bluuebunny/crossref_metadata_2025 huggingface dataset:
Final Safety Assessment of Thiodipropionic Acid and Its Dialkyl Esters as Used in Cosmetics
Authors: Diamante Catherine , Zondlo Fiume Monice , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: July 2010

Dilauryl thiodipropionate (DLTDP), dicetyl thiodipropionate, dimyristyl thiodipropionate, distearyl thiodipropionate, and ditridecyl thiodipropionate are dialkyl esters of their respective alcohols and thiodipropionic acid (TDPA) used in cosmetics. Ingested DLTDP was excreted in the urine as TDPA. Single-dose acute oral and parenteral studies and subchronic and chronic repeated dose oral studies did not suggest significant toxicity. Neither DLTDP nor TDPA was irritating to animal skin or eyes and they were not sensitizers. TDPA was neither a teratogen nor a reproductive toxicant. Genotoxicity studies were negative for TDPA and DLTDP. Clinical testing demonstrated some evidence of irritation but no sensitization or photosensitization. The Cosmetic Ingredient Review Expert Panel considered that the data from DLTDP reasonably may be extrapolated to the other dialkyl esters and concluded that these ingredients were safe for use in cosmetic products that are formulated to be nonirritating.
Final Report of the Amended Safety Assessment of Myristic Acid and Its Salts and Esters as Used in Cosmetics
Authors: Becker Lillian C. , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: July 2010

This report addresses the safety of the inorganic salts and esters of various fatty alcohols of myristic acid. Most of the esters are used as skin conditioning agents in many types of cosmetics in a range of concentrations. Myristate esters are readily hydrolyzed to the corresponding alcohols and acids, which are then further metabolized. Myristate salts readily dissociate in any likely cosmetic formulation. The Cosmetic Ingredient Review (CIR) Panel recognized that much of the data supporting the ingredients in this group were previously reviewed in safety assessments for related ingredients. Where specific data did not exist, the Panel considered structure—activity relationships in determining the safety of these ingredients as used in cosmetics. The Panel determined that myristic acid and its salts and esters are safe as cosmetic ingredients in the current practices of use and concentration.
Final Report of the Safety Assessment of Methylisothiazolinone
Authors: Burnett Christina L. , Bergfeld Wilma F. , Belsito Donald V. , Klaassen Curtis D. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: July 2010

Methylisothiazolinone (MIT) is a heterocyclic organic compound used as a preservative in cosmetics and personal care products in concentrations up to 0.01%. MIT is a colorless, clear liquid with a mild odor that is completely soluble in water; mostly soluble in acetonitrile, methanol, and hexane; and slightly soluble in xylene. Consistent with its solubility, dermal penetration is low. The Cosmetic Ingredient Review Expert Panel noted the in vitro evidence of neurotoxicity but concluded that the absence of any neurotoxicity findings in the many in vivo studies, including subchronic, chronic, and reproductive and developmental animal studies, suggests that MIT would not be neurotoxic as used in cosmetics. Although recognizing that MIT was a sensitizer in both animal and human studies, the panel concluded that there is a threshold dose response and that cosmetic products formulated to contain concentrations of MIT at 100 ppm (0.01%) or less would not be expected to pose a sensitization risk. Accordingly, MIT may be safely used as a preservative in cosmetics up to that concentration.
Multilevel Mixed-Measurement IRT Analysis: An Explication and Application to Self-Reported Emotions Across the World
Authors: Tay Louis , Diener Ed , Drasgow Fritz , Vermunt Jeroen K.
Published: July 2010

Dimensional approaches assume that all individuals within hierarchical units (e.g., organizations or countries) share the same measurement model. However, such models are less applicable when researchers are interested in obtaining classes of individuals who share the same measurement model across hierarchical units and to obtain hierarchical latent classes (LCs). The authors present the multilevel mixed-measurement item response theory (MMM-IRT) model as an alternative. This model yields classes of individuals with a common measurement model that spans across hierarchical units. In addition, hierarchical units are classified together to the extent that they share similar proportions of individual-level classes. The authors illustrate the MMM-IRT model with data on self-reported emotions from 121,740 individuals across 116 countries where four individual classes and five country classes were found. Theoretical and methodological implications concerning cross-cultural, multilevel, and measurement equivalence research are discussed.
Manufacturing of aluminum foam sandwich panels: comparison of a novel method with two different conventional methods
Authors: Nabavi A. , Khaki J. Vahdati
Published: July 2010

