bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship link between landward vergence in accretionary prisms and tsunami generation
Authors: Cubas Nadaya , Souloumiac Pauline , Singh Satish C. 
Published: August 2016

Abstract
The very large slip up to the subduction front of the 2011 Tohoku-Oki (Japan) earthquake has challenged our classic view of the megathrust undergoing only aseismic slip at shallow depth. Furthermore, the enhancement of tsunamis during frontal rupturing has increased concern about tsunami risks. Recent seismic reflection images from the Sumatra subduction zone show frontal landward-vergent thrusts in the accretionary prism in the area of supposed shallow ruptures and enhanced tsunamis. Using mechanical analysis, we here show that sudden and successive decreases of the effective friction along the megathrust are required to form landward-vergent frontal thrusts. These decreases are most likely caused by dynamic weakening mechanisms, such as thermal pressurization of the pore fluids related to the propagation of earthquakes to the seafloor. Therefore, landward vergence in accretionary prisms is indicative of past seafloor frontal ruptures and consequent tsunamis. The presence of landward-verging structures in the Cascadia and Sumatra accretionary prisms might indicate future frontal rupture of the shallowest portion of the megathrust, resulting in large tsunamis.
Uptake of childhood influenza vaccine from 2012–2013 to 2014–2015 in the UK and the implications for high-risk children: a retrospective observational cohort study
Authors: Rajaram Sankarasubramanian , Steffey Amy , Blak Betina , Hickman Matthew , Christensen Hannah , Caspard Herve 
Published: August 2016

ObjectivesTo evaluate changes in influenza vaccination rates in healthy and at-risk children following the implementation of the UK's childhood influenza immunisation programme.DesignObservational cohort study before and after initiation of the UK's childhood influenza immunisation programme over three influenza seasons (2012–2013, 2013–2014 and 2014–2015) using data from the Clinical Practice Research Datalink (CPRD).SettingMore than 500 primary care practices in the UK.PopulationAll individuals aged 2–17 years on 1 September, with at least 12 months of medical history documented in CPRD were retained in the analysis.InterventionStarting in 2013–2014, all children aged 2 and 3 years were offered influenza vaccination through general practice, and primary school-aged children were offered influenza vaccination in selected counties in England (described as pilot regions). The vaccination programme was extended to all children aged 4 years in England in 2014–2015.Main outcome measureCumulative vaccination rate from 1 September to 28 February of the next calendar year as assessed by a time-to-event statistical model (vaccination uptake). Age group, sex, region and type of high-risk medical condition were assessed as predictors.ResultsVaccination uptake increased considerably from 2012–2013 to 2013–2014 in targeted children aged 2–3 years, both in children with a high-risk medical condition (from 40.7% to 61.1%) and those without (from 1.0% to 43.0%). Vaccination rates increased also, though less markedly, in older children. In 2014–2015, vaccination rates remained higher than 40% in healthy children aged 2–3 years, although they decreased slightly from 2013–2014 (from 43.0% to 41.8%). Vaccination rates in older healthy children continued to increase, driven primarily by an increase in children aged 4 years to 31.3% in 2014–2015.ConclusionsThe introduction of a universal childhood vaccination policy in the UK increased vaccination rates for targeted children, including those with high-risk conditions.
Direct access to potential research participants for a cohort study using a confidentiality waiver included in UK National Health Service legal statutes
Authors: Taylor Rachel M , Fern Lorna A , Aslam Natasha , Whelan Jeremy S 
Published: August 2016

