bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking
Authors: Costenbader Karen H , Chang Shun-Chiao , De Vivo Immaculata , Plenge Robert , Karlson Elizabeth W
Published: May 2008

Introduction

PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA). We investigated whether polymorphisms in these genes were associated with RA in Caucasian women included in two large prospective cohorts, adjusting for confounding factors and testing for interactions with smoking.

Methods

We studied RA risk associated with PTPN22 (rs2476601), PADI-4 (rs2240340), and CTLA-4 (rs3087243) in the Nurses' Health Study (NHS) and NHSII. Participants in NHS were aged 30 to 55 years at entry in 1976; those in NHSII were aged 25 to 42 years at entry in 1989. We confirmed incident RA cases through to 2002 in NHS and to 2003 in NHSII by questionnaire and medical record review. We excluded reports not confirmed as RA. In a nested case-control design involving participants for whom there were samples for genetic analyses (45% of NHS and 25% of NHSII), each incident RA case was matched to a participant without RA by year of birth, menopausal status, and postmenopausal hormone use. Genotyping was performed using Taqman single nucleotide polymorphism allelic discrimination on the ABI 7900 HT (Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404 USA) with published primers. Human leukocyte antigen shared epitope (HLA-SE) genotyping was performed at high resolution. We employed conditional logistic regression analyses, adjusting for smoking and reproductive factors. We tested for additive and multiplicative interactions between each genotype and smoking.

Results

A total of 437 incident RA cases were matched to healthy female control individuals. Mean (± standard deviation) age at RA diagnosis was 55 (± 10), 57% of RA cases were rheumatoid factor (RF) positive, and 31% had radiographic erosions at diagnosis. PTPN22 was associated with increased RA risk (pooled odds ratio in multivariable dominant model = 1.46, 95% confidence interval [CI] = 1.02 to 2.08). The risk was stronger for RF-positive than for RF-negative RA. A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04). CTLA-4 and PADI-4 genotypes were not associated with RA risk in the pooled results (pooled odds ratios in multivariable dominant models: 1.27 [95% CI = 0.88 to 1.84] for CTLA-4 and 1.04 [95% CI = 0.77 to 1.40] for PADI-4). No gene-gene interaction was observed between PTPN22 and HLA-SE.

Conclusion

After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking.
Autoantibodies as potential biomarkers for breast cancer
Authors: Zhong Li , Ge Kun , Zu Jin-chi , Zhao Long-hua , Shen Wei-ke , Wang Jian-fei , Zhang Xiao-gang , Gao Xu , Hu Wanping , Yen Yun , Kernstine Kemp H
Published: May 2008

Introduction

Only a limited number of tumor markers for breast cancer are currently available. Antibodies to tumor-associated proteins may expand the number of available tumor markers for breast cancer and may be used together in a serum profile to enhance sensitivity and specificity.

Methods

In the present study, we interrogated a breast cancer cDNA T7 phage library for tumor-associated proteins using biopan enrichment techniques with sera from normal individuals and from breast cancer patients. The enrichment of tumor-associated proteins after biopanning was tested using a plaque-lift assay and immunochemical detection. The putative tumor-associated phage clones were collected for PCR and sequencing analysis. Unique and open reading frame phage-expressed proteins were then used to develop phage protein ELISAs to measure corresponding autoantibodies using 87 breast cancer patients and 87 normal serum samples. A logistic regression model and leave-one-out validation were used to evaluate predictive accuracies with a single marker as well as with combined markers. Identities of those selected proteins were revealed through the sequence BLAST program.

Results

We harvested 100 putative tumor-associated phage clones after biopan enrichment. Sequencing analysis revealed that six phage proteins were inframe and unique. Antibodies to these six phage-expressed proteins were measured by ELISAs, and the results showed that three of the phage clones had statistical significance in discriminating patients from normal individuals. BLAST results of the three proteins showed great matches to ASB-9, SERAC1, and RELT. Measurements of the three predictive phage proteins were combined in a logistic regression model that achieved 80% sensitivity and 100% specificity in prediction of sample status, whereas leave-one-out validation achieved 77.0% sensitivity and 82.8% specificity among 87 patient samples and 87 control samples. Receiver operating characteristic curve analysis and the leave-one-out method both showed that combined measurements of the three antibodies were more predictive of disease than any of the single antibodies studied, underscoring the importance of identifying multiple potential markers.

Conclusion

Serum autoantibody profiling is a promising approach for early detection and diagnosis of breast cancer. Rather than one autoantibody, a panel of autoantibodies appears preferable to achieve superior accuracy. Further refinements will need to be made to further improve the accuracy. Once refined, the assay must be applied to a prospective patient population to demonstrate applicability.
Adrenal insufficiency in prolonged critical illness
Authors: Wu Jenn-Yu , Hsu Szu-Chun , Ku Shih-Chi , Ho Chao-Chi , Yu Chong-Jen , Yang Pan-Chyr
Published: May 2008

Introduction

Adrenal insufficiency is common in critically ill patients and affects their prognosis, but little is known about how adrenal function changes during prolonged critical illness. This study was conducted to investigate dynamic changes in cortisol levels in patients with critical illness who do not improve after treatment.

