bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of molecular testing methods for the detection ofEGFRmutations in formalin-fixed paraffin-embedded tissue specimens of non-small cell lung cancer
Authors: Lopez-Rios Fernando , Angulo Barbara , Gomez Belen , Mair Debbie , Martinez Rebeca , Conde Esther , Shieh Felice , Tsai Julie , Vaks Jeffrey , Current Robert , Lawrence H Jeffrey , Gonzalez de Castro David 
Published: February 2013

AimTo conduct a methods correlation study of three different assays for the detection of mutations atEGFRgene in human formalin-fixed paraffin-embedded tumour (FFPET) specimens of non-small cell lung carcinomas (NSCLC).MethodsWe conducted a 2-site method comparison study of two european conformity (CE) in vitro diagnostic (IVD)-marked assays, the cobas EGFR Mutation Test and the Therascreen EGFR29 Mutation Kit, and 2× bidirectional Sanger sequencing. We blind-tested 124 NSCLC FFPET specimens with all three methods; the cobas test was performed at both sites. Positive (PPA) and negative percent agreements (NPA) were determined for the cobas test versus each of the other two methods. Specimens yielding discordant test results between methods were further tested using quantitative massively parallel pyrosequencing (MPP).ResultsPPA between cobas and Sanger was 98.8%; NPA was 79.3%. Overall there were seven discordant results. MPP confirmed an exon 19 deletion in two cases and L858R mutation in four cases. PPA between cobas and Therascreen was 98.9% and NPA was 100%. There was one discordant result. Reproducibility of the cobas test between the two sites was 99.2%.ConclusionsThe invalid rates for the cobas test and Therascreen were lower than Sanger sequencing. The cobas and Therascreen assays showed a high degree of concordance, and both were more sensitive for the detection of exon 19 deletion and L858R mutations than Sanger. The cobas test was highly reproducible between the two testing sites, used the least amount of DNA input and was the only test with automated results reporting.
Misclassification of the mediator matters when estimating indirect effects
Authors: Blakely Tony , McKenzie Sarah , Carter Kristie 
Published: February 2013

BackgroundConfounding of mediator–outcome associations resulting in collider biases causes systematic error when estimating direct and indirect effects. However, until recently little attention has been given to the impact of misclassification bias.ObjectiveTo quantify the impact of non-differential and independent misclassification of a dichotomous exposure and a dichotomous mediator on three target parameters: the total effect of exposure on outcome; the direct effect (by conditioning on the mediator); and the indirect effect (identified by the percentage reduction in the excess OR on adjusting for the mediator).MethodsSimulations were conducted for varying strength of associations between exposure, mediator and outcome, varying ratios of exposed to unexposed and mediator present to mediator absent, and varying sensitivity and specificity of exposure and mediator classification.ResultsORs before (total effect) and after adjustment (direct effect) for the mediator are both biased towards the null by non-differential misclassification of the exposure, but the percentage reduction in the excess OR is little affected by misclassification of exposure. Conversely, misclassification of the mediator rapidly biases the percentage reduction of the excess OR (indirect effect) downwards.ConclusionsIf the research objective is to quantify the proportion of the total association that is due to mediation (ie, indirect effect), then minimising non-differential misclassification bias of the mediator is more important than that for the exposure. Misclassification bias is an important source of error when estimating direct and indirect effects.
Atrial Fibrillation and Aortic Stenosis
Authors: Stortecky Stefan , Buellesfeld Lutz , Wenaweser Peter , Heg Dik , Pilgrim Thomas , Khattab Ahmed A. , Gloekler Steffen , Huber Christoph , Nietlispach Fabian , Meier Bernhard , Jüni Peter , Windecker Stephan 
Published: February 2013

Background—
Atrial fibrillation (AF) is an important risk factor for stroke and is common among elderly patients undergoing transcatheter aortic valve implantation. The aim of this study was to assess the impact of AF on clinical outcomes among patients undergoing transcatheter aortic valve implantation.

