bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoid Hyper‐ and Hypofunction
Authors: KIM JEANSOK J. , HALLER JÓZSEF
Published: October 2007

Abstract:  It is now well documented that both increased and decreased stress responses can profoundly affect cognition and behavior. This mini review presents possible neural mechanisms subserving stress effects on memory and aggression, particularly focusing on glucocorticoid (GC) hyper‐ and hypofunction. First, uncontrollable stress impedes hippocampal memory and long‐term potentiation (LTP). Because the hippocampus is important for the stability of long‐term memory and because LTP has qualities desirable of an information storage mechanism, it has been hypothesized that stress‐induced alterations in LTP contribute to memory impairments. Recent evidence suggests a neural–endocrine network comprising amygdala, prefrontal cortex (PFC), and glucocorticoids may be involved in regulating stress effects on hippocampal mnemonic functioning. Second, antisocial aggressiveness correlates with chronically decreased glucocorticoid production, and this condition leads in rats to behavioral–autonomic deficits reminiscent of the human disorder. Glucocorticoid deficiency‐induced antisocial aggressiveness results from functional changes in the PFC, medial and central amygdala, and altered serotonin and substance P neurotransmissions. Accordingly, a neurobiological understanding of how stress and glucocorticoid deficiency alter brain, cognition, and behavior is an important challenge facing modern neuroscience with broad implications for individual and social well‐being.
Metabolic Syndrome
Authors: ABRAHAM N.G. , BRUNNER E.J. , ERIKSSON J.W. , ROBERTSON R.P.
Published: October 2007

Abstract:  This article summarizes some aspects of stress in the metabolic syndrome at the psychosocial, tissue, and cellular levels. The metabolic syndrome is a valuable research concept for studying population health and social–biological translation. The cluster of cardiovascular risk factors labeled the metabolic syndrome is linked with low socioeconomic status. Systematic differences in diet and physical activity contribute to social patterning of the syndrome. In addition, psychosocial factors including chronic work stress are linked with its development. Psychosocial factors could lead to metabolic perturbations and increase cardiovascular risk via activation of neuroendocrine responses, for example, in the autonomic nervous system and in several hormonal pathways. High glucocorticoid levels will promote lipid storage in visceral rather than subcutaneous adipose tissue. Adipocytes secrete several proinflammatory cytokines, which considered major contributors to increase in oxidants and cell injury. Upregulation of heme oxygenase 1 (HO‐1) and peroxidase in the early development of diabetes produces a decrease in oxidative‐mediated injury. Increased HO activity is associated with a significant decrease in superoxide, endothelial cell shedding and blood pressure. Finally, it is proposed that overexpression of glutathione peroxidase in β cells may protect β cell deterioration from oxidative stress during development of diabetes and hyperglycemia and this may result in attenuation of β cell failure. If this proves to be the case, then the scene will be set to develop glutathione peroxidase mimetics for use in preclinical and clinical trials.
Stress, Immune Function, and Women's Reproduction
Authors: NEPOMNASCHY PABLO A. , SHEINER EYAL , MASTORAKOS GEORGE , ARCK PETRA C.
Published: October 2007

Abstract:  Only 23% of women will begin a successful pregnancy during the first menstrual cycle in their attempt to conceive.

1

A large number of these failed reproductive attempts are attributed to a broad set of pathologies, but across studies an important proportion of unsuccessful cycles is consistently left unexplained. Stress has become a commonly cited factor when discussing unexplained reproductive failures. Early research on the effect of stress on reproduction was plagued with methodological problems and lacked a solid theoretical framework. However, recent experimental, clinical and population‐based research provides new evidence and suggests novel biological mechanisms, which merit a fresh evaluation of the purported association. Here we briefly review the latest advancements in the study of the interplay between stress, the immune system and women's reproduction, discuss a proposed evolutionary origin for their relationship and examine the biological pathways that may mediate the connection between these three systems.
The Plant Host–Pathogen Interface
Authors: DAY BRAD , GRAHAM TERRY
Published: October 2007

