bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Acquired Inflammatory Conditions Are Synergistically Associated With Early Carotid Atherosclerosis
Authors: Markus Hugh S. , Labrum Robyn , Bevan Steve , Reindl Markus , Egger Georg , Wiedermann Christian J. , Xu Qingbo , Kiechl Stefan , Willeit Johann
Published: July 2006

Background and Purpose—

If chronic inflammation plays a causal role in atherogenesis, individuals with proinflammatory gene variants would be expected to develop more atherosclerosis. We recently found a synergistic association between 3 functional proinflammatory gene polymorphisms/haplotypes and smoking on carotid intima-media thickness (IMT). We replicated this finding in a second large population and extended the analysis by inclusion of other inflammatory conditions (chronic infection and obesity/abnormal glucose tolerance).

Methods—

Common carotid and femoral artery IMT was determined in the Bruneck Study population (n=810). Proinflammatory variants were determined in 3 genes (IL-6 [−174C, −572G, −597A haplotype], IL-1–receptor antagonist [VNTR *2], and endotoxin receptor CD-14 [−159C]).

Results—

There was a significant relationship between gene-variant score and carotid IMT: age- and sex-adjusted mean IMT in subjects with 0, 1, and ≥2 gene variants was 936, 987 and 1047 μm, respectively (
P
=0.001), and synergistic effects of gene-variant score and smoking on IMT measurements (
P
=0.040). Analogous findings were obtained for obesity/abnormal glucose tolerance and chronic infection. Interactive effects of gene-variant score and a risk factor score composed of the acquired inflammatory conditions were highly significant (
P
<0.001 each). Results were similar for femoral artery IMT.

Conclusions—

These results provide support for a causal role of inflammation in carotid atherosclerosis, and emphasize the importance of gene-gene and gene-environment interactions in this pathogenic pathway. This may help to explain the substantial variability of disease expression in subjects with proinflammatory risk factors such as smoking, diabetes and chronic infection.
Assessment of Implicit Meaning in the Design of Graphic Symbols for the Control of Recycled Water Use
Authors: Mellon Robert C. , Tsagarakis Konstantinos P.
Published: July 2006

This article describes the empirical development and validation of graphic symbols to be affixed to sources of recycled water. The symbols are intended to encourage the use of recycled water in ways that do not endanger the environment or public health. The current identification system does not provide specific information concerning levels of quality (pollution levels) of recycled water, nor does it provide positive comparative information. In the design and validation of more effective symbols, cognitive elicitation techniques were used to assess the normative implicit meaning of stimulus values of hue and brightness with respect to five levels of water quality. Although both hue and brightness choices were systematically related to water qualities, the implicit meaning of brightness values was clearer. A validity assessment of the untrained meanings of symbols based on brightness and supplemented by hue supported both their implicit comprehensibility and the empirical strategy employed in their design.
Metrics, Targets and Performance
Authors: Stevens Philip Andrew , Stokes Lucy , O'Mahony Mary
Published: July 2006

The setting and use of targets in the public sector has generated a growing amount of interest in the UK. This has occurred at a time when more analysts and policymakers are grasping the nettle of measuring performance in and of the public sector. We outline a typology of performance indicators and a set of desiderata. We compare the outcome of a performance management system — star ratings for acute hospital trusts in England — with a productivity measure analogous to those used in the analysis of the private sector. We find that the two are almost entirely unrelated. Although this may be the case for entirely proper reasons, it does raise questions as to the appropriateness of such indicators of performance, particularly over the long term.
The Hydrogen Economy as a Technological Bluff
Authors: Vanderburg Willem H.
Published: July 2006

The hydrogen economy is a technological bluff in its implied assurance that, despite the accelerating pace at which we are depleting the remaining half of our fossil fuels, our energy future is secure. Elementary thermodynamic considerations are developed to show that a hydrogen economy is about as feasible as a perpetual motion machine. Hydrogen is not an energy source but an energy carrier, and when produced renewably, it is an energy carrier to the second degree, with electricity being the energy carrier to the first degree. As such, it greatly elongates the chain of energy transformations required to deliver a desired service from a primary source of energy. There will undoubtedly be applications in which hydrogen may be essential, but they will be limited because the services it delivers will come at a substantial energy premium.
Hydrogen Highways: Lessons on the Energy Technology-Policy Interface
Authors: Waegel Alex , Byrne John , Tobin Daniel , Haney Bryan
Published: July 2006

The hydrogen economy has received increasing attention recently. Common reasons cited for investigating hydrogen energy options are improved energy security, reduced environmental impacts, and its contribution to a transition to sustainable energy sources. In anticipation of these benefits, national and local initiatives have been launched in the United States, creating pilot “roadmaps” and technology partnerships to explore hydrogen economy platforms. Although hydrogen can provide several positive improvements over a carbon- or uranium-based energy system, several problems are also likely. As well, competitive technologies (e.g., hybrid vehicles) may offer comparatively greater economic and/or environmental advantages. Before policies to advance a hydrogen energy economy proceed, it is vital that all aspects of hydrogen be compared with other available alternatives. Important questions to ask in this regard are whether a hydrogen economy can fulfill key energy needs and whether there are appropriate roles for hydrogen to play in a sustainable energy future.
Tourism and Gastronomy: Gastronomy's Influence on How Tourists Experience a Destination
Authors: Kivela Jakša , Crotts John C.
Published: July 2006

