bluuebunny/crossref_metadata_2025_split huggingface dataset:
005 An external validation of the PECARN clinical decision rule for minor head injury
Authors: Fuller G , Lecky F , Batchelor J , Dunning J 
Published: September 2011

Objectives and Backgrounds500 000 children present to UK hospitals annually following minor head injury (MHI). Mortality is low (6–10 per 100 000), and most patients can be safely discharged from emergency departments. However, a small proportion of children with significant intracranial pathology are at risk for deterioration. CT is the gold-standard for investigation of MHI, but resource limitations, and risks from ionising radiation and pharmacological sedation, preclude its universal use. Clinical decision rules (CDR) were recently developed in a North American population by the PECARN research group, to guide CT use in childhood MHI. Our aim was to externally validate the rule for children over 5 years in a UK setting.MethodsThe CHALICE database consists of all children (<16 years) presenting to the emergency departments of 10 northwest England hospitals with head injury between February 2000 and August 2002. A dataset of demographic, clinical, radiological and outcome variables were recorded prospectively, and clinically significant head injuries identified. CHALICE patients >5 years were categorised according to PECARN CDR predictors and outcomes (clinically important head injury [ciHI]: death from HI, neurosurgery, intubation >24 h, hospital admission >2 nights with positive CT head). We then calculated the sensitivity, specificity, and negative predictive value for identifying ciHI in the CHALICE population using the PECARN CDR.ResultsThe CHLAICE database consists of 22 772 children, with 65% males, and a mean age of 5.7 years. Following application of PECARN exclusion criteria a study population of 10 415 children aged >5 years were available for study. 2778 children met PECARN CT scanning criteria, and 246 had ciHI. Information for assessing severity of injury mechanism was incomplete (patient ejection and vehicle rollover variables absent). Data were present for all other PECARN predictors and outcomes. The PECARN rule demonstrated a sensitivity of 95% (95% CI 91 to 97), specificity of 75% (95% CI 74 to 76), and negative predictive value of 99.8% (95% CI 99.7 to 99.9) for the prediction of ciHI.ConclusionsThe PECARN clinical prediction rule for children >5 years performed well in a large UK cohort of children. Further work will examine refinements to the PECARN rule, and validate the CDR for children <2 years.
008 Risk assessment of patients presenting to the ED with chest pain and equivocal cardiac troponin T (cTnT) levels: the lost tribe?
Authors: Cook C , Krom A , Sood T 
Published: September 2011

Objectives and BackgroundsNew high-sensitivity cTnT assays are being used to determine myocardial necrosis. These tests include an equivocal range for myocardial necrosis (0.014–0.030 μg/l), data on both clinical risk and outcomes for this group are limited. There is no explicit national guidance on the management of patients presenting with chest pain and equivocal cTnT values.Objectives(1) Individually risk asses patients presenting to the ED with chest pain and equivocal cTnT values [0.014 to <0.03 μg/l] for future adverse cardiovascular events using the Global Registry of Acute Cardiac Events [GRACE] risk scoring system. (2) Record the referral/discharge pathways of these patients.MethodsPatients presenting to the ED with cTnTs in the equivocal range over a 1-month period were identified. Future risk of adverse cardiovascular events was retrospectively calculated using the GRACE risk scoring system.Results40 patients with cardiac type chest pain, adequate documentation and equivocal cTnT levels were identified. 49% of these patients were assessed as “high risk”, 36% “medium risk” and 15% “low risk” when retrospectively GRACE scored. Of the “high risk” patients, 58% were discharged home without any documentation of specialist involvement, in-patient [IP] investigation or follow-up. 72% of these patients may have been suitable for IP angiogram ± intervention within 96 h of admission, but just 15% of these patients received this.ConclusionsPatients with cTnT concentrations in the equivocal range present a diagnostic dilemma for the ED clinician. They appear at increased risk of ACS when applying clinical risk stratification using a GRACE score. This increase in risk appears poorly appreciated, leading to opportunities for intervention being missed.
A Novel Kinase Inhibitor, INCB28060, Blocks c-MET–Dependent Signaling, Neoplastic Activities, and Cross-Talk with EGFR and HER-3
Authors: Liu Xiangdong , Wang Qian , Yang Gengjie , Marando Cindy , Koblish Holly K. , Hall Leslie M. , Fridman Jordan S. , Behshad Elham , Wynn Richard , Li Yu , Boer Jason , Diamond Sharon , He Chunhong , Xu Meizhong , Zhuo Jincong , Yao Wenqing , Newton Robert C. , Scherle Peggy A. 
Published: September 2011