Abstract:  Perception of pathogens by their hosts is the outcome of a highly coordinated and sophisticated surveillance network, tightly regulated by both host and pathogen elicitors, effectors, and signaling processes. In this article, we focus on two relatively well‐studied host–pathogens systems, one involving a bacterial–plant interaction (Pseudomonas syringae–Arabidopsis) and the other involving an oomycete–plant interaction (Phytophthora sojae–soybean). We discuss the status of current research related to events occurring at the host–pathogen interface in these two systems, and how these events influence the organization and activation of resistance responses in the respective hosts. This recent research has revealed that in addition to the previously identified resistance machinery (R‐proteins, molecular chaperones, etc.), the dynamics of the cell wall, membrane trafficking, and the actin cytoskeleton are intimately associated with the activation of resistance in plants. Specifically, in Arabidopsis, a possible connection between the actin machinery and R‐protein‐ mediated induction of disease resistance is described. In the case of the P. sojae–soybean interaction, we describe the fact that a classical basal resistance elicitor, the cell wall glucan elicitor from the pathogen, can directly activate host hypersensitive cell death, which is apparently modulated in a race‐specific manner by the presence of R genes in the host.
New Molecular Mechanisms of Duodenal Ulceration
Authors: SZABO SANDOR , DENG XIAOMING , KHOMENKO TETYANA , CHEN LONGCHUAN , TOLSTANOVA GANNA , OSAPAY KLARA , SANDOR ZSUZSANNA , XIONG XIMING
Published: October 2007

Abstract:  Stress is a major etiologic factor in the pathogenesis of gastric and duodenal ulceration, as first described in rats by Hans Selye. In patients with “peptic ulcers” duodenal ulcers are more frequent than gastric ulcers (except in Japan). Thus, our research during the last three decades focused on the molecular mechanisms of duodenal ulcer in rodent models of chemically induced duodenal ulceration, and here we review our three recent findings: Endothelins (ET‐1), the immediate early gene egr‐1 and imbalance of angiogenic/antiangiogenic molecules. Namely, we found an enhanced expression and release of ET‐1 within 15–30 min after the administration of duodenal ulcerogen cysteamine, resulting in local ischemia that triggers the expression of hypoxia‐inducible factors (HIF‐1α). Our gene expression studies also revealed an early (0.5–2 h) increase in the expression of egr‐1 that is followed (12–24 h) by upregulation of angiogenic growth factors (e.g., VEGF, bFGF, PDGF). Surprisingly, this event is also associated with an enhanced production of angiostatin and endostatin that probably counteract the beneficial effect of angiogenic molecules. Thus, the initial injury to endothelial and epithelial cells in duodenal ulceration seems to be aggravated (and not initiated) by HCl and proteolytic enzymes. The resulting mucosal necrosis does not rapidly heal because of the imbalance of VEGF and angiostatin/endostatin, hence duodenal ulcers develop. The experimental ulcers Selye described morphologically are now characterized at the molecular and genome level, involving unexpected mediators like ET‐1, egr‐1 and angiogenesis‐related molecules.
Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma
Authors: Hanrahan Emer O. , Gonzalez-Angulo Ana M. , Giordano Sharon H. , Rouzier Roman , Broglio Kristine R. , Hortobagyi Gabriel N. , Valero Vicente
Published: October 2007

Purpose

With mammographic screening, the frequency of diagnosis of stage T1a,bN0M0 breast cancer has increased. Prognosis after locoregional therapy and benefit from adjuvant systemic therapy are poorly defined. We reviewed T1a,bN0M0 breast cancer cases registered in the Surveillance, Epidemiology, and End Results (SEER) Program to investigate the impact of prognostic factors on breast cancer–specific (BCSM) and non–breast cancer–related mortality.

Methods

We identified T1a,bN0M0 breast cancer cases registered in the SEER Program from 1988 to 2001, and used the Kaplan-Meier product limit method to describe overall survival (OS). We estimated the probabilities of death resulting from breast cancer and from other causes, and analyzed associations of patient and tumor characteristics with OS, BCSM, and non–breast cancer–related mortality using the log-rank test, Cox proportional hazards models, and a competing-risk model. We constructed nomograms to assist physicians in adjuvant therapy decision making.

Results

We identified 51,246 T1a,bN0M0 cases. Median follow-up was 64 months (range, 1 to 167 months). Median age at diagnosis was 65 years (range, 20 to 101 years). Ten-year probabilities of all-cause mortality and BCSM were 24% and 4%, respectively. Characteristics associated with increased probability of BCSM included age younger than 50 years at diagnosis, high tumor grade, estrogen receptor–negative status, progesterone receptor–negative status, and fewer than six nodes removed at axillary dissection. The constructed nomograms allow a comparison of predicted breast cancer–specific survival and non-breast cancer–specific survival in individual patients.

