bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Fetal Hemoglobin in the Treatment of Sickle Cell Disease
Authors: Fathallah Hassana , Atweh George F.
Published: November 2006

Reactivation of fetal hemoglobin (HbF) expression is an important therapeutic option in patients with hemoglobin disorders. In sickle cell disease (SCD), an increase in HbF inhibits the polymerization of sickle hemoglobin and the resulting pathophysiology. Hydroxyurea, an inducer of HbF, has already been approved for the treatment of patients with moderate and/or severe SCD. Recent clinical trials with other pharmacological inducers of HbF, such as butyrate and decitabine, have shown considerable promise. In this chapter, we highlight the important clinical trials with pharmacological inducers of HbF, discuss their mechanisms of action and speculate about the future of this therapeutic approach in the treatment of patients with SCD.
Immune Thrombocytopenic Purpura of Childhood
Authors: Nugent Diane J.
Published: November 2006

Immune mediated thrombocytopenia (ITP) is a common manifestation of autoimmune disease in children. Although patients often present with bruises, petechiae, and some mucosal bleeding, the incidence of life-threatening hemorrhage is rare (0.2–0.9%) but can be fatal when presenting in vital organs. A wide range of therapeutic regimens are currently in use, including observation alone, as the majority of children recover within 4–6 months regardless of treatment. A growing understanding of the pathophysiology of acute ITP in children has not impacted the controversy surrounding treatment, but has clarified the mechanism of action of the most frequently used agents in chronic ITP. Newer monoclonal antibodies such as Rituxan have proved very useful in chronic or refractory ITP and studies are ongoing to determine the best regimens using this form of immune modulation. Splenectomy and newer agents to boost platelet production are also under study in chronic ITP. Neonates may also have a form of immune thrombocytopenia with extensive bruising and thrombocytopenia called neonatal alloimmune thrombocytopenic purpura (NATP). Rather than autoantibodies, the platelet destruction is secondary to transplacental maternal IgG alloantibodies. During pregnancy mothers may become sensitized to platelet membrane antigens present on fetal platelets. These antibodies may result in serious bleeding, including intracranial hemorrhage in the perinatal period. Once identified, these mothers may require treatment during future pregnancies to minimize serious bleeding in the fetus and neonate. Treatment in utero and immediately following delivery is focused on restoring neonatal platelets to a safe level and preventing life-threatening bleeding.
Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study
Authors: Lim Unhee , Wang Sophia S. , Hartge Patricia , Cozen Wendy , Kelemen Linda E. , Chanock Stephen , Davis Scott , Blair Aaron , Schenk Maryjean , Rothman Nathaniel , Lan Qing
Published: November 2006

We previously reported a lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism. Evidence has linked genetic variants involved in one-carbon metabolism to NHL. We investigated 30 polymorphisms in 18 genes for their main effect on NHL among 1141 incident cases and 949 population-based controls and examined gene-nutrient interactions in a subgroup of 386 cases and 319 controls who provided detailed food-frequency information. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for age, sex, and race. We observed a decreased risk of NHL overall with BHMT Ex8+453A>T and increased risk with CBS Ex13+41C>T, FPGS Ex15-263T>C, and SHMT1 Ex12+138C>T and Ex12+236C>T. Furthermore, significant gene-nutrient interactions limited the protective association comparing high versus low vitamin B6 to FPGS Ex15-263T>C CC (OR = 0.22; 95% CI = 0.10-0.52), MTHFS IVS2-1411T>G TT/TG (OR = 0.54; 95% CI = 0.36-0.81), and MTR Ex26-20A>G AA (OR = 0.55; 95% CI = 0.35-0.86) genotypes, and the protective association of methionine to FTHFD Ex10-40G>T GG (OR = 0.63; 95% CI = 0.44-0.91), MTHFR Ex8-62A>C CC (OR = 0.13; 95% CI = 0.04-0.39), and MTRR Ex5+136T>C TT (OR = 0.67; 95% CI = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in one-carbon metabolism supports their etiologic involvement in lymphomagenesis.
Statistical analysis of an RNA titration series evaluates microarray precision and sensitivity on a whole-array basis
Authors: Holloway Andrew J , Oshlack Alicia , Diyagama Dileepa S , Bowtell David DL , Smyth Gordon K
Published: November 2006

Background

Concerns are often raised about the accuracy of microarray technologies and the degree of cross-platform agreement, but there are yet no methods which can unambiguously evaluate precision and sensitivity for these technologies on a whole-array basis.

