bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Phase II Trial of Sorafenib with Temsirolimus or Tipifarnib in Untreated Metastatic Melanoma (S0438)
Authors: Margolin Kim A. , Moon James , Flaherty Lawrence E. , Lao Christopher D. , Akerley Wallace L. , Othus Megan , Sosman Jeffrey A. , Kirkwood John M. , Sondak Vernon K.
Published: January 2012

Purpose: Signaling pathway stimulation by activating mutations of oncogenes occurs in most melanomas and can provide excellent targets for therapy, but the short-term therapeutic success is limited by intrinsic and acquired resistance. The mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT/mTOR pathways are activated in most cutaneous melanomas. The purpose of this trial was to prospectively evaluate 2 molecularly targeted drug combinations in patients with untreated metastatic melanoma.

Experimental Design: This randomized phase II study enrolled patients between May 2008 and November 2009 with nonocular melanoma, no prior systemic chemotherapy, and no history of brain metastasis. Arm A received oral sorafenib 200 mg twice daily plus i.v. temsirolimus 25 mg weekly; and arm B received oral sorafenib 400 mg every morning, 200 mg every night daily plus oral tipifarnib 100 mg twice daily, 3 weeks of every 4. The primary objectives were to evaluate progression-free survival (PFS), objective response rate, and toxicity for the 2 regimens.

Results: On arm A (63 evaluable patients), the median PFS was 2.1 months and median overall survival (OS) was 7 months. Three patients achieved partial response (PR). Thirty-nine evaluable patients were accrued to arm B, which closed after first-stage accrual; the median PFS was 1.8 months and OS was 7 months, with 1 patient achieving PR.

Conclusions: The combinations of molecularly targeted agents tested did not show sufficient activity to justify further use. Newer agents and improved patient selection by characterization of the molecular targets in individual tumors show great promise and should be incorporated into future studies, along with appropriate laboratory correlates. Clin Cancer Res; 18(4); 1129–37. ©2012 AACR.
New Gene-Immunotherapy Combining TRAIL-Lymphocytes and EpCAMxCD3 Bispecific Antibody for Tumor Targeting
Authors: Groth Ariane , Salnikov Alexei V. , Ottinger Sabine , Gladkich Jury , Liu Li , Kallifatidis Georgios , Salnikova Olga , Ryschich Eduard , Giese Nathalia , Giese Thomas , Momburg Frank , Büchler Markus W. , Moldenhauer Gerhard , Herr Ingrid
Published: January 2012

Purpose: To enhance T-cell responsiveness toward cancer cells, we overexpressed TRAIL in lymphocytes, as this death ligand induces tumor-specific apoptosis. To increase contact time of lymphocytes with tumor cells and thereby of TRAIL with its death receptors, lymphocytes were linked to the CD3 arm of bispecific antibody EpCAMxCD3, to guide the lymphocytes to tumor cells positive for the cancer stem cell marker EpCAM/ESA.

Experimental Design: Lymphocytes were transduced with TRAIL lentivirus and the antitumor effect in presence and absence of EpCAMxCD3 was evaluated in vitro and in xenograft studies using epithelial cell adhesion molecule (EpCAM)–positive pancreatic and prostate cancer cells.

Results: Compared with control lymphocytes, TRAIL-lymphocytes increased cytotoxicity and further induced expression of several apoptosis-related molecules. Cotransplantation of TRAIL-lymphocytes and tumor cells in mice or peritumoral injection of TRAIL-lymphocytes in larger xenografts retarded growth and induced apoptosis. Combination of TRAIL-lymphocytes with EpCAMxCD3 potentiated tumor eradication by enhancing antiapoptotic and antiproliferative signaling and by decreasing tumor vasculature. Intratumoral cyst formation was involved and associated with enhanced chemokine secretion and infiltration of mouse macrophages, suggesting contribution of an inflammatory host response. Most importantly, tumorigenicity of pancreatic cancer cells with cancer stem cell features resistant to conventional chemotherapy was strongly reduced.

Conclusions: This gene-immunotherapeutic approach may be a new tool to support endogenous immune responses toward cancer even in its advanced stages. Clin Cancer Res; 18(4); 1028–38. ©2012 AACR.
Fibroblast Growth Factor-2 Is an Important Factor that Maintains Cellular Immaturity and Contributes to Aggressiveness of Osteosarcoma
Authors: Shimizu Takatsune , Ishikawa Tomoki , Iwai Sayaka , Ueki Arisa , Sugihara Eiji , Onishi Nobuyuki , Kuninaka Shinji , Miyamoto Takeshi , Toyama Yoshiaki , Ijiri Hiroshi , Mori Hajime , Matsuzaki Yumi , Yaguchi Tomonori , Nishio Hiroshi , Kawakami Yutaka , Ikeda Yasuo , Saya Hideyuki
Published: January 2012

