bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Designs and End Points for Phase II Clinical Trials
Authors: Adjei Alex A. , Christian Michaele , Ivy Percy 
Published: March 2009

Abstract
The large number of negative phase III trials in oncology over the last several years has renewed interest in refining phase II oncology clinical trials to maximize the chances of success in phase III testing. More efficient phase II study designs will improve our ability to identify promising agents for testing while accurately identifying nonefficacious agents. Recognizing that new paradigms of phase II trial designs need to be developed, the Clinical Trial Design Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee has tackled the question of improving efficiency of phase II clinical trials. In this issue of CCR Focus, four of the major topics discussed are presented. First, the task force recommended that alternate phase II end points should be studied. Second, depending on the characteristics of the specific trial and study population, historical controls or a randomized design may be more appropriate. Third, rational incorporation of biomarkers into phase II trials should be encouraged. Last, novel imaging modalities will be critical in evaluating the clinical benefit of new cytostatic agents.
The NF-κB negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas
Authors: Novak Urban , Rinaldi Andrea , Kwee Ivo , Nandula Subhadra V. , Rancoita Paola M. V. , Compagno Mara , Cerri Michaela , Rossi Davide , Murty Vundavalli V. , Zucca Emanuele , Gaidano Gianluca , Dalla-Favera Riccardo , Pasqualucci Laura , Bhagat Govind , Bertoni Francesco 
Published: March 2009

Abstract
Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha–induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-κB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL). Inactivating mutations encoding truncated A20 proteins were identified in 6 (19%) of 32 MZLs, including 2 (18%) of 11 EMZLs, 3 (33%) of 9 NMZLs, and 1 (8%) of 12 SMZLs. Two additional unmutated nonsplenic MZLs also showed monoallelic or biallelic A20 deletions by fluorescent in situ hybridization (FISH) and/or SNP-arrays. Thus, A20 inactivation by either somatic mutation and/or deletion represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-κB activation.
Transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis
Authors: Maciąg Anna , Piazza Aurora , Riccardi Giovanna , Milano Anna 
Published: March 2009

Abstract

Background
The ESAT-6 (early secreted antigenic target, 6 kDa) family collects small mycobacterial proteins secreted by Mycobacterium tuberculosis, particularly in the early phase of growth. There are 23 ESAT-6 family members in M. tuberculosis H37Rv. In a previous work, we identified the Zur- dependent regulation of five proteins of the ESAT-6/CFP-10 family (esxG, esxH, esxQ, esxR, and esxS). esxG and esxH are part of ESAT-6 cluster 3, whose expression was already known to be induced by iron starvation.

Results
In this research, we performed EMSA experiments and transcriptional analysis of ESAT-6 cluster 3 in Mycobacterium smegmatis (msmeg0615-msmeg0625) and M. tuberculosis. In contrast to what we had observed in M. tuberculosis, we found that in M. smegmatis ESAT-6 cluster 3 responds only to iron and not to zinc. In both organisms we identified an internal promoter, a finding which suggests the presence of two transcriptional units and, by consequence, a differential expression of cluster 3 genes. We compared the expression of msmeg0615 and msmeg0620 in different growth and stress conditions by means of relative quantitative PCR. The expression of msmeg0615 and msmeg0620 genes was essentially similar; they appeared to be repressed in most of the tested conditions, with the exception of acid stress (pH 4.2) where msmeg0615 was about 4-fold induced, while msmeg0620 was repressed. Analysis revealed that in acid stress conditions M. tuberculosis rv0282 gene was 3-fold induced too, while rv0287 induction was almost insignificant.

Conclusion
In contrast with what has been reported for M. tuberculosis, our results suggest that in M. smegmatis only IdeR-dependent regulation is retained, while zinc has no effect on gene expression. The role of cluster 3 in M. tuberculosis virulence is still to be defined; however, iron- and zinc-dependent expression strongly suggests that cluster 3 is highly expressed in the infective process, and that the cluster contributes to the antigenic profile during the course of infection. Moreover, cluster 3 induction in acid stress conditions strengthens the hypothesis that cluster 3 is expressed in the course of infection.
In M. smegmatis, the expression of msmeg0615 and msmeg0620 genes is broadly similar in differing growth phases and in stress conditions, with the exception of acid stress (pH 4.2). Differences in expression between cluster 3 genes can be explained by the presence of internal promoters, both in M. smegmatis and M. tuberculosis.
Effect of Dietary Adherence with or without Exercise on Weight Loss: A Mechanistic Approach to a Global Problem
Authors: Del Corral Pedro , Chandler-Laney Paula C. , Casazza Krista , Gower Barbara A. , Hunter Gary R. 
Published: March 2009