Results

A methodology is described for evaluating the precision and sensitivity of whole-genome gene expression technologies such as microarrays. The method consists of an easy-to-construct titration series of RNA samples and an associated statistical analysis using non-linear regression. The method evaluates the precision and responsiveness of each microarray platform on a whole-array basis, i.e., using all the probes, without the need to match probes across platforms. An experiment is conducted to assess and compare four widely used microarray platforms. All four platforms are shown to have satisfactory precision but the commercial platforms are superior for resolving differential expression for genes at lower expression levels. The effective precision of the two-color platforms is improved by allowing for probe-specific dye-effects in the statistical model. The methodology is used to compare three data extraction algorithms for the Affymetrix platforms, demonstrating poor performance for the commonly used proprietary algorithm relative to the other algorithms. For probes which can be matched across platforms, the cross-platform variability is decomposed into within-platform and between-platform components, showing that platform disagreement is almost entirely systematic rather than due to measurement variability.

Conclusion

The results demonstrate good precision and sensitivity for all the platforms, but highlight the need for improved probe annotation. They quantify the extent to which cross-platform measures can be expected to be less accurate than within-platform comparisons for predicting disease progression or outcome.
An Electrowetting Microvalve
Authors: MOHSENI KAMRAN , DOLATABADI ALI
Published: November 2006

Abstract:  Numerical simulation of a zero‐leakage microvalve is investigated where a liquid droplet is used as a gate to regulate the flow in a T junction. The droplet gate is activated by changing its surface tension via an applied electric field. Numerical simulation of the droplet actuation is considered where the effect of electrowetting is imposed in the form of a modified boundary condition at the contact line. Numerical simulation is used to predict the droplet behavior and to design the valve. It is found that the pressure breakdown of the microvalve is significantly affected by the geometry of the T junction corners. It is expected that such a microvalve design will improve the sensitivity and performance of a wide variety of microfluidic devices.
Nucleation of Protein Crystals under the Influence of Solution Shear Flow
Authors: PENKOVA ANITA , PAN WEICHUN , HODJAOGLU FEYZIM , VEKILOV PETER G.
Published: November 2006

Abstract:  Several recent theories and simulations have predicted that shear flow could enhance, or, conversely, suppress the nucleation of crystals from solution. Such modulations would offer a pathway for nucleation control and provide a novel explanation for numerous mysteries in nucleation research. For experimental tests of the effects of shear flow on protein crystal nucleation, we found that if a protein solution droplet of ∼ 5 μL (2–3 mm diameter at base) is held on a hydrophobic substrate in an enclosed environment and in a quasi‐uniform constant electric field of 2 to 6 kV cm−1, a rotational flow with a maximum rate at the droplet top of ∼ 10 μm s−1 is induced. The shear rate varies from 10−3 to 10−1 s−1. The likely mechanism of the rotational flow involves adsorption of the protein and amphiphylic buffer molecules on the air–water interface and their redistribution in the electric field, leading to nonuniform surface tension of the droplet and surface tension‐driven flow. Observations of the number of nucleated crystals in 24‐ and 72‐h experiments with the proteins ferritin, apoferritin, and lysozyme revealed that the crystals are typically nucleated at a certain radius of the droplet, that is, at a preferred shear rate. Variations of the rotational flow velocity resulted in suppression or enhancement of the total number of nucleated crystals of ferritin and apoferritin, while all solution flow rates were found to enhance lysozyme crystal nucleation. These observations show that shear flow may strongly affect nucleation, and that for some systems, an optimal flow velocity, leading to fastest nucleation, exists. Comparison with the predictions of theories and simulations suggest that the formation of ordered nuclei in a “normal” protein solution cannot be affected by such low shear rates. We conclude that the flow acts by helping or suppressing the formation of ordered nuclei within mesoscopic metastable dense liquid clusters. Such clusters were recently shown to exist in protein solutions and to constitute the first step in the nucleation mechanism of many protein and nonprotein
systems.
Epoxy Resins in the Construction Industry
Authors: SPEE TON , VAN DUIVENBOODEN COR , TERWOERT JEROEN
Published: November 2006

Abstract:  Epoxy resins are used as coatings, adhesives, and in wood and concrete repair. However, epoxy resins can be highly irritating to the skin and are strong sensitizers. Some hardeners are carcinogenic. Based on the results of earlier Dutch studies, an international project on “best practices,”—Epoxy Code—with epoxy products was started. Partners were from Denmark, Germany, the Netherlands, and the UK. The “Code” deals with substitution, safe working procedures, safer tools, and skin protection. The feasibility of an internationally agreed “ranking system” for the health risks of epoxy products was studied. Such a ranking system should inform the user of the harmfulness of different epoxies and stimulate research on less harmful products by product developers.
Occupational Injury and Illness Meet the Labor Market
Authors: BODEN LESLIE I.
Published: November 2006