ObjectivesTo describe our experience of using a confidentiality waiver (Section 251) in the National Health Service (NHS) Act to identify and recruit potential research participants to a cohort study and consider its use in a wider research context.DesignMethodological discussion.SettingNHS Trusts in England.MethodsWe established a research recruitment process with quality health (QH), administrators of the National Cancer Patient Experience Survey, after an amendment to a Section 251 approval (reference number ECC-8-05d-2011). NHS Trusts agreeing to implement the process were requested to send the details of 16–24-year-olds, identified by a relevant ICD-10 code indicating a cancer diagnosis within a specified time period to QH. QH sent study information and a consent-to-be-contacted form which allowed QH to send details to BRIGHTLIGHT, for BRIGHTLIGHT to contact the treating team confirming eligibility and for an interviewer from Ipsos MORI to contact them. Written consent was to be obtained at interview.ResultsThe method was implemented in 98 trusts; 75 supplied patient details. QH sent information to 441 young people, of whom 64 (15%) responded. Of these, 23 had already consented to participate. Adverse events were reported by 6 (1%) invitees: 4 were distressed because they did not have cancer, their details being submitted to QH due to incorrect hospital coding, and 1 young person was distressed about their diagnosis and requested no further contact and 1 young person found out they had cancer from the invitation.ConclusionsApplication of Section 251 of the NHS Act (2006) to directly approach participants can facilitate recruitment to research projects where routinely collected NHS data are available to select eligible patients. The benefits of this method are that it requires fewer resources to recruit across multiple sites, and is quicker. Further information on the impact on bias and adverse event profile are required.
Echo-Doppler determinants of outcomes in patients with unoperated significant mitral regurgitation in current era
Authors: Rafique Asim M , Zarrini Parham , Singh Nirmal , Beigel Roy , Tadwalkar Rigved , Chonde Meshe , Slipczuk Leandro , Cercek Bojan , Kar Saibal , Siegel Robert J 
Published: August 2016

ObjectiveOne-half of patients with severe symptomatic mitral regurgitation (MR) do not undergo surgery due to comorbidities. We evaluated prognosticators of outcomes in patients with unoperated significant MR.MethodsIn this observational study, we retrospectively evaluated medical records of 75 consecutive patients with unoperated significant MR.ResultsAll-cause mortality was 39% at 5 years. Non-survivors (n=29) versus survivors (n=46) were: older (77±9.8 vs 68±14, p=0.006), had higher New York Heart Association (NYHA) class (2.7±0.8 vs 2.3±0.8, p=0.037), higher brain natriuretic peptide (1157±717 vs 427±502 pg/mL, p=0.024, n=18), more coronary artery disease (61% vs 35%, p=0.031), more frequent left ventricular ejection fraction <50% (20.7% vs 4.3%, p=0.026), more functional MR (41% vs 22%, p=0.069), higher mitral E/E′(12.7±4.6 vs 9.8±4, p=0.008), higher pulmonary artery systolic pressure (PASP; 52.6±18.7 vs 36.7±14, p <0.001), more ≥3+ tricuspid regurgitation (28% vs 4%, p=0.005) and more right ventricular dysfunction (26% vs 6%, p=0.035). Significant predictors of 5-year mortality were PASP (p=0.001) and E/E′(p=0.011) using multivariate regression analysis.ConclusionsPatients with unoperated significant MR have high mortality. Elevated PASP and mitral E/E′were the most significant predictors of 5-year survival in patients with unoperated significant MR. Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines provide a limited incorporation of echo-Doppler parameters in the preoperative risk stratification of patients with severe MR.
RANK Signaling Blockade Reduces Breast Cancer Recurrence by Inducing Tumor Cell Differentiation
Authors: Yoldi Guillermo , Pellegrini Pasquale , Trinidad Eva M. , Cordero Alex , Gomez-Miragaya Jorge , Serra-Musach Jordi , Dougall William C. , Muñoz Purificación , Pujana Miguel-Angel , Planelles Lourdes , González-Suárez Eva 
Published: August 2016

Abstract
RANK expression is associated with poor prognosis in breast cancer even though its therapeutic potential remains unknown. RANKL and its receptor RANK are downstream effectors of the progesterone signaling pathway. However, RANK expression is enriched in hormone receptor negative adenocarcinomas, suggesting additional roles for RANK signaling beyond its hormone-dependent function. Here, to explore the role of RANK signaling once tumors have developed, we use the mouse mammary tumor virus-Polyoma Middle T (MMTV-PyMT), which mimics RANK and RANKL expression patterns seen in human breast adenocarcinomas. Complementary genetic and pharmacologic approaches demonstrate that therapeutic inhibition of RANK signaling drastically reduces the cancer stem cell pool, decreases tumor and metastasis initiation, and enhances sensitivity to chemotherapy. Mechanistically, genome-wide expression analyses show that anti-RANKL therapy promotes lactogenic differentiation of tumor cells. Moreover, RANK signaling in tumor cells negatively regulates the expression of Ap2 transcription factors, and enhances the Wnt agonist Rspo1 and the Sca1-population, enriched in tumor-initiating cells. In addition, we found that expression of TFAP2B and the RANK inhibitor, OPG, in human breast cancer correlate and are associated with relapse-free tumors. These results support the use of RANKL inhibitors to reduce recurrence and metastasis in breast cancer patients based on its ability to induce tumor cell differentiation. Cancer Res; 76(19); 5857–69. ©2016 AACR.
Checkpoint Immunotherapy: Picking a Winner
Authors: Teng Michele W.L. , Khanna Rajiv , Smyth Mark J. 
Published: August 2016