Abstract
Context: Weight loss using low-calorie diets produces variable results, presumably due to a wide range of energy deficits and low-dietary adherence.
Objective: Our objective was to quantify the relationship between dietary adherence, weight loss, and severity of caloric restriction.
Design and Setting: Participants were randomized to diet only, diet-endurance training, or diet-resistance training until body mass index (BMI) was less than 25 kg/m2.
Participants: Healthy overweight (BMI 27–30) premenopausal women (n = 141) were included in the study.
Interventions: An 800-kcal/d−1 diet was provided, and the exercise groups were engaged in three sessions per week.
Main Outcomes: Dietary adherence, calculated from total energy expenditure determined by doubly labeled water measurements and dual-energy x-ray absorptiometry body composition changes, and degree of caloric restriction were determined.
Results: All groups had similar weight loss (∼12.1 ± 2.5 kg) and length of time to reach target BMI (∼158 ± 70 d). Caloric restriction averaged 59 ± 9%, and adherence to diet was 73 ± 34%. Adherence to diet was inversely associated to days to reach target BMI (r = −0.687; P &lt; 0.01) and caloric restriction (r = −0.349; P &lt; 0.01). Association between adherence to diet and percent weight lost as fat was positive for the diet-endurance training (r = 0.364; P &lt; 0.05) but negatively correlated for the diet-only group (r = −0.387; P &lt; 0.05).
Conclusions: Dietary adherence is strongly associated with rates of weight loss and adversely affected by the severity of caloric restriction. Weight loss programs should consider moderate caloric restriction relative to estimates of energy requirements, rather than generic low-calorie diets.
Ultrasonic assessment of wheel—rail contact evolution exposed to artificially induced wear
Authors: Pau M , Leban B 
Published: March 2009

One of the most important effects that wear originates on the wheel—rail system is represented by the significant changes introduced in contact area features and contact pressure distribution. In fact, in most cases, even regular operation gradually modifies the profile of the contacting elements so as to transform the original Hertzian counterformal conditions into a conformal contact characterized by lower average pressures and relevant alterations in the size and shape of the contact patch. On the basis of the aforementioned considerations, this study presents the results of a series of experimental tests carried out with an ultrasonic non-invasive technique, with the final purpose of assessing to what extent wear induces modifications in contact parameters. To this end, in a regular flanged wheel, increasing degrees of wear were artificially produced at the centre of the tread. The interface of the wheel—rail systems thus obtained was investigated with high-frequency ultrasonic waves and the observed coefficient of reflection (which is known to be related to contact conditions) was graphically processed to build contact maps from which to extract information about the size and shape of the contact area and pressure distribution. The results allowed the monitoring of the transition from counterformal to conformal contact, and helped to establish an empirical relationship between the amount of wear and both the contact area value and average pressure. Moreover, contact pressure distribution (obtained with a dedicate calibration procedure) showed that conformal contacts lose the original ‘one-peak’ pressure trend and exhibit a multi-peak configuration. Thus, the ultrasonic method confirmed its capabilities to faithfully monitor contact conditions even in the case of randomly altered geometries of the contacting elements and, in the specific case, may represent an effective tool in validating the wear simulation models.
Appearance of Anaphylactic Shock after Long-Term Intravenous Itraconazole Treatment
Authors: Chen Jie , Song Xianmin , Yang Peng , Wang Jianmin 
Published: March 2009

Objective: To report a rare but severe adverse effect of intravenous itraconazole, anaphylactic shock with hypotension and hypoxemia, in a female patient with acute lymphoblastic leukemia (ALL). Case Summary: A 36-year-old woman with ALL received antifungal therapy for pulmonary fungal infections. On day 17 of itraconazole treatment, she developed hypotension and hypoxemia shock after intravenous administration of itraconazole 200 mg, which was eventually reversed by steroid treatment. On days 18 and 19, the patient developed the same type of shock 2 more times in the course of itraconazole administration. These 2 episodes of shock occurred more quickly after intravenous itraconazole administration (100 mg on day 18, 40 mg on day 19), and were reversed by stopping itraconazole and applying steroid treatment. In the modified antifungal therapy, intravenous administration of itraconazole was replaced by oral administration of voriconazole 200 mg twice daily. Shock did not recur after discontinuation of itraconazole treatment. The Naranjo probability scale showed a probable relationship between itraconazole treatment and shock occurrence. Discussion: Itraconazole is a widely used antifungal drugs and is well tolerated. However, long-term itraconazole treatment might lead to serious and even life-threatening adverse effects such as anaphylactic shock, as seen in our patient. T cell reduction caused by immunosuppression and itraconazole accumulation in patients with ALL are considered to be important causal factors for this delayed-type hypersensitivity reaction. Conclusions: Anaphylactic shock represents a previously undocumented severe adverse effect associated with long-term itraconazole treatment; patients receiving this therapy and should be monitored closely.
Physician Use of Brand Versus Generic Drug Names in 1993–1994 and 2003-2004
Authors: Kwo Elizabeth C , Kamat Priya , Steinman Michael A 
Published: March 2009