Methods and Results—

Between August 2007 and October 2011, a total of 389 high-risk patients undergoing transcatheter aortic valve implantation were included into a prospective registry. AF was recorded in 131 patients (33.7%) with a mean CHA
2
DS
2
–VASC score of 4.5±1.2 and was paroxysmal in 26 (25.0%), persistent in 8 (7.7%), and permanent in 70 patients (67.3%). Patients with and without AF had similar baseline characteristics except for fewer revascularization procedures (coronary artery bypass grafting: 12% versus 22%;
P
=0.03) among AF patients. At 1 year, all-cause mortality was higher among patients with AF (30.9%) compared with those without AF (13.9%; hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.43–3.90;
P
=0.0008). This was observed irrespective of the type of AF (permanent, HR, 2.47; 95% CI, 1.40–4.38; persistent, HR, 3.60; 95% CI, 1.10–11.78; paroxysmal, HR, 2.88; 95% CI, 1.37–6.05). Mortality gradually increased with higher CHA
2
DS
2
–VASC scores (score 1–3: HR, 2.20; 95% CI, 0.92–5.27; score 6–8: HR, 4.12; 95% CI, 2.07–8.20). The risks of stroke (3.9% versus 5.1%; HR, 0.76; 95% CI, 0.23–1.96;
P
=0.47) and life-threatening bleeding (19.8% versus 14.7%; HR, 1.37; 95% CI, 0.86–2.19;
P
=0.19) were similar among patients with and without AF.

Conclusions—

AF is common among high-risk patients with severe aortic stenosis undergoing transcatheter aortic valve implantation and is associated with a >2-fold increased risk of all-cause and cardiovascular mortality, irrespective of the type of AF. The gradient of risk directly correlates with the CHA
2
DS
2
–VASC score.
Patient-Identified Factors Related to Heart Failure Readmissions
Authors: Retrum Jessica H. , Boggs Jennifer , Hersh Andrew , Wright Leslie , Main Deborah S. , Magid David J. , Allen Larry A. 
Published: February 2013

Background—
Although readmission after hospitalization for heart failure has received increasing attention, little is known about its root causes. Prior investigations have relied on administrative databases, chart review, and single-question surveys.

Methods and Results—
We performed semistructured 30- to 60-minute interviews of patients (n=28) readmitted within 6 months of index heart failure admission. Established qualitative approaches were used to analyze and to interpret data. Interview findings were the primary focus of the study, but patient information and provider comments from chart data were also consulted. Patient median age was 61 years; 29% were nonwhite; 50% were married; 32% had preserved ejection fraction; and median time from discharge to readmission was 31 days. Reasons for readmission were multifactorial and not easily categorized into mutually exclusive reasons. Five themes emerged as reasons cited for hospital readmission: distressing symptoms, unavoidable progression of illness, influence of psychosocial factors, good but imperfect self-care adherence, and health system failures.

Conclusions—
Our study provides the first systematic qualitative assessment of patient perspectives concerning heart failure readmission. Contrary to prior literature and distinct from what we found documented in the medical record, patient experiences were highly heterogeneous, not easily categorized as preventable or not preventable, and not easily attributed to a single cause. These findings suggest that future interventions designed to reduce heart failure readmissions should be multifaceted, should be systemic in nature, and should integrate patient input.
On the Thickness Ratio in the Quasigeostrophic Two-Layer Model of Baroclinic Instability
Authors: Nakamura Noboru , Wang Lei 
Published: February 2013

Abstract
It is shown that the classical quasigeostrophic two-layer model of baroclinic instability possesses an optimal ratio of layer thicknesses that maximizes the growth rate, given the basic-state shear (thermal wind), beta, and the mean Rossby radius. This ratio is interpreted as the vertical structure of the most unstable mode. For positive shear and beta, the optimal thickness of the lower layer approaches the midheight of the model in the limit of strong criticality (shear/beta) but it is proportional to criticality in the opposite limit. For a set of parameters typical of the earth’s midlatitudes, the growth rate maximizes at a lower-layer thickness substantially less than the midheight and at a correspondingly larger zonal wavenumber.
It is demonstrated that a turbulent baroclinic jet whose statistical steady state is marginally critical when run with equal layer thicknesses can remain highly supercritical when run with a nearly optimal thickness ratio.
Precipitation Partitioning, Tropical Clouds, and Intraseasonal Variability in GFDL AM2
Authors: Lin Yanluan , Zhao Ming , Ming Yi , Golaz Jean-Christophe , Donner Leo J. , Klein Stephen A. , Ramaswamy V. , Xie Shaocheng 
Published: February 2013