Abstract
Summary: Robust biomarkers of response that predict which patients will or will not respond to immune checkpoint blockade need to be identified. New data suggest that the presence of an adaptive immune signature in the tumor biopsies of patients with melanoma early on therapy compared to pretreatment can identify responders from nonresponders. Cancer Discov; 6(8); 818–20. ©2016 AACR.
See related article by Chen et al., p. 827.
WRF Forecasts of Great Plains Nocturnal Low-Level Jet-Driven MCSs. Part II: Differences between Strongly and Weakly Forced Low-Level Jet Environments
Authors: Squitieri Brian J. , Gallus William A. 
Published: August 2016

Abstract
The classic Great Plains southerly low-level jet (LLJ) is a primary factor in sustaining nocturnal convection. This study compares convection-allowing WRF forecasts of LLJ events associated with MCSs in strongly and weakly forced synoptic environments. The depth of the LLJs and magnitude, altitude, and times of the LLJ peak wind were evaluated in observations and WRF forecasts for 31 cases as well as for case subsets of strongly and weakly forced synoptic regimes. LLJs in strongly forced regimes were stronger, deeper, and peaked at higher altitudes and at earlier times compared to weakly forced cases. Mean error MCS-centered composites of WRF forecasts versus RUC analyses were derived at MCS initiation time for the LLJ atmospheric water vapor mixing ratio, LLJ total wind magnitude, convergence, most unstable convective available potential energy (MUCAPE), and most unstable convective inhibition (MUCIN). In most configurations, simulated MCSs in strongly and weakly forced regimes initiated to the north and east of observations, generally in a region where LLJ moisture, MUCAPE, and MUCIN fields were forecast well, with larger errors outside this region. However, WSM6 simulations for strongly forced cases showed a southward displacement in MCS initiation, where a combination of ambient environmental factors and microphysics impacts may simultaneously play a role in the location of forecast MCS initiation. Strongly forced observed and simulated MCSs initiated west of the LLJ axis and moved eastward into the LLJ, while observed and simulated MCSs in weakly forced environments traversed the termini of the LLJ. A northward bias existed for simulated MCS initiation and LLJ termini for weakly forced regimes.
Garcinol exhibits anti-proliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells
Authors: Ranjbarnejad T , Saidijam M , tafakh M sadat , Pourjafar M , Talebzadeh F , Najafi R 
Published: August 2016

Background: Colorectal cancer is the fourth leading cause of death. Various natural compounds are known to have antitumor properties. Garcinol, a polyisoprenylated benzophenone, has antioxidant and anti-inflammatory properties. In the current study, we investigated the anticancer activity of garcinol on human colorectal adenocarcinoma cell line (HT-29) human colon cancer cells. Methods: HT-29 cells were treated with various concentrations of garcinol for 24 h. The effect of garcinol on HT-29 cells proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; the mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were examined by quantitative real-time polymerase chain reaction; apoptosis was detected by proportion of sub-G1 cell; caspase 3 activity and prostaglandin E2 (PGE2) level were determined by enzyme-linked immunosorbent assay and HT-29 cells migration was assessed using scratch test. Results: Garcinol preconditioning markedly decreased the expression of mPGES-1, HIF-1α, VEGF, CXCR4, MMP-2, and MMP-9. The proportion of cells in sub-G1 phase and caspase 3 activity were increased by garcinol treatment whereas the cell proliferation, PGE2 level, and cell migration were decreased in these cells, compared to the control group. Conclusion: Our findings suggest that garcinol plays a critical role in elevating apoptosis and inhibiting HT-29 cells proliferation, angiogenesis, and invasion by suppressing the mPGES-1/PGE2/HIF-1α signaling pathways.
Myelitis in systemic lupus erythematosus: clinical characteristics and effect in accrual damage. A single-center experience
Authors: Quintanilla-González L , Atisha-Fregoso Y , Llorente L , Fragoso-Loyo H 
Published: August 2016