Osteosarcoma is the most frequent, nonhematopoietic, primary malignant tumor of bone. Histopathologically, osteosarcoma is characterized by complex mixtures of different cell types with bone formation. The role of environmental factors in the formation of such a complicated tissue structure as osteosarcoma remains to be elucidated. Here, a newly established murine osteosarcoma model was used to clarify the roles of environmental factors such as fibroblast growth factor-2 (Fgf2) or leukemia-inhibitory factor (Lif) in the maintenance of osteosarcoma cells in an immature state. These factors were highly expressed in tumor environmental stromal cells, rather than in osteosarcoma cells, and they potently suppressed osteogenic differentiation of osteosarcoma cells in vitro and in vivo. Further investigation revealed that the hyperactivation of extracellular signal–regulated kinase (Erk)1/2 induced by these factors affected in the process of osteosarcoma differentiation. In addition, Fgf2 enhanced both proliferation and migratory activity of osteosarcoma cells and modulated the sensitivity of cells to an anticancer drug. The results of the present study suggest that the histology of osteosarcoma tumors which consist of immature tumor cells and pathologic bone formations could be generated dependent on the distribution of such environmental factors. The combined blockade of the signaling pathways of several growth factors, including Fgf2, might be useful in controlling the aggressiveness of osteosarcoma. Mol Cancer Res; 10(3); 454–68. ©2012 AACR.
Systemic-to-Pulmonary Collateral Flow, as Measured by Cardiac Magnetic Resonance Imaging, Is Associated With Acute Post-Fontan Clinical Outcomes
Authors: Glatz Andrew C. , Rome Jonathan J. , Small Adam J. , Gillespie Matthew J. , Dori Yoav , Harris Matthew A. , Keller Marc S. , Fogel Mark A. , Whitehead Kevin K.
Published: January 2012

Background—

Systemic-pulmonary collateral (SPC) flow occurs commonly in single ventricle patients after superior cavo-pulmonary connection, with unclear clinical significance. We sought to evaluate the association between SPC flow and acute post-Fontan clinical outcomes using a novel method of quantifying SPC flow by cardiac magnetic resonance (CMR) imaging.

Methods and Results—

All patients who had SPC flow quantified by CMR imaging before Fontan were retrospectively reviewed to assess for acute clinical outcomes after Fontan completion. Forty-four subjects were included who had Fontan completion between May 2008 and September 2010. SPC flow prior to Fontan measured 1.5±0.9 L/min/m
2
, accounting for 31±11% of total aortic flow and 44±15% of total pulmonary venous flow. There was a significant linear association between natural log-transformed duration of hospitalization and SPC flow as a proportion of total aortic (rho=0.31,
P
=0.04) and total pulmonary venous flow (rho=0.29,
P
=0.05). After adjustment for Fontan type and presence of a fenestration, absolute SPC flow was significantly associated with hospital duration ≥7 days (odds ratio [OR]=9.2,
P
=0.02) and chest tube duration ≥10 days (OR=22.7,
P
=0.009). Similar associations exist for SPC flow as a percentage of total aortic (OR=1.09,
P
=0.048 for hospitalization ≥7 days; OR=1.24,
P
=0.007 for chest tube duration ≥10 days) and total pulmonary venous flow (OR=1.07,
P
=0.048 for hospitalization ≥7 days; OR=1.18,
P
=0.006 for chest tube duration ≥10 days).

Conclusions—

Increasing SPC flow before Fontan, as measured by CMR imaging, is associated with increased duration of hospitalization and chest tube following Fontan completion.
An Algorithm for Testing Unidimensionality and Clustering Items in Rasch Measurement
Authors: Debelak Rudolf , Arendasy Martin
Published: January 2012

A new approach to identify item clusters fitting the Rasch model is described and evaluated using simulated and real data. The proposed method is based on hierarchical cluster analysis and constructs clusters of items that show a good fit to the Rasch model. It thus gives an estimate of the number of independent scales satisfying the postulates of sufficiency of total number of correctly answered items for a person’s proficiency, unidimensionality, and local independence that can be constructed from an item set. The method is also compared with the application of a principal components analysis based on tetrachoric correlations. In general, the proposed method was shown to provide practically usable results especially for large person samples.
Balancing Flexible Constraints and Measurement Precision in Computerized Adaptive Testing
Authors: Moyer Eric L. , Galindo Jennifer L. , Dodd Barbara G.
Published: January 2012

Managing test specifications—both multiple nonstatistical constraints and flexibly defined constraints—has become an important part of designing item selection procedures for computerized adaptive tests (CATs) in achievement testing. This study compared the effectiveness of three procedures: constrained CAT, flexible modified constrained CAT, and the weighted penalty model in balancing multiple flexible constraints and maximizing measurement precision in a fixed-length CAT. The study also addressed the effect of two different test lengths—25 items and 50 items—and of including or excluding the randomesque item exposure control procedure with the three methods, all of which were found effective in selecting items that met flexible test constraints when used in the item selection process for longer tests. When the randomesque method was included to control for item exposure, the weighted penalty model and the flexible modified constrained CAT models performed better than did the constrained CAT procedure in maintaining measurement precision. When no item exposure control method was used in the item selection process, no practical difference was found in the measurement precision of each balancing method.
The Componential Model of Reading
Authors: Ortiz Miriam , Folsom Jessica S. , Al Otaiba Stephanie , Greulich Luana , Thomas-Tate Shurita , Connor Carol M.
Published: January 2012

