bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality among synthetic fiber workers exposed to glycerol polyglycidyl ether
Authors: Lanes Stephan F. , Rothman Kenneth J. , Soden Kevin J. , Amsel Jonathan , Dreyer Nancy A.
Published: April 2007

We studied mortality among 8,878 employees who worked at any time from 1965 to 1988 at a synthetic fibers plant in North Carolina that used a finishing agent containing glyceroi polyglycidyl ether. Some glycidyl ethers are mutagenic and tumorigenic in laboratory animals. The main route of exposure to workers was inhalation of the spray mist, although there was also skin contact. We identified 553 deaths in the cohort and the standardized mortality ratio (SMR) from all causes of death combined was 0.80. For most causes of death, mortality rates in the cohort were similar to mortality rates in the U.S. population. Among categories with at least five observed deaths, the largest effect estimate was for cancer of the central nervous system (SMR = 1.77), and the SMR for lung cancer was 0.94. The cancer categories of central nervous system (brain) and ‘other’ lymphopoietic cancers (lymphoma and myeloma) showed weak associations with duration of employment. In case‐control analyses in which we utilized work history data to compute effect estimates by duration of exposure, we found no increased risk of lung cancer or brain cancer among employees with more than 5 years of exposure. Effect estimates for lymphoma and myeloma tended to increase with duration of exposure, although there were only seven deaths in this category and the effect estimates were very imprecise. To date, this study has identified no clear carcinogenic effect of glycerol polyglycidyl ether, but plausible induction periods have not yet elapsed. The cohort should continue to be monitored to obtain more precise estimates after moderate or long induction times. © 1994 Wiley‐Liss, Inc.
Biological monitoring of exposure to low concentrations of styrene
Authors: Ong C. N. , Shi C. Y. , Chia S. E. , Chua S. C. , Ong H. Y. , Lee B. L. , Ng T. P. , Teramoto K.
Published: April 2007

A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end‐of‐shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end‐of‐shift MA, PGA, and MA + PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA + PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure. © 1994 Wiley‐Liss, Inc.
Evaluation of the association of acute overshift change in pulmonary function and atopy using OSHA cotton dust surveillance data
Authors: Md Elizabeth Jennison , Jacobs Robert R.
Published: April 2007

OSHA surveillance data were collected for 769 individuals employed in four different cotton textile mills. Current workers were asked to complete a questionnaire about personal and family history of atopy or asthma. Both surveillance and survey data were available for 502 individuals. The prevalence of atopy in the population as reported by questionnaire was 18%, while asthma was reported by 4%. Dust levels at the four mills were in compliance with the cotton dust standard during the period of surveillance. No relationship was found between a self‐reported history of atopy or asthma and the magnitude or frequency of acute overshift declines in forced expiratory volume during 1 second (FEV1). Nonsmokers had annual changes in FEV1 and forced vital capacity (FVC) comparable to nonexposed populations. In one of the four mills surveyed, annual declines in FEV1 and FVC for current smokers were significantly greater than declines for smokers in the other mills or the general smoking population (p < 0.02). This mill effect was also observed for subjects who were categorized as atopic (p < 0.02). For nonsmokers there appears to be no significant adverse health effect from exposure to the levels of cotton dust observed in these mills. © 1994 Wiley‐Liss, Inc.
Causes of mortality in primary and secondary school teachers
Authors: Rosenman Kenneth D.
Published: April 2007

A proportionate mortality study was conducted on 809 deaths occurring among New Jersey primary and secondary teachers between 1980 and 1984. Three separate sets of expected number of deaths were used, based on U.S. and New Jersey proportionate mortality ratios in the general population and proportionate cancer mortality ratios. Increased cause of death was found for digestive, breast, other genital, and lymphopoietic cancer, and motor vehicle accidents for white female teachers; digestive cancer, heart disease, and nonmalignant genitourinary disease for white male teachers; digestive, brain, and thyroid cancer in black female teachers; and kidney and prostate cancer in black male teachers. Deficits in lung cancer were found for white male teachers and in heart disease for white and black female teachers. Mortality ratios were examined by duration worked and latency since first hired. Further analysis using a nested‐case control methodology is recommended. © 1994 Wiley‐Liss, Inc.
National conference on ergonomics, safety, and health in construction summary report
Authors: Ringen Knut
Published: April 2007

Decision makers from the construction industry, labor unions, government, and academia met in Washington, DC, July 18 to 22 to focus for the first time as a group on the work‐related safety and health problems of construction workers. The National Conference on Ergonomics, Safety, and Health in Construction drew more than 750 participants, including experts in economics, engineering, ergonomics, industrial hygiene, insurance, public health, public policy, and occupational and rehabilitative medicine.
Assessment of cancer clusters using limited cohort data with spreadsheets: Application to a leukemia cluster among rubber workers
Authors: Smith Allan H. , Duggan Heather M. , Wright Catherine
Published: April 2007

