAR-WNP, the authors also performed a case study focused on an unusual tide event that occurred at the south coast of Japan in September 2011. MOVE-Seto succeeds in reproducing a significant sea level rise associated with this event, indicating the effectiveness of the newly developed system for coastal sea level variability.
Cough-induced rib fractures
Authors: Sano Atsushi , Tashiro Ken , Fukuda Tsutomu 
Published: July 2015

Background Occasionally, patients who complain of chest pain after the onset of coughing are diagnosed with rib fractures. We investigated the characteristics of cough-induced rib fractures. Methods Between April 2008 and December 2013, 17 patients were referred to our hospital with chest pain after the onset of coughing. Rib radiography was performed, focusing on the location of the chest pain. When the patient had other signs and symptoms such as fever or persistent cough, computed tomography of the chest was carried out. We analyzed the data retrospectively. Results Rib fractures were found in 14 of the 17 patients. The age of the patients ranged from 14 to 86 years (median 39.5 years). Ten patients were female and 4 were male. Three patients had chronic lung disease. There was a single rib fracture in 9 patients, and 5 had two or more fractures. The middle and lower ribs were the most commonly involved; the 10th rib was fractured most frequently. Conclusions Cough-induced rib fractures occur in every age group regardless of the presence or absence of underlying disease. Since rib fractures often occur in the lower and middle ribs, rib radiography is useful for diagnosis.