Abstract
Purpose: The c-MET receptor tyrosine kinase plays important roles in the formation, progression, and dissemination of human cancer and presents an attractive therapeutic target. This study describes the preclinical characterization of INCB28060, a novel inhibitor of c-MET kinase.
Experimental Design: Studies were conducted using a series of in vitro and in vivo biochemical and biological experiments.
Results: INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. This inhibitor potently blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET–dependent tumor cell lines. As a result, INCB28060 potently inhibits c-MET–dependent tumor cell proliferation and migration and effectively induces apoptosis in vitro. Oral dosing of INCB28060 results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET–driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition. In a further exploration of potential interactions between c-MET and other signaling pathways, we found that activated c-MET positively regulates the activity of epidermal growth factor receptors (EGFR) and HER-3, as well as expression of their ligands. These effects are reversed with INCB28060 treatment. Finally, we confirmed that circulating hepatocyte growth factor levels are significantly elevated in patients with various cancers.
Conclusions: Activated c-MET has pleiotropic effects on multiple cancer-promoting signaling pathways and may play a critical role in driving tumor cell growth and survival. INCB28060 is a potent and selective c-MET kinase inhibitor that may have therapeutic potential in cancer treatment. Clin Cancer Res; 17(22); 7127–38. ©2011 AACR.
Telomerase Peptide Vaccination in NSCLC: A Phase II Trial in Stage III Patients Vaccinated after Chemoradiotherapy and an 8-Year Update on a Phase I/II Trial
Authors: Brunsvig Paal Fr. , Kyte Jon Amund , Kersten Christian , Sundstrøm Stein , Møller Mona , Nyakas Marta , Hansen Gaute L. , Gaudernack Gustav , Aamdal Steinar 
Published: September 2011

AbstractPurpose: We report two clinical trials in non–small cell lung cancer (NSCLC) patients evaluating immune response, toxicity, and clinical outcome after vaccination with the telomerase peptide GV1001: a phase II trial (CTN-2006) in patients vaccinated after chemoradiotherapy and an 8-year update on a previously reported phase I/II trial (CTN-2000).Experimental Design: CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy × 30) and weekly docetaxel (20 mg/m2), followed by GV1001 vaccination. CTN-2000: 26 patients were vaccinated with two telomerase peptides (GV1001 and I540). The immune responses were evaluated by T-cell proliferation and cytokine assays.Results: CTN-2006 trial: a GV1001-specific immune response developed in 16/20 evaluable patients. Long-term immunomonitoring showed persisting responses in 13 subjects. Serious adverse events were not observed. Immune responders recorded a median PFS of 371 days, compared with 182 days for nonresponders (P = 0.20). CTN-2000 trial update: 13/24 evaluable subjects developed a GV1001 response. The immune responders achieved increased survival compared with nonresponders (median 19 months vs. 3.5 months; P &lt; 0.001). Follow-up of four long-time survivors showed that they all harbored durable GV1001-specific T-cell memory responses and IFNγhigh/IL-10low/IL-4low cytokine profiles. Two patients are free of disease after 108 and 93 months, respectively.Conclusions: Vaccination with GV1001 is well tolerated, immunizes the majority of NSCLC patients and establishes durable T-cell memory. The considerable immune response rate and low toxicity in the phase II trial support the concept of combining chemoradiotherapy with vaccination. The survival advantage observed for immune responders warrants a randomized trial. Clin Cancer Res; 17(21); 6847–57. ©2011 AACR.
Clinical Implementation of Comprehensive Strategies to Characterize Cancer Genomes: Opportunities and Challenges
Authors: MacConaill Laura E. , Van Hummelen Paul , Meyerson Matthew , Hahn William C. 
Published: September 2011