Abstract:  Recent labor economics studies in the United States and Canada have demonstrated that occupational injuries and illnesses often lead to substantial lost earnings for workers and their families. Other studies have shown substantial long‐term lost earnings attributable to large‐scale layoffs, where no health impairment has taken place. This article uses evidence from these and other studies of apparently different situations to draw inferences about how managers' actions and public policy choices can affect the costs of occupational injuries and illnesses. Although primary prevention remains the policy of choice, reduction in the impact of workplace injuries and illnesses can decrease the costs of these events and can provide substantial benefits. This article proposes two hypotheses and discusses the evidence for each:
(a) Loss of the job held at the onset of illness or injury increases time off work and exacerbates workers' lost earnings.
(b) Workers' losses may be substantially reduced by policies that encourage employers to rehire people recovering from or disabled by workplace injuries and illnesses.
Children's Environmental Health Research—Highlights from the Columbia Center for Children's Environmental Health
Authors: PERERA FREDERICA , VISWANATHAN SHEILA , WHYATT ROBIN , TANG DELIANG , MILLER RACHEL L. , RAUH VIRGINIA
Published: November 2006

Abstract:  A growing body of evidence has been generated indicating that the fetus, infant, and young child are especially susceptible to environmental toxicants as diverse as polycyclic aromatic hydrocarbons (PAHs), pesticides, lead, mercury, polychlorinated biphenyls (PCBs), and environmental tobacco smoke (ETS). Exposures to these toxicants may be related to the increases in recent decades in childhood asthma, cancer, and developmental disability. The Columbia Center for Children's Environmental Health (CCCEH), located in New York City, has developed four cohorts around the world to elucidate the relationships between these exposures and childhood illness. This article summarizes the recent findings from the Center's projects in the context of current research in children's environmental health.
Adverse Health Effects of Fluoro‐Edenitic Fibers
Authors: BRUNO CATERINA , COMBA PIETRO , ZONA AMERIGO
Published: November 2006

Abstract:  Subsequent to the detection of a cluster of mesothelioma cases in the Sicilian town of Biancavilla, located at the slopes of Etna volcano, ad hoc epidemiological studies and environmental monitoring suggested an etiological role of an asbestiform fiber present in a stone quarry. The fiber was shown to constitute a new mineral species named fluoro‐edenite. Fluoro‐edenitic fibers were found in the materials extracted from the quarry and used in the local building industry, as well as in soils.
Besides the risk of mesothelioma, residents in Biancavilla showed a significantly increased mortality from chronic obstructive pulmonary disease, which was particularly evident among women. In the light of these findings, Biancavilla was defined a site of national interest for environmental reclamation. The first preventive action involved termination of quarrying activity, covering with asphalt of roads previously paved with local soil materials, and removal of sources of dust in the urban area. Concurrent to the implementation of environmental cleanup, some specific “second generation” studies are now being designed and performed, namely morbidity surveys based on hospital discharge cards, monitoring of fibers in sputum and health surveillance in selected population groups. In this frame, special emphasis is given to the issue of communication, both to the general public and to target groups like family doctors, teachers, and media professionals. This experience could represent a useful basis for the elaboration of a strategy to approach similar environmental issues.
Getting It Right the First Time
Authors: BALBUS JOHN M. , FLORINI KAREN , DENISON RICHARD A. , WALSH SCOTT A.
Published: November 2006

Abstract:  Nanotechnology, the design and manipulation of materials at the atomic scale, may well revolutionize many of the ways our society manufactures products, produces energy, and treats diseases. Innovative nanotechnology products are already reaching the market in a wide variety of consumer products. Some of the observed properties of nanomaterials call into question the adequacy of current methods for determining hazard and exposure, and for controlling resulting risks. Given the limitations of existing regulatory tools and policies, two distinct kinds of initiatives are urgently needed: first, a major increase in the federal investment nanomaterial risk research, and second, rapid development and implementation of voluntary standards of care pending development of adequate regulatory safeguards. The U.S. government should increase federal funding for nanomaterial risk research under the National Nanotechnology Initiative to at least $100 million annually for the next several years. Several voluntary programs are currently at various stages of evolution, though the eventual outputs of each of these are still far from clear. Ultimately, effective regulatory safeguards, harmonized globally, are necessary to provide a level playing field for industry while adequately protecting human health and the environment.
Progress of Epidemiological and Molecular Epidemiological Studies on Benzene in China
Authors: LI GUILAN , YIN SONGNIAN
Published: November 2006

Abstract:  Benzene is an organic solvent that has been used in industry for about 100 years throughout the world. Since 1973, a series of toxicological and molecular epidemiological studies on benzene were conducted by researchers at the Chinese Academy of Preventive Medicine (CAPM) (1973–1986) and subsequently by a collaboration between the CAPM and the National Cancer Institute (NCI) in the United States that began in 1986, which was joined by investigators from the University of California at Berkeley, the University of North Carolina at Chapel Hill, and New York University. The findings demonstrated that the risk of leukemia and lymphoma among benzene‐exposed workers was significantly increased, with elevated risks for leukemia present not only at higher exposure but also among workers exposed to under 10 ppm. Therefore, the benzene permissible level was decreased to 1.8 ppm (6 mg/m3) and benzene‐induced leukemia is treated as an occupational cancer in China. The benzene permissible level is 1.0 in the United States and in several other developed countries and it has been suggested to be decreased to 0.5 ppm (ACGIH). A number of potential biomarkers are related to benzene exposure and poisoning. Some of these are benzene oxide–protein adducts, chromosome aberration of lymphocytes, and GPA mutations in erythrocytes, a decrease in B cell and CD4–T cell counts in peripheral blood, and altered expression of CXCL16, ZNF331, JUN, and PF4 in lymphocytes. Variation in multiple benzene metabolizing genes may be associated with risk of benzene hematotoxicity, including CYP2E1, MPO, NQO1, and GSTT1.
Residual Hazard Assessment Related to Handling of Antineoplastic Drugs
Authors: TURCI ROBERTA , MINOIA CLAUDIO
Published: November 2006

