bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pertussis Toxin Exacerbates and Prolongs Airway Inflammatory Responses during Bordetella pertussis Infection
Authors: Connelly Carey E. , Sun Yezhou , Carbonetti Nicholas H. 
Published: October 2012

ABSTRACTThroughout infection, pathogenic bacteria induce dramatic changes in host transcriptional repertoires. An understanding of how bacterial factors influence host reprogramming will provide insight into disease pathogenesis. In the human respiratory pathogenBordetella pertussis, the causative agent of whooping cough, pertussis toxin (PT) is a key virulence factor that promotes colonization, suppresses innate immune responses during early infection, and causes systemic disease symptoms. To determine the full extent of PT-associated gene regulation in the airways through the peak of infection, we measured global transcriptional profiles in the lungs of BALB/c mice infected with wild-type (WT) or PT-deficient (ΔPT)B. pertussis. ΔPT bacteria were inoculated at a dose equivalent to the WT dose and at a high dose (ΔPThigh) to distinguish effects caused by higher bacterial loads achieved in WT infection from effects associated with PT. The results demonstrated that PT was associated with a significant upregulation of immune and inflammatory response genes as well as several other genes implicated in airway pathology. In contrast to the early, transient responses observed for ΔPThighinfection, WT infection induced a prolonged expression of inflammatory genes and increased the extent and duration of lung histopathology. In addition, the administration of purified PT to ΔPThigh-infected mice 1 day after bacterial inoculation exacerbated and prolonged inflammatory responses and airway pathology. These data indicate that PT not only is associated with exacerbated host airway responses during peakB. pertussisinfection but also may inhibit host mechanisms of attenuating and resolving inflammation in the airways, suggesting possible links between PT and pertussis disease symptoms.
Vomiting should be a prompt predictor of stroke outcome
Authors: Shigematsu Kazuo , Shimamura Osamu , Nakano Hiromi , Watanabe Yoshiyuki , Sekimoto Tatsuyuki , Shimizu Kouichiro , Nishizawa Akihiko , Makino Masahiro 
Published: September 2012

BackgroundTo predict the outcome of stroke at an acute stage is important but still difficult. Vomiting is one of the commonest symptoms in stroke patients. The aim of this study is threefold: first, to examine the percentage of vomiting in each of the three major categories of strokes; second, to investigate the association between vomiting and other characteristics and third, to determine the correlation between vomiting and mortality.MethodsWe investigated the existence or absence of vomiting in stroke patients in the Kyoto prefecture cohort. We compared the characteristics of patients with and without vomiting. We calculated the HR for death in both types of patients, adjusted for age, sex, blood pressure, arrhythmia, tobacco and alcohol use and paresis.ResultsOf the 1968 confirmed stroke patients, 1349 (68.5%) had cerebral infarction (CI), 459 (23.3%) had cerebral haemorrhage (CH) and 152 (7.7%) had subarachnoid haemorrhage (SAH). Vomiting was seen in 14.5% of all stroke patients. When subdivided according to stroke type, vomiting was observed in 8.7% of CI, 23.7% of CH and 36.8% of SAH cases. HR for death and 95% CI were 5.06 and 3.26 to 7.84 (p<0.001) when all stroke patients were considered, 5.27 and 2.56 to 10.83 (p<0.001) in CI, 2.82 and 1.33 to 5.99 (p=0.007) in CH and 5.07 and 1.87 to 13.76 (p=0.001) in SAH.ConclusionsCompared with patients without vomiting, the risk of death was significantly higher in patients with vomiting at the onset of stroke. Vomiting should be an early predictor of the outcome.
Competency-based training: who benefits?
Authors: Brightwell Alexandra , Grant Janet 
Published: September 2012