This paper presents methods for initial investigation of occupational cancer clusters using limited data. Phase 1 of the methods developed uses basic data from the cluster of cases, but with cohort data limited to the size of the workforce at the plant. Phase 2 of the methods requires knowledge of the number of workers entering and leaving the workforce in each year. In the absence of data concerning age, the spreadsheet programs explore a variety of worker age distributions in synthetic cohort analyses. The methods were used to assess a cluster of six cases of leukemia with an average duration of work of 11 years in a tire manufacturing plant. It was concluded that the relative risk for the age range 30‐50 was at least 7, providing further evidence for the association of leukemia with work in tire manufacture. The use of spreadsheet programs can provide a valuable first step assessment of apparent workplace cancer clusters.
Use of state workers' compensation data for occupational carpal tunnel syndrome surveillance: A feasibility study in massachusetts
Authors: Korrick Susan A. , Rest Kathleen M. , Davis Letitia K. , Christiani David C.
Published: April 2007

The purpose of this study was to determine the feasibility of using Massachusetts workers' compensation data for passive surveillance of occupational carpal tunnel syndrome (OCTS). Workers' compensation claims for OCTS (n = 358) and for possible cases of OCTS (n = 1,121) active during the first 6 months of 1989 were identified. The availability and distribution of demographic and employment descriptors were assessed. Medical records on a sample of the claims were reviewed to validate the diagnosis of OCTS. Age, gender, and occupation were available for less than 47% of the reported cases of OCTS. The majority (88%) of cases on whom medical record review was performed had a physician's diagnosis of carpal tunnel syndrome (CTS), and most of this group had confirmatory nerve conduction studies or electromyography. However, there were fundamental limitations to workers' compensation based disease surveillance in Massachusetts, including underascertainment of cases, potential ascertainment biases, delayed case reporting, limited access to specific diagnostic information, and incomplete and sometimes inaccurate information. These limitations are likely to be applicable in many, if not most, states and must be made clear in any analyses based on workers' compensation data.
Mortality among danish merchant seamen from 1970 to 1985
Authors: Brandt L. P. A. , Kirk N. U. , Jensen O. C. , Hansen H. L.
Published: April 2007

A retrospective cohort study was performed to analyze the mortality patterns of Danish merchant seamen in the period 1970‐1985. The population census in 1970 in Denmark was the source of information on individual occupation, age, and marital status. All men aged 20‐64 years and economically active in 1970 were included. Computerized linkage with the Danish Mortality Register gave information about the deceased persons' date and cause of death. An increased overall mortality among all groups of seamen was found, being highest for deck and engine crew members. The overall mortality was strongly dependent on age and marital status. The highest mortality rate ratios (MRR) were found among young seamen and unmarried seamen. MRRs of 1.90 and 2.47 for cancer of the respiratory system were found among engine officers and crew. The MRRs for accidents and suicide were increased for all seamen, and were highest for crew members, among whom the MRR from accidents was stable within age groups but fell for suicide with increasing age. The same pattern was found with cirrhosis of the liver, although this was positively associated with increasing age. Excess mortality from ischemic heart disease was only found among engine crew (MRR = 1.43). This study confirms earlier findings of high mortality among seafarers. Negative selection into the occupation, occupational environmental factors, and lack of health and safety promotion programs and education could be causes of the high mortality.
Retrospective cohort study of workers of a synthetic textiles plant in quebec: I. General mortality
Authors: Goldberg Mark S. , Thériault Gilles
Published: April 2007

This paper presents results from a retrospective cohort study of workers of a synthetic textiles plant in Quebec. This plant has been the subject of a previous case‐control study, in which an excess risk of colorectal cancer was observed. The cohort consisted of 7,487 men and 2,724 women who had worked at least 1 year at the plant and who were either working in 1947 or were newly employed between 1947 and 1977. The period of follow‐up was from 1947 to 1986, thus yielding 307,278 person‐years of observation.

Mortality rates for most causes of death were less than expected; the standardized mortality ratio (SMR) for all causes of death among men was 0.73 (95% confidence interval (CI): 0.70‐0.77) and among women it was 0.77 (95%CI: 0.68‐0.87). For men, the SMR for all neoplasms was 0.76 (95% CI: 0.69‐0.83) and for colorectal cancer it was 0.69 (95%CI: 0.52‐0.92). For women, the SMR for all neoplasms was 1.01 (95%CI: 0.83‐1.22) and for colorectal cancer it was 1.02 (95%CI: 0.57‐1.69). Among men, risks for ischemic heart disease increased with increasing length of service at the plant, even though the SMRs were less than unity (overall SMR = 0.76; 95%CI: 0.70‐0.83); no trend was observed for women.