In this study, a novel method for manufacturing metal foam sandwich panels via self-propagating high temperature synthesis (SHS) has been introduced. In this method, a powder mixture of metallic aluminum and copper oxide was placed in core—sheet interface, and then sandwich panel was heated under static pressure. During heating, SHS reaction (3CuO + 2Al = + 3Cu, ΔH < 0) occurred in the interface. The generated heat from this exothermic reaction caused sheets to join the core by melting the interface and nearby. In order to evaluate the shear strength of the interface, the shear test was applied to the manufactured sandwich panels and its results were compared with sandwich panels, which were produced by diffusion and adhesive bonding processes. Furthermore, by the aid of energy dispersive spectrometer and X-ray diffraction analyses, the formation of copper in the core—sheet interface and its diffusion into the sheets and the core were investigated. The results showed that metal foam sandwich panels produced by using SHS method have higher joint strength than those produced by diffusion and adhesive bonding processes, and the maximum shear strength of the interface was achieved in shorter heating time. Significantly, this innovating method for manufacturing metal foam sandwich panels can be applied as a proper and alternative method.
Hippocampal atrophy in relapsing-remitting and primary progressive MS: a comparative study
Authors: Anderson VM , Fisniku LK , Khaleeli Z. , Summers MM , Penny SA , Altmann DR , Thompson AJ , Ron MA , Miller DH
Published: July 2010

Background: In multiple sclerosis (MS), demyelination and neuroaxonal damage are seen in the hippocampus, and MRI has revealed hippocampal atrophy.

Objectives: To investigate and compare hippocampal volume loss in patients with relapsing—remitting MS (RRMS) and primary progressive MS (PPMS) using manual volumetry, and explore its association with memory dysfunction.

Methods: Hippocampi were manually delineated on volumetric MRI of 34 patients with RRMS, 23 patients with PPMS and 18 controls. Patients underwent neuropsychological tests of verbal and visuospatial recall memory. Linear regression was used to compare hippocampal volumes between subject groups, and to assess the association with memory function.

Results: Hippocampal volumes were smaller in MS patients compared with controls, and were similar in patients with RRMS and PPMS. The mean decrease in hippocampal volume in MS patients was 317 mm3 (9.4%; 95% CI 86 to 549; p = 0.008) on the right and 284 mm3 (8.9%; 95% CI 61 to 508; p = 0.013) on the left. A borderline association of hippocampal volume with memory performance was observed only in patients with PPMS.

Conclusion: Hippocampal atrophy occurs in patients with RRMS and PPMS. Factors additional to hippocampal atrophy may impact on memory performance.
Broadening Psychology’s Contribution to Addressing Issues of HIV/AIDS, Poverty and Nutrition
Authors: Tomlinson Mark , Rohleder Poul , Swartz Leslie , Drimie Scott , Kagee Ashraf
Published: July 2010

HIV/AIDS, more than any other public health problem, challenges dominant models of the role of psychology in health promotion and prevention. This paper focuses on poverty and resulting food insecurity as a structural risk factor for HIV infection. The paper considers the role of health psychology in global health concerns and argues that, while individual-based interventions are important, health psychology needs to shift to playing a proper role in broader level initiatives. Health psychology, in thinking about global health concerns such as HIV, needs to view an understanding of health, education and nutrition delivery programmes in low resourced contexts as at the core of the discipline.
Privilege and Status in an Unequal Society: Shifting the Focus of Health Promotion Research to Include the Maintenance of Advantage
Authors: Stephens Christine
Published: July 2010

There has been a great deal of social policy and health promotion practice directed toward the inclusion of underprivileged groups with the aim of improving their health. This focus on disadvantaged people and poor communities, to help them empower themselves and improve their lot, often fails because it ignores the role of the broader society. We neglect to note the crucial part that the advantaged play in perpetuating inequalities. Theory and empirical work from sociology and anthropology points to the everyday ways in which privileged people are able to maintain their advantage and even hi-jack the benefits of public health programmes designed to improve the health of the poor. Some examples from these other disciplines suggest ways in which a social psychological perspective can contribute to an understanding of how inequalities and poverty are perpetuated in everyday life. These understandings will inform the effectiveness of social programmes to reduce inequalities.
WALL-E’s world: animating Badiou’s philosophy
Authors: Shaw Ian Graham Ronald
Published: July 2010

This article illustrates the philosophy of Alain Badiou through Pixar’s 2008 animation ‘WALL-E’. The fictional story tells of a toxic planet Earth long abandoned following an ecological disaster. Humanity now exists in a floating brave new world; a spaceship whose passengers’ everyday existence is drowned by a consumptive slumber. That is, until a robot named WALL-E comes aboard and changes things forever. The purpose of making this connection between philosophy and film is not to trivialize Badiou’s work, but rather to open it up, pull it apart, and synchronize it with a movie that is saturated with Badiouian themes. Beneath the complexities of Being and Event’s set-theory and the Logics of Worlds’ algebra, lay a set of ideas that are fizzing with creativity and disruptive potential. WALL-E gives these political and philosophical ideas a lived expression to a wide audience. The central motif of the article is that the finitude of appearance in a world is constantly overrun by the infinitude of being, and this requires a new theorization of site-based geographies. From the miraculous discovery of a plant growing on a dead Earth, to the tumultuous arrival of WALL-E onboard a spaceship that he never belonged to, the stability of a world is always threatened by a ‘point of excess’, called the site. Three interrelated concepts of Badiou’s will be animated in this article: atonic and tensed worlds, sites, and subjects
Copper and Ceruloplasmin Abnormalities in Alzheimer’s Disease
Authors: Brewer George J. , Kanzer Steve H. , Zimmerman Earl A. , Celmins Dzintra F. , Heckman Susan M. , Dick Robert
Published: July 2010