Gastronomy is becoming an important attribute in the development of niche travel and niche destinations. Although the literature supports the view that there is a connection between tourism and gastronomy, little is known about gastronomy tourists. For example, is there a gastronomy-tourism market segment? Does a destination's gastronomy contribute to the tourists' quality of experiences while visiting the destination? Do tourists return to the destination to resample its gastronomy? This study was undertaken in Hong Kong, which is arguably a city destination that offers unique and diverse gastronomy. The results of the study provide evidence suggesting that motivation to travel for gastronomy reasons is a valid construct. Also, the results of the data analysis reveal that gastronomy plays a major role in the way tourists experience the destination, and indicate that some travelers would return to the same destination to savor its unique gastronomy. Implications for practitioners are also discussed.
Importance of Hotel Website Dimensions and Attributes: Perceptions of Online Browsers and Online Purchasers
Authors: Law Rob , Hsu Cathy H. C.
Published: July 2006

The recent introduction of Internet technology to general business has led to its wide-scale application in the hotel industry. Consumers have been increasingly using the Internet to search for accommodation-related information on hotel Websites. To facilitate a better understanding of e-commerce, hospitality and tourism researchers have shown the importance of establishing content-rich and user-friendly Websites. The existing hospitality literature, however, has a very limited number of published articles that investigated the perceptions of hotel Website users on the importance of specific features on hotel Websites. The absence of prior studies on assessing the importance of hotel Website dimensions and attributes is particularly true in the comparison of online browsers who only search for information and online purchasers who have made online bookings. This article reports on a study that examined these two groups of international hotel Website users on their perceived importance level of specific dimensions and attributes on hotel Websites. Empirical evidence indicates that there was no significant difference in most of the included dimensions and attributes between these two groups of users. In addition, the respondents viewed that the included dimensions and attributes are important on Websites of 3-star or above hotels.
Imatinib mesylate selectively impairs expansion of memory cytotoxic T cells without affecting the control of primary viral infections
Authors: Mumprecht Sabine , Matter Matthias , Pavelic Viktor , Ochsenbein Adrian F.
Published: July 2006

Imatinib mesylate (imatinib) is a potent inhibitor of defined tyrosine kinases (TKs) and is effective in the treatment of malignancies characterized by constitutive activation of these TKs such as chronic myeloid leukemia and gastrointestinal stromal tumors. TKs also play an important role in T-cell receptor (TCR) signal transduction. Inhibitory as well as stimulating effects of imatinib on T cells and dendritic cells have been described. Here, we analyzed the effects of imatinib treatment on antiviral immune responses in vivo. Primary cytotoxic T-cell (CTL) responses were not impaired in imatinib-treated mice after infection with lymphocytic choriomeningitis virus (LCMV) or after immunization with a tumor cell line expressing LCMV glycoprotein (LCMV-GP). Similarly, neutralizing antibody responses to vesicular stomatitis virus (VSV) were not affected. In contrast, secondary expansion of LCMV-specific memory CTLs was reduced in vitro and in vivo, resulting in impaired protection against reinfection. In addition, imatinib treatment delayed the onset of diabetes in a CTL-induced diabetes model. In summary, imatinib treatment in vivo selectively inhibits the expansion of antigen-experienced memory CTLs without affecting primary T- or B-cell responses. Therefore, imatinib may be efficacious in the suppression of CTL-mediated immunopathology in autoimmune diseases without the risk of acquiring viral infections.
Integrative roles of transforming growth factor-α in the cytoprotection mechanisms of gastric mucosal injury
Authors: Kosone Takashi , Takagi Hitoshi , Kakizaki Satoru , Sohara Naondo , Horiguchi Norio , Sato Ken , Yoneda Masashi , Takeuchi Toshiyuki , Mori Masatomo
Published: August 2006

Background

Transforming growth factor α (TGFα) protects against gastric mucosal injury and facilitates wound healing. However, its overexpression is known to induce hypertrophic gastropathy resembling Menetrier's disease in transgenic (TG) mice on an FVB background, as one of the authors reported previously. We studied another TGFα-expressing mouse line on a CD1 background, whose gastric mucosa appears normal. Since this TG mouse had a strong resistance to ethanol-induced gastric injury, we considered the long-term effect of TGFα on several gastric protection mechanisms.

Methods

TGFα-expressing transgenic (TG) mouse lines bearing human TGFα cDNA under the control of the mouse metallothionein gene I promoter were generated on a CD1 mouse background, and analyzed their ethanol injury-resistant phenotypes produced by TGFα.