Conclusion

Overall, the prognosis of patients with T1a,bN0M0 breast cancer is excellent. However, subgroups of patients who are at higher risk of BCSM and who should be considered for adjuvant systemic therapy can be identified.
Phase III, Double-Blind, Controlled Trial of Atamestane Plus Toremifene Compared With Letrozole in Postmenopausal Women With Advanced Receptor-Positive Breast Cancer
Authors: Goss Paul , Bondarenko Igor N. , Manikhas Georgiy N. , Pendergrass Kelly B. , Miller Wilson H. , Langecker Peter , Blanchett Dennis
Published: October 2007

Purpose

To compare time to progression (TTP) with a steroidal aromatase inhibitor (AI) atamestane (ATA) combined with toremifene (TOR; complete estrogen blockade) versus letrozole (LET) in receptor-positive advanced breast cancer (ABC).

Patients and Methods

Eligibility included postmenopausal receptor-positive ABC and adjuvant hormonal therapy completed more than 12 months prior to study entry. Participants received daily ATA 500 mg with TOR 60 mg (ATA + TOR), or letrozole 2.5 mg (LET). The primary end point was TTP, whereas secondary objectives included objective response (OR), overall survival (OS), and time to treatment failure (TTF). The study had 80% power to detect a 25% increase in TTP assuming a TTP of 9.4 months in the LET population.

Results

A total of 865 patients were randomly assigned (434 to ATA + TOR and 431 to LET) in 60 centers in the United States, Canada, Russia, and Ukraine. Baseline characteristics were balanced. Median TTP was identical in the two arms at 11.2 months (P < .92). Median TTF was similar at 9.24 months (ATA + TOR) versus 10.44 months (LET). The hazard ratios (LET/ATA + TOR) were 1.00 (95% CI, 0.92 to 1.08) for TTP, 0.99 (95% CI, 0.92 to 1.06) for TTF, and 0.98 (95% CI, 0.87 to 1.11) for OS. OR occurred in 30% of patients receiving ATA + TOR and in 36% of patients receiving LET (P < .1). Adverse events (AEs) were similar for patients receiving ATA + TOR versus LET, and serious AEs were 10% v 11%, respectively.

Conclusion

TTP for patients receiving ATA + TOR was identical to that for patients receiving LET, representing the first endocrine therapy comparable to LET in ABC. Unlike in the Anastrozole, Tamoxifen, and Combined trial, addition of an antiestrogen did not decrease efficacy of the AI. Future studies of AIs in combination with more effective selective estrogen receptor modulators or selective receptor downregulators is warranted.
Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer
Authors: de Maat Michiel F.G. , van de Velde Cornelis J.H. , Umetani Naoyuki , de Heer Pieter , Putter Hein , van Hoesel Anneke Q. , Meijer Gerrit A. , van Grieken Nicole C. , Kuppen Peter J.K. , Bilchik Anton J. , Tollenaar Rob A.E.M. , Hoon Dave S.B.
Published: October 2007

Purpose

Overexpression of cyclooxygenase-2 (COX-2) in gastric cancer has been shown to enhance tumor progression. We investigated whether silencing by promoter region hypermethylation of the COX-2 gene contributes to disease outcome in gastric cancer.

Materials and Methods

COX-2 methylation status was initially assessed by capillary array electrophoresis methylation–specific polymerase chain reaction (CAE-MSP) and COX-2 protein expression by immunohistochemistry (IHC) in 40 primary gastric cancer tissues in a pilot study. Prognostic end points of correlative studies of COX-2 methylation status were time to recurrence, overall survival, and standard clinicopathologic features. CAE-MSP analysis was then validated in a second independent gastric cancer population (n = 137).

Results

COX-2 methylation was detected in 23% and 28% of the pilot and validation patient groups, respectively. COX-2 expression (IHC) in gastric tumors inversely correlated with COX-2 gene methylation status in the pilot study (P = .02). COX-2 methylation in tumors was significantly associated with lower T, N, and TNM stage in the validation patient group (P = .02, P = .006, and P = .008, respectively). Patients with COX-2 methylated tumors had significantly longer time to recurrence and improved overall survival in a multivariate analysis in the validation patient group (hazard ratio[HR], 0.49; 95% CI, 0.24% to 0.99%; HR, 0.62; 95% CI, 0.38% to 0.99%, respectively).