Objective The purpose of this study was to describe the clinical characteristics of acute transverse myelitis, including the time of their presentation, and to evaluate their effect on accrual damage in patients with systemic lupus erythematosus (SLE). Methods Patients with SLE who were hospitalized because of incident, noninfectious myelitis at our institute between January 1997 and December 2013 were identified. As a control group, we selected for each of the patients in the study group one SLE patient hospitalized at the closest date to the case due to other severe non-neuropsychiatric (NP) SLE manifestation, with no history of NP manifestations or noninfectious disease. Clinical characteristics, laboratory results, treatment, disease activity (SLEDAI-2K), and damage (SLICC/ACR-DI) were collected from medical charts at the index hospitalization and one year after hospitalization. Results Demographics and SLE characteristics, including age at SLE diagnosis and time since SLE diagnosis to hospitalization, were comparable in patients with myelitis and controls. At hospitalization, disease activity and cumulative damage were similar in both groups. Patients with myelitis received more aggressive treatment than controls. One year after hospitalization, two of the 15 patients who completed follow-up had symptom improvement without neurologic sequelae, and 13 of them had some improvement of symptoms with neurologic sequelae. Four patients died in the myelitis group, three of them of infectious diseases, and one of alveolar hemorrhage. No patient died because of myelopathy and in the control group no patient died, although three were lost during the follow-up. Disease activity and treatment did not differ between both groups. However, cumulative damage was higher among the patients with myelitis than controls (1.9 ± 0.9 vs 0.75 ± 0.9; p = 0.003). Conclusion Patients with myelitis have clinical characteristics similar to those observed in non-NP SLE and receive more aggressive treatment. Furthermore, myelitis is associated with a significant increase in accrual damage compared with severe non-NP manifestations.
Urban Health System and Climate Resilience—Surat Case Study
Authors: Desai Vikas K. , Rathi Suresh K. , Desai Hemant 
Published: August 2016

The demographic transition with rapid urbanisation corresponds with the challenges of urban infrastructure development. Urban health is an outcome of complex interaction of many urban factors including governance and finance. Coupled with this, climate change has overarching influence on these factors and a challenge to development, health and survival. Therefore, understanding impact of climate change with reference to urban health and development should be on high priority. Changes in climatic patterns may alter the distribution of vector species and increase its spread in new areas. An increase in temperature and relative humidity may enlarge the transmission window. Effluent emissions to water bodies and salination of rivers through sea level rise may increase the incidence of water borne diseases. Deaths due to heat wave are reported from several parts of the country. Every city is different and success of city specific urban health programme depends on city specific planning as well as public health preparedness for climate change. Hence, study of Climate and Health brings out threshold levels of climate resilience. Surat city experience of Urban health revealed that good governance and Finance were considered most important factors including Urban health system, community participation, Inter-sectoral convergence, disease surveillance, health information system, Public–private partnership, participation of academic institutions and cross learning. One of the major advocacy areas UHCRC is embarking in is ‘Inclusion of Climate resilience in Health and Health in Climate Resilience Planning’.
ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis
Authors: Khoury Samia J , Rochon James , Ding Linna , Byron Margie , Ryker Kristin , Tosta Patti , Gao Wendy , Freedman Mark S , Arnold Douglas L , Sayre Peter H , Smilek Dawn E ,   On behalf of the ACCLAIM Study Group
Published: August 2016