This study, framed by the component model of reading (CMR), examined the relative importance of kindergarten-entry predictors of first grade reading performance. Specifically, elements within the ecological domain included dialect, maternal education, amount of preschool, and home literacy; elements within the psychological domain included teacher-reported academic competence, social skills, and behavior; and elements within the cognitive domain included initial vocabulary, phonological, and morpho-syntactic skills, and alphabetic and word recognition skills. Data were obtained for 224 culturally diverse kindergarteners (58% Black, 34% White, and 8% Hispanic or other; 58% received free or reduced-price lunch) from a larger study conducted in seven predominantly high poverty schools ( n = 20 classrooms) in a midsized city school district in northern Florida. Results from a hierarchical multiple regression (with variables in the ecological domain entered first, followed by the psychological and cognitive domains) revealed a model that explained roughly 56% of the variance in first grade reading achievement, using fall-of-kindergarten predictors. Letter-word reading and morpho-syntactic skill were the strongest significant predictors. The findings largely support the CMR model as a means to understand individual differences in reading acquisition and, in turn, to support data-based instructional decisions for a wider range of children.
Incubating and Sustaining
Authors: Ritchie Scott
Published: January 2012

In spite of the U.S. corporatized education “reform” movement where the curriculum has been narrowed and teachers are pressured to teach to the test, many educators enact critical pedagogical practices that seek to make school a place that is equitable, democratic, collaborative, just, and humane. Using data from an in-depth qualitative interview study with eight critical P-12 U.S. teachers, the author found that teacher networks play important roles in helping people decide to become critical educators who teach for social justice and in sustaining their critical teaching once they are in the classroom. This article argues that it is imperative for teacher educators to use social justice networks to recruit prospective teachers and to help existing teacher candidates form and connect with networks. These practices may bring new teachers committed to social justice into the field of education and sustain the work of those already teaching for justice.
Development of Immunotoxicity Testing Strategies for Immunomodulatory Drugs
Authors: Kawabata Thomas T. , Evans Ellen W.
Published: January 2012

The ICH S8 immunotoxicity testing guideline for human pharmaceuticals was published in 2006 and was intended to provide guidance for assessing the immunotoxicity potential of low-molecular-weight drugs that are not intended to alter the immune system. For drugs intended to modulate the immune system, immunotoxicity testing strategies are generally developed on a case-by-case approach since the targets, intended patient population, and mechanisms of action of the test compound will determine the type of testing needed. Some of the general principles of ICH S8, however, may be applied to immunotoxicity testing strategies for immunomodulatory drugs. A weight-of-evidence approach using factors discussed in ICH S8 in concert with an assessment of the potential value of additional immunotoxicity testing should be considered. For most situations, immunotoxicity studies with immunomodulatory compounds evaluate off-target effects on the immune system and exaggerated pharmacology. The potential use of data from these studies and considerations such as translatability to humans are discussed.
The Draf III Mucosal Grafting Technique
Authors: Conger Bryant T. , Riley Kristen , Woodworth Bradford A.
Published: January 2012

Objective

The Draf III procedure is an advanced surgical option for frontal sinus disease refractory to endoscopic frontal sinusotomy and is used to expose the anterior limit of resection of the skull base during endoscopic management of anterior skull base tumors. Our objective was to evaluate outcomes of a strategy using mucosal grafts to decrease postoperative closure.

Study Design

Prospective cohort.

Setting

Tertiary care facility.

Subjects and Methods

Patients requiring a Draf III procedure were prospectively enrolled in the study. Demographics, reason for the procedure, percentage graft viability, and complications were recorded. The primary outcome measure was anterior‐posterior (AP) diameter at 3 months.

Results

Mucosal grafting was performed during 29 Draf III procedures from 2008 to 2011. Twenty‐seven patients (average age, 58 years) were available for measurement at 3 months (average postoperative follow‐up, 15.4 months; range, 3–30 months). Reasons for the procedure included tumor (n = 14), chronic rhinosinusitis (CRS) with frontal ostium stenosis (n = 12), and trauma (n = 1). Average intraoperative AP diameter was 11.7 mm. All patients met the definition of success (<50% reduction in diameter), maintaining a patent combined frontal sinus ostium for the duration of follow‐up (average diameter 10.8 mm at 3 months). Nine patients with CRS and frontal ostium stenosis had openings similar to the entire cohort (>1‐year follow‐up; average, 19.3 months) with significant symptom reduction (SNOT‐22 preop 62.3 ± 20.8 vs 3 months 27.8 ± 14.8 and 1 year 21.4 ± 13.6; P <. 0001).

Conclusion

Cicatricial stenosis and osteoneogenesis are common following the Draf III procedure. This study indicates that the use of mucosal grafts may assist with postoperative stenosis and should be considered a routine strategy for preventing closure.
Jones Fracture Fixation
Authors: Orr Justin D. , Glisson Richard R. , Nunley James A.
Published: January 2012

Background: Stabilization of fifth metatarsal Jones fractures with intramedullary screw fixation is the most common method for surgical fixation when operative treatment is indicated. Conventional partially threaded screws of various diameters are routinely used for Jones fracture fixation. Recently, the use of tapered variable pitch screws has become popular, but information regarding their performance in Jones fracture fixation is limited. No previous studies have compared conventional and tapered variable pitch screws in Jones fracture fixation under physiologic cyclic loading conditions.