Results

In the TG mucosa, blood flow was well maintained after ethanol injury. Further, neural and inducible types of NO synthases were consistently and widely expressed in the TG mucosa, compared with the limited distribution of neural type NO synthase in the luminal pit region of the wild-type (WT) mucosa. COX-2 and its upstream transcription factor NfkB were constitutively elevated in the TG mucosa even before ethanol administration, whereas they were induced in the same region of the WT mucosa only after ethanol injury. Two anti-apoptotic proteins, HSP70 and Bcl-2, were upregulated in the TG mucosa even before ethanol administration, while they were not expressed in the WT mucosa before the injury. Furthermore, pro-caspase 3 activation was inhibited in the TG mucosa, while it was converted to the active form in the WT mucosa following ethanol administration.

Conclusion

We conclude that TGFα maintains the gastric mucosal defense against gastric injury by integrating other cytoprotective mechanisms.
Total knee arthroplasty: good agreement of clinical severity scores between patients and consultants
Authors: Ebinesan Ananthan D , Sarai Bhupinder S , Walley Gayle , Bridgman Stephen , Maffulli Nicola
Published: August 2006

Background

Nearly 20,000 patients per year in the UK receive total knee arthroplasty (TKA). One of the problems faced by the health services of many developed countries is the length of time patients spend waiting for elective treatment. We therefore report the results of a study in which the Salisbury Priority Scoring System (SPSS) was used by both the surgeon and their patients to ascertain whether there were differences between the surgeon generated and patient generated Salisbury Priority Scores.

Methods

The Salisbury Priority Scoring System (SPSS) was used to assign relative priority to patients with knee osteoarthritis as part of a randomised controlled trial comparing the standard medial parapatellar approach versus the sub-vastus approach in TKA. The operating surgeons and each patient completed the SPSS at the same pre-assessment clinic. The SPSS assesses four criteria, namely progression of disease, pain or distress, disability or dependence on others, and loss of usual occupation. Crosstabs and agreement measures (Cohen's kappa) were performed.

Results

Overall, the four SPSS criteria showed a kappa value of 0.526, 0.796, 0.813, and 0.820, respectively, showing moderate to very good agreement between the patient and the operating consultant. Male patients showed better agreement than female patients.

Conclusion

The Salisbury Priority Scoring System is a good means of assessing patients' needs in relation to elective surgery, with high agreement between the patient and the operating surgeon.
Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
Authors: El Awady Mostafa K , El Din Noha G Badr , El Garf Wael T , Youssef Samar S , Omran Moataza H , El Abd Jasmin , Goueli Said A
Published: July 2006

Background

Hepatitis C (HCV) viral infection is a serious medical problem in Egypt and it has a devastating impact on the Egyptian economy. It is estimated that over 15% of Egyptians are infected by the virus and thus finding a cure for this disease is of utmost importance. Current therapies for hepatitis C virus (HCV) genotype 4 with interferon/ribavirin have not been successful and thus the development of alternative therapy for this genotype is disparately needed.

Results

Although previous studies utilizing viral subgenomic or full cDNA fragments linked to reporter genes transfected into adhered cells or in a cell free system showed promise, demonstration of efficient viral replication was lacking. Thus, we utilized HepG2 cells infected with native HCV RNA genomes in a replication competent system and used antisense phosphorothioate Oligonucleotides (S-ODN) against stem loop IIId and the AUG translation start site of the viral polyprotein precursor to monitor viral replication. We were able to show complete arrest of intracellular replication of HCV-4 at 1 uM S-ODN, thus providing a proof of concept for the potential antiviral activity of S-ODN on native genomic replication of HCV genotype 4.

Conclusion

We have successfully demonstrated that by using two S-ODNs [(S-ODN1 (nt 326–348) and S-ODN-2 (nt 264–282)], we were able to completely inhibit viral replication in culture, thus confirming earlier reports on subgenomic constructs and suggesting a potential therapeutic value in HCV type 4.
Service user involvement in training: the trainees' view
Authors: Vijayakrishnan Ajay , Rutherford Joan , Miller Steve , Drummond Lynne M.
Published: August 2006

Aims and Method

A questionnaire survey was conducted of trainees across the South-West London and St George's Basic Specialist Training Scheme in Psychiatry to explore their attitudes towards service user involvement in training.

Results

Fifty-two completed questionnaires were received; 20 trainees (38%) had not attended teaching sessions where a user was present; 35 trainees (67%) were agreeable to service user involvement in examinations. Reservations concerned the objectivity of service users in examination rating and their role as an expert on assessing the trainee's skill. Awareness of user involvement strategies and policies in their trusts were not matched with actual participation.

Clinical Implications

Service users should be involved in teaching in an expert capacity and also in examinations, with safeguards regarding transparency and objectivity of the marking schemes in place.
Double-Blind, Placebo-Controlled Study of Quality of Life, Hematologic End Points, and Safety of Weekly Epoetin Alfa in Children With Cancer Receiving Myelosuppressive Chemotherapy
Authors: Razzouk Bassem I. , Hord Jeffrey D. , Hockenberry Marilyn , Hinds Pamela S. , Feusner James , Williams Denise , Rackoff Wayne R.
Published: July 2006

Purpose

To evaluate the effects of once-weekly epoetin alfa (EPO) on health-related quality of life (HRQOL), hemoglobin (Hb), transfusions, and tolerability in children with cancer.