Methods

This observational cohort study was performed in the intensive care units of a university hospital. We studied acutely ill patients with initial cortisol level above 34 μg/dl, but who did not improve after treatment and in whom follow-up cortisol levels were determined during critical illness. All clinical information and outcomes were recorded.

Results

Fifty-seven patients were included. Ten patients had follow-up cortisol levels above 34 μg/dl, 32 patients had levels between 34 and 15 μg/dl, and 15 patients had levels under 15 μg/dl. Outcomes did not differ significantly among the three groups with different follow-up cortisol levels. In Cox regression analysis, those patients who survived to hospital discharge with second cortisol levels under 15 μg/dl had a longer hospital length of stay (odds ratio = 14.8, 95% confidence interval = 2.4 to 90.0; P = 0.004).

Conclusion

The majority of acutely ill patients who remained in a critical condition had decreased serum cortisol levels. Depressed cortisol levels at follow up may lead to worse clinical outcomes. We propose that repeated adrenal function testing be conducted in patients with prolonged critical illness.
Image-ray tracing for joint 3D seismic velocity estimation and time-to-depth conversion
Authors: Iversen Einar , Tygel Martin
Published: May 2008

Seismic time migration is known for its ability to generate well-focused and interpretable images, based on a velocity field specified in the time domain. A fundamental requirement of this time-migration velocity field is that lateral variations are small. In the case of 3D time migration for symmetric elementary waves (e.g., primary PP reflections/diffractions, for which the incident and departing elementary waves at the reflection/diffraction point are pressure [P] waves), the time-migration velocity is a function depending on four variables: three coordinates specifying a trace point location in the time-migration domain and one angle, the so-called migration azimuth. Based on a time-migration velocity field available for a single azimuth, we have developed a method providing an image-ray transformation between the time-migration domain and the depth domain. The transformation is obtained by a process in which image rays and isotropic depth-domain velocity parameters for their propagation are esti-mated simultaneously. The depth-domain velocity field and image-ray transformation generated by the process have useful applications. The estimated velocity field can be used, for example, as an initial macrovelocity model for depth migration and tomographic inversion. The image-ray transformation provides a basis for time-to-depth conversion of a complete time-migrated seismic data set or horizons interpreted in the time-migration domain. This time-to-depth conversion can be performed without the need of an a priori known velocity model in the depth domain. Our approach has similarities as well as differences compared with a recently published method based on knowledge of time-migration velocity fields for at least three migration azimuths. We show that it is sufficient, as a minimum, to give as input a time-migration velocity field for one azimuth only. A practical consequence of this simplified input is that the image-ray transformation and its corresponding depth-domain velocity field can be generated more easily.
MDM2 SNP309 Is Associated With Poor Outcome in B-Cell Chronic Lymphocytic Leukemia
Authors: Gryshchenko Irina , Hofbauer Sebastian , Stoecher Markus , Daniel Peter T. , Steurer Michael , Gaiger Alexander , Eigenberger Karin , Greil Richard , Tinhofer Inge
Published: May 2008

Purpose

A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has been negatively associated with onset and outcome of disease in solid tumors. Because inactivation of p53 by deletion and/or mutations also impacts on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL), we assessed the role of the SNP309 genotype in B-CLL.

Patients and Methods

The frequency of SNP309 T/T, T/G, or G/G genotypes and the p53 status (wild type, mutated, or deleted) were assessed and correlated with clinical outcome in 140 B-CLL patients and a second independent cohort. In addition, the correlation of the MDM2 SNP309 genotype with the MDM2 protein expression level in B-CLL cells was evaluated by immunoblotting.

Results

A significant negative association of the SNP309 T/G and G/G genotypes with overall survival was seen (T/G genotype, relative risk = 3.7; 95% CI, 1.2 to 11.5; P = .02; G/G genotype, relative risk = 9.1; 95% CI, 2.4 to 35.1; P = .001), but no correlation with incidence or onset of B-CLL was observed. The influence of the heterozygous SNP309 T/G genotype on treatment-free survival depended on the p53 status but not on the CD38, Zap-70, or IgVH mutational status or Rai stage of B-CLL patients. The unfavorable SNP309 T/G and G/G genotypes were associated with a gene-dosage–dependent increase of MDM2 expression.

Conclusion

The MDM2 SNP309 genotype influencing MDM2 expression levels was identified as an additional independent risk factor in B-CLL. Targeting MDM2-p53 interactions might emerge as a successful treatment strategy for B-CLL.
Utilization and Outcomes of Minimally Invasive Radical Prostatectomy
Authors: Hu Jim C. , Wang Qin , Pashos Chris L. , Lipsitz Stuart R. , Keating Nancy L.
Published: May 2008

Purpose

Demand for minimally invasive radical prostatectomy (MIRP) to treat prostate cancer is increasing; however, outcomes remain unclear. We assessed utilization, complications, lengths of stay, and salvage therapy rates for MIRP versus open radical prostatectomy assessed whether MIRP surgeon volume is associated with better outcomes.

Methods

We identified 2,702 men undergoing MIRP and open radical prostatectomy during 2003 to 2005 from a national 5% sample of Medicare beneficiaries. We assessed the association between surgical approach and outcomes, adjusting for surgeon volume, age, race, comorbidity, and geographic region.