AbstractA set of Geophysical Fluid Dynamics Laboratory (GFDL) Atmospheric Model version 2 (AM2) sensitivity simulations by varying an entrainment threshold rate to control deep convection occurrence are used to investigate how cumulus parameterization impacts tropical cloud and precipitation characteristics. In the tropics, model convective precipitation (CP) is frequent and light, while large-scale precipitation (LSP) is intermittent and strong. With deep convection inhibited, CP decreases significantly over land and LSP increases prominently over ocean. This results in an overall redistribution of precipitation from land to ocean. A composite analysis reveals that cloud fraction (low and middle) and cloud condensate associated with LSP are substantially larger than those associated with CP. With about the same total precipitation and precipitation frequency distribution over the tropics, simulations having greater LSP fraction tend to have larger cloud condensate and low and middle cloud fraction.Simulations having a greater LSP fraction tend to be drier and colder in the upper troposphere. The induced unstable stratification supports strong transient wind perturbations and LSP. Greater LSP also contributes to greater intraseasonal (20–100 days) precipitation variability. Model LSP has a close connection to the low-level convergence via the resolved grid-scale dynamics and, thus, a close coupling with the surface heat flux. Such wind–evaporation feedback is essential to the development and maintenance of LSP and enhances model precipitation variability. LSP has stronger dependence and sensitivity on column moisture than CP. The moisture–convection feedback, critical to tropical intraseasonal variability, is enhanced in simulations with large LSP. Strong precipitation variability accompanied by a worse mean state implies that an optimal precipitation partitioning is critical to model tropical climate simulation.
The Development and Assessment of a Model-, Grid-, and Basin-Independent Tropical Cyclone Detection Scheme
Authors: Tory K. J. , Chand S. S. , Dare R. A. , McBride J. L. 
Published: February 2013

Abstract
A novel approach to tropical cyclone (TC) detection in coarse-resolution numerical model data is introduced and assessed. This approach differs from traditional detectors in two main ways. First, it was developed and tuned using 20 yr of ECMWF Interim Re-Analysis (ERA-Interim) data, rather than using climate model data. This ensures that the detector is independent of any climate models to which it will later be applied. Second, only relatively large-scale parameters resolvable in climate models are included, in order to minimize any grid-resolution dependence on parameter thresholds. This approach is taken in an attempt to construct a unified TC detection procedure applicable to all climate models without the need for any further tuning or adjustment.
Unlike traditional detectors that seek to identify TCs directly, the authors' method seeks to identify conditions favorable for TC formation. Favorable TC formation regions at the center of closed circulations in the lower troposphere to the midtroposphere are identified using a low-deformation vorticity parameter. Additional relative and specific humidity thresholds are applied to ensure the thermodynamic environment is favorable, and a vertical wind shear threshold is applied to eliminate storms in a destructive shear environment. A further requirement is that thresholds for all parameters must be satisfied for at least 48 h before a TC is deemed to have developed.
A thorough assessment of the detector performance is provided. It is demonstrated that the method reproduces realistic TC genesis frequency and spatial distributions in the ERA-Interim data. Application of the detector to four climate models is presented in a companion paper.
Characteristics and Mechanism of the 10–20-Day Oscillation of Spring Rainfall over Southern China
Authors: Pan Weijuan , Mao Jiangyu , Wu Guoxiong 
Published: February 2013