Purpose: To determine whether biomechanical differences exist between appropriately sized conventional partially threaded screws and tapered variable pitch screws under physiologic cyclic loading conditions with regard to Jones fracture fixation.

Study Design: Controlled laboratory study.

Methods: Simulated Jones fractures were created in 23 matched pairs of fresh-frozen fifth metatarsals. One bone from each pair was stabilized with a conventional partially threaded screw and the contralateral bone with a tapered variable pitch screw. Initial compression, as well as fracture site compression, angulation, and bending stiffness, was compared between groups throughout 1000 physiologic cyclic loads.

Results: Conventional partially threaded screws obtained significantly greater initial compression compared with tapered variable pitch screws. Significantly greater compression was maintained throughout cyclic loading with conventional screw fixation compared with tapered variable pitch screws. Fracture site angulation was significantly greater using tapered variable pitch screws from the tenth load cycle through completion of cyclic loading. Despite a trend toward increased fracture site bending stiffness when using conventional screws, no difference in fixation stiffness was demonstrable between the 2 screw types.

Conclusion: In this cadaveric Jones fracture fixation model, conventional partially threaded screws provided improved fracture site compression and decreased fracture site angulation but offered no advantage in improving fracture site stiffness compared with tapered variable pitch screws. These results provide empirical evidence to guide implant selection decision making for operative fixation of Jones fractures.

Clinical Relevance: While the use of tapered variable pitch screws is a potential alternative for fixation of fifth metatarsal Jones fractures, conventional partially threaded screws may provide better biomechanical stability, the effect of which on fracture healing is unknown.
Percutaneous Endoscopic Gastrostomy as a Method of Nutrition Support in Children With Chronic Kidney Disease
Authors: Adamczyk Piotr , Banaszak Beata , Szczepańska Maria , Morawiec‐Knysak Aurelia , Szprynger Krystyna , Budziński Dariusz , Karpe Jacek , Ziora Katarzyna
Published: January 2012

Chronic kidney disease (CKD) exerts a significant impact on children's growth and development. In infants and children with CKD, feeding‐related problems are not infrequent, leading to protein‐energy malnutrition and resulting in retarded physical development. Because spontaneous energy intake is usually inadequate in children with CKD, special dietary counseling with supportive procedures are often required. Placement of a percutaneous endoscopic gastrostomy (PEG) tube is one practical way to allow home tube feeding. Such nutrition support is valuable in children with CKD, and although it is not free from complications and technical problems, it seems to be helpful in providing required nutrition intake. In this report, the authors describe their own experience with PEG implantation and use in 3 children with CKD.
Prevalence of Vitamin D Insufficiency Among Breast Cancer Survivors
Authors: Trukova Kristen P. , Grutsch James , Lammersfeld Carolyn , Liepa George
Published: January 2012

Background: Recent research has linked inadequate vitamin D levels with risk of breast cancer, but there are less data regarding the actual concentrations of vitamin D in women who have survived breast cancer. The objective of this study was to determine if vitamin D insufficiency is a prevalent problem for female breast cancer survivors who have completed treatment for breast cancer. Methods: Ninety‐nine breast cancer survivors and a control population of 54 women with no history of breast cancer participated in this study. Serum 25‐hydroxy vitamin D concentrations were measured throughout 2007. Dietary and supplemental intake of vitamin D was assessed by a food frequency questionnaire. Zip code of residence was used to evaluate potential for skin production of vitamin D. Results: Vitamin D insufficiency (<32 ng/mL) was observed in 76 of 99 (77%) of breast cancer survivors and 51 of 54 (94%) of controls. Women taking vitamin D supplements >1000 IU/d were less likely to exhibit vitamin D insufficiency, but supplementation did not guarantee sufficiency. Conclusion: Vitamin D insufficiency appears to be prevalent among both controls and breast cancer survivors. Vitamin D status should be routinely evaluated for all women as part of regular preventive care if supplemental vitamin D intake is <1000 IU daily.
Selection of Top 10 Quality Indicators for Nutrition Therapy
Authors: Verotti Cristiane Comeron Gimenez , Torrinhas Raquel Susana Matos de Miranda , Cecconello Ivan , Waitzberg Dan Linetzky
Published: January 2012