Results

MIRP utilization increased from 12.2% in 2003 to 31.4% in 2005. Men undergoing MIRP versus open radical prostatectomy had fewer perioperative complications (29.8% v 36.4%; P = .002) and shorter lengths of stay (1.4 v 4.4 days; P < .001); however, they were more likely to receive salvage therapy (27.8% v 9.1%, P < .001). In adjusted analyses, MIRP versus open radical prostatectomy was associated with fewer perioperative complications (odds ratio [OR], 0.73; 95% CI, 0.60 to 0.90), shorter lengths of stay (parameter estimate, −2.99; 95% CI, −3.45 to −2.53) but more anastomotic strictures (OR, 1.40; 95% CI, 1.04 to 1.87) and higher rates of salvage therapy (OR, 3.67; 95% CI, 2.81 to 4.81). Patients of high-volume MIRP experienced fewer anastomotic strictures (OR, 0.93; 95% CI, 0.87 to 0.99) and less salvage therapy (OR, 0.92; 95% CI, 0.88 to 0.98).

Conclusion

Men undergoing MIRP versus open radical prostatectomy have lower risk for perioperative complications and shorter lengths of stay, but are at higher risk for salvage therapy and anastomotic strictures. However, risk for these unfavorable outcomes decreases with increasing MIRP surgical volume.
Safety and Efficacy of Darbepoetin Alfa in Previously Untreated Extensive-Stage Small-Cell Lung Cancer Treated With Platinum Plus Etoposide
Authors: Pirker Robert , Ramlau Rodryg A. , Schuette Wolfgang , Zatloukal Petr , Ferreira Irene , Lillie Tom , Vansteenkiste Johan F.
Published: May 2008

Purpose

A placebo-controlled, double-blind, randomized, phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alfa could increase patient survival.

Patients and Methods

Darbepoetin alfa (300 μg) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy (carboplatin plus etoposide or cisplatin plus etoposide) plus 3 weeks after the last dose of chemotherapy. Patients with disease progression were observed until death or until all patients completed their end-of-study visit and 496 deaths had occurred. The two coprimary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival; statistical testing of survival was done if change in hemoglobin was significant at P < .05.

Results

The study enrolled 600 patients. Patients' hemoglobin levels dropped due to the myelosuppressive chemotherapy; however, treatment with darbepoetin alfa maintained hemoglobin levels significantly higher than placebo (P < .001). There was no statistically significant difference in overall survival between the treatment groups (hazard ratio [HR], 0.93; 95% CI, 0.78 to 1.11; P = .431). As expected, darbepoetin alfa was associated with a higher incidence of thromboembolic events (darbepoetin alfa, 9%; placebo, 5%). The transfusion risk was lower in the darbepoetin versus placebo group (HR, 0.40; 95% CI, 0.29 to 0.55).

Conclusion

The results of this study did not demonstrate improved survival after treatment with darbepoetin alfa; however, they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia.
Erlotinib for Advanced Non–Small-Cell Lung Cancer in the Elderly: An Analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21
Authors: Wheatley-Price Paul , Ding Keyue , Seymour Lesley , Clark Gary M. , Shepherd Frances A.
Published: May 2008

Purpose

National Cancer Institute of Canada Clinical Trials Group Study BR.21 established erlotinib as a standard of care in patients with non–small-cell lung cancer (NSCLC) after failure of first- or second-line chemotherapy. The current study analyzes the influence of age on outcomes in BR.21.

Patients and Methods

BR.21 was a double-blind phase III trial that randomly assigned 731 patients to erlotinib 150 mg daily or placebo. End points included progression-free survival and overall survival (OS), response, quality of life (QOL), drug exposure, and toxicity, which are analyzed in this retrospective study by the following two age groups: ≥ 70 years (elderly) or less than 70 years (young).

Results

There were 163 elderly patients (112 on erlotinib, 51 on placebo) and 568 young patients (376 on erlotinib, 192 on placebo). There was no significant difference between age groups randomly assigned to erlotinib or placebo in progression-free survival (elderly: 3.0 v 2.1 months; hazard ratio [HR] = 0.63; 95% CI, 0.44 to 0.90; P = .009; young: 2.1 v 1.8 months; HR = 0.64; 95% CI, 0.53 to 0.76; P < .0001; interaction, P = .77) or OS (elderly: 7.6 v 5.0 months; HR = 0.92; 95% CI, 0.64 to 1.34; P = .67; young: 6.4 v 4.7 months; HR = 0.73; 95% CI, 0.61 to 0.89; P = .0014; interaction, P = .31). Response rates were similar between age groups. Elderly patients, compared with young patients, had significantly more overall and severe (grade 3 and 4) toxicity (35% v 18%; P < .001), were more likely to discontinue treatment as a result of treatment-related toxicity (12% v 3%; P < .0001), and had lower relative dose-intensity (64% v 82% received > 90% planned dose; P < .001).

Conclusion

Elderly patients treated with erlotinib gain similar survival and QOL benefits as younger patients but experience greater toxicity.
Hyperghrelinemia Precedes Obesity in Prader-Willi Syndrome
Authors: Feigerlová Eva , Diene Gwenaëlle , Conte-Auriol Françoise , Molinas Catherine , Gennero Isabelle , Salles Jean-Pierre , Arnaud Catherine , Tauber Maïthé
Published: May 2008

Background: High plasma ghrelin levels have been reported in Prader-Willi syndrome (PWS). However, little is known about plasma ghrelin in these children during the first years of life characterized by a failure to thrive.