Abstract
Competency based training describes progression through training referenced to the demonstrated ability to perform certain tasks. In recent years, this has become the dominant curriculum model. We seek to examine who benefits from a competency based approach to medical education. For the regulators and service, the apparent advantage is in terms of apparent measurable accountability and flexibility. For assessors, the promise of competence based assessments in the workplace to provide a reliable and objective measurement of a trainee's performance has not been demonstrated in practice. For the doctor in training, there is very little evidence to show benefit from competency based training. Competency based training places emphasis on individual skills rather than overall learning experience thus risks diminishing the role of the trainee in the workplace. Any form of medical education that devalues workplace based learning will ultimately harm the profession and, in turn, patient care.
Contributions of Recent and Past Sexual Partnerships on Incident Human Papillomavirus Detection: Acquisition and Reactivation in Older Women
Authors: Rositch Anne F. , Burke Anne E. , Viscidi Raphael P. , Silver Michelle I. , Chang Kathryn , Gravitt Patti E. 
Published: September 2012

Abstract
Understanding the fraction of newly detected human papillomavirus (HPV) infections due to acquisition and reactivation has important implications on screening strategies and prevention of HPV-associated neoplasia. Information on sexual activity and cervical samples for HPV DNA detection using Roche Linear Array were collected semiannually for two years from 700 women ages 35 to 60 years. Incidence and potential fraction of HPV associated with new and lifetime sexual partnerships were estimated using Poisson regression. Cox frailty models were used to estimate hazard ratios (HR) for potential risk factors of incident HPV detection. Recent and lifetime numbers of sexual partners were both strongly associated with incident HPV detection. However, only 13% of incident detections were attributed to new sexual partners, whereas 72% were attributed to 5 or more lifetime sexual partners. Furthermore, 155 of 183 (85%) incident HPV detections occurred during periods of sexual abstinence or monogamy, and were strongly associated with cumulative lifetime sexual exposure [HR: 4.1, 95% confidence interval (CI): 2.0–8.4). This association increased with increasing age. These data challenge the paradigm that incident HPV detection is driven by current sexual behavior and new viral acquisition in older women. Our observation that most incident HPV infection was attributable to past, not current, sexual behavior at older ages supports a natural history model of viral latency and reactivation. As the more highly exposed baby-boomer generation of women with sexual debut after the sexual revolution transition to menopause, the implications of HPV reactivation at older ages on cervical cancer risk and screening recommendations should be carefully evaluated. Cancer Res; 72(23); 6183–90. ©2012 AACR.
Molecular Pathways: The Metabolic Regulator Estrogen-Related Receptor α as a Therapeutic Target in Cancer
Authors: Chang Ching-yi , McDonnell Donald P. 
Published: September 2012

Abstract
The estrogen-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily of transcription factors whose activity is regulated by the expression level and/or activity of its obligate coregulators, peroxisome proliferator-activated receptor γ coactivator-1 α and β (PGC-1α or PGC-1β). Under normal physiologic conditions, and in responding to different environmental stimuli, the ERRα/PGC-1 complex is involved in regulating metabolic homeostasis under conditions of high energy demand in brown adipocytes, proliferating T cells, and muscle. Interestingly, increased expression and activity of the ERRα/PGC-1 axis has also been shown to correlate with unfavorable clinical outcomes in both breast and ovarian tumors. The observation that ERRα activity is manifest in all breast tumor subtypes with particularly high activity being evident in ERα-negative, HER2-positive, and triple-negative breast cancers has raised significant interest in targeting this receptor for the treatment of those breast cancers for which therapeutic options are limited. Clin Cancer Res; 18(22); 6089–95. ©2012 AACR.
Outcomes of Phase II Clinical Trials with Single-Agent Therapies in Advanced/Metastatic Non–Small Cell Lung Cancer Published between 2000 and 2009
Authors: Janku Filip , Berry Donald A. , Gong Jing , Parsons Henrique A. , Stewart David J. , Kurzrock Razelle 
Published: September 2012