The idea that copper may play a role in the pathogenesis of Alzheimer’s disease is gaining momentum. Serum copper and ceruloplasmin were measured by both enzymatic (eCp) and immunologic (iCp) methods in 28 patients with Alzheimer’s disease and 29 age-matched controls. ‘‘Free copper’’ was determined by subtracting copper accounted for in the eCp assay from total serum copper. Percentage free copper, that is the proportion of serum copper not bound to ceruloplasmin, was significantly elevated in patients with Alzheimer’s compared to controls. There was significantly more ‘‘defective’’ ceruloplasmin, which is apoceruloplamin lacking its copper, in Alzheimer’s disease than in normal controls. This abnormality may precede the clinical onset of the disease and help predict risk of disease onset. Increased exposure to environmental copper (eg, the spread of copper plumbing and the use of copper in supplements) and/or defective ceruloplasmin function may play a role in the current epidemic of Alzheimer’s disease.
Influence of Vascular Oxidative Stress and Inflammation on the Development and Progression of Atherosclerosis
Authors: Bronas Ulf G. , Dengel Donald R.
Published: July 2010

Cardiovascular disease (CVD) risk factors such as hypertension, diabetes, dyslipidemia, smoking, physical inactivity, and obesity increase production of vascular reactive oxygen species (ROS), which results in a reduction of bioavailable nitric oxide and ultimately endothelial dysfunction and endothelial cell activation. ROS appears to mediate the inflammatory pathways that participate in the development and progression of atherosclerosis. There are numerous markers of oxidative stress and inflammation available for assessing the therapeutic response to interventions, but few are currently recommended for clinical use. Exercise training improves endothelial function via several mechanisms, including increased endothelial nitric oxide synthase—nitric oxide (eNOS-NO)— mediated production, increased activity and amount of antioxidants, attenuated ROS production, and an apparent reduction in systemic inflammation, possibly related to an increase in myokines resulting from skeletal muscle activation. Dietary antioxidant supplementation may improve endothelial function, oxidative stress, and inflammation, but much controversy exists regarding the use of antioxidant supplementation in primary and secondary CVD prevention. The purpose of this article is to review the contribution of vascular oxidative stress and activation of the inflammatory pathways in the pathogenesis of CVD and to review common methods used in clinical research to assess vascular oxidative stress and inflammation in response to therapeutic lifestyle interventions.
Sample size calculations for evaluating treatment policies in multi-stage designs
Authors: Dawson Ree , Lavori Philip W
Published: July 2010

Background Sequential multiple assignment randomized (SMAR) designs are used to evaluate treatment policies, also known as adaptive treatment strategies (ATS). The determination of SMAR sample sizes is challenging because of the sequential and adaptive nature of ATS, and the multi-stage randomized assignment used to evaluate them.

Purpose We derive sample size formulae appropriate for the nested structure of successive SMAR randomizations. This nesting gives rise to ATS that have overlapping data, and hence between-strategy covariance. We focus on the case when covariance is substantial enough to reduce sample size through improved inferential efficiency.

Methods Our design calculations draw upon two distinct methodologies for SMAR trials, using the equality of the optimal semi-parametric and Bayesian predictive estimators of standard error. This ‘hybrid’ approach produces a generalization of the t-test power calculation that is carried out in terms of effect size and regression quantities familiar to the trialist.

Results Simulation studies support the reasonableness of underlying assumptions as well as the adequacy of the approximation to between-strategy covariance when it is substantial. Investigation of the sensitivity of formulae to misspecification shows that the greatest influence is due to changes in effect size, which is an a priori clinical judgment on the part of the trialist.

Limitations We have restricted simulation investigation to SMAR studies of two and three stages, although the methods are fully general in that they apply to ‘K-stage’ trials.