Objective: The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years.

Subjects and Methods: Forty children with PWS [24 boys, 16 girls, median age 3.6 yr, median body mass index (BMI) Z-score 0.3] were compared with 84 controls (57 boys, 27 girls, median age 4.2 yr median BMI Z-score 0.1). Children were then divided into two groups according to age and GH treatment.

Results: Median plasma ghrelin levels were significantly higher in children with PWS, compared with controls at any age (568 vs. 173, P < 0.0001) and decreased with age in both groups (P < 0.0001). In the whole group of PWS, we found an inverse relationship between ghrelin and BMI Z-score, insulin, homeostasis model assessment insulin resistance index, leptin, and lean mass. Plasma ghrelin levels were higher in children with PWS than controls, both in the youngest children below 3 yr who were not receiving GH (771 vs. 233, P < 0.0001) and in the children older than 3 yr, all of whom were treated with GH (428 vs. 159, P < 0.0001).

Conclusions: Plasma ghrelin levels in children with PWS are elevated at any age, including during the first years of life, thus preceding the development of obesity.
Absence of an Acute Insulin Response Predicts Onset of Type 2 Diabetes in a Caucasian Population with Impaired Glucose Tolerance
Authors: Nijpels G. , Boorsma W. , Dekker J. M. , Hoeksema F. , Kostense P. J. , Bouter L. M. , Heine R. J.
Published: May 2008

Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population.

Objectives: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population.

Design, Setting, and Participants: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests.

Results: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60–12.67] for absence of first insulin peak, 1.58 (95% CI 0.60–4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65–4.88) for lowest vs. highest tertile of the disposition index.

Conclusions: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.
Urinary Prolactin as a Reliable Marker for Preeclampsia, Its Severity, and the Occurrence of Adverse Pregnancy Outcomes
Authors: Leaños-Miranda Alfredo , Márquez-Acosta Janeth , Cárdenas-Mondragón Guadalupe María , Chinolla-Arellano Zarela Lizbeth , Rivera-Leaños Roxana , Bermejo-Huerta Sara , Romero-Arauz Juan Fernando , Alvarez-Jiménez Guadalupe , Ramos-León Julio César , Ulloa-Aguirre Alfredo
Published: May 2008

Context: It has been proposed that preeclampsia may result from of an imbalance in angiogenic factors. Although prolactin (PRL) is mainly related to lactation, it is also involved in other biological functions, including angiogenesis.

Objective: Our objective was to determine the relationship among preeclampsia, serum and urinary PRL (uPRL) levels, and excretion of antiangiogenic PRL fragments in urine.

Study design: Using a cross-sectional design, uPRL and serum PRL levels, and the presence of PRL isoforms were determined in 546 pregnant women: 207 healthy pregnant, 124 with gestational hypertension, 48 with mild preeclampsia, and 167 with severe preeclampsia (sPE).

Results: uPRL concentrations were significantly (P < 0.001) higher in preeclampsia (11.99 ng/mg creatinine) than in healthy pregnancy (0.20 ng/mg creatinine) and gestational hypertension (0.19 ng/mg creatinine), and were even higher in sPE compared with mild preeclampsia (21.20 vs. 2.77 ng/mg creatinine, respectively; P < 0.001). Antiangiogenic PRL fragments (14–16 kDa) were detected in 21.6% of urine samples from women with sPE but in none from other groups. Patients with hemolysis, elevated liver enzymes, low platelet count syndrome, and/or eclampsia, placental abruption, acute renal failure, and pulmonary edema exhibited highest uPRL concentrations (P ≤ 0.028) and frequency of antiangiogenic PRL fragments in urine (P ≤ 0.036). High-serum PRL levels were associated with sPE independently of gestational age, proteinuria, and prolactinuria (P = 0.032).

Conclusions: Preeclampsia is characterized by increased uPRL excretion. uPRL concentrations and their isoforms appear to be suitable markers to assess the severity of preeclampsia and occurrence of adverse outcomes. PRL and and/or its isoforms might be involved in the pathophysiology of preeclampsia.
Gender Specificity of Body Adiposity and Circulating Adiponectin, Visfatin, Insulin, and Insulin Growth Factor-I at Term Birth: Relation to Prenatal Growth
Authors: Ibáñez Lourdes , Sebastiani Giorgia , Lopez-Bermejo Abel , Díaz Marta , Gómez-Roig Maria Dolores , de Zegher Francis
Published: May 2008

Context: Fetal development is thought to be gender specific for adiposity and circulating insulin and IGF-I but not adipokinemia, as judged by serum visfatin and adiponectin at term birth. We studied the potential relationship between these gender specificities and fetal growth.

Setting: The study was conducted at a university hospital.

Study Population: Subjects included 96 strictly matched neonates born appropriate for gestational age (AGA; 24 girls, 24 boys) or small for gestational age (SGA; 24 girls, 24 boys).

Main Outcomes: Outcomes included serum insulin, IGF-I, visfatin, total and high-molecular-weight (HMW) adiponectin, osteocalcin at term birth, and neonatal body composition by absorptiometry.