Abstract:  Despite improvement of operating procedures and publication of safety guidelines, contamination is still observed in healthcare settings where antineoplastic drugs (ADs) are handled. Even after cleaning work areas, some residual contamination may still be present. Zero percent contamination is not a realistic goal, but the scientific community should set zero contamination as its main goal. The strategies to reach this objective may be traced based on the followings: (a) a wider number of drugs should be monitored; (b) safety equipment and devices must be available to the workers; (c) the likely source of widespread contamination in workplaces is the safety cabinet; (d) direct determination of the parent drug or its metabolite in urine is the recommended approach because it provides higher sensitivity and specificity; (e) reliable analytical methods are necessary to measure the extent of contamination; and (f) analytical methods intended to be applied for routine testing must be assessed through method validation studies. These studies rely on the determination of overall method performance parameters including uncertainty measurement. Our laboratory has developed and validated a number of analytical methods for the determination of several drugs in environmental and biological samples. Surveys were carried out in several hospitals, and there has been progressive, significant decrease in the number of positive samples, mostly due to the improvement of working procedures and safety measures.
Chemical Safety and Health Conditions among Hungarian Hospital Nurses
Authors: TOMPA ANNA , JAKAB MÁTYÁS , BIRÓ ANNA , MAGYAR BALÁZS , FODOR ZOLTÁN , KLUPP TIBOR , MAJOR JENÖ
Published: November 2006

Abstract:  In the present study genotoxicological and immunotoxicological follow‐up investigations were made on 811 donors including 94 unexposed controls and 717 nurses with various working conditions from different hospitals (The Hungarian Nurse Study). The nurses were exposed to different chemicals: cytostatic drugs, anesthetic, and sterilizing gases, such as ethylene oxide (ETO) and formaldehyde. The measured biomarkers were: clinical laboratory routine tests, completed with genotoxicological (chromosome aberrations [CA], sister chromatid exchange [SCE]), and immune‐toxicological monitoring (ratio of lymphocyte subpopulations, lymphocyte activation markers, and leukocyte oxidative burst). The highest rate of genotoxicologically affected donors (25.4%) was found in the group of cytostatic drug‐exposed nurses. Comparing geno‐ and immunotoxicological effect markers, we found that among genotoxicologically affected donors the frequency of helper T cell (Th) lymphocytes, the ratio of activated T and B cells increased, whereas the oxidative burst of leukocytes decreased. In hospitals with lack of protective measures increased CA yields were observed compared to those with ISO 9001 quality control or equivalent measures. Anemia, serum glucose level, thyroid dysfunctions, benign, and malignant tumors were more frequent in the exposed groups than in controls. The hygienic standard of the working environment is the basic risk factor for the vulnerability of nurses. On the basis of these results, it is suggested, that the used cytogenetic and immunological biomarkers are appropriate to detect early susceptibility to diseases. The Hungarian Nurse Study proved that the use of safety measures could protect against occupational exposure at work sites handling cytostatic drugs, anesthetic, and sterilizing gases.
Environmental Impacts and Costs of Energy
Authors: RABL ARI , SPADARO JOSEPH V.
Published: November 2006

Abstract:  Environmental damage is one of the main justifications for continued efforts to reduce energy consumption and to shift to cleaner sources such as solar energy. In recent years there has been much progress in the analysis of environmental damages, in particular thanks to the ExternE (External Costs of Energy) Project of the European Commission. This article presents a summary of the methodology and key results for the external costs of the major energy technologies. Even though the uncertainties are large, the results provide substantial evidence that the classical air pollutants (particles, Nox, and SO2) from fossil fuels impose significant public health costs, comparable to the cost of global warming from CO2 emissions. The total external costs are relatively low for natural gas (in the range of about 0.5–1 eurocents/kWh for most EU countries), but much higher for coal and lignite (in the range of about 2–6 eurocents/kWh for most EU countries). By contrast, the external costs of nuclear, wind, and photovoltaics are very low. The external costs of hydro are extremely variable from site to site, and the ones of biomass depend strongly on the specific technologies used and can be quite large for combustion.
Lung Tumor Risk Estimates from Rat Studies with Not Specifically Toxic Granular Dusts
Authors: ROLLER MARKUS , POTT FRIEDRICH
Published: November 2006