Conclusion

Hypermethylation of COX-2 gene promoter was identified as an independent prognostic factor in gastric cancer patients. The results suggest promoter hypermethylation to be an important regulatory mechanism of COX-2 expression in gastric cancer and an important prognostic biomarker.
CNS or Bone Marrow Involvement As Risk Factors for Poor Survival in Post-Transplantation Lymphoproliferative Disorders in Children After Solid Organ Transplantation
Authors: Maecker Britta , Jack Thomas , Zimmermann Martin , Abdul-Khaliq Hashim , Burdelski Martin , Fuchs Alexandra , Hoyer Peter , Koepf Sabine , Kraemer Ulrike , Laube Guido F. , Müller-Wiefel Dirk E. , Netz Heinrich , Pohl Martin , Toenshoff Burkhard , Wagner Hans-Joachim , Wallot Michael , Welte Karl , Melter Michael , Offner Gisela , Klein Christoph
Published: October 2007

Purpose

To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation.

Patients and Methods

A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses.

Results

PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year).

Conclusion

Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.
Assessment of Response to Induction Therapy and Its Influence on 5-Year Failure-Free Survival in Group III Rhabdomyosarcoma: The Intergroup Rhabdomyosarcoma Study-IV Experience—A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group
Authors: Burke Megan , Anderson James R. , Kao Simon C. , Rodeberg David , Qualman Stephen J. , Wolden Suzanne L. , Meyer William H. , Breitfeld Philip P.
Published: October 2007

Purpose

Initial response to induction chemotherapy predicts failure-free survival (FFS) in osteosarcoma and Ewing's sarcoma. For Intergroup Rhabdomyosarcoma Study (IRS) IV patients with group III rhabdomyosarcoma, we assessed whether reported response assessed by anatomic imaging at week 8 predicted FFS.

Patients and Methods

We studied 444 group III patients who received induction therapy, had response assessed at week 8 by anatomic imaging, and continued with protocol therapy. Induction chemotherapy was generally followed by radiation therapy (RT) starting after week 9. Response to induction therapy was determined at weeks 0 and 8. Local institutions coded response.

Results

Response rate for the entire cohort at week 8 was 77% (95% CI, 73% to 81%; complete response [CR], 21%; partial response [PR], 56%) but response had no influence on FFS (P = .57). Two hundred seventy-two patients received standard-timing RT at week 9 and thus only chemotherapy during induction. Response rate was 81% (95% CI, 76% to 86%; CR, 22%; PR, 59%). In these patients, response did not influence FFS except for those with alveolar histology. One hundred thirty-two other patients received chemotherapy and RT during induction (up-front RT). Response rate was 65% (95% CI, 57% to 73%; CR, 12%; PR, 53%), but response had no influence on FFS (P = .69). Forty patients received no RT at all (protocol violation) and response to induction therapy had no effect on FFS.

Conclusion

In IRS-IV, response rate to induction therapy was 77% in group III patients, was independent of histology, and had no influence on FFS overall.
Prospective Study of the Correlation Between Postoperative Computed Tomography Scan and Primary Surgeon Assessment in Patients With Advanced Ovarian, Tubal, and Peritoneal Carcinoma Reported to Have Undergone Primary Surgical Cytoreduction to Residual Disease 1 cm or Less
Authors: Chi Dennis S. , Ramirez Pedro T. , Teitcher Jerrold B. , Mironov Svetlana , Sarasohn Debra M. , Iyer Revathy B. , Eisenhauer Eric L. , Abu-Rustum Nadeem R. , Sonoda Yukio , Levine Douglas A. , Brown Carol L. , Aghajanian Carol , Gershenson David M. , Hoskins William J. , Hricak Hedvig , Barakat Richard R.
Published: October 2007

Purpose

To compare surgeons' operative assessments of residual disease (RD) to those identified on postoperative computed tomography (CT) scans in patients with advanced ovarian carcinoma reported to have undergone optimal primary cytoreduction.

Patients and Methods

All patients at one of two institutions, who were scheduled to have primary surgery for presumed advanced ovarian cancer, were asked to consent to a postoperative CT scan if cytoreduction to ≤ 1 cm RD was reported. CT scan findings were graded using a qualitative analysis scale from 1 (normal) to 5 (definitely malignant).