Results: Cord insulin and IGF-I levels were higher in girls than boys (P ≤ 0.01), in both the AGA and SGA subpopulation. In AGA newborns, fat and lean mass were each gender specific (P < 0.0001), whereas visfatin and total and HMW adiponectin were not. Conversely, in SGA newborns, visfatin and HMW adiponectin were gender specific (higher levels in girls), whereas body adiposity was not. In SGA fetuses, the distribution of adiponectin isoforms was in both genders shifted toward HMW (P < 0.005 vs. AGA). Cord osteocalcin did not differ by either gender or birth weight.

Conclusion: At term birth, the gender specificity of adiposity and circulating visfatin and HMW adiponectin appeared to depend on prenatal growth, whereas the gender specificity of insulin and IGF-I levels did not. The fetal shift in adiponectin isoforms may contribute to explain why SGA newborns tend to be hypersensitive to insulin.
Synthesis and Chiral Recognition of Novel Regioselectively Substituted Amylose Derivatives
Authors: Kondo Shunsuke , Yamamoto Chiyo , Kamigaito Masami , Okamoto Yoshio
Published: May 2008

Two novel amylose derivatives 1a and 1b bearing different substituents at 2-, 3-, and 6-positions of a glucose ring have been successfully synthesized, and their abilities of enantiomer resolution in high-performance liquid chromatography (HPLC) have been evaluated. These derivatives exhibited the ability comparable or better to the commercial amylose-based column, Chiralpak AD.
Catalytic Activity of Partially Oxidized Transition-metal Carbide–Nitride for Oxygen Reduction Reaction in Sulfuric Acid
Authors: Ohgi Yoshiro , Ishihara Akimitsu , Shibata Yohei , Mitsushima Shigenori , Ota Ken-ichiro
Published: May 2008

In order to commercialize polymer electrolyte fuel cells (PEFCs) widely, partially oxidized transition-metal carbide–nitride (TM-C–N; TM = Ti, Zr, and Ta) have been investigated as new cathodes without platinum. The specimens were prepared by the electrophoretic deposition of the transition-metal carbide–nitride on titanium plate and were heat-treated at 1000 °C under flowing 2%-H2/N2 gas containing ca. 0.25% oxygen. Partially oxidized Ta-based catalysts had highest catalytic activity, followed by Ti- and Zr-based catalysts.
Radical Copolymerizations of Vinyl Monomers in a Porous Coordination Polymer
Authors: Uemura Takashi , Ono Yukari , Kitagawa Susumu
Published: May 2008

Radical copolymerizations of vinyl monomers, such as styrene, methyl methacrylate, and vinyl acetate, in the nanochannels of a porous coordination polymer have been studied. The results are compared with those obtained for the corresponding free radical copolymerizations, which shows a spatial confinement effect on the monomer reactivity ratios in this system.
Quantification of Rosmarinic Acid Levels by near Infrared Spectroscopy in Laboratory Culture Grown Spearmint Plantlets
Authors: Berhow Mark A. , Rayford Warren E. , Vaughn Steven F. , Palmquist Debra , Tisserat Brent
Published: May 2008

A method for the rapid quantification of rosmarinic acid (RA) in tissues of spearmint using near infrared (NIR) spectroscopy was developed by correlating with the results of methanol extracts analysed on an HPLC photo-diode array (PDA) system. NIR and HPLC analyses performed on over 500 samples were used to develop an NIR analytical algorithm. Applying this algorithm resulted in very good calibration statistics for the prediction of RA concentrations in dried powdered samples prepared from the cultured mints (r 2 = 0.90, SEP=3.1 RPD = 2.6). NIR can be used to rapidly and accurately quantitate the levels of this secondary metabolite in plant samples. High positive correlations occur between CO2 levels and spearmint plantlet growth (fresh weight), morphogenetic responses (leaves, roots and shoots) and production of the secondary metabolite rosmarinic acid.
A case–control study of seated immobility at work as a risk factor for venous thromboembolism
Authors: West Jill , Perrin Kyle , Aldington Sarah , Weatherall Mark , Beasley Richard
Published: May 2008

Summary

Objective

To determine the relative risk of prolonged seated immobility at work in patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE).

Design

A case–control study: cases and controls completed an interviewer-administered questionnaire to obtain information on risk factors for venous thromboembolism (VTE), including prolonged seated immobility at work. Univariate and multivariate logistic regression was used to determine the association between predicted variables and the probability of being a case or control.

Participants

Cases were patients <65 years old attending the Wellington Hospital Outpatient VTE Clinic following hospital discharge for DVT and/or PE. Controls were patients <65 years old admitted to the Coronary Care Unit at Wellington Hospital.

Setting

The Wellington Hospital Outpatient VTE Clinic and Coronary Care Unit.

Main outcome measures

Odds ratio of VTE for prolonged seated immobility.

Results

There were 97 cases (53 DVT, 29 PE, 15 DVT and PE), and 106 controls. In the multivariate analysis the odds ratio of VTE for prolonged seated immobility at work was 1.8 (95% CI 0.71–4.8). The maximum number of hours seated at work was associated with VTE, with the risk increasing by 10% per hour longer seated (odds ratio 1.1, 95% CI 1.0–1.2). The maximum number of hours seated at work without getting up was associated with VTE, with the risk increasing by 20% per hour longer seated (odds ratio 1.2, 95% CI 0.96–1.6).