Methods

Anemic patients 5 years to 18 years of age receiving myelosuppressive chemotherapy for nonmyeloid malignancies, excluding brain tumors, received intravenous EPO 600 units/kg to 900 units/kg or placebo once-weekly for 16 weeks. Patients and parents completed the pediatric health-related quality-of-life generic scales (GS) and cancer-specific scales (CS).

Results

One hundred eleven patients received EPO and 111 patients received placebo. Mean final values for GS total score (P = .763 among patients; P = .219 among parents) and CS domain scores (P ≥ .238; P ≥ .081, respectively) were not significantly different between treatment groups. EPO-treated patients had greater increases in Hb overall (P = .002) and were more likely to be transfusion free after 4 weeks (38.7% v 22.5%; P = .010). Change in Hb was correlated with change in PedsQL-GCS total score in the EPO group (r = 0.242; P = .018), but was not in the placebo group (r = 0.086; P = .430). Adverse events were comparable between treatment groups.

Conclusion

This study confirmed the tolerability and hematologic benefits of once-weekly EPO in children with cancer. No significant difference in HRQOL was detected between treatment groups, but a significant positive correlation was observed between Hb changes and HRQOL changes in the EPO group. Additional studies are warranted to assess HRQOL when anemia is managed optimally in children with cancer.
Clinical Characteristics Affect the Impact of an Uninformative DNA Test Result: The Course of Worry and Distress Experienced by Women Who Apply for Genetic Testing for Breast Cancer
Authors: van Dijk Sandra , Timmermans Daniëlle R.M. , Meijers-Heijboer Hanne , Tibben Aad , van Asperen Christi J. , Otten Wilma
Published: July 2006

Purpose

DNA mutation testing for breast cancer usually yields an uninformative result, which is a negative result in the absence of a known BRCA mutation within the family. However, few data are available on the psychological impact of this result. Moreover, the clinical heterogeneity within this group has not yet been considered. This study provides prospective data about the course of cancer-specific worry and distress for different groups of test applicants.

Patients and Methods

All DNA test applicants (n = 238) completed three questionnaires: before and 1 and 7 months after disclosure of a DNA mutation test. With repeated-measures analysis of variance, differences were assessed between BRCA1/2-positive women (n = 42), BRCA1/2–true-negative women (n = 43), and women with an uninformative test result (n = 153).

Results

On the group level, women with an uninformative result seemed to be reassured after disclosure (P < .001), but to a lesser extent than those women who received a true-negative result. However, not all women with an uninformative result reacted similarly: higher levels of worry and distress could be explained by relatively straightforward clinical variables, namely a personal history of cancer (P ≤ .001) and a higher pedigree-based risk (P ≤ .005). Furthermore, these clinical variables determined whether these women were either comparable to women who received a true-negative result or to BRCA mutation carriers.

Conclusion

Women with an uninformative result form a heterogeneous group of test applicants. The subpopulation of those with both a personal history of cancer and a relatively high pedigree-based risk expressed the highest levels of worry 7 months after DNA testing.
Prospective Study of Incidence and Severity of Epiphora and Canalicular Stenosis in Patients With Metastatic Breast Cancer Receiving Docetaxel
Authors: Esmaeli Bita , Amin Sapna , Valero Vicente , Adinin Rosnie , Arbuckle Rebecca , Banay Roberto , Do Kim-Anh , Rivera Edgardo
Published: July 2006

Purpose

To determine the incidence and severity of epiphora and canalicular stenosis in patients receiving docetaxel weekly or every 3 weeks.

Patients and Methods

In this prospective trial, each patient underwent an ophthalmologic examination and probing and irrigation of the lacrimal drainage apparatus at baseline and every 4 to 6 weeks after initiation of docetaxel. During each visit, epiphora and canalicular stenosis were graded. Patients with epiphora were treated with tobramycin and dexamethasone drops. If epiphora worsened or if findings on probing and irrigation suggested further canalicular narrowing, silicone intubation was offered.

Results

Twenty-eight patients received docetaxel weekly, and 28 patients received docetaxel every 3 weeks. Eighteen patients (64%) who received weekly docetaxel developed epiphora. Epiphora was mild in seven patients, moderate in five, and severe in six. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Nine patients had worsened canalicular stenosis; six underwent surgery. The median cumulative docetaxel dose was 496.5 mg at onset of epiphora and 889.5 mg at surgery. Eleven patients (39%) who received docetaxel every 3 weeks developed epiphora. The median cumulative docetaxel dose at onset of epiphora in this group was 420 mg. Epiphora was mild in nine patients, moderate in one, and severe in one. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Two patients underwent surgery.