Conclusions Practical guidance is needed to allow the trialist to size a SMAR design using the derived methods. To this end, we define ATS to be ‘distinct’ when they differ by at least the (minimal) size of effect deemed to be clinically relevant. Simulation results suggest that the number of subjects needed to distinguish distinct strategies will be significantly reduced by adjustment for covariance only when small effects are of interest.
Using bevacizumab with different chemotherapeutic regimens in metastatic colorectal cancer: balancing utility with low toxicity
Authors: Chong G. , Tebbutt N.C.
Published: July 2010

The addition of bevacizumab to currently available treatment options for metastatic colorectal cancer has changed the traditional chemotherapy-based paradigm. In this review we cover published clinical trials pertaining to the toxicity and efficacy of bevacizumab for metastatic colorectal cancer. Several randomized trials have studied combinations of irinotecan, oxaliplatin, 5-fluorouracil or capecitabine with bevacizumab. Efficacy in terms of progression-free survival and overall survival has been improved to varying degrees with the addition of bevacizumab. Bevacizumab’s distinctive toxicity profile has been well demonstrated in these trials, and has been shown to be manageable. However, certain patient groups, such as the elderly, may require particular toxicity considerations with bevacizumab. The optimal timing, dose and duration of bevacizumab-containing therapy have yet to be fully determined. Further randomized data, particularly for patients with potentially resectable liver metastases, are required in order to fully define the role of bevacizumab in the increasingly complex management paradigm for this disease.
Bevacizumab in the treatment of patients with advanced breast cancer: where have we landed?
Authors: Dirix L.Y. , Van Dam P.A. , Prove A.M. , Vermeulen P.B.
Published: July 2010

Vast preclinical and clinical evidence has made angiogenesis one of the hallmarks of cancer. In many human tumours, vascular endothelial growth factor (VEGF) has been identified as the crucial mediator of this process. Initial studies suggested that angiogenesis, and VEGF in particular, could be inhibited without the risk of major side effects. After the pivotal data in first-line studies in patients with colorectal cancer, numerous clinical trials have been undertaken in patients with breast cancer. This review attempts to update these investigations and define the role of anti-VEGF antibody treatment in advanced breast cancer.
Revisiting an Old Therapy
Authors: Paul Sophia C. , Saba Mojdeh , Berger Karen
Published: July 2010

The use of theophylline for the treatment of asthma has decreased significantly over the past few decades. Nonetheless, clinicians may still encounter patients with theophylline-based asthma regimens. While theophylline’s exact mechanism of action is not defined, new theories infer that the benefit of theophylline is due to its anti-inflammatory, rather than bronchodilatory, effects. Clinical trials have explored the combination of theophylline with lower doses of corticosteroids as a steroid-sparing strategy. Complex pharmacokinetics, significant adverse effects, and interpatient variability have contributed to the decreased use of this medication for asthma. Clinicians should be cognizant of the appropriate initial dosing, variety of formulations, and timing of theophylline levels to reduce toxicity and better control asthma symptoms. This review summarizes literature supporting the use of low-dose theophylline as an adjunct to corticosteroids in asthma, as well as pharmacokinetics, drug interactions, and adverse effects associated with its traditional dosing strategy.
Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells
Authors: Kochenderfer James N. , Yu Zhiya , Frasheri Dorina , Restifo Nicholas P. , Rosenberg Steven A.
Published: July 2010

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)–expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19–CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19–CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19–CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19–CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19–CAR-transduced T-cell infusion. Anti-CD19–CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19–CAR-transduced T cells in a clinically relevant murine model.
Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy
Authors: Kantarjian Hagop M. , Giles Francis J. , Greenberg Peter L. , Paquette Ron L. , Wang Eunice S. , Gabrilove Janice L. , Garcia-Manero Guillermo , Hu Kuolung , Franklin Janet L. , Berger Dietmar P.
Published: July 2010

We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs ≥ 50 × 109/L) and randomized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 μg, romiplostim 750 μg, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy. This study was registered at www.clinicaltrials.gov as #NCT00321711.
Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
Authors: Lugli Enrico , Goldman Carolyn K. , Perera Liyanage P. , Smedley Jeremy , Pung Rhonda , Yovandich Jason L. , Creekmore Stephen P. , Waldmann Thomas A. , Roederer Mario
Published: July 2010

Interleukin-15 (IL-15) is a cytokine with potential therapeutic application in individuals with cancer or immunodeficiency to promote natural killer (NK)– and T-cell activation and proliferation or in vaccination protocols to generate long-lived memory T cells. Here we report that 10-50 μg/kg IL-15 administered intravenously daily for 12 days to rhesus macaques has both short- and long-lasting effects on T-cell homeostasis. Peripheral blood lymphopenia preceded a dramatic expansion of NK cells and memory CD8 T cells in the circulation, particularly a 4-fold expansion of central memory CD8 T cells and a 6-fold expansion of effector memory CD8 T cells. This expansion is a consequence of their activation in multiple tissues. A concomitant inverted CD4/CD8 T-cell ratio was observed throughout the body at day 13, a result of preferential CD8 expansion. Expanded T- and NK-cell populations declined in the blood soon after IL-15 was stopped, suggesting migration to extralymphoid sites. By day 48, homeostasis appears restored throughout the body, with the exception of the maintenance of an inverted CD4/CD8 ratio in lymph nodes. Thus, IL-15 generates a dramatic expansion of short-lived memory CD8 T cells and NK cells in immunocompetent macaques and has long-term effects on the balance of CD4+ and CD8+ T cells.
Graph-based clustering and characterization of repetitive sequences in next-generation sequencing data
Authors: Novák Petr , Neumann Pavel , Macas Jiří
Published: July 2010