Conclusions

This study provides preliminary evidence that prolonged seated immobility at work may represent a risk factor for VTE.
Significance of limb trauma as an initiating factor in chronic leg ulceration
Authors: Kulkarni S R , Gohel M S , Whyman M R , Poskitt K R
Published: May 2008

Objectives

To assess differences in clinical outcomes between patients with traumatic and spontaneous leg ulcers.

Methods

Consecutive leg ulcer follow-up patients seen between April 2004 and October 2005 in a specialist leg ulcer clinic were asked about the mechanism of the original ulceration. Twenty-four-week healing and 12-month recurrence rates were calculated using Kaplan-Meier analysis and outcomes were compared between groups with traumatic and spontaneous ulcers.

Results

Of the 300 patients assessed, 38 were excluded (incomplete data). In the remaining 262 patients, cause of ulceration was traumatic in 116/262 (44%) and spontaneous in 146/262 (56%). Age, ankle brachial pressure index <0.85 and venous reflux were equally distributed between groups with traumatic and spontaneous ulcers ( P = 0.470, 0.793, 0.965 respectively, Chi-square test). Twenty-four-week healing rates were 81% for traumatic and 67% for spontaneous ulcers ( P = 0.015, Log-Rank test). Twelve-month recurrence rates were 32% for traumatic and 33% for spontaneous ulcers ( P = 0.970, Log-rank test). Patients with traumatic ulcers suffered a total of 53 ulcer recurrences (median 0, range 0–4) compared with 89 in patients with spontaneous ulcers (median 0, range 0–8) ( P < 0.001, Mann-Whitney U test).

Conclusion

Approximately half of all leg ulcer patients recall a traumatic event. When managed in leg ulcer clinic, traumatic ulcers heal faster and recur less frequently than spontaneous ulcers.
Correlation of haemodynamics and ankle mobility with clinical classes of clinical, aetiological, anatomical and pathological classification in venous disease
Authors: Cavalheri G , de Godoy J M P , Belczak C E Q
Published: May 2008

Objectives

To correlate venous haemodynamic parameters of lower limbs and amplitude of ankle mobility with the clinical, aetiological, anatomical and pathological classification (CEAP) for venous disease.

Methods

Two hundred and eighty-four lower limbs of 142 Caucasian women were evaluated and distributed in six groups according to the CEAP classification: Group I = C0 and C1 ( n = 24); Group II = C2 ( n = 30); Group III = C3 ( n = 27); Group IV = C4 ( n = 23); Group V = C5 ( n = 20) and Group VI = C6 ( n = 18). Goniometric examinations of ankle joints and air plethysmography (APG) were performed. Analysis of variance and the Bonferroni correction, Kruskal-Wallis' non-parametric and Dunn tests were utilized for statistical analysis with the level of significance being set at 5% ( P value < 0.05).

Results

There were significant restrictions in ankle mobility seen by goniometry at the C5 stage. In addition, significant changes in the venous-filling index were identified at C2, changes in the ejection fraction at C4 and changes in the residual volume fraction at the C4 stage.

Conclusion

The evolution of the clinical state of ankles affected by venous diseases is correlated to a reduction of joint mobility and haemodynamic alterations identified using APG.
Aminaphtone in idiopathic cyclic oedema syndrome
Authors: Pereira de Godoy J M
Published: May 2008

Objectives

Idiopathic cyclic oedema syndrome is a group of clinical conditions that exhibit a vascular capillary hyperpermeability accompanied by oedema caused by the interstitial retention of fluid. The objective of the current study was to evaluate the efficacy of aminaphtone in the treatment of idiopathic cyclic oedema.

Methods

A total of 15 female patients with clinical diagnosis of idiopathic cyclic oedema and aged between 22 and 49 years and a mean of 37.7 years were evaluated. After diagnosis, the patients were submitted to lower limb volumetry and asked to record the weight in the morning and evening at fixed times. One tablet of aminaphtone was prescribed every 8 h and on the fifth day the patients were reassessed. Percentages and the paired t-test were utilized for statistical analysis, with an alpha error of 5% considered acceptable ( P value <0.05).

Results

A significant reduction in limb size was detected after treatment using aminaphtone ( P value <0.0001) with losses between 9 g and 370 g, and an average loss of 116.9 g. Variations in weights in the morning and evening were significant ( P value <0.00001) with a maximum difference of 3 kg and a minimum of 120 g. Improvements were reported for 70% of patients.

Conclusion

Aminaphtone is efficacious in the reduction of oedema in patients with idiopathic cyclic oedema.
Arterial disease but not hypertension predisposes to varicose veins
Authors: Mäkivaara L A , Ahti T M , Luukkaala T , Hakama M , Laurikka J O
Published: May 2008

Objectives

The aim of the study was to find out if persons with cardiovascular diseases (CVD) (arterial disease or hypertension) have additional risk of varicose veins (VV) compared with those without arterial disease (AD) or hypertension.