Abstract:  Since 1985 several carcinogenicity studies have been published about lung tumors in rats after exposure to respirable granular biodurable particles without known significant specific toxicity (abbreviation of this complex definition by the three letters GBP to substitute the former term inert dusts). During this time, the relevance of the carcinogenicity of GBP in rats was questioned, for example, because no lung tumors from GBP were found in hamsters and carcinogenicity in mice was questionable. However, the carcinogenesis and the tumor risk from quartz appear similar in men and rats, and the effects of GBP in rats appear not to differ, on principle, from that of quartz, but at a much higher dose level. We calculated the excess risk (ER) of GBP in rats from the final results of an instillation study with 16 GBP types in connection with results of inhalation experiments with carbon black, titanium dioxide, and diesel particles. Retained particle volume together with some indicator of particle size was identified as the best suitable dose metric and the dose‐response relationships were analyzed on the basis of the multistage model. By relating the results to the available dose–response slopes after inhalation, ER for workplace‐like exposure were calculated for three particle size classes and an exposure to 0.3 mg/m3 (density 2–2.5 g/mL); mean diameter 1.8–4 μm (GBP‐fine‐large): ER 0.1%; 0.09–0.2 μm (GBP‐fine‐small): ER 0.2%; 0.01–0.03 μm (GBP‐ultra‐fine): ER 0.5%.
Systematic Approach to Evaluating Trade‐Offs among Fuel Options
Authors: DAVIS J. MICHAEL , THOMAS VALERIE M.
Published: November 2006

Abstract:  The fuel additive methyl tertiary butyl ether (MTBE) has been used in an effort to improve air quality in the United States, but other undesirable effects, particularly the contamination of water resources, were eventually judged to outweigh any air quality benefits it may have offered. The experience with MTBE offers many lessons, including the need to evaluate potential positive and negative environmental impacts associated with fuel choices using a comprehensive approach that combines a product life‐cycle perspective with the risk assessment paradigm. Such an approach, referred to as “comprehensive environmental assessment” (CEA), is illustrated here by highlighting some of the issues that might be considered in evaluating reformulated gasoline (RFG) produced with MTBE, ethanol, or no oxygenate.
Chinese Workers and Labor Conditions from State Industry to Globalized Factories
Authors: THORBORG MARINA
Published: November 2006

Abstract: This article discusses administrative obstacles in China that hinder the full integration of the rural population into the mainstream of development during a period of rapid industrialization. The Chinese household registration only for urban residents with its golden contents of cradle‐to‐grave security has become a formidable stumbling block that perpetuates the status of rural migrants as second‐class citizens in their own country. Rural migrant workers are excluded from certain types of jobs and are not eligible for many benefits that urbanites have, such as health, education, and unemployment protection. These workers must also pay a number of fees and work for lower minimum wages than the local residents. With a precarious legal existence in urban areas, they are easy prey to unscrupulous officials and employers. Because they are not allowed to form independent trade unions, their best option is to vote with their feet and leave the firms with the worst conditions; this is exactly what they did from 2004. Given this situation, the debate on Corporate Social Responsibility (CSR) took a new turn with not only nongovernmental organizations (NGOs) pushing it but with a wider range of employers and, of late, Chinese officials promoting their version of CSR. In the campaign to promote minimum labor standards, the norms set down in the Social Accountability 8000 were included in the CSR, recognizing the right to free collective bargaining and free trade unions but were excluded in the Chinese version even though the World Trade Organization (WTO) agreements recognized these rights.
Asbestos Ban in India
Authors: JOSHI TUSHAR KANT , BHUVA UTTPAL B. , KATOCH PRIYANKA
Published: November 2006

Abstract:  Rapidly industrializing India is described by the International Monetary Fund as a young, disciplined, and vibrant economy with a projected growth of 6.7
%
for 2005. The total workforce of 397 million has only 7% of workers employed in the organized sector with construction, where asbestos exposure is prevalent, employing 4.4%. The domestic production of asbestos declined from 20,111 tons in 1998–1999 to 14,340 tons in 2002–2003. The imports from Russia and Canada increased from 61,474 tons in 1997–1998 to 97,884 tons in 2001–2002. The production of asbestos cement products went up from 0.68 million tons in 1993–1994 to 1.38 million tons in 2002–2003. The asbestos industry has been delicensed since March 2003. The number of asbestos‐based units stood at 32, with the western state of Maharashtra having the largest number. According to official figures, the industry employs 8000 workers. The occupational exposure standard is still 2 fibers/mL, worse still, mesothelioma is not recognized as an occupational disease. The latest cancer registry data have no information on mesothelioma. The health and safety legislation does not cover 93% of workers in the unorganized sector where asbestos exposures are extremely high. Workers remain uninformed and untrained in dealing with asbestos exposure. Enforcement agencies are not fully conscious of the risks of asbestos exposure. Industrial hygiene assessment is seldom carried out and pathologists do not receive training in identifying mesothelioma histopathologically. The lack of political will and powerful influence of the asbestos industry are pushing India toward a disaster of unimaginable proportion.
Results of a Long‐Term Carcinogenicity Bioassay on Sprague‐Dawley Rats Exposed to Sodium Arsenite Administered in Drinking Water
Authors: SOFFRITTI MORANDO , BELPOGGI FIORELLA , DEGLI ESPOSTI DAVIDE , LAMBERTINI LUCA
Published: November 2006