Background: The identification of useful quality indicators for nutrition therapy (QINTs) is of great interest and a challenge. This study attempted to identify the 10 QINTs that best suit the practice of quality control in nutrition therapy (NT) by evaluating the opinion of experts in NT with the use of psychometric techniques and statistical tools. Methods: Thirty‐six QINTs available for clinical application in Brazil were assessed in 2 distinct phases. In phase 1, 26 nutrition experts ranked QINTs by scoring 4 attributes (utility, simplicity, objectivity, low cost) to assess each QINT on a 5‐point Likert scale. The top 10 QINTs were identified from the 10 best scores obtained, and the reliability of expert opinion for each indicator was assessed by Cronbach's α. In phase 2, experts provided feedback regarding the selected top 10 QINTs by answering 2 closed questions. Results: The top 10 QINTs, in descending order, are the frequency of nutrition screening of hospitalized patients, diarrhea, involuntary withdrawal of enteral feeding tubes, feeding tube obstruction, fasting longer than 24 hours, glycemic dysfunction, estimated energy expenditure and protein needs, central venous catheter infection, compliance of NT indication, and frequency of application of subjective global assessment. Opinions were consistent among the interviewed experts. During feedback, 96% of experts were satisfied with the top 10 QINTs, and 100% had considered them in accordance with their previous opinion. Conclusion: The top 10 QINTs were identified according to their usefulness in clinical practice by obtaining adequate agreement and representativeness of opinion of nutrition experts.
Case Report of Acute Thiamine Deficiency Occurring as a Complication of Vitamin‐Free Parenteral Nutrition
Authors: Ferrie Suzie
Published: January 2012

Parenteral nutrition (PN) is a relatively recent life‐saving development in medicine but brings with it a range of new potential complications. Much of our knowledge about the signs and symptoms of individual micronutrient deficiencies comes from observations of patients receiving PN, and an example of this is the pivotal paper by Velez and colleagues published in Journal of Parenteral and Enteral Nutrition in 1985. This case report was the first published study to identify acute thiamine deficiency with cardiopathy and metabolic acidosis occurring in adult patients receiving vitamin‐free PN. Although the importance of thiamine has been recognized since the late 19th century, it is still unclear exactly what dose is required for full repletion of a deficient patient, and further research would be useful to elucidate this question.
The Story of the Evolution of a Unique Tai Chi Form
Authors: Robins Jo Lynne W. , Elswick R. K. , McCain Nancy L.
Published: January 2012

The purpose of this article is to introduce a unique tai chi form that has been successfully implemented in two large randomized clinical trials. The intervention is composed of a series of tai chi movements chosen for their particular meanings, thus adding a cognitive component to the practice of a moving meditation. Over the last decade, the intervention has continued to evolve as it has been used in different populations. Most recently, medical qigong has been integrated to strengthen its potential impact on a variety of biobehavioral measures associated with cardiometabolic risk in women. Following an appraisal of the authors’ process as well as the philosophy, practice, and research of tai chi and qigong, the authors share the story of their intervention to contribute to the evolving research of these safe, well-received, low-cost, and beneficial practices.
Effect of welding residual stress on plastic buckling of axially compressed cylindrical shells with patterned welds
Authors: Yu Chulin , Chen Zhiping , Wang Ji , Yan Shunjuan , Yang Licai
Published: January 2012

An experimental–numerical investigation of the effect of welding residual stress on plastic buckling of axially compressed cylindrical shells with patterned welds is carried out. Two cylindrical shell specimens with different pattern of welds are made according to manufacturing process used in engineering. Their initial geometric imperfections, axial and circumferential strain, buckling load, etc., are experimentally obtained. Inherent strain method used for simulating welding residual stress field is presented. Two different numerical modeling methods for the purpose of evaluating the effect of welding residual stress on plastic buckling are illustrated and the validity is verified by experiment. It is found that, load–displacement curve before buckling is altered, plastic buckling critical load is decreased to some extent, and the buckling deformation such as the number and the uniformity of waveforms of circumferential welds are changed when welding residual stress exists. For the above phenomena, the reason why welding residual stress has an influence on plastic buckling is also quantitatively analyzed from the point of stress variation.
Design and simulation of a steering gearbox with variable transmission ratio
Authors: Alexandru Petre , Macaveiu Dragoş , Alexandru Cătălin
Published: January 2012

This article presents the geometric and functional characteristics of a steering gearbox with variable transmission ratio, which contains a translating wheel (circular curved rack) in gearing with an eccentric sector (segment). The solution requires no special technology because it uses conventional involute gears, being obtained/derived from a classic gearbox with constant ratio by changing the gearing characteristics. The precision of the steering system and the reversibility of the gearing are not affected by these modifications, the driver having a good/safe control of the vehicle. This gearbox can be used for the steering systems of some low-power vehicles, assuring an increased actuating torque (less effort); in this way, the assistance (hydraulic power steering or electric power steering) can be avoided. The study is focused on the following objectives: formulating the theoretical bases, establishing the geometrical parameters, and simulating the functionality of the gearbox, based on the specific requirements of the vehicles’ steering system. Important conclusions have been drawn on the influence of some specific parameters in terms of insuring good gearing conditions, such as the variation of the distances between axes and the variation of the clearance between teeth.
Investigation of bending fatigue strength limit of alloy steel gear teeth
Authors: Bian X X , Zhou G , Liwei  , Tan J Z
Published: January 2012

An experimental investigation was conducted on the single-tooth pulsating bending fatigue of 38SiMnMo alloy steel at a frequency range of 140–150 Hz. Using both up–down test method and S–N curve extension method, statistical data in terms of curves and endurance limits were analysed. The testing and analytical results indicated that the ‘platform’ of fatigue curves exists and the S–N curve cannot be extended to the cyclic basic number Nb in order to obtain the endurance limit. Furthermore, on the basis of the life distribution optimization, the three-parameter Weibull distribution was used for statistical data analysis. The statistical analysis showed that the bending endurance limit of 38SiMnMo alloy steel gears estimated at 99 per cent reliability and 95 per cent confidence was 284 MPa, which was located at the slightly low part of the mean line in the chart range illustrated in the standards ISO6336 and GB3480. The results demonstrated that the method described in this article was valuable.
Influence of train dynamic modelling strategy on the prediction of track–ground vibrations induced by railway traffic
Authors: Costa Pedro Alves , Calçada Rui , Cardoso António Silva
Published: January 2012