Abstract
An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use of such agents. As the number of genetic alterations that provide diagnostic and/or therapeutic information increases, the comprehensive characterization of cancer genomes will be necessary to understand the spectrum of distinct genomic alterations in cancer, to identify patients who are likely to respond to particular therapies, and to facilitate the selection of treatment modalities. Rapid developments in new technologies for genomic analysis now provide the means to perform comprehensive analyses of cancer genomes. In this article, we review the current state of cancer genome analysis and discuss the challenges and opportunities necessary to implement these technologies in a clinical setting.
Significance: Rapid advances in sequencing technologies now make it possible to contemplate the use of genome scale interrogation in clinical samples, which is likely to accelerate efforts to match treatments to patients. However, major challenges in technology, clinical trial design, legal and social implications, healthcare information technology, and insurance and reimbursement remain. Identifying and addressing these challenges will facilitate the implementation of personalized cancer medicine. Cancer Discovery; 1(4): 297–311. ©2011 AACR.
The Potential Benefits of BIM in the Further Pursuit of Biomarker Discovery in Cancer Therapeutics
Authors: Yoshida Takeshi , Haura Eric B. 
Published: September 2011

Abstract
In this issue of Cancer Discovery, Faber and colleagues demonstrate that the basal expression of BIM is positively correlated with the amount of apoptosis induced by the corresponding tyrosine kinase inhibitor treatment within the same subtype of several oncogene-addicted cancer cell types. Their results suggest that pre-treatment assessment of BIM levels can identify patients who would benefit from molecularly targeted therapies even after biomarker-based patient selection. Cancer Discovery; 1(4); 289–90. ©2011 AACR.
Commentary on Faber et al., p. 352.
Will Amazonia Dry Out? Magnitude and Causes of Change from IPCC Climate Model Projections
Authors: Cook Brian , Zeng Ning , Yoon Jin-Ho 
Published: September 2011

Abstract
The Amazon rain forest may undergo significant change in response to future climate change. To determine the likelihood and causes of such changes, the authors analyzed the output of 24 models from the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) and a dynamic vegetation model, Vegetation–Global–Atmosphere–Soil (VEGAS), driven by these climate output. Their results suggest that the core of the Amazon rain forest should remain largely stable because rainfall in the core of the basin is projected to increase in nearly all models. However, the periphery, notably the southern edge of Amazonia and farther south into central Brazil (SAB), is in danger of drying out, driven by two main processes. First, a decline in precipitation of 11% during the southern Amazonia’s dry season (May–September) reduces soil moisture. Two dynamical mechanisms may explain the forecast reduction in dry season rainfall: 1) a general subtropical drying under global warming when the dry season southern Amazon basin is under the control of subtropical high pressure and 2) a stronger north–south tropical Atlantic sea surface temperature gradient and, to a lesser degree, a warmer eastern equatorial Pacific. The drying corresponds to a lengthening of the dry season by approximately 10 days. The decline in soil moisture occurs despite an increase in precipitation during the wet season, because of nonlinear responses in hydrology associated with the decline in dry season precipitation, ecosystem dynamics, and an increase in evaporative demand due to the general warming. In terms of ecosystem response, higher maintenance cost and reduced productivity under warming may also have additional adverse impact. Although the IPCC models have substantial intermodel variation in precipitation change, these latter two hydroecological effects are highly robust because of the general warming simulated by all models. As a result, when forced by these climate projections, a dynamic vegetation model VEGAS projects an enhancement of fire risk by 20%–30% in the SAB region. Fire danger reaches its peak in Amazonia during the dry season, and this danger is expected to increase primarily because of the reduction in soil moisture and the decrease in dry season rainfall. VEGAS also projects a reduction of about 0.77 in leaf area index (LAI) over the SAB region. The vegetation response may be partially mediated by the CO2 fertilization effect, because a sensitivity experiment without CO2 fertilization shows a higher 0.89 decrease in LAI. Southern Amazonia is currently under intense human influence as a result of deforestation and land-use change. Should this direct human impact continue at present rates, added pressure to the region’s ecosystems from climate change may subject the region to profound changes in the twenty-first century.
An Investigation of a Commercial Aircraft Encounter with Severe Clear-Air Turbulence over Western Greenland
Authors: Sharman R. D. , Doyle J. D. , Shapiro M. A. 
Published: September 2011