Background: Physicians often refer to drugs by their brand names, which can result in brand name drugs being dispensed even when bioequivalent generic alternatives are available. As a result, use of brand-name terminology may result in increased drug costs. Objective: To evaluate how often physicians use brand and generic names of drugs, how the use of terminology changes over time, and factors associated with this change. Methods: This was a serial cross-sectional study using data from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey in 1993/1994 and 2003/2004. Over the 4 study years, data were collected on 376,383 subjects. Using forms completed by physicians that described medication regimens, we determined the proportion of drug names that were recorded using brand vs nonproprietary (ie, generic) terminology. Results: In 1993/1994, the 25 most commonly mentioned drugs were referred to by their brand names a median of 89% of the time. Over the ensuing decade, use of brand-name terminology decreased by a median of 11%. Drugs that first faced generic competition within 10 years of the baseline study year had large declines in brand-name use (43–58% decline), whereas drugs that first faced generic competition more than 10 years before or after the baseline study year had minimal change in brand-name use (2–3% decline; p = 0.02 for difference in rate of decline among drug groups). Year of drug introduction, baseline rate of brand-name use, clinical setting, and national region were not associated with reductions in brand-name use. Conclusions: Brand-name terminology is commonly used and decreases over time with the introduction of generic competition. Interventions that standardize medication-naming practices may hasten this decline and increase use of nonproprietary terminology in medicine.
A Review of Contamination Related Hydraulic Pump Problems in Japanese Injection Molding, Extrusion and Rubber Molding Industries
Authors: Sasaki A 
Published: March 2009

It is known that contamination of hydraulic oil is one of the major factors causing hydraulic pump problems. Many test reports on contaminant sensibility of hydraulic pumps have been published with new oil and standard dusts but the results of these tests could not guarantee to predict in-service performance. This report describes three cases investigated.
The first investigation was done on hydraulic pumps used for injection molding machines application. The causes of pump problems were examined by analysis of maintenance records. The second investigation was performed to determine overhaul frequency of hydraulic pumps used for aluminum extruders. By introducing a new method of hydraulic oil management which reduces oil oxidation products, pump life was extended from 3000 to 15000 hours. The third investigation was done to determine the relationship between pump problems and contamination levels of hydraulic oils of 411 rubber molding machines for 20 months. The results showed that pump problems appeared at half the recommended oil lifetimes for these fluids.
These studies showed that the cause of pump problems was clogging of suction strainers leading to pump cavitation. The clogged strainers were washed with several different solvents to identify the causes of suction strainer clogging. Clogging of suction strainers was attributable to sticky oxidation products of hydraulic oils. Electrostatic oil cleaners removed not only micron range solid particles but also submicron size particles. Hydraulic pump problems have been substantially reduced by introducing this new method of contamination control.
The Gamma Wear Test for Hydraulic Fluid Qualifications
Authors: Tessmann RK , Heer DJ 
Published: March 2009

The qualification of fluids for use in a hydraulic system has been a major concern to component manufacturers for several years. The primary issue in a hydraulic system is the compatibility of the fluid with the main pump in the system. There are several bench-type wear tests for the evaluation of fluids, however, most of these are not intended specifically for hydraulic fluids but were developed for lubrication fluids. Therefore, many engineers have relied upon the pump tests which were available in order to select the fluid to be used in their hydraulic system. The testing of a hydraulic pump to qualify a hydraulic fluid is very time consuming and expensive.
This paper reviews several of the more wide-spread bench-type tests which are used to evaluate hydraulic fluids. However, the main purpose of the paper is to describe a new test system for evaluating the anti-wear characteristics of hydraulic fluids called the Gamma Wear Test System.
Colorado Begins Superpave Validation
Authors: Aschenbrener T , LaForce R , Shuler S 
Published: March 2009