Conclusion

Epiphora occurred in 64% of patients in the weekly group and in 39% of patients in the every-3-weeks group. Moderate or severe canalicular stenosis was seen in about one-third of patients in the weekly group and in none of the patients in the every-3-weeks group.
Residual Disease Monitoring in Childhood Acute Myeloid Leukemia by Multiparameter Flow Cytometry: The MRD-AML-BFM Study Group
Authors: Langebrake Claudia , Creutzig Ursula , Dworzak Michael , Hrusak Ondrej , Mejstrikova Ester , Griesinger Frank , Zimmermann Martin , Reinhardt Dirk
Published: July 2006

Purpose

Monitoring of residual disease (RD) by flow cytometry in childhood acute myeloid leukemia (AML) may predict outcome. However, the optimal time points for investigation, the best antibody combinations, and most importantly, the clinical impact of RD analysis remain unclear.

Patients and Methods

Five hundred forty-two specimens of 150 children enrolled in the AML-Berlin-Frankfurt-Muenster (BFM) 98 study were analyzed by four-color immunophenotyping at up to four predefined time points during treatment. For each of the 12 leukemia-associated immunophenotypes and time points, a threshold level based on a previous retrospective analysis of another cohort of children with AML and on control bone marrows was determined.

Results

Regarding all four time points, there is a statistically significant difference in the 3-year event-free survival (EFS) in those children presenting with immunologically detectable blasts at 3 or more time points. The levels at bone marrow puncture (BMP) 1 and BMP2 turned out to have the most significant predictive value for 3-year-EFS: 71% ± 6% versus 48% ± 9%, PLog-Rank = .029 and 70% ± 6% versus 50% ± 7%, PLog-Rank = .033), resulting in a more than two-fold risk of relapse. In a multivariate analysis, using a combined risk classification based on morphologically determined blasts at BMP1 and BMP2, French-American-British classification, and cytogenetics, the influence of immunologically determined RD was no longer statistically significant.

Conclusion

RD monitoring before second induction has the same predictive value as examining levels at four different time points during intensive chemotherapy. Compared with commonly defined risk factors in the AML-BFM studies, flow cytometry does not provide additional information for outcome prediction, but may be helpful to evaluate the remission status at day 28.
Phase I Single-Dose Study of Intracavitary-Administered Iodine-131-TM-601 in Adults With Recurrent High-Grade Glioma
Authors: Mamelak Adam N. , Rosenfeld Steven , Bucholz Richard , Raubitschek Andrew , Nabors L. Burt , Fiveash John B. , Shen Sui , Khazaeli M.B. , Colcher David , Liu An , Osman Medhat , Guthrie Bart , Schade-Bijur Susan , Hablitz Diana M. , Alvarez Vernon L. , Gonda Matthew A.
Published: July 2006

Purpose

TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) –TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma.

Patients and Methods

Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of ≥ 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I.

Results

Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months.

Conclusion

A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.
Decision Analysis for Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer
Authors: Lee J. Jack , Bekele B. Nebiyou , Zhou Xian , Cantor Scott B. , Komaki Ritsuko , Lee Jin Soo
Published: July 2006

Purpose

Prophylactic cranial irradiation (PCI) has been shown to provide survival benefit in patients with limited disease small-cell lung cancer (LD-SCLC) who have achieved complete response. However, PCI may also produce long-term neurotoxicity (NT). The benefits and risks of PCI in LD-SCLC are evaluated.

Methods

We developed a decision-analytic model to compare quality-adjusted life expectancy (QALE) in a cohort of SCLC patients who do or do not receive PCI by varying survival rates and the frequency and severity of PCI-related NT. Sensitivity analyses were applied to examine the robustness of the optimal decision.

Results

At current published survival rates (26% 5-year survival rate with PCI and 22% without PCI) and a low NT rate, PCI offered a benefit over no PCI (QALE = 4.31 and 3.70 for mild NT severity; QALE = 4.09 and 3.70 for substantial NT severity, respectively). With a moderate NT rate, PCI was still preferred. If the PCI survival rate increased to 40%, PCI outperformed no PCI with a mild NT severity. However, no PCI was preferred over PCI (QALE = 5.72 v 5.47) with substantial NT severity. Two-way sensitivity analyses showed that PCI was preferred for low NT rates, mild NT severity, and low long-term survival rates. Otherwise, no PCI was preferred.

Conclusion

The current data suggest PCI offers better QALE than no PCI in LD-SCLC patients who have achieved complete response. As the survival rate for SCLC patients continues to improve, NT rate and NT severity must be controlled to maintain a favorable benefit-risk ratio for recommending PCI.
Phase I Study of Depsipeptide in Pediatric Patients With Refractory Solid Tumors: A Children's Oncology Group Report
Authors: Fouladi Maryam , Furman Wayne L. , Chin Thomas , Freeman Burgess B. , Dudkin Lorina , Stewart Clinton F. , Krailo Mark D. , Speights Roseanne , Ingle Ashish M. , Houghton Peter J. , Wright John , Adamson Peter C. , Blaney Susan M.
Published: July 2006

Purpose

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the histone deacetylase inhibitor, depsipeptide, in children with refractory or recurrent solid tumors.