AbstractThis study presents digital flight data recorder (DFDR) analyses and high-resolution numerical simulations relevant to a severe clear-air turbulence (CAT) encounter over western Greenland by a Boeing 777 aircraft at 10-km elevation at 1305 UTC 25 May 2010. The environmental flow was dominated by an extratropical cyclone to the southeast of the Greenland tip, resulting in easterly flow at all levels. The results of the analyses indicate that the CAT encounter was related to mountain-wave breaking on the western lee (downslope) of the Greenland plateau. The simulations were not of especially high resolution (5-km horizontal grid spacing) by today’s standards, yet the simulation results do produce large-amplitude lee waves and overturning in good agreement with the encounter location as indicated by the DFDR. The success of this and other simulations in reproducing mountain-wave turbulence (MWT) events suggests that operational implementation of high-resolution nonhydrostatic simulation models, possibly an ensemble of models, over MWT-prone areas could produce more reliable forecasts of MWT than are currently available using gravity-wave-drag or MWT-postprocessing algorithms derived from global weather prediction models of relatively coarse scale.
Reply
Authors: Cook Garry D. , Nicholls Michael J. 
Published: September 2011

AbstractA reexamination of the wind hazard from tropical cyclones for the city of Darwin (Northern Territory), Australia, by Cook and Nicholls concluded that its wind hazard is substantially underestimated by its allocation to region C in the Australian wind code. This conclusion was dismissed by Harper et al. on the basis of interpretation of anemometer records and Dvorak central pressure estimates as well as criticism of the simple technique and data used to interpret historic records. Of the 44 years of historical anemometer records presented by Harper et al. for Darwin, however, only one record was for a direct hit by an intense tropical cyclone. The other records derive from distant and/or weak tropical cyclones, which are not applicable to understanding the wind hazard at long return periods. The Dvorak central pressure estimates from which Harper et al. conclude that Port Hedland (Western Australia), Australia, has a greater wind hazard than Darwin does, when back transformed to Dvorak current-intensity values and gust speeds, indicate the converse. The simple technique used to derive wind hazard from historical cyclone occurrence is defended in detail and shown to produce estimates of wind hazard that are close to those accepted for five locations on the hurricane-affected coastline of the U.S. mainland. Thus the criticisms by Harper et al. of Cook and Nicholl’s work are shown to be invalid and the original conclusion that Darwin’s wind hazard is substantially underestimated in the current Australian wind code is supported.
Attitudes to childhood overweight and obesity: The limits of cultural explanations
Authors: Chakrabarti Suparna , Abbott Stephen 
Published: September 2011