Abstract
The intraseasonal oscillations (ISOs) of southern China spring rainfall (SCSR) are examined based on daily rain gauge rainfall data and NCEP/Department of Energy Reanalysis 2 (NCEP-2) products for the period 1980–2008. The objective of this study is to reveal the structure and propagation of the dominant ISO of SCSR as well as its driving mechanisms, thereby gaining an understanding of the causes of extreme wet and dry SCSR.
The EOF analysis and power spectrum analysis show that the 10–20-day oscillation is a predominant ISO of SCSR in most years. Composite analyses and wave-activity propagation diagnosis demonstrate that the 10–20-day oscillation of SCSR is characterized by an alternate occurrence of a huge anomalous anticyclone (cyclone) encircling the Tibetan Plateau in the lower troposphere, with anomalous low-level northeasterly (southwesterly) winds prevailing over southern China, producing lower-tropospheric divergence (convergence). In the middle and upper troposphere, the oscillation appears as a southeastward propagating coherent wave train made up of a series of anomalous cyclones and anticyclones, which are aligned in a northwest–southeast direction. This whole wave train also drifts eastward, with strong upper-tropospheric convergence (divergence) alternately superimposed over the lower-tropospheric divergence (convergence) within and south of the Yangtze basin, resulting in deficient (excessive) rainfall in southern China. The thermal structure of the 10–20-day ISO of SCSR and its association with the mechanical–thermal forcing of the Tibetan Plateau are also explored.
Basaloid Squamous Cell Carcinoma of the Oropharynx: An Analysis of 650 Cases
Authors: Fritsch Valerie A. , Lentsch Eric J. 
Published: February 2013

ObjectiveBasaloid squamous cell carcinoma (BSCC) is considered an aggressive squamous cell carcinoma (SCC) variant. However, we hypothesized that BSCC of the oropharynx may carry a similar prognosis to SCC. A series of exclusively oropharyngeal BSCC patients has not been previously reported. Our objective was to describe the clinical presentation and prognosis of BSCC in a large series of patients with BSCC of the oropharynx and to compare these with a series of patients with conventional‐type oropharyngeal SCC.Study DesignRetrospective analysis of population‐based data.SettingData reported by the Surveillance, Epidemiology, and End Results (SEER) program are based on medical records of patients who are treated at academic medical centers, community and county hospitals, and health maintenance organizations.Subjects and MethodsClinicopathologic data and disease‐specific survival (DSS) were compared between 650 patients with oropharyngeal BSCC and 19,484 with SCC.ResultsHigh‐grade tumors and nodal metastasis were more common in the BSCC group (P <. 02). On multivariable analysis controlling for disease stage, BSCC patients had improved DSS (P <. 001). More BSCC patients received multimodality treatment (P <. 001). Disease‐specific survival was similar in BSCC and SCC patients who were treated with primary surgery; however, among patients who received radiotherapy, DSS was better for those with BSCC (P <. 04).ConclusionAnalysis of the largest oropharyngeal BSCC series to date demonstrates that BSCC of the oropharynx carries a more favorable prognosis than conventional‐type oropharyngeal SCC.
The value of preoperative PET–CT in papillary thyroid cancer
Authors: Kim Byung Seup , Ryu Han Suk , Kang Kyung Ho 
Published: February 2013

Objective To evaluate the clinical usefulness of preoperative positron emission tomography–computed tomography (PET–CT) in primary papillary thyroid cancer (PTC). Methods Preoperative PET–CT scans of patients with biopsy-confirmed PTC who were undergoing thyroidectomy were examined and the maximum standardized uptake value (SUVmax) of 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) was calculated. Demographic and clinical data were obtained from medical records. Tumour tissue was pathologically classified according to World Health Organization guidelines. Univariate and multivariate analyses were performed to determined the demographic, clinical and pathological factors affecting PET positivity and SUVmax. Results The study included 194 patients. Multivariate analysis indicated that patients were significantly more likely to be PET positive if they were female, had larger tumours (>1 cm), coexisting pathology (nodular hyperplasia or Hashimoto’s thyroiditis) or nonfollicular variant PTC. SUVmax <2.0 indicated possible follicular variant PTC. Conclusions PET-positive results were unrelated to extrathyroidal extension and lymph node metastasis. PET positivity was related to larger tumour size and implied coexisting pathology. PET negativity or low SUVmax suggested possible follicular variant PTC.
Apoptotic cell death in rat epididymis following epichlorohydrin treatment
Authors: Lee I.-C. , Kim K.-H. , Kim S.-H. , Baek H.-S. , Moon C. , Kim S.-H. , Yun W.-K. , Nam K.-H. , Kim H.-C. , Kim J.-C. 
Published: February 2013