Patients and Methods

Depsipeptide was administered as a 4-hour infusion weekly for 3 consecutive weeks every 28 days at dose levels of 10 mg/m2, 13 mg/m2, 17 mg/m2, and 22 mg/m2. Pharmacokinetics and histone acetylation studies were performed in the first course. The levels of H3 histone and acetyl-H3 histone were evaluated in peripheral blood mononuclear cells (PBMC) using immunofluorescence techniques.

Results

There were 24 patients, and 18 who were assessable were enrolled. DLTs included reversible, asymptomatic T-wave inversions, without any associated changes in troponin levels or evidence of ventricular dysfunction, in the inferior leads in two patients at 22 mg/m2 and in the lateral leads in one patient at 13 mg/m2 (n = 1), and transient asymptomatic sick sinus syndrome and hypocalcemia in one patient at 17 mg/m2. At the MTD (17 mg/m2), the median depsipeptide clearance was 6.8 L/h/m2 with an area under the plasma depsipeptide concentration-time curve from 0 to infinity of 2,414 ng/mL/h, similar to adults. Accumulation of acetylated H3 histones was seen in all patients in a dose independent manner, with maximal accumulation at a median of 4 hours, (range, 0 hours to 20 hours) after the end of the infusion. No objective tumor responses were observed.

Conclusion

Depsipeptide is well tolerated in children with recurrent or refractory solid tumors when administered weekly for 3 consecutive weeks every 28 days and inhibits histone deacetylase activity in PBMC in a dose-independent manner. The recommended phase II dose in children with solid tumors is 17 mg/m2.
Increasing Negative Lymph Node Count Is Independently Associated With Improved Long-Term Survival in Stage IIIB and IIIC Colon Cancer
Authors: Johnson Paul M. , Porter Geoff A. , Ricciardi Rocco , Baxter Nancy N.
Published: July 2006

Purpose

The purpose of this study was to examine the impact of the number of negative lymph nodes on survival in patients with stage III colon cancer.

Patients and Methods

Patients who underwent surgery for stage III colon cancer between January 1988 and December 1997 were identified from the Surveillance, Epidemiology and End Results cancer registry. The number of negative and positive nodes was determined for 20,702 eligible patients. Disease-specific survival was examined by substage according to the number of negative nodes identified. A proportional hazards model was constructed to determine the effect of the number of negative nodes on survival.

Results

For stage IIIB and IIIC patients, there was a significant decrease in disease-specific mortality as the number of negative nodes increased; cumulative 5-year cancer mortality was 27% in stage IIIB patients with 13 or more negative nodes identified versus 45% in those with three or fewer negative lymph nodes evaluated (P < .0001). In patients with stage IIIC cancer, those with 13 or more negative nodes had a 5-year mortality of 42% versus 65% in those with three or fewer negative lymph nodes evaluated (P < .0001). There was no association between the number of negative nodes identified and disease-specific survival for patients with stage IIIA disease. After controlling for the number of positive nodes, a higher number of negative nodes was found to be independently associated with improved disease-specific survival.

Conclusion

The number of negative nodes is an important independent prognostic factor for patients with stage IIIB and IIIC colon cancer.
Preadipocytes Mediate Lipopolysaccharide-Induced Inflammation and Insulin Resistance in Primary Cultures of Newly Differentiated Human Adipocytes
Authors: Chung Soonkyu , LaPoint Kathleen , Martinez Kristina , Kennedy Arion , Boysen Sandberg Maria , McIntosh Michael K.
Published: July 2006

Recent data suggest that proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. However, characterization of the cell types involved in inflammation and how these cells promote insulin resistance in human adipocytes are unclear. We simulated acute inflammation using the endotoxin lipopolysaccharide (LPS) to define the roles of nonadipocytes in primary cultures of human adipocytes. LPS induction of the mRNA levels of proinflammatory cytokines (e.g. IL-6, TNF-α, and IL-1β) and chemokines (e.g. IL-8, monocyte chemoattractant protein-1) occurred primarily in the nonadipocyte fraction of newly differentiated human adipocytes. Nonadipocytes were characterized as preadipocytes based on their abundant mRNA levels of preadipocyte markers preadipocyte factor-1 and adipocyte enhancer protein-1 and only trace levels of markers for macrophages and myocytes. The essential role of preadipocytes in inflammation was confirmed by modulating the degree of differentiation in the cultures from approximately 0–90%. LPS-induced proinflammatory cytokine/chemokine expression and nuclear factor-κB and MAPK signaling decreased as differentiation increased. LPS-induced cytokine/chemokine expression in preadipocytes was associated with: 1) decreased adipogenic gene expression, 2) decreased ligand-induced activation of a peroxisome proliferator activated receptor (PPAR)-γ reporter construct and increased phosphorylation of PPARγ, and 3) decreased insulin-stimulated glucose uptake. Collectively, these data demonstrate that LPS induces nuclear factor-κB- and MAPK-dependent proinflammatory cytokine/chemokine expression primarily in preadipocytes, which triggers the suppression of PPARγ activity and insulin responsiveness in human adipocytes.
Gonadotropin-Releasing Hormone-II Messenger Ribonucleic Acid and Protein Content in the Mammalian Brain Are Modulated by Food Intake
Authors: Kauffman Alexander S. , Bojkowska Karolina , Wills Aileen , Rissman Emilie F.
Published: July 2006