Abstract:  Arsenic (As) is a metal found in nature whose acute and chronic toxic effects have been known for decades. Hundreds of millions of people are at risk of exposure to As and its various chemical forms which can occur in the occupational and general environment in air, water, soil, food, and medicines. Several epidemiological studies have shown that prolonged exposure to As can induce various types of malignant tumors in humans, namely, skin, lung, liver, kidney, and bladder cancers. These effects have been observed particularly in geographic areas where people are exposed to well water with high concentrations of As. While the risks of As at high concentrations are well documented, there is still a great deal of uncertainty regarding the risk of exposure to As at very low levels. This uncertainty is due to the absence of adequate epidemiological data and the insufficiency of experimental data currently available. Given the limited evidence demonstrating the carcinogenic potential of As in animals, a long‐term carcinogenicity bioassay on sodium arsenite (NaAsO2) was performed at the Cesare Maltoni Cancer Research Center (CMCRC) of the European Ramazzini Foundation (ERF). NaAsO2 was administrated with drinking water at concentrations of 200, 100, 50, or 0 mg/L, for 104 weeks to Sprague‐Dawley rats (50/sex/group), 8 weeks old at the start of the study. The animals were monitored until spontaneous death at which time each animal underwent complete necropsy. Histopathological evaluation of all pathological lesions and of all organs and tissues collected was routinely performed on each animal. The results demonstrate that in our experimental conditions NaAsO2 induces sparse benign and malignant tumors among treated rats. The types of tumors observed are infrequent in the strain of Sprague‐Dawley rats of the colony used in our laboratory, namely, lung adenomas and carcinomas, kidney adenomas/papillomas and carcinomas, and bladder carcinomas. Notably, an elevated incidence of these types of oncological lesions is also observed among people living in geographical areas where As is present at higher concentrations in drinking water.
Results of Long‐Term Carcinogenicity Bioassay on Sprague‐Dawley Rats Exposed to Aspartame Administered in Feed
Authors: BELPOGGI FIORELLA , SOFFRITTI MORANDO , PADOVANI MICHELA , ESPOSTI DAVIDE DEGLI , LAURIOLA MICHELINA , MINARDI FRANCO
Published: November 2006

Abstract:  Aspartame (APM) is one of the most widely used artificial sweeteners in the world. Its ever‐growing use in more than 6000 products, such as soft drinks, chewing gum, candy, desserts, etc., has been accompanied by rising consumer concerns regarding its safety, in particular its potential long‐term carcinogenic effects. In light of the inadequacy of the carcinogenicity bioassays performed in the 1970s and 1980s, a long‐term mega‐experiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation on groups of male and female Sprague‐Dawley rats (100–150/sex/group), 8 weeks old at the start of the experiment. APM was administered in feed at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. Treatment lasted until spontaneous death of the animals. The results of the study demonstrate that APM causes: (a) an increased incidence of malignant tumor‐bearing animals, with a positive significant trend in both sexes, and in particular in females treated at 50,000 ppm (P≤ 0.01) when compared to controls; (b) an increase in lymphomas–leukemias, with a positive significant trend in both sexes, and in particular in females treated at doses of 100,000 (P≤ 0.01), 50,000 (P≤ 0.01), 10,000 (P≤ 0.05), 2000 (P≤ 0.05), and 400 ppm (P≤ 0.01); (c) a statistically significant increased incidence, with a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in females and particularly in those treated at 100,000 ppm (P≤ 0.05); and (d) an increased incidence of malignant schwannomas of the peripheral nerves, with a positive trend in males (P≤ 0.05). The results of this mega‐experiment indicate that APM, in the tested experimental conditions, is a multipotential carcinogenic agent.
PDZRN3 (LNX3, SEMCAP3) is required for the differentiation of C2C12 myoblasts into myotubes
Authors: Ko Ji-Ae , Kimura Yoshihiro , Matsuura Kenji , Yamamoto Hisato , Gondo Toshikazu , Inui Makoto
Published: November 2006