This paper presents a study developed in order to identify the influence and relevance of the mechanical properties of the train in the prediction of vibrations induced by passenger railway traffic. Based on experimental data and numerical simulation, a discussion about the influence of the modelling strategy adopted for the train simulation is performed. Special emphasis is placed on the study of the influence of the unsprung and semi-sprung masses of the train on the train–track interaction mechanism. From the developed study it was found that the modelling strategy adopted for the train simulation is a key factor in the prediction of the free-field vibrations. Moreover, the accuracy of the prediction is considerably increased if the train simulation considers the unsprung and semi-sprung (bogies) masses of the train.
Model-based fault diagnosis for aerospace systems: a survey
Authors: Marzat J , Piet-Lahanier H , Damongeot F , Walter E
Published: January 2012

This survey of model-based fault diagnosis focuses on those methods that are applicable to aerospace systems. To highlight the characteristics of aerospace models, generic non-linear dynamical modelling from flight mechanics is recalled and a unifying representation of sensor and actuator faults is presented. An extensive bibliographical review supports a description of the key points of fault detection methods that rely on analytical redundancy. The approaches that best suit the constraints of the field are emphasized and recommendations for future developments in in-flight fault diagnosis are provided.
Performance study of an inlet in supersonic flow
Authors: Soltani Mohammad R , Farahani Mohammad
Published: January 2012

The performance characteristics of an axisymmetric inlet at its design and off-design operational conditions are experimentally investigated. The model is tested for wide ranges of free stream Mach numbers, M∞ = 1.5–2.5, and mass flow rates. For each test, the pressure recovery, the mass flow passing through the inlet and the pressure distribution over the spike and the cowl are measured. In addition, the shock wave formed in front of the inlet is visualized. The characteristic curve of the inlet is then obtained for each free stream Mach number. As the Mach number is increased, the pressure recovery is reduced, but the maximum value of the mass flow rate grows up. Variations of the mass flow affect the surface pressure over both the front portion of the cowl and the entire surface of the spike. Further, it has changed both pressure and Mach number at the end of the diffuser, which would consequently affect the performance of the propulsion system. In addition, contrary to the internal boundary layer, the external one far from the cowl lip has been found to be almost independent of the inlet mass flow rate for a constant free stream Mach number.
Cost-range trade-off of intermediate stop operations of long-range transport airplanes
Authors: Martinez-Val Rodrigo , Perez Emilio , Cuerno Cristina , Palacin Jose F
Published: January 2012

The objective of this study is to show the environmental and operating cost savings that could be achieved if long-range transport aircraft were designed for shorter ranges, and long-range flights were operated with an intermediate stop, obviously, with the drawback of longer trip duration and the increase in the number of flight cycles. The maximum take-off weight and operating empty weight, the main design variables of transport airplanes, noticeably diminish. The overall result depends on the length of the route, the extra distance due to the detour, the location of the intermediate airport and the technology level (range factor and operating empty weight fraction with respect to the maximum take-off weight). In all the routes analysed, the uneven splitting between both legs plays a secondary role. It is shown that long routes are well adapted to intermediate stop operations, particularly when the airliner serving the route has been designed for a medium range. However, intermediate stop operations produce a negative impact for medium and short city pair distances, since the reduction in aircraft weight is more than counterbalanced by the extra fuel and time required in the non-cruise phases of the flights.
Integrated motion planning and trajectory control system for unmanned air vehicles
Authors: Karimi J , Pourtakdoust Seid H
Published: January 2012

Motion planning and trajectory control are two basic challenges of unmanned vehicles. In motion planning problem, feasible trajectories are developed while nonlinear dynamic model and performance constraints of the vehicle under utility are considered. In this study, motion planning is performed via an enhanced particle swarm optimization algorithm. The resulting offline generated trajectories are tracked using a nonlinear trajectory control system methodology. The Lyapunov-based constrained backstepping approach and command filters are utilized in designing the trajectory control system. Command filters smoothen the input signals and provide their derivatives. Evaluation of the proposed integrated approach in several simulated scenarios has effectively demonstrated the potential of both algorithms in generating optimal contour matching trajectories as well as excellent tracking capability of the trajectory control system.
Change We Can Believe In
Authors: Johnson India R. , Fujita Kentaro
Published: January 2012

People are motivated to defend and rationalize the status quo, a phenomenon known as system justification. We propose the existence of a second, countervailing system-level motivation: system-change motivation, which is concerned with bettering the status quo over time. The opportunity to receive diagnostic information about the status quo pits the two system-level motives against each other. Whereas system justification promotes a preference for positive information about the status quo, system-change motivation promotes a preference for negative information about the status quo. In three experiments, we found that people preferred negative over positive feedback about the status quo when it was presented as being changeable. Our findings are the first to suggest the operation of a system-change motive.
Carrot Eaters or Moving Heads
Authors: Deng Wei (Sophia) , Sloutsky Vladimir M.
Published: January 2012