Background

The investigation of plant genome structure and evolution requires comprehensive characterization of repetitive sequences that make up the majority of higher plant nuclear DNA. Since genome-wide characterization of repetitive elements is complicated by their high abundance and diversity, novel approaches based on massively-parallel sequencing are being adapted to facilitate the analysis. It has recently been demonstrated that the low-pass genome sequencing provided by a single 454 sequencing reaction is sufficient to capture information about all major repeat families, thus providing the opportunity for efficient repeat investigation in a wide range of species. However, the development of appropriate data mining tools is required in order to fully utilize this sequencing data for repeat characterization.

Results

We adapted a graph-based approach for similarity-based partitioning of whole genome 454 sequence reads in order to build clusters made of the reads derived from individual repeat families. The information about cluster sizes was utilized for assessing the proportion and composition of repeats in the genomes of two model species, Pisum sativum and Glycine max, differing in genome size and 454 sequencing coverage. Moreover, statistical analysis and visual inspection of the topology of the cluster graphs using a newly developed program tool, SeqGrapheR, were shown to be helpful in distinguishing basic types of repeats and investigating sequence variability within repeat families.

Conclusions

Repetitive regions of plant genomes can be efficiently characterized by the presented graph-based analysis and the graph representation of repeats can be further used to assess the variability and evolutionary divergence of repeat families, discover and characterize novel elements, and aid in subsequent assembly of their consensus sequences.
Continued improvement of cardiovascular mortality in Hungary - impact of increased cardio-metabolic prescriptions
Authors: Balogh Sandor , Papp Renata , Jozan Peter , Csaszar Albert
Published: July 2010

Background

During the last 35 years the poor ranking of Hungary on the list of life expectancy at birth among European countries, has not changed. In 1970 our lag behind the leading European countries was the smallest. The gap was growing between 1970 and 1993 but from 1994 onwards the life expectancy at birth in Hungary has increased continuously and somewhat faster than in other European countries. The aim of this study was to analyze the association between decreasing cardiovascular mortality rates, as a main cause of death and the increase in cardio-metabolic prescriptions and possible changes in lifestyle behavior.

Methods

Analyses were conducted on national data concerning cardiovascular mortality and the number of cardio-metabolic drug prescription per capita. The association between yearly rates of cardiovascular events and changes in antihypertensive, antilipidemic and antidiabetic prescription rates was analyzed. The changes in other cardiovascular risk factors, like lifestyle were also considered.

Results

We observed a remarkable decline of mortality due to stroke and acute myocardial infarction (AMI). The fall was significantly associated with all prescription rates. The proportion of each treatment type responsible for suppression of specific mortality rates is different. All treatment types comparably improved stroke mortality, while antilipidemic therapy improved AMI outcome.

Conclusions

These results emphasize the importance of a comprehensive strategy that maximizes the population coverage of effective treatments. Hungary appears to be at the beginning of the fourth stage of epidemiologic transition, i.e. it has entered the stage of delayed chronic noninfectious diseases.
GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes
Authors: Li Aiguo , Bozdag Serdar , Kotliarov Yuri , Fine Howard A
Published: July 2010

Background

Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine.

Results

We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA)-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework.

Conclusions

GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.
The association of higher levels of within-normal-limits liver enzymes and the prevalence of the metabolic syndrome
Authors: Steinvil Arie , Shapira Itzhak , Ben-Bassat Orit Kliuk , Cohen Michael , Vered Yaffa , Berliner Shlomo , Rogowski Ori
Published: July 2010

Background

Metabolic syndrome (MetS) is frequently characterized by elevated liver enzymes, including gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT). Our objective was to evaluate the range of prevalence of MetS in apparently healthy individuals whose liver enzyme concentrations were all within-normal-range.

Methods

We have performed a cross sectional analysis on participants of the Tel-Aviv medical center inflammation survey (TAMCIS) recruited between the years 2003-2009. Analyzed were a cohort of 6,561 men and 3,389 women.

Results

The prevalence of MetS increased significantly from the first quintile to the fifth for both GGT and ALT, all the five quintiles being in the normal range. Logistic regression analysis for the presence of MetS showed crude odds ratios of 2.7 and 2.4 between the first and fourth quintiles and 3.6 and 3.2 for the fifth quintile in men and women respectively for ALT. For GGT the respective odds being 3.6 and 3.2 for the fourth quintile and 3.9 and 3.4 for the fifth quintile in men and women, respectively.