Abstract
Purpose: We analyzed the outcomes of single-agent phase II clinical trials in non–small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity.
Exoerimental Design: Data on response rate (RR), progression-free survival (PFS), and overall survival (OS) from all English language, single-agent phase II trials in advanced/metastatic NSCLC indexed by PubMed (January 2000 through December 2009) were abstracted.
Results: A total of 143 single-agent phase II trials (7,701 patients) were identified. The median RR was 10%, PFS 2.8 months, and OS 7.6 months. RR and PFS correlated with OS (r = 0.46, P &lt; 0.001, r = 0.52, P &lt; 0.001, respectively) and RR correlated with PFS (r = 0.61, P &lt; 0.001). Treatment arms enriched for patients with molecular targets had a higher median RR (48.8% vs. 9.7%, P = 0.005), longer median PFS (6 vs. 2.8 months, P = 0.005), and OS (11.3 vs. 7.5 months, P = 0.05) as compared with those of unselected patients. In multivariate analysis, only studies enriched for patients with molecular targets or including drugs that eventually gained FDA/EMA approval were associated with a higher RR, and longer PFS/OS.
Conclusions: In phase II trials in NSCLC, RR and PFS correlated with OS. Studies enriched for patients with putative molecular drug targets were associated with higher therapeutic benefit as compared with those of unselected populations. Clin Cancer Res; 18(22); 6356–63. ©2012 AACR.
Measurement of Tumor VEGF-A Levels with 89Zr-Bevacizumab PET as an Early Biomarker for the Antiangiogenic Effect of Everolimus Treatment in an Ovarian Cancer Xenograft Model
Authors: van der Bilt Arne R.M. , van Scheltinga Anton G.T. Terwisscha , Timmer-Bosscha Hetty , Schröder Carolien P. , Pot Linda , Kosterink Jos G.W. , van der Zee Ate G.J. , Lub-de Hooge Marjolijn N. , de Jong Steven , de Vries Elisabeth G.E. , Reyners Anna K.L. 
Published: September 2012

Abstract
Purpose: The mTOR pathway is frequently activated in ovarian cancers. mTOR inhibitors, such as everolimus, can reduce VEGF-A production by cancer cells. We investigated whether early everolimus treatment effects could be monitored by positron emission tomography (PET) with 89Zr-bevacizumab.
Experimental Design: The effect of everolimus on VEGF-A secretion was determined in a panel of human ovarian cancer cell lines and in A2780luc+ ovarian cancer cells xenografted subcutaneously in BALB/c mice. Mice received daily 10 mg/kg everolimus intraperitoneally (i.p.) for 14 days. PET scans with the tracer 89Zr-labeled bevacizumab were conducted before and after treatment. Ex vivo89Zr-bevacizumab biodistribution and correlative tissue analyses were conducted. Tumor VEGF-A levels were measured with ELISA and mean vascular density (MVD) was determined with immunohistochemistry.
Results: Everolimus treatment reduced VEGF-A levels in the supernatant of all cell lines. Everolimus lowered 89Zr-bevacizumab tumor uptake by 21.7% ± 4.0% [mean standardized uptake value (SUVmean) 2.3 ± 0.2 vs. 2.9 ± 0.2, P &lt; 0.01]. Ex vivo biodistribution also showed lower tracer uptake in the tumors of treated as compared with control animals (7.8 ± 0.8%ID/g vs. 14.0 ± 1.7%ID/g, P &lt; 0.01), whereas no differences were observed for other tissues. This coincided with lower VEGF-A protein levels in tumor lysates in treated versus untreated tumors (P = 0.04) and reduced MVD (P &lt; 0.01).
Conclusion: Tumor VEGF-A levels are decreased by everolimus. 89Zr-bevacizumab PET could be used to monitor tumor VEGF-A levels as an early biomarker of the antiangiogenic effect of mTOR inhibitor therapy. Clin Cancer Res; 18(22); 6306–14. ©2012 AACR.
An Improvement of Roughness Height Parameterization of the Surface Energy Balance System (SEBS) over the Tibetan Plateau
Authors: Chen Xuelong , Su Zhongbo , Ma Yaoming , Yang Kun , Wen Jun , Zhang Yu 
Published: September 2012

AbstractRoughness height for heat transfer is a crucial parameter in the estimation of sensible heat flux. In this study, the performance of the Surface Energy Balance System (SEBS) has been tested and evaluated for typical land surfaces on the Tibetan Plateau on the basis of time series of observations at four sites with bare soil, sparse canopy, dense canopy, and snow surface, respectively. Both under- and overestimation at low and high sensible heat fluxes by SEBS was discovered. Through sensitivity analyses, it was identified that these biases are related to the SEBS parameterization of bare soil’s excess resistance to heat transfer (kB−1, where k is the von Kármán constant and B−1 is the Stanton number). The kB−1 of bare soil in SEBS was replaced. The results show that the revised model performs better than the original model.
Characteristics of Precipitating Convective Systems Accounting for the Summer Rainfall of Tropical and Subtropical South America
Authors: Romatschke Ulrike , Houze Robert A. 
Published: September 2012