PDZRN3 contains a RING-finger motif in its N-terminal region, two PDZ domains in its central region and a consensus-binding motif for PDZ domains at its C-terminus. It was identified in silico as a homolog of the protein known as LNX1 or SEMCAP1, which possesses ubiquitin ligase activity and binds the membrane protein Semaphorin 4C. However, PDZRN3 itself has not previously been characterized. We have now evaluated the properties and functions of PDZRN3. The PDZRN3 gene was shown to be expressed in various human tissues including the heart, skeletal muscle and liver and its expression in mouse skeletal muscle was developmentally regulated. Both the differentiation of C2C12 mouse skeletal myoblasts into myotubes and injury-induced muscle regeneration in vivo were found to be accompanied by up-regulation of PDZRN3. The differentiation-associated increase in the expression of PDZRN3 in C2C12 cells follows that of myogenin and precedes that of myosin heavy chain. Depletion of PDZRN3 by RNA interference inhibited the formation of myotubes as well as the associated up-regulation of myosin heavy chain in C2C12 cells. Our data suggest that PDZRN3 plays an essential role in the differentiation of myoblasts into myotubes by acting either downstream or independently of myogenin.
The utilization of systematic outcome mapping to improve performance management in health care
Authors: Persaud D David , Nestman Lawrence
Published: November 2006

Performance management is an important mechanism for ensuring accountability and improving the quality of health-care services. The last decade has witnessed a proliferation in the development of performance measurement systems for assessing health-care processes and outcomes at the program, hospital, district, system and national level. This has allowed for comparison and benchmarking between similar aspects of care at each of these levels. Unfortunately, most performance systems are devoid of clear mechanisms for translating feedback from measures into strategies for action, thus leaving largely unfulfilled the quality and management aspect necessary to improve health-care services. Therefore, the thinking that goes into designing these systems must change. This article outlines a management framework called systematic outcome mapping that provides for performance management rather than just performance measurement by allowing for quality improvement to be built into performance indicator development. It utilizes evidence-based medicine and expert consensus opinion to establish linkages between processes of care and their outcomes with the clear intent that feedback from information provided by performance indicators can be used to modify health-care activities so as to improve health outcomes. This fulfils the quality improvement aspect of performance measurement and makes it an integral part of a performance management framework that reinforces organizational learning through feedback from outcomes and the assessment of organizational routines.
Consumer determinants of the use of health plan information in plan selection
Authors: Oetjen Dawn , Fottler Myron D , Unruh Lynn Y , Rehman Zia
Published: November 2006

One of the major issues in achieving optimum levels of performance in health-care markets is to enhance consumer understanding of their health plan choices in order to facilitate the expansion of 'high-value' health plans at the expense of 'low-value' health plans. The Federal government offers employees many choices of health plans and provides large amounts of information on all of these options through (1) comparative written health plan information, (2) information from the health plans themselves, and (3) comparative health plan information on the Internet. The present study examines the degree to which 1722 Federal employees in the Department of Health and Human Services utilized health plan information from the above three sources in making their annual health plan selection. Results indicate that most employees (64%) used at least one information source, with written information from health plans the most common (53%), followed by comparative written information in The Guide (32%) and the Internet (16%). Those employees who regularly search for information prior to making an important purchase, those with a short time in their current plan, those with family coverage, Whites, African-Americans, and men were all more likely to use health plan information to make their annual choice. The Internet was accessed more often by younger and higher paid employees. Implications for policy and future research are discussed.
Allopurinol as Adjuvant Therapy in Poorly Responsive or Treatment Refractory Schizophrenia
Authors: Buie Larry W , Oertel Maryann D , Cala Suzanne O
Published: November 2006

Objective:

To review the available literature evaluating the effectiveness of allopurinol for poorly responsive or treatment refractory schizophrenia.

Data Sources:

Searches of MEDLINE (1966–October 2006), the Cochrane Library, and International Pharmaceutical Abstracts (1970–October 2006) were conducted using the terms allopurinol and schizophrenia. Limits were set to select studies conducted in humans.

Study Selection and Data Extraction:

All articles identified from the data sources were evaluated. All case reports or clinical trials located were included in the review.

Data Synthesis:

Dopamine has been implicated for many years in the pathophysiology of schizophrenia, and the typical antipsychotics, via blockade of dopaminergic neurotransmission, have provided relief for patients with positive symptoms. However, because dopamine blockade does not relieve all symptoms of schizophrenia, it is now evident that many neurotransmitters may be involved in the pathogenesis of schizophrenia. Therefore, atypical antipsychotics, which target multiple neurotransmitters, have emerged as first-line therapies. An evolving body of evidence also supports a purinergic hypothesis for schizophrenia. Increased adenosinergic transmission is thought to reduce the affinity of dopamine agonists for dopamine receptors. Allopurinol, a xanthine oxidase inhibitor, may increase circulating pools of adenosine and may ultimately have antipsychotic and anxiolytic effects. Growing evidence for use of allopurinol as adjunctive therapy has been reported in both case reports and small clinical trials.