Conclusions

A relatively high prevalence of MetS was noted in a cohort of apparently healthy individuals with liver enzyme concentrations within-normal-limits. Practical consequences include the need to follow up these enzyme concentrations as continuous variables and to take into consideration that even relatively small elevations within the normal range might reflect the presence of dysmetabolism.
Superior vena cava syndrome in a patient with previous cardiac surgery: what else should we suspect?
Authors: Dedeilias Panagiotis , Nenekidis Ioannis , Hountis Panagiotis , Prokakis Christos , Dolou Paraskevi , Apostolakis Efstratios , Koletsis Efstratios N
Published: July 2010

Background

Although mediastinal tumors compressing or invading the superior vena cava represent the major causes of the superior vena cava syndrome, benign processes may also be involved in the pathogenesis of this medical emergency. One of the rarest benign causes is a pseudoaneurysm developing in patients previously having heart surgery.

Case report

We present the case of a large pseudoaneurysm of the ascending aorta, five years after primary surgery, with a significant compression of the right mediastinal venous system causing superior vena cava syndrome, detected at chest CT angiography. Perioperative findings showed two rush out points both coming from the distal aortic suture line which was performed five years ago. The patient underwent reoperation under circulatory arrest facilitating safe exploration and repair of the distal anastomotic leaks

Conclusion

Enhanced chest CT should be always undertaken in all patients with superior vena cava syndrome, especially in those previously having cardiac or aortic surgery to correctly evaluate the presence of a pseudoaneurysm. Mass effect to the superior vena cava makes necessary an open surgical treatment of the pseudoaneurysm so as to concurrently resolve the right mediastinal venous system's compression. Surgery should be performed in terms of safe approach to avoid exsanguination and cerebral malperfusion.
Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer
Authors: Gong Youling , Wang Shichao , Zhou Lin , Liu Yongmei , Xu Yong , Lu You , Bai Sen , Fu Yuchuan , Xu Qingfeng , Jiang Qingfeng
Published: July 2010

Purpose

To study the impacts of multileaf collimators (MLC) width [standard MLC width of 10 mm (sMLC) and micro-MLC width of 4 mm (mMLC)] in the intensity-modulated radiotherapy (IMRT) planning for the upper thoracic esophageal cancer (UTEC).

Methods and materials

10 patients with UTEC were retrospectively planned with the sMLC and the mMLC. The monitor unites (MUs) and dose volume histogram-based parameters [conformity index (CI) and homogeneous index (HI)] were compared between the IMRT plans with sMLC and with mMLC.

Results

The IMRT plans with the mMLC were more efficient (average MUs: 703.1 ± 68.3) than plans with the sMLC (average MUs: 833.4 ± 73.8) (p < 0.05). Also, compared to plans with the sMLC, the plans with the mMLC showed advantages in dose coverage of the planning gross tumor volume (Pgtv) (CI 0.706 ± 0.056/HI 1.093 ± 0.021) and the planning target volume (PTV) (CI 0.707 ± 0.029/HI 1.315 ± 0.013) (p < 0.05). In addition, the significant dose sparing in the D5 (3260.3 ± 374.0 vs 3404.5 ± 374.4)/gEUD (1815.1 ± 281.7 vs 1849.2 ± 297.6) of the spinal cord, the V10 (33.2 ± 6.5 vs 34.0 ± 6.7), V20 (16.0 ± 4.6 vs 16.6 ± 4.7), MLD (866.2 ± 174.1 vs 887.9 ± 172.1) and gEUD (938.6 ± 175.2 vs 956.8 ± 171.0) of the lungs were observed in the plans with the mMLC, respectively (p < 0.05).

Conclusions

Comparing to the sMLC, the mMLC not only demonstrated higher efficiencies and more optimal target coverage, but also considerably improved the dose sparing of OARs in the IMRT planning for UTEC.
Mild Renal Dysfunction Is a Risk Factor for a Decrease in Bone Mineral Density and Vertebral Fractures in Japanese Postmenopausal Women
Authors: Kaji Hiroshi , Yamauchi Mika , Yamaguchi Toru , Shigematsu Takashi , Sugimoto Toshitsugu
Published: July 2010

Context: The effect of mild renal dysfunction on bone mineral density and fracture risk is uncertain.

Objective: We evaluated whether mild renal dysfunction would affect bone mineral density (BMD) and the risk of vertebral fractures (VFs) in 659 postmenopausal women.