SMRs and relative risks were also calculated according to duration of employment in each processing unit. Of the scores of associations tested, very few showed increased risks. Of those showing increased risks, the data were not persuasive in indicating a connection with work at the plant; nevertheless, some of these associations may be worth following up in future studies. The following associations of potential significance were observed: all cancers, liver‐and gallbladder cancers, non‐Hodgkin's lymphomas. and reticulum cell sarcoma in the cellulose acetate fiber manufacturing unit; all cancers in the polypropylene and cellulose triacetate extrusion unit and in the janitor unit; leukemias in the unexposed unit; ischemic heart disease in the maintenance and janitor units; and cerebrovascular disease in the weaving unit.
Exposure assessment in epidemiologic studies of birth defects by industrial hygiene review of maternal interviews
Authors: Katz Elizabeth A. , Shaw Gary M. , Schaffer Donna M.
Published: April 2007

In epidemiologic studies of birth defects, occupational titles have frequently been used as surrogates for exposure. To avoid the error associated with such proxy exposure measures, we have designed a process in which an industrial hygienist systematically imputes exposures derived from maternal interviews. In response to a structured questionnaire, mothers of cases and controls recalled occupational and nonoccupational tasks performed or products used around the time of conception. Maternal exposures were then assigned to several a priori defined categories by an industrial hygienist. The central exposure category consists of 74 chemical families, e.g., alcohols, lead compounds. Other exposure categories are individual chemical compounds; nonchemical agents, e.g., ionizing radiation, infectious diseases; and product end‐use categories, e.g., insecticides, combustion products. A detailed description of this approach and its exposure assessment potential is presented using exposure data from 220 maternal interviews.
Prenatal lead exposure in relation to gestational age and birth weight: A review of epidemiologic studies
Authors: Andrews Kurtis W. , Savitz David A. , Hertz‐Picciotto Irva
Published: April 2007

Although the adverse effect on pregnancy outcomes at high levels of lead exposure in the workplace has been recognized for years, there is uncertainty regarding the impact of exposure at the lower community exposure levels commonly encountered today. This review summarizes the epidemiologic literature and discusses pertinent methodologic issues and possible sources of interstudy variation. The authors conclude that prenatal lead exposure is unlikely to increase the risk of premature membrane rupture but does appear to increase the risk of preterm delivery. Whether prenatal lead exposure decreases gestational age in terms of infants is unclear. Prenatal lead exposure also appears to be associated with reduced birth weight, but results vary in relation to study design and degree of control for confounding. Adjustment for gestational age, a possible confounder of the birth weight‐lead exposure association, did not yield clearer results.
Colorectal cancer incidence in pattern and model makers: Evidence from a screening program
Authors: Demers Raymond Y. , Parsons Kenneth C.
Published: April 2007

This study is designed to evaluate the efficacy of colorectal cancer screening in a high risk population of pattern and model makers. The cohort of 1,641 white male automotive pattern and model makers was identified in 1981, and offered colorectal cancer screening. The program involved periodic 60 cm flexible sigmoid examination, stool occult blood testing, and digital rectal examination. Screening was offered in 1981, 1982, 1985, 1988, and 1991. Approximately 60% of those eligible participated in at least one screening examination. Nonparticipants showed a relative risk for incident colorectal cancer of over 10, compared to those who participated at least once in the screening. Cohort tracking has accumulated 10 years; results suggest a benefit to colorectal cancer screening in this population.
Exposure to magnetic fields among electrical workers in relation to leukemia risk in Los Angeles County
Authors: London Stephanie J. , Bowman Joseph D. , Sobel Eugene , Thomas Duncan C. , Garabrant David H. , Pearce Neil , Bernstein Leslie , Peters John M.
Published: April 2007

To Address the hypotheses that electrical workers are exposed to higher magnetic fields and are at higher risk of leukemia than nonelectrical workers, we performed a registry‐based case‐control study among men aged 20–64 years with known occupation who were diagnosed with cancer in Los Angeles County between 1972 and 1990. Controls were men with cancers other than those of the central nervous system or leukemia. Magnetic field measurements on workers in each electrical occupation and in a random sample of occupations presumed to be nonelectrical were used to estimate magnetic field exposures for each occupation. Among men in electrical occupations, 121 leukemias were diagnosed. With the exception of electrical engineers, magnetic field exposures were higher among workers in electrical occupations than in nonelectrical occupations. A weakly positive trend in leukemia risk across average occupational magnetic field exposure was observed (odds ratio [OR] per 10 milligauss increase in average magnetic field = 1.2, 95% confidence interval [CI] 1.0–1.5). A slightly stronger association was observed for chronic myloid leukemia, although only 28 cases occurred among electrical workers (OR 10 milligauss increase = 1.6, 95% CI = 1.2–2.0). The results were not materially altered by adjustment for exposure to several agents known or suspected to cause leukemia. Although not conclusive, these results are consistent with findings from studies based on job title alone that electrical workers may be at slightly increased risk of leukemia.
Pleural mesothelioma: A descriptive analysis based on a case‐control study and mortality data in Ile de France, 1987–1990
Authors: Iwatsubo Yuriko , Pairon Jean‐Claude , de Beaune Corinne Archambault , Chamming's Soizic , Bignon Jean , Brochard Patrick
Published: April 2007

Incidence rates of pleural mesothelioma in Ile de France were examined for the period 1987–1990, on the basis of information collected in a case‐control study. This study was designed to include all new cases of pleural mesothelioma occurring in the region. On the other hand, mortality rates from pleural malignancies in the same region were examined on the basis of death certificates recorded by INSERM for the same period.