AbstractTen years of Tropical Rainfall Measuring Mission precipitation radar data are used to study the physical properties of the precipitating cloud systems that account for the summer rainfall of tropical and subtropical South America. Radar echoes in the continental subtropics tend to be of an intensely convective nature, especially at the eastern foothills of the Andes where diurnally forced deep convective cells of small horizontal scale form when moist low-level flow is driven toward the foothills in connection with a midlatitude disturbance. As the disturbance moves east over the La Plata basin, nocturnal convective systems of larger horizontal scale with wide stratiform regions occur in a zone of general convergence. Precipitation in the continental tropics is generally produced by convective systems with greater stratiform composition. At the northeastern foothills of the central Andes, radar echoes of nocturnal convective systems of medium to large horizontal scale occur where moist low-level flow is lifted over the foothills. Growth of systems to large size is inhibited by daytime divergence at the foothills. Over the Amazon basin, daytime systems are also smaller than nocturnal systems. Radar echoes of precipitation over the Brazilian Highlands are generally smaller in horizontal scale, more convective, and mostly occur during the afternoon over elevated terrain. In the oceanic South Atlantic convergence zone, radar echoes grow to extremely large sizes. They are highly stratiform in nature and occur during all times of the day except late evening when convergence is weakened as a response to continental heating.
Horizontal Momentum Diffusion in GCMs Using the Dynamic Smagorinsky Model
Authors: Schaefer-Rolffs Urs , Becker Erich 
Published: September 2012

Abstract
A dynamic version of Smagorinsky’s diffusion scheme is presented that is applicable for large-eddy simulations (LES) of the atmospheric dynamics. The approach is motivated (i) by the incompatibility of conventional hyperdiffusion schemes with the conservation laws, and (ii) because the conventional Smagorinsky model (which fulfills the conservation laws) does not maintain scale invariance, which is mandatory for a correct simulation of the macroturbulent kinetic energy spectrum. The authors derive a two-dimensional (horizontal) formulation of the dynamic Smagorinsky model (DSM) and present three solutions of the so-called Germano identity: the method of least squares, a solution without invariance of the Smagorinsky parameter, and a tensor-norm solution. The applicability of the tensor-norm approach is confirmed in simulations with the Kühlungsborn mechanistic general circulation model (KMCM). The standard spectral dynamical core of the model facilitates the implementation of the test filter procedure of the DSM. Various energy spectra simulated with the DSM and the conventional Smagorinsky scheme are presented. In particular, the results show that only the DSM allows for a reasonable spectrum at all scales. Latitude–height cross sections of zonal-mean fluid variables are given and show that the DSM preserves the main features of the atmospheric dynamics. The best ratio for the test-filter scale to the resolution scale is found to be 1.33, resulting in dynamically determined Smagorinsky parameters cS from 0.10 to 0.22 in the troposphere. This result is very similar to other values of cS found in previous three-dimensional applications of the DSM.
Spectral Analyses of the Polygonal Eye of Typhoon Sinlaku
Authors: Itano Toshihisa , Hosoya Muneyuki 
Published: September 2012

Abstract
The geometry and behavior of the polygonal eye of Typhoon Sinlaku (T0216) are presented both objectively and quantitatively based on the ground-based radar data by using two types of spectral analyses (i.e., Fourier analysis and time–space cross-spectral analysis). The analyses reveal that the azimuthal wavenumber-2 perturbation is dominant even when the apparent shape of the eye seems pentagonal. Then the wavenumber-5 perturbation dominates second in most of the analytical period although it becomes most dominant during the typhoon’s passage over Okinawa Island, Japan. The counterclockwise phase shift is seen not only in these perturbations but also in, at least, the wavenumber-4, -5, and -6 perturbations. Except for the wavenumber-2 perturbation, the angular velocities are around 130° h−1 and almost coincide with each other. The radial wind profile estimated from the surface observational data suggests the existence of a ring-shaped high-vorticity region enclosing the core of the typhoon. This implies that the formation of the pentagonal eye can be attributed to wave breaking caused by barotropic instability of the circular flow constituting this typhoon. Such a possibility is also discussed by performing the linear stability analysis based on the nondivergent barotropic vorticity equation.
Twenty-One Years of Verification from the HIRLAM NWP System
Authors: Eerola Kalle 
Published: September 2012