Main Outcome Measures: Creatinine clearance (CCr) and the estimated glomerular filtration rate (eGFR) were calculated using the Cockcroft-Gault and the Modification of Diet in Renal Disease formulas, respectively. BMD was measured by dual-energy x-ray absorptiometry. Renal function was categorized by the criteria of the Kidney Disease Outcomes Quality Initiative Committee.

Results: Comparison of fracture prevalence by chronic kidney disease stages revealed that the group of stage 3 or greater by eGFR had a significantly higher rate of VFs (45.3%) than stages 1 (23.8%) and 2 (25.3%) groups. In the stage 2 group, there were significant positive correlations between eGFR and BMD values at the femoral neck and radius as well as between CCr and BMD values at all sites. Moreover, postmenopausal women with VFs had lower eGFR and CCr than those without VFs in stage 2. When multivariable logistic regression analysis was performed with the presence of VFs as a dependent variable and CCr levels adjusted for years after menopause, smoking habit, alcohol intake, and lumbar spine BMD as an independent variable, CCr levels were identified as a factor associated with the presence of VFs in postmenopausal women with chronic kidney disease stage 2.

Conclusions: The present study indicates that postmenopausal women with mild renal dysfunction are at increased risk for BMD decrease and VFs.
Macroscopic stiffening of embryonic tissues via microtubules, RhoGEF and the assembly of contractile bundles of actomyosin
Authors: Zhou Jian , Kim Hye Young , Wang James H.-C. , Davidson Lance A.
Published: July 2010

During morphogenesis, forces generated by cells are coordinated and channeled by the viscoelastic properties of the embryo. Microtubules and F-actin are considered to be two of the most important structural elements within living cells accounting for both force production and mechanical stiffness. In this paper, we investigate the contribution of microtubules to the stiffness of converging and extending dorsal tissues in Xenopus laevis embryos using cell biological, biophysical and embryological techniques. Surprisingly, we discovered that depolymerizing microtubules stiffens embryonic tissues by three- to fourfold. We attribute tissue stiffening to Xlfc, a previously identified RhoGEF, which binds microtubules and regulates the actomyosin cytoskeleton. Combining drug treatments and Xlfc activation and knockdown lead us to the conclusion that mechanical properties of tissues such as viscoelasticity can be regulated through RhoGTPase pathways and rule out a direct contribution of microtubules to tissue stiffness in the frog embryo. We can rescue nocodazole-induced stiffening with drugs that reduce actomyosin contractility and can partially rescue morphogenetic defects that affect stiffened embryos. We support these conclusions with a multi-scale analysis of cytoskeletal dynamics, tissue-scale traction and measurements of tissue stiffness to separate the role of microtubules from RhoGEF activation. These findings suggest a re-evaluation of the effects of nocodazole and increased focus on the role of Rho family GTPases as regulators of the mechanical properties of cells and their mechanical interactions with surrounding tissues.
Sec5, a member of the exocyst complex, mediatesDrosophilaembryo cellularization
Authors: Murthy Mala , Teodoro Rita O. , Miller Tamara P. , Schwarz Thomas L.
Published: July 2010

Cellularization of the Drosophila embryo is the process by which a syncytium of ∼6000 nuclei is subdivided into discrete cells. In order to individualize the cells, massive membrane addition needs to occur by a process that is not fully understood. The exocyst complex is required for some, but not all, forms of exocytosis and plays a role in directing vesicles to appropriate domains of the plasma membrane. Sec5 is a central component of this complex and we here report the isolation of a new allele of sec5 that has a temperature-sensitive phenotype. Using this allele, we investigated whether the exocyst complex is required for cellularization. Embryos from germline clones of the sec5ts1 allele progress normally through cycle 13. At cellularization, however, cleavage furrows do not invaginate between nuclei and consequently cells do not form. A zygotically translated membrane protein, Neurotactin, is not inserted into the plasma membrane and instead accumulates in cytoplasmic puncta. During cellularization, Sec5 becomes concentrated at the apical end of the lateral membranes, which is likely to be the major site of membrane addition. Subsequently, Sec5 concentrates at the sub-apical complex, indicating a role for Sec5 in the polarized epithelium. Thus, the exocyst is necessary for, and is likely to direct, the polarized addition of new membrane during this form of cytokinesis.
Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling
Authors: Rocha Pedro P. , Scholze Manuela , Bleiß Wilfrid , Schrewe Heinrich
Published: July 2010