GnRH-II is the most evolutionarily conserved member of the GnRH peptide family. In mammals, GnRH-II has been shown to regulate reproductive and feeding behaviors. In female musk shrews, GnRH-II treatment increases mating behaviors and decreases food intake. Although GnRH-II-containing neurons are known to reside in the midbrain, the neural sites of GnRH-II action are undetermined, as is the degree to which GnRH-II is regulated by energy availability. To determine whether GnRH-II function is affected by changes in food intake, we analyzed the levels of GnRH-II mRNA in the midbrain and GnRH-II protein in numerous target regions. Adult musk shrews were ad libitum fed, food restricted, or food restricted and refed for varying durations. Compared with ad libitum levels, food restriction decreased, and 90 min of refeeding reinstated, GnRH-II mRNA levels in midbrain and GnRH-II peptide in several target areas including the medial habenula and ventromedial nucleus. Refeeding for 90 min also reinstated female sexual behavior in underfed shrews. In male shrews, abundant GnRH-II peptide was present in all sites assayed, including the preoptic area, a region with only low GnRH-II in females. In contrast to females, food restriction did not affect GnRH-II protein in male brains or inhibit their mating behavior. Our results further define the relationship between GnRH-II, energy balance, and reproduction, and suggest that food restriction may inhibit female reproduction by reducing GnRH-II output to several brain nuclei. We postulate that this highly conserved neuropeptide functions similarly in other mammals, including humans, to fine-tune reproductive efforts with periods of sufficient energy resources.
An Introduction to Unwrapping Algorithms for the Realistic Construction of Pattern Shapes
Authors: Ball A , Cader R
Published: July 2006

Many manufacturing processes involve wrapping a sheet of material over a surface. This paper focuses on wrappings where there is free movement of the sheets and the surfaces are almost developable. The approach is predominantly geometric and the key issues are the definition of almost developable surfaces and the distinction between flattening and unwrapping algorithms. There is an industrial case study to construct the pattern shape for a ceramic pot decoration.
Shortening Tool Setting Time for Transfer Presses
Authors: Behrens B-A , Doege E , Krimm R
Published: July 2006

The production processes of sheet metal products with complex geometries often use transfer presses to obtain fully formed workpieces from a single machine. The job of adjusting a new multistage tool set increases with the number of stages because the deformations of the frame, the bottom platen, and the ram vary with the different applied loads. Each of the forces applied by the stages causes a specific deformation of the machine, while each stage is also influenced by all other stages. The Institute for Metal Forming and Metal Forming Machine Tools (University of Hanover, Germany) has developed a new computer-based setup system for multistage tools. Once the machine properties have been measured, the system calculates the deformation of the machine on the basis of the forming forces measured during the tool setting process. The use of the developed system will help to shorten the first set-up of new tool sets. Manufacturers of sheet metal products are expecting significant time savings.
Development of an Effective Measurement System for Burr Geometry
Authors: Ko S L , Park S W
Published: July 2006

The triangulation method, conoscopic holography method, and interferometry method were analysed for the effective measurement of microburr geometry formed while microdrilling. A cylinder with a diameter of 0.5 mm was used to show that the conoscopic holography method is effective for measuring steep slope surfaces. A program for the three-dimensional display and analysis of measured burr was developed. Burrs formed on a curved surface were compensated and measured successfully using the basic surface compensation function. The maximum burr height, burr volume, average burr height, and average burr thickness were also calculated. The burr measurement system is composed of a laser sensor, an XY table, a controller, and the burr measurement program. Burrs formed from drilling 3 mm holes and microblanking were measured successfully. For microburrs less than 20 μm, a high-definition Conoprobe sensor equipped with a CMM precision table was used.
Analysis of Grinding Chip Temperature and Energy Partitioning in High-Efficiency Deep Grinding
Authors: Jin T , Stephenson D J
Published: July 2006

A new approach is introduced to refine the analysis for the chip energy in the highefficiency deep grinding process, by considering the heat partitioning at the chip formation area. The analysis for the chip-work subsystem has been combined with the whole thermal system to derive the grinding temperature on the workpiece surface. The variation of chip temperature with material removal rate under different grinding conditions was investigated, and the relationship between the chip temperature and workpiece contact temperature was derived. The grinding temperatures obtained using different approaches were compared with ‘measured temperatures’, estimated from the depth of thermal damage observed on ground samples.
Development and Validation of Sliding and Non-Matching Grid Technology for Control Surface Representation
Authors: Fenwick C L , Allen C B
Published: July 2006