How do words affect generalization, and how do these effects change during development? One theory posits that even early in development, linguistic labels function as category markers and thus are different from the features of the stimuli they represent. Another theory holds that early in development, labels are akin to other features, but that they may become category markers in the course of development. We addressed this issue in two experiments with 4- to 5-year-olds and adults. In both experiments, participants performed a categorization task (in which they predicted a category label) and an induction task (in which they predicted a missing feature). In the latter task, the category label was pitted against a highly salient feature, such that reliance on the label and reliance on the salient feature would result in different patterns of responses. Results indicated that children relied on the salient feature when performing induction, whereas many adults relied on the category label. These results suggest that early in development, labels are no more than features, but that they may become category markers in the course of development.
Malignant Glomus Tumor of the Leg Developed in the Context of a Superficial Typical Glomus Tumor
Authors: Lancerotto Luca , Salmaso Roberto , Sartore Leonardo , Bassetto Franco
Published: January 2012

A 41-year-old man presented with a 2-cm painful subcutaneous nodule in his right leg, which had been present for more than 10 years and was recently enlarging. Histologically, the tumor was composed of sheets and nests of cells with variable cytomorphology, including typical round/ovoid glomus cells with clear cytoplasm and well-defined borders, small cells, and spindle cells. Numerous medium to large vessels were present. Nodules with moderate to high cellularity, nuclear atypia, and frequent mitotic figures (42 per 50 high-power fields) were noted. Immunohistochemistry showed cytoplasmic and membranous expression of smooth-muscle actin, vimentin, and membranous expression of type IV collagen. Whereas superficiality, dimensions, and long-term follow-up may suggest classification as a symplastic or uncertain potential glomus tumor (GT), histological features and immunoprofile are indicative of malignant nodules developed in a typical GT. The follow-up has been negative for recurrence/metastases. A search of the literature revealed 17 cases of malignant GTs between 1995 and 2010, all fatal, of which 10 had skin as the primary site.
Lack of tumor uptake of 131-I labeled rituximab in a patient with a CD20 positive lymphoma lesion
Authors: Tran L , Huitema ADR , Vogel WV , Beijnen JH , Baars JW
Published: January 2012

Radioimmunotherapy has emerged as a treatment modality for patients with CD20 positive B-cell non-Hodgkin’s lymphoma (NHL). Prior to administration of a therapeutic dose, confirmation of uptake of the radiolabeled compound in tumor locations and calculation of an appropriate dose can be performed using a diagnostic dose and subsequent imaging. We report the case of a 69-year-old male with a relapsed mantle cell lymphoma scheduled for radioimmunotherapy, where diagnostic imaging with 131-I labeled rituximab revealed unexpected new insights with implications for treatment. Persistence of the mantle cell lymphoma in a lymph node in the left arm was demonstrated by an 18-F fluorodeoxyglucose scan. However, a scan after a diagnostic dose of 131-I labeled rituximab did not show any uptake of the tracer, even though subsequent cytological analysis unequivocally confirmed a CD20 positive B-cell population in the lesion. The administration of a therapeutic dose of 131-I labeled rituximab was therefore cancelled. We here discuss the mechanisms that may explain lack of targeting in a proven CD20-positive lymphoma and provide recommendations for further studies.
Trends in Excipient Safety Evaluation
Authors: Osterberg Robert E. , DeMerlis Christopher C. , Hobson David W. , McGovern Timothy J.
Published: January 2012

Excipients are used in all drug products and in most food products. New technologies are being tested to increase the amount or rate of absorption of drugs and new and novel excipients may be included among them. New physical approaches such as nanoparticles of drug and excipients or lysosomes may offer better drug delivery especially of hard to absorb or difficult to formulate oral drugs. New excipients may improve or mask the flavor of foods, drugs, and dietary supplements. Recently, impurities in drug products have become subject to greater scrutiny and various international and national guidelines, guidances, and regulations have been proposed and accepted for use; excipient evaluation is included in these efforts. This symposium discussed new developmental concepts, guidelines/guidances and regulations involving impurities in excipients, new drug delivery systems involving excipients, and thoughts for possible improvement to these guidelines to promote faster regulatory acceptance of these substances.
The mental health and psychosocial effects of organized violence: A qualitative study in northern Haiti
Authors: Bolton Paul , Surkan Pamela J. , Gray Amber E. , Desmousseaux Marine
Published: January 2012