Objectives: To explore attitudes to and beliefs about childhood overweight and obesity among Bangladeshi mothers and to check maternal perceptions of their children’s weight status. Design: Mixed methods cross-sectional study. Setting: A general practice in East London, UK. Methods: Qualitative interviews with 14 mothers; weighing and measuring 22 children. Results: Mothers were generally aware of broad health promotion messages about diet and exercise, but many tended to under-estimate their children’s weight status. Differences in view did not reflect in any simple way English language skills, and the range of views reflected those in the majority population. Conclusion: Health promotion initiatives should assess individual needs; membership of a Bangladeshi community does not necessarily predict knowledge, beliefs or behaviour, and assumptions that this community is different from others are misleading.
Utilizing polypropylene fibers to improve physical and mechanical properties of concrete
Authors: Bagherzadeh Roohollah , Sadeghi Abdol-Hossein , Latifi Masoud 
Published: September 2011

The influence of polypropylene fibers has been studied in different proportioning and fiber aspect ratios to improve physical and mechanical properties of fiber-reinforced concretes. Fibers are used in two different lengths (12 mm and 19 mm) and proportions (0.1% and 0.3%) in concrete mixture design. Hardened concrete properties, such as 7- and 28-day compressive strength, splitting tensile strength, flexural strength, water and air absorption, and restrained shrinkage cracking were evaluated. No statistically significant effects were observed for polypropylene fibers on the compressive strength of concrete, while toughness indexes, splitting tensile and flexural strength and durability parameters showed an increase in the presence of polypropylene fibers. Increased fiber availability (fiber aspect ratio) in the concrete matrix, in addition to the ability of longer polypropylene fibers to bridge on the micro cracks, are suggested as the reasons for the enhancement in mechanical properties. Finally, crack width in fiber-reinforced concrete is calculated analytically with fiber property variables (fiber type, length, diameter and proportion). Results are compared with experimental values and concluded that with an increase in fiber length and/or decrease in fiber diameter crack width, decrease significantly.
Low Range of Ankle Dorsiflexion Predisposes for Patellar Tendinopathy in Junior Elite Basketball Players
Authors: Backman Ludvig J. , Danielson Patrik 
Published: September 2011

Background: Patellar tendinopathy (PT) is one of the most common reasons for sport-induced pain of the knee. Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon. Purpose: The purpose of this 1-year prospective study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT, including ankle dorsiflexion range in the dominant and nondominant leg. Data were collected over a 1-year period and follow-up, including reexamination, was made at the end of the year. Results: Seventy-five players met the inclusion criteria. At the follow-up, 12 players (16.0%) had developed unilateral PT. These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players, with a mean difference of −4.7° ( P = .038) for the dominant limb and −5.1° ( P = .024) for the nondominant limb. Complementary statistical analysis showed that players with dorsiflexion range less than 36.5° had a risk of 18.5% to 29.4% of developing PT within a year, as compared with 1.8% to 2.1% for players with dorsiflexion range greater than 36.5°. Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain (mean difference, −1.5° to −2.5°), although this was only statistically significant for nondominant legs. Conclusion: This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players. In the studied material, an ankle dorsiflexion range of 36.5° was found to be the most appropriate cutoff point for prognostic screening. This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions. A history of ankle sprains might contribute to reduced ankle dorsiflexion range.
Numerical investigation of high-pressure turbine blade tip flows: analysis of aerodynamics
Authors: Vass P , Arts T 
Published: September 2011

The current contribution reports on the validation and analysis of three-dimensional computational results of the flow around four distinct high-pressure turbine blade tip geometries (TG1, 2, 3, and 4 hereinafter), taking into account the effect of the entire internal cooling setup inside the blade, at design exit Mach number: M = 0.8, and high exit Reynolds number: Re C = 900 000. Three of the four geometries represent different tip design solutions – TG1: full squealer rim; TG2: single squealer on the suction side; TG3: partial suction and pressure side squealer, and one (TG4) models TG1 in worn condition. This article provides a comparison between the different geometries from the aerodynamic point of view, analyses the losses, and evaluates the distinct design solutions. An assessment of the effect of the uneven rubbing of the blade tip was performed as well. TG1 was found to be the top performer followed by TG3 and TG2. According to the investigations, the effect of rubbing increased the kinetic loss coefficient by 10–15 per cent.