Aeroservoelastic simulation of realistic configurations requires the representation of moving control surfaces. Once a control surface is deflected, for example, at the trailing edge of a wing, the surface is no longer continuous and this is considered here. A sliding grid approach is used to allow control surface deflection within a multiblock-structured grid framework. Two methods of information transfer between patched (non-matching) grids are developed and tested in this paper: the first involving halo interpolation and the second, conservative flux interpolation. Results are presented for a range of test cases involving steady and unsteady flows using non-matching and sliding interfaces at block boundaries. It is shown that both methods can be applied to the example of a wing with a deflected control surface, where no advantage is gained by using a significantly more complex, conservative method.
Charge-Transfer Molecular Complexes of Thianes with σ and π Electron Acceptors
Authors: Hamed Maher M A , Mohamed Mona B , Mahmoud Mohamed R
Published: July 2006

Charge-transfer complexes of cyclic thioethers with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; tetracyanoethylene; chloranil as π-acceptors and with iodine as a σ-acceptor, have been investigated. The spectral characteristics and stability of the formed CT complexes were examined, and are discussed in terms of the donor molecular structure, the nature of the electron acceptor and the solvent polarity. It is deduced that the formed CT complexes are mainly of the weak n–π or n–σ type, where the ground-state wave function is described primarily in terms of the nonbonding structure (D–A). The ionization potentials of the donors were calculated based on the CT energies of their CT complexes. Moreover, solid 1 : 1 CT complexes were synthesized and characterized.
Oxidation Potentials and Absorption Spectra of Phenothiazine Derivatives I. Benzophenothiazines and Triphenodithiazine
Authors: Urasaki Naoyuki , Yoshida Sadamu , Ogawa Takashi , Kozawa Kozo , Uchida Tokiko
Published: July 2006

The homogeneous electrochemical oxidations of four phenothiazine derivatives, three isomers of benzophenothiazine and triphenodithiazine, were studied in acetonitrile solution together with phenothiazine itself. Their first and second redox potentials were determined by means of cyclic voltammetry. In all the materials examined, reversible one-electron oxidations were characterized. The electrogenerated cation radicals, except for triphenodithiazine, underwent a second one-electron oxidation and, after a subsequent chemical transformation, formed the corresponding benzophenothiazinium cations. For triphenodithiazine, only the first oxidation potential was observable under our experimental conditions. The electronic states of both the intermediates and the final products of electrolytic oxidation were identified by their electronic absorption spectra and electron spin resonance absorption spectra. The values of the first oxidation potential of the benzophenothiazines were proportional to the ionization energies, which were given by molecular orbital calculations.
The Phase Transition in the Gel State of the 1,3 : 2,4-Di-O-benzylidene-d-sorbitol/Ethylene Glycol System
Authors: Yamasaki Seiji , Tsutsumi Hisao
Published: July 2006

In chiral oil gelators, only 1,3 : 2,4-di-O-benzylidene-d-sorbitol (d-DBS) can form gels with alcoholic solvents. The d-DBS concentration dependence of the state in the binary system d-DBS/ethylene glycol, were studied using optical, rheological and spectral measurements. Based on the changes in the transmission and mechanical properties, two phase transition points, which depended upon the d-DBS concentration, were observed at 10 and 30 mM. The low-concentration point was the critical gel concentration. The gel was formed above 10 mM. d-DBS formed spherical domains in the gel between 10—30 mM and made continuous crystals on the entire gel above 30 mM. The aggregated structure of d-DBS in ethylene glycol was studied, utilizing electronic and circular dichroism measurements. According to the gelation, the absorption of the transition moment along the long axis of the benzene ring was red-shifted. The relative orientation changed in 10—30 mM from the hyperchromism and hypochromism of the electronic absorptions, but was fixed above 30 mM. d-DBS exhibited remarkable CD enhancements due to the formation of a gel. The concentration dependence of the molar ellipticities of the CD absorptions was similar to the tendency of the electronic spectra. This indicated that the aggregated structure was changed, depending upon the d-DBS concentration in ethylene glycol; the optical and mechanical properties were related to the aggregated structure which d-DBS formed.
Structure Analysis of Adsorbed Layers Formed from Methanol on Platinum Electrodes with an Electrochemical Quartz Crystal Microbalance
Authors: Shimazu Katsuaki , Kaneda Kyohei , Kita Hideaki
Published: July 2006

The adsorbed species formed from methanol on platinum electrodes have been examined with an electrochemical quartz crystal microbalance (EQCM). The mass of the adsorbed species per surface platinum site was determined from the frequency response of the EQCM, together with number of electrons per Pt site required to oxidize the adsorbed species and coverage from the current response of the EQCM. These values were used to calculate the molar mass of the adsorbed species and the number of adsorption sites. The average composition of the adsorbed species was similar both in 0.1 M HClO4 and 0.01 M NaOH, and was COH2.0—2.4. The composition was independent of the adsorption time and the adsorption potential unless the coverage was below 0.2, where accurate determination of the composition was not possible. The average number of adsorption sites was 3.0 in 0.1 M HClO4 and 2.6 in 0.01M NaOH.