The Mediator complex is commonly seen as a molecular bridge that connects DNA-bound transcription factors to the RNA polymerase II (Pol II) machinery. It is a large complex of 30 subunits that is present in all eukaryotes. The Med12 subunit has been implicated not only in the regulation of Pol II activity, but also in the binding of transcription factors to the bulk of the Mediator complex. We targeted Med12 in mouse embryonic stem cells to investigate the in vivo function of this subunit. We report here the developmental defects of Med12 hypomorphic mutants that have a drastic reduction in Med12 protein levels. These mutants fail to develop beyond embryonic day 10 and have severe defects in neural tube closure, axis elongation, somitogenesis and heart formation. We show that in Med12 hypomorphic embryos, the Wnt/planar cell polarity pathway is disrupted and that canonical Wnt/β-catenin signaling is impaired. In agreement with this, embryos that are incapable of Med12 expression failed to establish the anterior visceral endoderm or activate brachyury expression, and did not complete gastrulation.
Skid Steering-Based Control of a Robotic Vehicle with Six in-Wheel Drives
Authors: Kang J , Kim W , Lee J , Yi K
Published: July 2010

This paper describes a driving control algorithm based on a skid steering for a robotic vehicle with articulated suspension (RVAS). The RVAS is a kind of unmanned ground vehicle based on a skid steering using an independent in-wheel drive at each wheel. The driving control algorithm consists of four parts: a speed controller for following a desired speed, a lateral motion controller that computes a yaw moment input to track a desired yaw rate or a desired trajectory according to the control mode, a longitudinal tyre force distribution algorithm that determines an optimal desired longitudinal tyre force, and a wheel torque controller that determines a wheel torque command at each wheel in order to keep the slip ratio at each wheel below a limit value as well as to track the desired tyre force. Longitudinal and vertical tyre force estimators are required for the optimal tyre force distribution and wheel slip control. A dynamic model of the RVAS for simulation study is developed and validated using the vehicle test data. Simulation and vehicle tests are conducted in order to evaluate the proposed driving controller. It is found from simulation and vehicle test results that the proposed driving controller provides a satisfactory motion control performance according to the control mode.
Ride-Comfort-Oriented Suspension Optimization Using the Pseudo-Excitation Method
Authors: Sun W , Xu W-T , Lin J-H , Kennedy D , Williams F W
Published: July 2010

The main purpose of this article is to optimize the stiffness and damping parameters of suspension systems to improve the ride comfort of a coach by using the pseudo-excitation method (PEM) and the method of moving asymptotes (MMA). The finite element model of the coach under investigation has 1778 degrees of freedom. The surface roughness of the highway is regarded as a spatial stationary random process, which is accurately transformed into the superposition of a series of deterministic pseudo-harmonic surface unevennesses by using PEM. By doing so, the proposed method considerably simplifies the solution of the vibration equations, the derivation of sensitivities of various random responses, and the execution of the optimization process. MMA is applied to solve the ride comfort optimization problem. The proposed method is well justified by the numerical example.
Hydraulically Interconnected Vehicle Suspension: Optimization and Sensitivity Analysis
Authors: Smith W A , Zhang N
Published: July 2010

This paper extends recent research on vehicles with hydraulically interconnected suspension (HIS) systems. Such suspension schemes have received considerable attention in the research community over the last few years. This is due, in part, to their reported ability to provide stiffness and damping rates dependent on the suspension mode of operation (i.e. the bounce, roll, pitch, or articulation of the unsprung masses relative to the sprung mass), rather than relying on the stiffness and damping characteristics of the single wheel stations.

In this paper, the optimization of such a system is considered. Use is made of a previously derived four-degree-of-freedom model of a roll-plane half-car fitted with a typical antiroll HIS system. Objective functions are then developed, based on the desire to improve ride comfort and to minimize suspension working space and tyre normal force fluctuations. With this formulation, a large number of optimal solutions are found and presented graphically, and the performance limitations and trade-offs between the desired objectives are illustrated. To contextualize these results, a similar optimization process is applied to a half-car with a conventional independent suspension. Four optimal parameter combinations are then selected as base points for further examination of the HIS vehicle. This is done by way of a basic sensitivity analysis, based on the local method, which involves single-parameter perturbations about a base point.

The objective of the paper is to outline the dynamic performance, trade-offs, and limitations of an HIS-equipped vehicle, and to identify the system's most important parameters.
Engagement capability of face-dog clutches on heavy duty automated mechanical transmissions with transmission brake
Authors: Bóka G , Lovas L , Márialigeti J , Trencséni B
Published: July 2010

This paper focuses on the engagement process of face-dog clutches on heavy duty automated mechanical transmissions (AMTs) considering special engagement conditions caused by the actuation of an electro-pneumatic transmission brake. A dynamic model of the transmission brake—single face-dog clutch system is developed and the engagement probability map characterizing the engagement capability of face-dog clutches under different engagement conditions is determined through numerical simulations for different gears of a given AMT. A region of engagement conditions is recognized where the engagement of the face-dog clutch is not ensured. Parameters influencing that region are highlighted. Optimal engagement conditions providing major gearshift comfort are given for the cases of stopped and moving vehicles. Simulation results are partly validated through statistical evaluation of measurement data obtained from a series of measurements performed on a gearbox test bench.