Background: Costimulatory blockade of T lymphocytes with the CTLA4-Ig fusion protein abatacept could be an effective treatment for the immune-mediated neuroinflammatory disease relapsing-remitting multiple sclerosis (RRMS). Objective: To evaluate efficacy and safety of abatacept in RRMS. Methods: ACCLAIM (A Cooperative Clinical Study of Abatacept in Multiple Sclerosis) was a Phase II, randomized, double-blind, placebo-controlled, multi-center trial. In all, 65 of 123 planned participants with RRMS were randomized to monthly intravenous infusions of abatacept or placebo for 24 weeks in a 2:1 ratio, switched to the opposite treatment at 28 weeks, and received their final dose of study medication at 52 weeks. Enrollment was closed early due to slow accrual. The primary endpoint was the mean number of new gadolinium-enhancing (Gd+) lesions obtained on magnetic resonance imaging (MRI) scans performed every 4 weeks. Results: No statistically significant differences were observed in mean number of new Gd+ MRI lesions between the abatacept and placebo groups. No statistically significant differences were observed in other MRI and clinical parameters of RRMS disease activity. Abatacept was well tolerated. Conclusion: The ACCLAIM study did not demonstrate efficacy of abatacept in reducing the number of new Gd+ MRI lesions, or clinical measures of disease activity in RRMS.
Data quality evaluation for observational multiple sclerosis registries
Authors: Kalincik Tomas , Kuhle Jens , Pucci Eugenio , Rojas Juan Ignacio , Tsolaki Magda , Sirbu Carmen-Adella , Slee Mark , Butzkueven Helmut ,   On behalf of the MSBase Scientific Leadership Group and MSBase Study Group
Published: August 2016

Objective: Objective and reproducible evaluation of data quality is of paramount importance for studies of ‘real-world’ observational data. Here, we summarise a standardised data quality, density and generalisability process implemented by MSBase, a global multiple sclerosis (MS) cohort study. Methods: Error rate, data density score and generalisability score were developed using all 35,869 patients enrolled in MSBase as of November 2015. The data density score was calculated across six domains (follow-up, demography, visits, MS relapses, paraclinical data and therapy) and emphasised data completeness. The error rate evaluated syntactic accuracy and consistency of data. The generalisability score evaluated believability of the demographic and treatment information. Correlations among the three scores and the number of patients per centre were evaluated. Results: Errors were identified at the median rate of 3 per 100 patient-years. The generalisability score indicated the samples’ representativeness of the known MS epidemiology. Moderate correlation between the density and generalisability scores (ρ = 0.58) and a weak correlation between the error rate and the other two scores (ρ = −0.32 to −0.33) were observed. The generalisability score was strongly correlated with centre size (ρ = 0.79). Conclusion: The implemented scores enable objective evaluation of the quality of observational MS data, with an impact on the design of future analyses.
Evaluation and Management of Athletes With Long QT Syndrome
Authors: Gomez Andrew T. , Prutkin Jordan M. , Rao Ashwin L. 
Published: August 2016

Context: The congenital long QT syndrome (LQTS) is an inherited channelopathy known for its electrocardiographic manifestations of QT prolongation and its hallmark arrhythmia, torsades de pointes (TdP). TdP can lead to syncope or sudden death and is often precipitated by triggers such as physical exertion or emotional stress. Given that athletes may be at particular risk for adverse outcomes, those suspected of having LQTS should be evaluated, risk stratified, treated, and receive appropriate counseling by providers with sufficient expertise according to the latest guidelines. Evidence Acquisition: The following keywords were used to query MEDLINE and PubMed through 2016: LQTS, LQT1, LQT2, LQT3, long QT, long QTc, prolonged QT, prolonged QTc, QT interval, QTc interval, channelopathy, channelopathies, athletes, torsades de pointes, and sudden cardiac death. Selected articles within this primary search, in addition to relevant references from those articles, were reviewed for relevant information and data. Articles with pertinent information regarding pathophysiology, evaluation, diagnosis, genetic testing, treatment, and guidelines for athletes were included, particularly those published in the prior 2 decades. Study Design: Clinical review. Level of Evidence: Level 3. Results: Diagnosis of LQTS involves eliciting the patient’s family history, clinical history, and evaluation of electrocardiographic findings. Genetic testing for common mutations can confirm suspected cases. β-Blockers represent the mainstay of treatment, though interventions such as implantable cardioverter-defibrillator placement or left cardiac sympathetic denervation may be required. Properly evaluated and treated athletes with LQTS have a low risk of cardiac events. Conclusion: Detection and management of LQTS in the athletic population is crucial given the possibility of adverse outcomes with the stress of athletic participation. Preparticipation screening examinations should include a thorough clinical and family history. Screening electrocardiograms may display key findings consistent with LQTS while genetic testing can confirm the diagnosis. Formerly considered a strict contraindication to athletic participation, LQTS is now an increasingly manageable entity with proper evaluation and treatment by qualified and experienced providers.