A large difference was found between the two types of data. Average annual incidence rates were 7.5 per million among men and 1.6 per million among women. Average annual mortality rates due to primary pleural malignancies were 25.2 per million in males and 8.9 per million in females. This study confirms discordances between incidence and mortality data for pleural malignancies already reported in several countries. However, contrasting with some previous reports, the annual mortality rate from pleural malignancies was higher than the incidence rate of mesothelioma in this study. This emphasizes the usefulness of a specific investigation to explain such discordances, prior to comparison of data from one country to another.
No interaction between the serotonin transporter polymorphism (5‐HTTLPR) and childhood adversity or recent stressful life events on symptoms of depression: Results from two community surveys
Authors: Chipman P. , Jorm A.F. , Prior M. , Sanson A. , Smart D. , Tan X. , Easteal S.
Published: April 2007

In this study we investigated interactions between the 5‐HTTLPR genotype and environmental risk factors (G × E) on symptoms of depression in two large Australian community samples of adolescents and young adults. We postulated that a significant interaction between the 5‐HTTLPR genotype and environmental risk factors of childhood adversity or stressful life events on symptoms of depression would be observed in subjects with at least one short allele (s/l or s/s) compared with subjects with no short alleles (l/l). We did not find significant G × E interactions between the 5‐HTTLPR genotype and recent stressful life events or childhood adversity on symptoms of depression in our sample populations. However, we did find adolescents aged 17–18 years homozygous for the long allele (l/l) and exposed to persistently high levels of family adversity over a 6‐year period were at a greater risk of depression than subjects with the same genotype exposed to no or persistently low levels of family adversity. This interaction should be interpreted cautiously due to the small number of depressed subjects in the sample with persistently high levels of family adversity. © 2007 Wiley‐Liss, Inc.
Deprotonierende Metallierungen mit 'at‐Verbindungen: Synergie, Synthese und Strukturaufbau
Authors: Mulvey Robert E. , Mongin Florence , Uchiyama Masanobu , Kondo Yoshinori
Published: April 2007

In der organischen Synthesechemie werden Monometallspezies wie Organolithiumverbindungen seit langem für Deprotonierungsreaktionen genutzt. In den letzten Jahren ist mit den 'at‐Komplexen eine neue Klasse von Metallierungsreagentien hinzugetreten, die das Syntheserepertoire metallorganischer Spezies ergänzt. Dank eines frei wählbaren Metallzentrums (Magnesium, Zink oder Aluminium), frei wählbarer Liganden (in Art und Anzahl) und eines frei wählbaren sekundären Metallzentrums (eines Alkalimetalls wie Lithium oder Natrium) sind 'at‐Komplexe äußerst vielseitige basische Reagentien, deren synergetische Reaktionsweisen mit den homometallischen Magnesium‐, Zink‐ oder Aluminiumverbindungen nicht beobachtet werden. Deprotonierungen mit metallorganischen 'at‐Komplexen haben neue Perspektiven in der organischen Chemie eröffnet, mit ungewöhnlichen Reaktivitäten und manchmal unvorhergesehenen Regioselektivitäten.
In Situ and Operando Spectroscopy for Assessing Mechanisms of Gas Sensing
Authors: Gurlo Alexander , Riedel Ralf
Published: April 2007

The mechanistic description of gas sensing on inorganic, organic, and polymeric materials is of great scientific and technological interest. The understanding of surface and bulk reactions responsible for gas‐sensing effects will lead to increased selectivity and sensitivity in the chemical determination of gases and thus to the development of better sensors. In recent years, spectroscopic tools have been developed to follow the physicochemical processes taking place in an active sensing element in real time and under operating conditions. Thus, the monitoring of the processes in “living” gas sensors is no longer an unsolvable problem. This Review gives an overview of in situ and operando spectroscopic techniques for the study of gas‐sensing mechanisms on solid‐state sensors.
Deprotonative Metalation Using Ate Compounds: Synergy, Synthesis, and Structure Building
Authors: Mulvey Robert E. , Mongin Florence , Uchiyama Masanobu , Kondo Yoshinori
Published: April 2007

Historically, single‐metal organometallic species such as organolithium compounds have been the reagents of choice in synthetic organic chemistry for performing deprotonation reactions. Over the past few years, a complementary new class of metalating agents has started to emerge. Owing to a variable central metal (magnesium, zinc, or aluminum), variable ligands (both in their nature and number), and a variable second metallic center (an alkali metal such as lithium or sodium), “ate” complexes are highly versatile bases that exhibit a synergic chemistry which cannot be replicated by the homometallic magnesium, zinc, or aluminum compounds on their own. Deprotonation accomplished by using these organometallic ate complexes has opened up new perspectives in organic chemistry with unprecedented reactivities and sometimes unusual and unpredictable regioselectivities.
Advances in molecular biology of hibernation in mammals
Authors: Andrews Matthew T.
Published: April 2007