Methods

We studied, using a validated questionnaire, the prevalence and incidence of VVs in those with and without CVD in a population of 4903 including 40-, 50- and 60-year-old men and women in Tampere, Finland. During the five years of follow-up, we had a special interest on the appearance of new VVs in those without VVs at entry ( n = 3065).

Results

We found a higher prevalence of VVs in persons with CVD than in those without CVD (with sex and age adjusted odds ratio [OR] 1.3 [95% confidence interval, CI 1.1–1.5]). The prevalence of VVs was higher in persons with AD (OR 1.7 [CI 1.4–2.2]), but not in persons with hypertension (OR 1.1 [CI 0.9–1.2]) than in those who were free of AD or hypertension, respectively. Subjects with AD had higher incidence of VVs (incidence odds ratio, IOR 1.4 [CI 0.8–2.7]) than subjects without AD and the effect was statistically significant in women (IOR 2.2 [CI 1.1–4.5]). Also the incidence of VVs was more affected by AD than by hypertension (IOR 1.1 [CI 0.7–1.8]).

Conclusion

There seems to exist a relatively strong additional risk of VVs in persons with AD and practically none in those with hypertension compared to those without.
Epidemiology of chronic venous disease
Authors: Robertson L , Evans C , Fowkes F G R
Published: May 2008

Chronic venous disease of the legs occurs commonly in the general population in the Western world. Estimates of the prevalence of varicose veins vary widely from 2–56% in men and from 1–60% in women. These variations reflect differences in variability of study populations including age, race and gender, methods of measurement and disease definition. Definitions of chronic venous disease may rely on reports of varicose veins by study participants, based on self-diagnosis or recall of a diagnosis, or on a standardized physical examination. Venous ulceration is less common, affecting approximately 0.3% of the adult population. Age and pregnancy have been established as risk factors for developing varicose veins. Evidence on other risk factors for venous disease is inconclusive. Prolonged standing has been proposed, but results of studies should be interpreted with caution given the difficulty in measuring levels of posture. Obesity has been suggested as a risk factor in women, but appears to be an aggravating factor rather than a primary cause. Other postulated risk factors include dietary intake and smoking, but evidence is lacking. Longitudinal studies using standardized methods of evaluation are required before the true incidence of chronic venous disease and associated risk factors can be determined.
Is arteriovenous shunting involved in the development of varicosities? A study of the intraluminal pressure and oxygen content in varicose veins
Authors: Murphy M A , Hands L
Published: May 2008

Objectives

Arteriovenous (AV) shunting has been postulated as the underlying cause of varicose veins. The aim of this study was to analyse pressure and oxygen content in primary varicose veins in order to determine evidence of arterial shunting.

Methods

Thirty-nine patients with varicose veins underwent cannulation of varicosities. The pressure and the blood oxygen content within varicosities were measured in different positions and during exercise. Similar measurements were made in the long saphenous veins of 10 control subjects without venous disease.

Results

Mean pressure in varicose veins in the supine position was 12.3 mmHg (Standard deviation [SD] 3.6 mmHg). Control subjects had similar pressures measured in the long saphenous vein. No pulsatile pressure tracings were obtained. Varicosity pressures in the erect position averaged 66 mmHg (SD 9 mmHg). In all cases, the pressure correlated with the distance of the varicosity from the heart. Pressure reduction in varicosities after exercise was significantly less than that in control subjects. Recovery time (RT 90) was also significantly shorter than in the control group. Mean venous pO2 in varicosities was 4.5 kPa (SD 1.0) in the supine position dropping to 3.9 kPa (SD 0.9) on standing; these values were not significantly different to samples from control subjects.

Conclusions

AV shunting is unlikely to be a causative factor in the development of primary varicose veins.
Digital Piracy: A Competitive Analysis
Authors: Jain Sanjay
Published: May 2008

In recent years, the issue of copyright protection for intellectual properties such as computer software, music CDs, and videos has become increasingly important. It is often claimed that illegal copying of intellectual property costs companies billions of dollars in lost revenues and reduces firms' incentives to innovate. Some researchers have shown that copying can be beneficial to firms when there are strong network effects and copying expands the market. In this paper, we first examine the impact of illegal copying of software and other similar intellectual properties on firms' prices, profits, and quality choices, even when there are no network effects and the market is saturated. We show that contrary to the claims of manufacturers, there are conditions under which copying can increase firms' profits, lead to better quality products, and increase social welfare. This is because weaker copyright protection enables firms to reduce price competition by allowing price-sensitive consumers to copy. Thus, weaker copyright protection can serve as a coordination device to reduce price competition. We also examine how equilibrium copyright enforcement is affected by network externalities. In contrast to previous research, we show that strong network effects can sometimes lead to a firm choosing higher levels of copyright protection. Our results show that in the presence of strong network effects, stronger copyright enforcement by one firm can serve as a coordinating device to reduce price competition.
Optimal Second-Stage Outsourcing
Authors: Saouma Richard
Published: May 2008