Epichlorohydrin (ECH) is an antifertility agent that acts both as an epididymal toxicant and an agent capable of directly affecting sperm motility. This study identified the time course of apoptotic cell death in rat epididymides after ECH treatment. Rats were administrated with a single oral dose of ECH (50 mg/kg). ECH-induced apoptotic changes were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and its related mechanism was confirmed by Western blot analysis and colorimetric assay. The TUNEL assay showed that the number of apoptotic cells increased at 8 h, reached a maximum level at 12 h, and then decreased progressively. The Western blot analysis demonstrated no significant changes in proapoptotic Bcl-2-associated X (Bax) and anti-apoptotic Bcl-2 expression during the time course of the study. However, phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) and phospho-c-Jun amino-terminal kinase (p-JNK) expression increased at 8–24 h. Caspase-3 and caspase-8 activities also increased at 8–48 h and 12–48 h, respectively, in the same manner as p-p38 MAPK and p-JNK expression. These results indicate that ECH induced apoptotic changes in rat epididymides and that the apoptotic cell death may be related more to the MAPK pathway than to the mitochondrial pathway.
Lupus nephritis: a 15‐year multi‐centre experience in the UK
Authors: Hui M , Garner R , Rees F , Bavakunji R , Daniel P , Varughese S , Srikanth A , Andres M , Pearce F , Leung J , Lim K , Regan M , Lanyon P 
Published: February 2013

Objectives Our aim was to audit the outcome of lupus nephritis (LN) at three East Midlands centres. Methods We undertook a retrospective review of all biopsy-proven LN types III–V 1995–2010. Results In total, 61 patients with LN were identified, with a median follow-up of 68 months. LN was present at the time of systemic lupus erythematosus (SLE) diagnosis in 20 patients. The median time from SLE diagnosis to the first LN episode was 5.3 years. Some 35 patients received IV cyclophosphamide and 17 received mycophenolate mofetil (MMF) as induction therapy; 81.8% of those treated with cyclophosphamide and 81.3% with MMF had at least ‘improved’ according to the ACR-response criteria 6 months from induction; 33.3% and 37.5%, respectively, had a ‘complete’ response. MMF and azathioprine were the most frequently used maintenance therapy. We found that 32.8% experienced a flare after a mean post-induction time of 3.5 years, irrespective of the maintenance therapy used, and 43.8% of partial responders flared compared with 4.8% of complete responders. End-stage renal failure developed in 8.2%. Conclusions Overall, outcomes (response, flare-rate, end-stage renal failure) were comparable with European clinical studies. Partial responders are more likely to flare compared with complete responders. The results highlight that LN can occur, and flare, after many years of SLE, emphasizing the importance of continued vigilance for LN in all patients.
Labor induction and augmentation in women with multiple sclerosis
Authors: Lu E , Zhu F , van der Kop ML , Dahlgren L , Synnes A , Sadovnick AD , Traboulsee A , Tremlett H ,   the British Columbia Multiple Sclerosis Clinic Neurologists
Published: February 2013

Background: Fatigue and pelvic organ dysfunction are common among women with multiple sclerosis (MS), which may prolong labor and increase the risk of labor induction and/or augmentation. Objective: We set out to investigate the association between MS and related clinical factors (disease duration and the Expanded Disability Status Scale, EDSS) with labor induction/augmentation. Methods: Data from the British Columbia (BC) MS database were linked with the BC Perinatal Database Registry. Multivariable models were used to compare the likelihood of labor induction and augmentation between attempted vaginal deliveries (1998–2009) in women with MS ( n=381) and the general population ( n=2615). Results: In the MS cohort, 94/381 deliveries (25%) required labor induction and 147/381 deliveries (39%) required labor augmentation. Having MS was not associated with labor induction (adjusted odds ratio (OR)=0.91; 95% confidence interval (CI)=0.68–1.22, p=0.54) or augmentation (adjusted OR=0.91; 95% CI=0.72–1.15, p=0.43), but was associated with multiple methods of labor induction (OR=1.94; 95% CI=1.23–3.06, p=0.004). A higher EDSS score was associated with an increased risk of labor induction (adjusted p=0.04), but not labor augmentation (adjusted p > 0.5). Disease duration was not associated with either outcome (adjusted p > 0.2). Conclusions: Greater intervention may be required to initiate labor for women with a higher degree of disability due to MS.