Mammalian hibernation is characterized by profound reductions in metabolism, oxygen consumption and heart rate. As a result, the animal enters a state of suspended animation where core body temperatures can plummet as low as −2.9°C. Not only can hibernating mammals survive these physiological extremes, but they also return to a normothermic state of activity without reperfusion injury or other ill effects. This review examines recent findings on the genes, proteins and small molecules that control the induction and maintenance of hibernation in mammals. The molecular events involved with remodeling metabolism, inducing hypothermia and maintaining organ function are discussed and considered with respect to analogous processes in non‐hibernating mammals such as mice and humans. The advent of sequenced genomes from three distantly related hibernators, a bat, hedgehog and ground squirrel, provides additional opportunities for molecular biologists to explore the mechanistic aspects of this biological adaptation in greater detail. BioEssays 29:431–440, 2007. © 2007 Wiley Periodicals, Inc.
Lentiviral nuclear import: a complex interplay between virus and host
Authors: De Rijck Jan , Vandekerckhove Linos , Christ Frauke , Debyser Zeger
Published: April 2007

Although the capacity to infect non‐dividing cells is a hallmark of lentiviruses, nuclear import is still barely understood. More than 100 research papers have been dedicated to this topic during the last 15 years, yet, more questions have been raised than answers. The signal‐facilitating translocation of the viral preintegration complex (PIC) through the nuclear pore complex (NPC) remains unknown. It is clear, however, that nuclear import is the result of a complex interplay between viral and cellular components. In this review, we discuss the current knowledge on nuclear import. We focus on the controversies and pitfalls and discuss the interplay between virus and host. BioEssays 29:441–451, 2007. © 2007 Wiley Periodicals, Inc.
Genetic connections of the actin cytoskeleton and beyond
Authors: Percipalle Piergiorgio
Published: April 2007

Actin is a key protein in numerous cellular functions. One recent study has identified a large set of genes, associated with the actin cytoskeleton, which could be grouped into a wide spectrum of cytoplasmic and nuclear functions, such as protein biosynthesis and gene transcription.1 Deletions of many of the identified genes affected cellular actin organization,1 suggesting a functional link between different actin fractions probably regulated through changes in actin dynamics. The data are very exciting; speculations on the crosstalk between cytoplasmic and nuclear actin fractions in different cellular contexts may help placing the results in perspective to further understand how actin‐mediated signalling affects cellular functions, such as gene expression. BioEssays 29:407–411, 2007. © 2007 Wiley Periodicals, Inc.
The potential for the formation of the arginine biosynthetic enzymes and its masking during evolution
Authors: Maas Werner K.
Published: April 2007

The present account spans the history of arginine regulation from its discovery in 1955 until the present. In 1957 I demonstrated that not only added arginine but also internally produced arginine represses enzyme formation and that the potential for enzyme synthesis is in excess of what is required for growth. In 1959 I located the regulatory gene argR encoding the arginine repressor. An unusual feature of this research was the finding that in E. coli B, in contrast to E. coli K12, arginine synthesis is permanently repressed, independent of arginine. This was due to a single amino acid difference between the two repressors. Recent studies showed that, in natural populations of E. coli, K12‐type regulation is much more frequent than B‐type regulation, and that E. coli B evolved from a strain with K12‐type regulation. In competition experiments, E. coli K12 was found to be favored in the presence of arginine and E. coli B in its absence, showing that contrary to expectations permanently turned off regulation is favored over negative regulation in some environments. BioEssays 29:484–488, 2007. © 2007 Wiley Periodicals, Inc.
Influence of local and residual structures on the scaling behavior and dimensions of unfolded proteins
Authors: Wang Zhisong , Plaxco Kevin W. , Makarov Dmitrii E.
Published: April 2007

Although recent spectroscopic studies of chemically denatured proteins hint at significant nonrandom residual structure, the results of extensive small angle X‐ray scattering studies suggest random coil behavior, calling for a coherent understanding of these seemingly contradicting observations. Here, we report the results of a Monte Carlo study of the effects of two types of local structures, α helix and Polyproline II (PPII) helix, on the dimensions of random coil polyalanine chains viewed as a model of highly denatured proteins. We find that although Flory's power law scaling, long regarded as a signature of random coil behavior, holds for chains containing up to 90% α or PPII helix, the absolute magnitude of the chain dimensions is sensitive to helix content. As residual α helix content increases, the chain contracts until it reaches a minimum radius at ∼70% helix, after which the chain dimensions expand rapidly. With an α helix content of ∼20%, corresponding to the Ramachandran probability of being in the helical basin, experimentally observed radii of gyration are recovered. Experimental radii are similarly recovered at an α helix content of ∼87%, providing an explanation for the previously puzzling experimental finding that the dimensions of the highly helical methanol‐induced unfolded state are experimentally indistinguishable from those of the helix‐poor urea‐unfolded state. In contrast, the radius of gyration increases monotonically with increasing PPII content, and is always more expanded than the dimensions observed experimentally. These results suggest that PPII is unlikely the sole, dominant preferred conformation for unfolded proteins. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 321–328, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A validated high‐performance liquid chromatographic method for the determination of moclobemide and its two metabolites in human plasma and application to pharmacokinetic studies
Authors: Plenis Alina , Chmielewska Aleksandra , Konieczna Lucyna , Lamparczyk Henryk
Published: April 2007