One of the first applications of Superpave technology in Colorado was at a high traffic intersection near Denver in 1994. The project was developed to demonstrate whether Superpave asphalt technology could solve a recurring problem of rutting in a very severe traffic environment. Although the project was designed for an anticipated 8 million ESALs, recent traffic classification analysis indicates traffic is over 30 million ESALs in 20 years. In spite of this significant difference the Superpave asphalt materials are performing well. However, as would be expected, the control section developed ruts in the wheelpaths six months after construction.
The Superpave concept originally included both a mixture design method and an analysis system which was intended to determine the adequacy of the materials with respect to rutting and cracking distress. However, when this project was conceived and built, the analysis portion of Superpave had not been fully developed. Therefore, in the absence of a means to evaluate the structural ability of the design mixture by Superpave methods, the French Rut Tester and Hamburg Wheel Tracking Device were used to determine the adequacy of the design and construction mixtures. Analysis of results indicates field performance of asphalt mixtures may be predictable with respect to rutting.
This paper documents the planning, design, construction and two year performance of this very high traffic asphalt concrete intersection.
Construction Considerations in the Field Application of the Superpave Mix Design System
Authors: Noureldin AS 
Published: March 2009

Establishment of relationships between asphalt content and distress levels (rutting, fatigue cracking, and low temperature cracking) during the mix design process is one of the major advantages of the SUPERPAVE mix design system.
These relationships, which are specific for the mix under consideration, can be employed to predict the expected loss in the distress oriented pavement life resulting from any deviation in asphalt content from the target optimum value. Those expected losses in pavement life can be used as rational basis for the construction related pay adjustment factors. The pay adjustment factors in this case will have the advantage of being “mix specific”.
The overall pavement performance life may be significantly affected when the specified asphalt content, aggregate gradation (job mix formula) and degree of compaction are not achieved in situ. Quantification of these effects is essential for rational pay adjustment factors in asphalt pavement construction.
This paper presents a scheme that employs data obtained during the SUPERPAVE mix design process to predict the “mix specific” expected loss (or gain) in pavement performance life resulting from any in situ deviation in asphalt content, aggregate gradation and relative compaction from the specified job mix formula and degree of compaction tolerance bands.
The proposed scheme can be easily programmed and become as part of the structure of the SUPERPAVE software.
Moisture Performance Analysis of EPS Frost Insulation
Authors: Ojanen T , Kokko E 
Published: March 2009

A horizontal layer of expanded polystyrene foam (EPS) is widely used as a frost insulation of building foundations in the Nordic countries. The performance properties of the insulation depend strongly on the moisture level of the material. Experimental methods are needed to produce samples for testing the material properties in realistic moisture conditions.
The objective was to analyse the moisture loads and the wetting mechanisms of horizontal EPS frost insulation. Typical wetting tests, water immersion and diffusive water vapour absorption tests, were studied and the results were compared with the data from site investigations. Usually these tests give higher moisture contents of EPS than what are detected in drained frost insulation applications. Also the effect of different parameters, like the immersion depth and temperature gradient were studied.
Special attention was paid to study the effect of diffusion on the wetting process. Numerical simulation showed that under real working conditions the long period diffusive moisture absorption in EPS frost insulation remained lower than 1 % Vol. Moisture performance was determined experimentally as a function of the distance between the insulation and the free water level in the ground. The main moisture loads and the principles for good moisture performance of frost insulation are presented.
The Effects of Training on the Risk of Avalanche Fatality
Authors: Burtscher M , Nachbauer W 
Published: March 2009

The fatal hazard of avalanches is obvious; however, there are no satisfactory solutions for prevention. For many years skiing and mountaineering associations have endeavored to increase mountaineering safety by information programs and instruction courses. However, the effectiveness of such efforts regarding “avalanche safety” remains unclear. Therefore, we studied the influence of training level on the death frequencies in back country skiers in Austria from 1986 through 1995.
The avalanche accidents during mountain sport activities in Austria from 1986 through 1995 were recorded. The number of persons involved in mountain sports and the frequency and duration of such involvement were compiled on the basis of a representative Austrian-wide survey taken in 1984 and in a 1989 microcensus. The training level is assumed to be higher for members of mountaineering associations than nonmembers.
Based on available information regarding the numbers of Austrian members and nonmembers of mountaineering associations and their annual skiing exposure times, relative risk calculations were carried out for these groups.
The overall avalanche fatality rate in back country skiers was low (1 death per 333 350 back country skiing days for members of alpine associations). However, the relative risk to have a fatal avalanche accident was about two times higher in members as compared with nonmembers, which indicates an increasing death risk with increasing training level.
It was observed that current training programs and information were inadequate for reducing the risk of deaths produced by avalanches. In fact it appeared that the present programs and information resulted in underestimation of the risk of avalanche or perhaps encouraged higher risk-taking behavior.