Historically, organized violence has been a chronic pervasive problem in Haiti. We set out to elicit Haitians’ views on its effects to guide the development of interventions. In March 2006 we studied a population in the slum area of Cap-Haitien, Haiti’s second largest city, and the nearby towns of Milot and Limbe. A convenience sample of adults was asked to free list all current problems affecting victims of organized violence. Two major categories emerged: psychological problems and financial problems. The psychological problems of “feeling startled and loss of self control,” “sadness/grief,” “continuing to suffer from reliving/reexperiencing past events,” “problems in the head/mental problems,” “deep suffering in the heart,” and “thinking too much” emerged as themes from key-informant interviews. These may correspond to constructs of depression, dysthymia, and anxiety disorders including posttraumatic stress disorder in psychiatric nosology. The development of effective interventions can therefore consider those known to be effective for these problems in other settings. However in selecting interventions, considerations must also include local acceptability, perceived causes of problems, and their social effects.
‘People will die because of the BBC’: British newspaper reaction to the BBC Gaza appeal decision
Authors: Thomas Ryan J , Hindman Elizabeth Blanks
Published: January 2012

This study examines the responses of British national newspaper editorials and op-eds to the BBC’s January 2009 decision not to air an appeal by the Disasters Emergency Committee to raise money for refugees in the Gaza region. We find six prominent themes in national newspaper discourse: (1) the BBC demonstrating blatant disregard for human life; (2) the BBC ‘taking sides’; (3) raising questions as to whether the BBC was ever impartial; (4) the decision situated as part of a broader narrative of failure; (5) the decision running counter to the BBC’s public service mission; and (6) broader questions raised over the BBC’s future. Our findings indicate that the BBC’s role in British life is under continued debate. This has implications for the organization in a time when its role is under scrutiny and threat from commercial forces.
Comparative efficacy and safety of fenofibrate/pravastatin plus ezetimibe triple therapy and simvastatin/ezetimibe dual therapy in type 2 diabetic patients with mixed hyperlipidaemia and cardiovascular disease
Authors: Farnier Michel , Retterstøl Kjetil , Steinmetz Armin , Császár Albert
Published: January 2012

Background:

This study was designed to compare the efficacy and safety of a fenofibrate/pravastatin 160/40 mg fixed-dose combination plus ezetimibe 10 mg triple therapy and simvastatin 20 mg plus ezetimibe 10 mg dual therapy in patients with type 2 diabetes, mixed hyperlipidaemia and cardiovascular disease.

Method:

After a 6-week run-in period on simvastatin 20 mg, 273 patients with non-high-density lipoprotein cholesterol (non-HDL-C) ≥ 100 mg/dl or low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl were randomised to receive 12-week treatment with triple therapy or dual therapy, followed by a 12-week safety period during which all patients received the triple therapy.

Results:

At week 12, similar significant decreases in non-HDL-C were observed with both treatments. The triple therapy has induced a greater decrease in triglycerides (between-treatment difference: −14.6%, p = 0.007) and the dual therapy a greater decrease in LDL-C (between-treatment difference: +5.3%, p = 0.05). Both treatments were generally well tolerated.

Conclusion:

The fenofibrate/pravastatin plus ezetimibe therapy improves the global atherogenic lipid profile in type 2 diabetic patients with mixed hyperlipidaemia.
Gender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: Results from the DIAD study
Authors: Tandon Suman , Wackers Frans JT , Inzucchi Silvio E , Bansal Shanti , Staib Lawrence H , Chyun Deborah A , Davey Janice A , Young Lawrence H ,   for the DIAD Investigators
Published: January 2012

Gender differences in cardiovascular outcomes were compared in asymptomatic men and women with type 2 diabetes (T2DM) in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Of 1123 participants, 290 men and 271 women were randomised to screening with stress myocardial perfusion imaging (MPI); 311 men and 251 women were randomised to no screening. Follow-up was 4.8±0.9 years for the occurrence of cardiac events (CE; cardiac death or non-fatal myocardial infarction). The frequency of abnormal screening was similar in men (24%) and women (19%), ( p=0.2), although women trended to have smaller MPI abnormalities. CE rates were lower in women than men (1.7% vs. 3.8%, p=0.04). No CEs occurred in 17 high-risk (UKPDS risk engine) women, whereas 14 (11.2%) occurred in 125 high-risk men. Asymptomatic women with T2DM have significantly better cardiac outcomes than their male counterparts and represent a subgroup for which screening for coronary artery disease does not appear warranted.
Transumbilical Single-Incision Laparoscopy Surgery Splenectomy Plus Pericaudial Devascularization in One Case With Portal Hypertension
Authors: Jing Kong , Shuo-Dong Wu , Ying Fan
Published: January 2012

Objective. Single-incision laparoscopy surgery (SILS) has rapidly developed as both a cosmetic advantage of natural orifice translumenal endoscopic surgery and a standard surgical procedure. In this article, the authors report on the new technique of SILS splenectomy plus pericaudial devascularization with conventional laparoscopic instruments. Methods. The technique of SILS splenectomy plus pericaudial devascularization in one patient with portal hypertension was introduced. Results. The procedure was feasible with conventional laparoscopic instruments. Operative time was 240 minutes, and blood loss was 350 mL. No intraoperative or postoperative complications, such as secondary hemorrhage or pancreatic leakage, were recorded. The patient was fully recovered, and the single umbilical scar was well healed. Conclusion. SILS splenectomy plus pericaudial devascularization is feasible when performed by experienced laparoscopic surgeons. It may have the same cosmetic advantage as natural orifice translumenal endoscopic surgery and may offer the safety of conventional laparoscopic operation. As far as the authors are aware, this is the first report.