A rapid and sensitive reversed‐phase high‐performance liquid chromatographic method (RP‐HPLC) with ultraviolet detection has been developed for the determination of moclobemide and its metabolites, p‐chloro‐N‐(‐2‐morpholinoethyl)benzamide N′‐oxide (Ro 12‐5637) and p‐chloro‐N‐[2‐(3‐oxomorpholino)ethyl]‐benzamide (Ro 12‐8095), in human plasma. The assay was performed after single liquid–liquid extraction with dichloromethane at alkaline pH using phenacetin as the internal standard. Chromatographic separation was performed on a C18 column using a mixture of acetonitrile and water (25:75, v/v), adjusted to pH 2.7 with ortho‐phosphoric acid, as mobile phase. Spectrophotometric detection was performed at 239 nm. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The quantification limit for moclobemide and Ro 12‐8095 was 10 ng/mL, and for Ro 12‐5637 was 30 ng/mL. Linearity of the method was confirmed for the range 20–2500 ng/mL for moclobemide (r = 0.9998), 20–1750 ng/mL for Ro 12‐8095 (r = 0.9996) and 30–350 ng/mL for Ro 12‐5637 (r = 0.9991). Moreover, within‐day and between‐day precisions and accuracies of the method were established. The described method was successfully applied in pharmacokinetic studies of parent drug and its two metabolites after a single oral administration of 150 mg of moclobemide to 20 healthy volunteers. Copyright © 2007 John Wiley & Sons, Ltd.
Application of AXAFS Spectroscopy to Transition‐Metal Oxides: Influence of the Nearest and Next Nearest Neighbour Shells in Vanadium Oxides
Authors: Keller Daphne E. , Weckhuysen Bert M. , Koningsberger Diek C.
Published: April 2007

The influence of changes in coordination number, interatomic distances, and oxidation state on the intensity and centroid position of the Fourier transform (FT) of the atomic X‐ray absorption fine structure (AXAFS) peak of vanadium oxide bulk model compounds and alumina‐supported vanadium oxide clusters has been investigated. Using Na3VO4 and V2O5 as model compounds, it has been shown that the nearest neighbour shells have a pronounced influence on the AXAFS intensity; specifically, a 40 % decrease in intensity was observed between these two compounds. Secondly, the influence of partial reduction of the vanadium oxide species has been determined; this led to a 50 % decrease in the AXAFS intensity and to an increase in the centroid position. Furthermore, the influence of the vanadium oxide loading has been assessed. A non‐linear relationship between the vanadium oxide loading and the AXAFS intensity has been found, indicating that the AXAFS intensity is sensitive to the formation of VOV bridging bonds between the vanadium VO4 clusters. The results show that AXAFS can be used to probe the relative energy level of the vanadium valence orbitals.
Exhaustive Analysis of Frontal Copolymerization of Functionalized Monovinyl and Divinyl Monomers
Authors: Pujari Narahari S. , Inamdar Satish R. , Ambekar Jalindar D. , Kulkarni B. D. , Ponrathnam Surendra
Published: April 2007

A series of copolymers of 2‐hydroxyethyl methacrylate (HEMA)/glycidyl methacrylate (GMA) and ethylene dimethacrylate (EGDM) were synthesized by frontal polymerization (FP). This study was conducted to investigate the effect of crosslink density, type and concentration of initiator, the use of a complex initiator system, porogen, and diluent on the most relevant parameters of FP, such as sustainability of the front, temperature profile, front velocity, and yield. The products were also characterized for intruded pore volume, pore‐size distribution, epoxy‐functionality number, and surface morphology. Higher crosslink densities (CLDs) and initiator concentration produced higher front velocities, whereas no trend in front temperature was noted. A complex initiation system was effective in stabilizing and increasing the polymerization yield. Relative to suspension polymerization (SP), FP products synthesized without a solvent were microporous, whereas micro‐to‐macroporous products were obtained in the presence of a solvent (for HEMA–EGDM polymers). We also present, explain, and discuss the exotic patterns observed under a microscope. We observed two basic types of spatial patterns, namely, planar and nonplanar patterns. The type of planar pattern observed under scanning electron microscopy (SEM) has a spatial impulse that appears as a loop followed by regular periodic motion in the radial and axial directions. This behavior gives rise to a repeating pattern that is a few microns thick. Also, nonplanar patterns, namely, layered concentric rings and winding staircase patterns, were observed under SEM.
De Novo Synthesis of Uronic Acid Building Blocks for Assembly of Heparin Oligosaccharides
Authors: Adibekian Alexander , Bindschädler Pascal , Timmer Mattie S. M. , Noti Christian , Schützenmeister Nina , Seeberger Peter H.
Published: April 2007

An efficient de novo synthesis of uronic acid building blocks is described. The synthetic strategy relies on the stereoselective elongation of thioacetal protected dialdehydes 12 a and 17. The dialdehydes are prepared from D‐xylose, a cheap and commercially available source. A highly stereoselective MgBr2⋅OEt2‐mediated Mukaiyama aldol addition to C4‐aldehyde 12 a is performed to obtain D‐glucuronic acid building block 16, whereas L‐iduronic acid building block 22 is prepared by MgBr2⋅OEt2‐mediated cyanation of C5‐aldehyde 17. Synthesis of a heparin disaccharide demonstrates the utility of the de novo strategy for the assembly of glycosaminoglycan oligosaccharides.
Dual Reactivity Pattern of Allenolates “On Water”: The Chemical Basis for Efficient Allenolate‐Driven Organocatalytic Systems
Authors: González‐Cruz David , Tejedor David , de Armas Pedro , García‐Tellado Fernando
Published: April 2007