Abstract
The High-Resolution Limited-Area Model (HIRLAM) international research program maintains a synoptic-scale NWP system. At the Finnish Meteorological Institute, the HIRLAM system has been run operationally since 1990. The HIRLAM forecasts from 1990 to 2012 have been verified against the numerical analysis. In 2-day forecasts, the monthly rms error of the mean sea level pressure has decreased from about 4 to about 2 hPa; that is, the error is now about half of the value it was in the early 1990s. Similar reduction is seen in the 500-hPa height. The negative bias has decreased significantly. In addition, the dependence on the weather regime, measured as the correlation between the North Atlantic Oscillation (NAO) index and rms error, has decreased. The reason for these improvements can often be attributed to changes in the HIRLAM system. A single improvement, improving most significantly the forecast skill, is the rerun concept, which improves the HIRLAM first guess by utilizing the high-quality ECMWF analysis. Verifying against observations or against the initial analysis gives similar results for a 48-h forecast. For a 6-h forecast, however, the field verification gives lower rms error values and lower bias values. In summary, the results indicate that the goal of the HIRLAM program has been fulfilled: to develop and maintain an up-to-date NWP system for 1- and 2-day forecasts on a limited domain.
Quantifying Glenoid Bone Loss in Anterior Shoulder Instability
Authors: Bois Aaron J. , Fening Stephen D. , Polster Josh , Jones Morgan H. , Miniaci Anthony 
Published: September 2012

Background: Glenoid support is critical for stability of the glenohumeral joint. An accepted noninvasive method of quantifying glenoid bone loss does not exist. Purpose: To perform independent evaluations of the reliability and accuracy of standard 2-dimensional (2-D) and 3-dimensional (3-D) computed tomography (CT) measurements of glenoid bone deficiency. Study Design: Descriptive laboratory study. Methods: Two sawbone models were used; one served as a model for 2 anterior glenoid defects and the other for 2 anteroinferior defects. For each scapular model, predefect and defect data were collected for a total of 6 data sets. Each sample underwent 3-D laser scanning followed by CT scanning. Six physicians measured linear indicators of bone loss (defect length and width-to-length ratio) on both 2-D and 3-D CT and quantified bone loss using the glenoid index method on 2-D CT and using the glenoid index, ratio, and Pico methods on 3-D CT. The intraclass correlation coefficient (ICC) was used to assess agreement, and percentage error was used to compare radiographic and true measurements. Results: With use of 2-D CT, the glenoid index and defect length measurements had the least percentage error (−4.13% and 7.68%, respectively); agreement was very good (ICC, .81) for defect length only. With use of 3-D CT, defect length (0.29%) and the Pico1 method (4.93%) had the least percentage error. Agreement was very good for all linear indicators of bone loss (range, .85-.90) and for the ratio linear and Pico surface area methods used to quantify bone loss (range, .84-.98). Overall, 3-D CT results demonstrated better agreement and accuracy compared to 2-D CT. Conclusion: None of the methods assessed in this study using 2-D CT was found to be valid, and therefore, 2-D CT is not recommended for these methods. However, the length of glenoid defects can be reliably and accurately measured on 3-D CT. The Pico and ratio techniques are most reliable; however, the Pico1 method accurately quantifies glenoid bone loss in both the anterior and anteroinferior locations. Future work is required to implement valid imaging techniques of glenoid bone loss into clinical practice. Clinical Relevance: This is one of the only studies to date that has investigated both the reliability and accuracy of multiple indicators and quantification methods that evaluate glenoid bone loss in anterior glenohumeral instability. These data are critical to ensure valid methods are used for preoperative assessment and to determine when a glenoid bone augmentation procedure is indicated.