Manufacturers have recently begun outsourcing product assembly and completion tasks to their suppliers. Such outsourcing solves several contracting problems but generates new incentive frictions between manufacturers and their suppliers. In this paper, we analyze a manufacturer's decision to outsource an assembly (second-stage) task to a preestablished supplier. We find that outsourcing second-stage tasks becomes more attractive as the cost of either the first- or second-stage activity rises. Outsourcing becomes less attractive when the supplier is unable to accept large levels of liability. The manufacturer is shown to prefer more testing when she outsources assembly to her supplier as opposed to when she assembles products in house. Last, we find that the contracting frictions identified persist when the supplier's work can be tested individually, albeit imperfectly.
Research Note—Customer Loyalty Programs: Are They Profitable?
Authors: Singh Siddharth S. , Jain Dipak C. , Krishnan Trichy V.
Published: May 2008

Loyalty programs are very common in practice. Many researchers have worked at understanding the impact of loyalty programs on market competition and the mechanism behind it. Interestingly, almost all of the studies have explored a symmetric equilibrium where both of the competing firms offer a loyalty program. To our knowledge, the extant literature has not investigated in-depth whether asymmetric equilibrium can exist where only one firm chooses to offer a loyalty program and the other firm chooses to compete via lowering prices. Such a question is important because some markets do support such asymmetric equilibriums with respect to loyalty programs. Also, the existence of asymmetric equilibrium shows that a loyalty program need not be profitable for some firms.

In this paper, we use a game-theoretic framework to investigate specific types of customer loyalty programs that provide benefit to loyal customers in the form of discount over market prices. The model considers consumer switching and includes two types of consumer heterogeneity. The first type of heterogeneity concerns the differences between customers with respect to their liking for loyalty programs, and the second type concerns the differences among the loyalty program members with respect to their ability to collect enough loyalty points to redeem loyalty rewards. By analyzing a duopoly market, we find that both symmetric equilibrium (i.e., where both competing firms offer the loyalty program) and asymmetric equilibrium (i.e., where one firm alone offers the loyalty program) can be sustained. The paper explores conditions for the existence of these two equilibriums.
Managing an Assemble-to-Order System with Returns
Authors: DeCroix Gregory A. , Song Jing-Sheng , Zipkin Paul H.
Published: May 2008

We consider a multiproduct assemble-to-order (ATO) system, in which inventory is kept only at the component level and the finished products are assembled in response to customer demands. In addition to stochastic demand for finished products, the system experiences stochastic returns of subsets of components, which can then be used to satisfy subsequent demands. The system is managed over an infinite horizon using a component-level base-stock policy. We identify several ways in which returns complicate the behavior of the system, and we demonstrate how to handle these additional complexities when calculating or approximating key order-based performance metrics, including the immediate fill rate, the fill rate within a time window, and average backorders. We also present a method for computing a near-optimal base-stock policy. We use these results to address managerial questions on both operational and product-design levels. For example, we find that tracking product-based (as opposed to component-based) return information appears to provide much less value than tracking product-based demand information, and we explore the impact of the number of products, component lead times, and different patterns of component returns (joint versus independent returns, returns of common versus dedicated components) on the value of component commonality.
Route Design for Lean Production Systems
Authors: Ohlmann Jeffrey W. , Fry Michael J. , Thomas Barrett W.
Published: May 2008

We consider the problem of routing a fleet of vehicles to pick up components from a network of suppliers and to deliver them to a fixed depot in a lean production system. The pursuit of low work-in-process inventory and production smoothing throughout the system introduces complicating side constraints, creating an enriched case of the vehicle routing problem with time windows and split deliveries. We present a two-phase routing and scheduling approach to address this problem. The routing phase consists of a nested tabu search heuristic that iterates between determining the suppliers' visit frequencies and developing vehicle routes. Given a routing plan, the scheduling phase determines the timing of supplier visits using a binary integer program designed to promote production leveling. Through computational testing on real-world data sets, we compare our solutions to those in the literature and those used by practitioners in the industry.
The Case for Standardisation of the Management of Gallstones Spilled and not Retrieved at Laparoscopic Cholecystectomy
Authors: Mullerat J , Cooper K , Box B , Soin B
Published: May 2008

INTRODUCTION

This observational study was carried out to establish how surgeons performing laparoscopic cholecystectomy currently deal with the issue of spilled gallstones.

MATERIALS AND METHODS

A questionnaire was circulated amongst laparoscopic surgeons attending the annual conference of the Association of Laparoscopic Surgery of Great Britain and Ireland in November 2006.

RESULTS

Eighty-two surgeons completed the questionnaire. Only half of surgeons inform patients when gallstones are spilled. Less than 30% of surgeons inform general practitioners (GPs) of this complication, when it occurs. Less than a quarter of surgeons include this information in the consent literature provided to patients.

CONCLUSIONS

We recommend that trusts review their policy towards spilled stones either by local audit or adopt the guidance given by the UK Healthcare Commission. While some surgeons feel informing patients and GPs may unnecessarily heighten anxiety from an uncommon complication, our review of the literature suggests this position is not tenable in the current medicolegal climate.
What next for the specialist library?
Authors: Setterfield Polly , Sams Steffi
Published: May 2008

Since 2006 the team behind the Specialist Library for Surgery, Theatres and Anaesthesia (http://www.library.nhs.uk/theatres/) has worked hard to develop a collection of resources relevant to the theatres community. The efforts have paid off and the library is attracting more and more visitors. In February 2008 we achieved a major milestone and broke the 10,000 barrier for the number of unique visits per month. In our most recent article on the library we touched on what we envisioned for the future. Here we aim to investigate the practicalities of realising these visions.