A study of the reactivity pattern associated with zwitterionic allenolates “on water” is reported. This study establishes the chemical basis for two organocatalyzed allenolate‐driven reaction networks operating “on water”. The first one is a chemodifferentiating three building block (ABB′) three‐component reaction (ABB′ 3CR) manifold comprising terminal alkynoates and aldehydes. The manifold produces propargylic enol ethers 3 with higher average efficiency than their homologues in organic solvents. The second one is a novel organocatalytic system elicited by the reaction of alkynoates and nitrones in the presence of tertiary amines or phosphines. While terminal alkynoates afford 2,3,5‐trisubstituted 2,3‐dihydroisoxazoles 5 and propargylic N‐hydroxylamines 6, internal alkynoates selectively afford the 2,3,4,5‐tetrasusbstituted 2,3‐dihydroisoxazaole 10. Importantly, in both cases, the 2,3‐dihydroisoxazole ring is obtained as a sole regioisomer.
Photochemically Initiated Single Polymer Immobilization
Authors: Yan Mingdi
Published: April 2007

This Concept article surveys methods for attaching single polymer molecules on solid substrates. A general approach to single polymer immobilization based on the photochemistry of perfluorophenylazides is elaborated.
In‐vivo high‐resolution X‐ray microtomography for liver and spleen tumor assessment in mice
Authors: Almajdub M. , Nejjari M. , Poncet G. , Magnier L. , Chereul E. , Roche C. , Janier M.
Published: April 2007

The present study sought to validate the use of glycery1‐2‐oley‐1,3‐bis‐[7‐(3‐amino‐2,4,6‐triiodophenyl)‐ heptanoate] (DHOG) contrast agent for mouse spleen tumor and liver metastasis imaging by high‐resolution X‐ray microtomography. Three groups of female nude mice were compared: controls (n = 5), and mice injected with 2.5 × 106 STC1 tumor cells in the spleen, imaged at 15 days (group G15, n = 5) and at 30 days (group G30, n = 5, of which one died before imaging). Micro‐CT scans (X‐ray voltage, 50 kVp; anode current, 200 µA; exposure time, 632 ms; 180 rotational steps resulting in 35 µm isotropic spatial resolution) were acquired at 0, 0.75, 2 and 4 h after i.v. injection of DHOG. CT number (Hounsfield units: HU) and contrast‐to‐noise ratios (CNR) were determined in three organs. Statistical analysis was performed by Mann–Whitney U‐test. Contrast enhancement in normal spleen and liver increased, respectively to 1020 ± 159 and 351 ± 27 HU over baseline at 4 h, and 482 ± 3 and 203 ± 14 HU on day 6 after a single contrast injection. Automated three‐dimensional reconstruction and modeling of the spleen provided accurate and quantifiable images. Spleen tumor and liver metastases did not take up DHOG, making them detectable in contrast to the increased signal in normal tissue. The smallest liver metastasis detected measured 0.3 mm in diameter. High‐resolution X‐ray micro‐CT in living mice using DHOG contrast agent allowed visualization and volume quantification of normal spleen and of spleen tumor and its liver metastases. Copyright © 2007 John Wiley & Sons, Ltd.
Economic burden of metastatic bone disease in the U.S.
Authors: Schulman Kathy L. , Kohles Joseph
Published: April 2007

BACKGROUND

Previous research has documented the prevalence of primary bone cancer; however, there are few data available regarding the impact of metastatic bone disease (MBD) on national expenditure. In this study, the authors quantified the prevalence and direct medical care costs of patients with MBD and the resulting cost impact on U.S. oncology expenditure.

METHODS

Anonymous, patient‐level data on health care utilization and cost were obtained from the Thomson Medstat MarketScan research databases. In total, 396,200 patients who were diagnosed with cancer between 2000 and 2004 were selected for the study. Patients with MBD were matched subsequently to non‐MBD controls. A 2‐part linear regression model was used to compare cases with controls to quantify the incremental cost associated with the disease.

RESULTS

Cancer prevalence in the U.S. during the study period was estimated at 4,861,987 cases annually, and 5.3% (n = 256,137) of those patients had MBD. Rates of MBD were highest in patients with multiple myeloma (28.8%) and lung cancer (15.6%). The mean direct medical cost for all cancers combined was $75,329 for patients with MBD and $31,382 for controls. Regression‐adjusted, incremental costs were $44,442 (P < .001) across all cancer types. The incremental cost was highest for patients with multiple myeloma ($63,455) and lowest for patients with lung cancer ($24,946).