Conclusions:

Clinical trials show that adjuvant allopurinol may provide benefit to patients who are poorly responsive to current treatments for schizophrenia. Allopurinol is well tolerated by most patients. However, larger, randomized clinical trials need to be performed to determine the magnitude of this benefit, whether allopurinol should be routinely used as adjuvant therapy to antipsychotics, and which patient population is most likely to benefit from allopurinol use. For patients with limited options, allopurinol in doses of 300 mg once or twice daily may improve psychotic symptoms, especially refractory positive symptoms.
BRIEF REPORT: Effectiveness of Individual and Dyadic Training Protocols: The Influence of Trainee Interaction Anxiety
Authors: Arthur Winfred , Young Brian , Jordan Jeffrey A. , Shebilske Wayne L.
Published: November 2006

The present study focuses on the consequences of the social dynamics that are created whenever two or more individuals are brought together for the purpose of training. An investigation of the role of individual differences in interaction anxiety on training outcomes demonstrated that the comparative effectiveness of dyadic versus individual protocols for computer-based training is moderated by trainees' level of interaction anxiety. Specifically, assignment to a dyadic protocol adversely affected the performance of high-interaction-anxiety participants but appeared to be advantageous for low-interaction-anxiety participants. Implications are discussed for changing the design and implementation of computer-based protocols for training groups and individuals in military and industrial training centers.
The Impact of Cross-Training on Team Functioning: An Empirical Investigation
Authors: Volpe Catherine E. , Cannon-Bowers Janis A. , Salas Eduardo , Spector Paul E.
Published: November 2006

The effects of cross-training (presence vs. absence) and workload (high vs. low) on team processes, communication, and task performance were examined. Eighty male undergraduate students were randomly assigned to one of four training conditions: cross-training, low workload; cross-training, high workload; no cross-training, low workload; and no cross-training, high workload. Results indicated that cross-training was an important determinant of effective teamwork process, communication, and performance. Predicted interactions between cross-training and workload were not supported. Implications for the design and implementation of cross-training as a means to improve team functioning are discussed.
Time-to-Collision Estimation in a Simulated Driving Task
Authors: Sidaway Ben , Fairweather Malcolm , Sekiya Hiro , Mcnitt-Gray Jill
Published: November 2006

Three experiments are reported that examine the role of visual information in the estimation of time to collision. Participants were shown video clips taken from within a car as it approached a stationary target. In the first two experiments the videos were occluded either at a constant time before collision or at a constant distance from the collision. Approach velocity and viewing time were also manipulated. The third experiment again varied approach velocity but did not occlude the video prior to collision with the target. In all three experiments the participants were required to press a pedal when they estimated that collision occurred. Results from all experiments indicated that approach velocity had the greatest influence on the accuracy of collision estimation, and accuracy improved with increasing velocity. Varying viewing time from 1 to 8 s had little effect on estimation accuracy. These results emphasize the role of global optic flow rate in the judgment of time of collision.
Automatic Speech Recognition in Adverse Environments
Authors: Baber Chris , Noyes Jan
Published: November 2006

Technological developments in automatic speech recognition (ASR) technology over the last couple of decades have resulted in ASR being considered for use in an ever-increasing number of applications. However, a number of physical and psychological environments are still deemed inappropriate for this technology. Several of the stressors creating adverse environments are considered here, in conjunction with their effects on human speech production, human performance in general, and the implications for ASR system design. We propose that a combination of continuing technological developments, together with the application of system engineering and human factors, will lead to ensuring the attainment of robust ASR performance in a number of environments previously considered as high risk.
Toward a Quantitative Definition of Manual Lifting Postures
Authors: Burgess-Limerick Robin , Abernethy Bruce
Published: November 2006

Manual lifting techniques are commonly defined in terms of the postures adopted at the start of the lift. Quantitative definition is problematic, however, because the absolute joint angles adopted to lift an object are influenced by task parameters, such as the initial height of the load. We present an argument for the use of a postural index (the ratio of knee flexion from normal standing to the sum of ankle, hip, and lumbar vertebral flexion) to define the postures adopted at the start of lifting. Stooped postures adopted at the start of a lift correspond to postural indices close to 0, whereas full squat postures correspond to postural indices close to 1. We use angular kinematic data gathered from 71 individuals lifting loads of varying mass from a range of starting heights to illustrate the utility of this index. Although average absolute joint angles were influenced by load mass and initial load height, the average postural index remained unchanged. For example, changes in starting height from 9 cm to 63 cm accounted for between 19% and 67% of the variance in joint positions at the start of the lift but only 1% of the variance in average postural index. This suggests that the postural index provides a method of defining lifting posture that is independent of specific joint positions
Methodological and Analytical Concerns on the Pilot Selection Research of Park and Lee (1992)
Authors: Damos Diane L. , Koonce Jefferson M.
Published: November 2006

In 1992, Park and Lee published a paper in Human Factors on the use of a computerized battery to select pilots for the Korean Air Force. In the present article we describe problems associated with the selection, implementation, and administration of the tasks constituting the computerized battery in Park and Lee. Problems associated with the data analysis are also discussed and focus on factor interpretation and nonindependent statistical tests. We offer some general guidelines for developing computerized pilot selection batteries and data analysis.