CONCLUSIONS

The national cost burden for patients with MBD was estimated at $12.6 billion, which is 17% of the $74 billion in total direct medical cost estimated by the National Institutes of Health, suggesting that MBD is a significant driver of overall oncology cost. Cancer 2007. © 2007 American Cancer Society.
Food and drug administration expanded access to treatment
Authors: Freedman Ralph S. , Markman Maurie
Published: April 2007

On December 14, 2006, the FDA published simultaneously in the Federal Register their proposed rules amending regulations for expanded access to investigational drugs and for charging patients for investigational drugs. These proposed rules, if approved, could have important implications for patients, providers, and for Pharma.
Role of diagnostic and ablative minimally invasive surgery for pediatric malignancies
Authors: Metzelder Martin L. , Kuebler Joachim F. , Shimotakahara Akihiro , Glueer Sylvia , Grigull Lorenz , Ure Benno M.
Published: April 2007

BACKGROUND

The use of minimally invasive surgery (MIS) in pediatric cancer is a matter of debate. The diagnostic and ablative roles of MIS were evaluated in a consecutive series of children with malignancies.

METHODS

A prospective study, including all patients, who underwent abdominal and thoracic surgery for confirmed or highly suspected pediatric cancer was performed from September, 2000, to December, 2005. An interdisciplinary panel approved the indication for minimally invasive or conventional surgery.

RESULTS

At a single institution, 301 operations were performed on 276 children with cancer. A minimally invasive approach was attempted in 90 of these patients (30%) and successfully employed in 69 (77%) of the operations. However, 21 operations (23%) were converted to an open approach. Regarding the abdominal operations attempted laparoscopically, 41 abdominal operations for biopsy or staging purposes were attempted laparoscopically (53%), but 6 were converted. In all, 139 abdominal resections were performed and 24 were attempted laparoscopically. Ten of these (42%) were converted. In 34 thoracic operations requiring biopsy, thoracoscopy was attempted in 14 (41%) and was successful in all but 1 (93%). Fifty‐one thoracic tumors were resected and the thoracoscopic approach was attempted in 11 (22%) and successful in 7 (14%). Conversions from a minimally invasive operation to an open procedure occurred mainly due to limited visibility. Three bleeding complications occurred with 1 patient requiring a blood transfusion. In addition, 1 small bowel injury occurred with immediate laparoscopic closure. There were no port site recurrences after a median of 39 months.

CONCLUSIONS

MIS is a reliable diagnostic tool for pediatric abdominal and thoracic malignancy. The role of ablative MIS in pediatric cancer remains limited. Cancer 2007. © 2007 American Cancer Society.
A magnetoelectronic register file cell for a self‐checkpointing microprocessor
Authors: Navale Nitin , Lundgren Erica , Carter Nicholas P.
Published: April 2007

A self‐checkpointing microprocessor periodically copies the state of the currently executing program to on‐chip non‐volatile storage, allowing it to resume execution of the program at the last checkpoint after a power supply interruption or shutdown. In this paper, we present a register file cell for a self‐checkpointing microprocessor that integrates a magnetoelectronic non‐volatile memory cell into a register cell similar to the one used in the Itanium 2 microprocessor. Our design allows the contents of each bit in the register file to be checkpointed simultaneously, reducing the time required to take a checkpoint to a few clock cycles, without compromising the performance of the register file during normal read and write operations. Because the area of the base register file cell is determined by the wiring tracks it requires, adding self‐checkpointing to the cell only increases its area by 6%. Similarly, adding self‐checkpointing has effectively no impact on the cell's performance, only increasing read and write times from 299 to 300 ps, even when the additional load on the bit lines from the larger cells is considered. Copyright © 2007 John Wiley & Sons, Ltd.
Towards a circuit theory for metallic single‐electron tunnelling devices
Authors: Hoekstra J.
Published: April 2007

A circuit theory for metallic single‐electron tunnelling (SET) junctions is presented. In detail circuits with a single SET junction in arbitrary environments are described. Based on the conservation of energy in the circuits—a fundamental circuit theorem—equivalent circuit elements are proposed and possible physical justifications are presented. The resulting model represents the tunnel event by an impulse current source, the junction by a charged capacitor, and the tunnelling condition as a discrete process based on local circuit parameters—and may include a tunnelling time. Simple examples illustrate Coulomb blockade, Coulomb oscillations, and continuous direct tunnelling. Copyright © 2007 John Wiley & Sons, Ltd.
Octreotide for relapsing sulfonylurea‐induced hypoglycemia in a dialysis patient
Authors: Yavari Arash , Ostermann Marlies , MacLean Douglas , Scoble John
Published: April 2007

BACKGROUND

Hypoglycemia is the principle adverse effect of sulfonylurea, especially in patients with renal failure. Conventional treatment consists of hypertonic dextrose, sometimes combined with glucagon. However, paradoxically both agents can stimulate insulin secretion and induce rebound hypoglycemia.

PATIENT

We present the case of a hemodialysis patient with relapsing gliclazide‐induced hypoglycemia in the context of sepsis.

RESULTS

Our patient failed to respond to regular infusions of hypertonic dextrose and oral carbohydrates. His hypoglycemia only resolved after a single dose of octreotide. The pathophysiology of recurrent sulfonylurea‐induced hypoglycemia and the challenges of current therapies are discussed. The somatostatin analogue octreotide inhibits insulin release and has been proposed as an antidote for sulfonylurea overdose.

CONCLUSIONS

We propose that octreotide has a clinical role in the treatment of patients with renal failure and sulfonylurea‐ induced hypoglycemia.