Results

From January 2001 to September 2006, 285 patients were enrolled. A total of 78 patients met eligibility criteria and had postoperative CT scans. In 41 cases (52%), postoperative scan findings correlated with the surgical report of no RD more than 1 cm, and in seven cases (9%), the CT findings were indeterminate. In 10 cases (13%), more than 1 cm RD was noted by the radiologist as probably malignant, and in 20 cases (26%), definitely malignant. In these 30 cases, the radiologically reported median largest residual mass was 1.9 cm (range, 1.1 to 5.1), with RD more than 1 cm reported most commonly in the right upper quadrant (15 patients [50%]) and central abdomen (nine patients [30%]).

Conclusion

There was only a 52% correlation between surgeons' assessments and postoperative CT scan evaluations of RD in patients reported to have undergone optimal cytoreduction. Further study is required to determine whether this lack of correlation is due to rapid interval tumor regrowth, RD underestimated by the surgeons, and/or overestimated by the radiologists; and to determine the clinical implications of these discrepancies.
Phase III Trial of Protracted Compared With Split-Course Chemoradiation for Esophageal Carcinoma: Fédération Francophone de Cancérologie Digestive 9102
Authors: Crehange Gilles , Maingon Philippe , Peignaux Karine , N′guyen Tan Dat , Mirabel Xavier , Marchal Christian , Verrelle Pierre , Roullet Bernard , Bonnetain Franck , Bedenne Laurent
Published: October 2007

Purpose

Chemoradiotherapy (CRT) is an alternative to surgery for resectable locally advanced esophageal carcinoma (RLA-EC). We investigated the heterogeneity of the treatment benefits across subgroups of patients, defined according to the radiation scheme.

Patients and Methods

Between February 1993 and December 2000, 451 patients were enrolled. The following two schemes were allowed: protracted radiotherapy (P-RT), which scheduled 46 Gy over 4.5 weeks or split-course radiotherapy (SC-RT) with two 1-week courses of 15 Gy. Two courses of cisplatin and fluorouracil were delivered concomitantly. In case of exclusive CRT, a further course of 20 Gy over 2 weeks in the P-RT group and one 1-week course of 15 Gy in the SC-RT group were delivered with three courses of chemotherapy. SC-RT and P-RT were administered to 285 patients (64%) and 161 patients (36%), respectively.

Results

For P-RT versus SC-RT, the response rate to induction CRT was 67% v 68%, respectively (P = .09), and 2-year local relapse-free survival rate was 76.7% v 56.8%, respectively (P = .002). Shorter tumor length and P-RT were associated with better local control in multivariate analysis (P = .002 for both). After a median follow-up time of 47.4 months, 2-year overall survival rate was 37.1% for P-RT compared with 30.5% for SC-RT (P = .25). Independent prognostic factors on survival were tumor diameter (P = .02), weight loss of 10% or less (P = .05), and response to induction CRT (P = .002).

Conclusion

Patients with RLA-EC treated with P-RT had better local control than patients treated with SC-RT. Response to induction CRT is a determinant prognostic factor on survival.
Prophylactic Cranial Irradiation in Operable Stage IIIA Non–Small-Cell Lung Cancer Treated With Neoadjuvant Chemoradiotherapy: Results From a German Multicenter Randomized Trial
Authors: Pöttgen Christoph , Eberhardt Wilfried , Grannass Andreas , Korfee Soenke , Stüben Georg , Teschler Helmut , Stamatis Georgios , Wagner Horst , Passlick Bernward , Petersen Volker , Budach Volker , Wilhelm Hans , Wanke Isabel , Hirche Herbert , Wilke Hans-Jochen , Stuschke Martin
Published: October 2007

Purpose

To investigate the role of prophylactic cranial irradiation (PCI) within a trimodality protocol (chemotherapy, chemoradiotherapy, surgery) for patients with operable stage IIIA non–small-cell lung cancer (NSCLC).

Patients and Methods

After mediastinoscopic staging, patients with operable stage IIIA NSCLC were enrolled to a German multicenter trial and randomly assigned to receive either primary resection followed by adjuvant thoracic radiation therapy (50 to 60 Gy; arm A) or preoperative chemotherapy (cisplatin/etoposide [PE]; three cycles) followed by concurrent chemoradiotherapy (PE plus 45 Gy; 1.5 Gy twice per day) and definitive surgery (arm B), respectively. Patients in arm B were scheduled to receive PCI (30 Gy; 2 Gy daily fractions).

Results

One hundred twelve patients were randomly assigned between November 1994 and July 2001. One hundred six patients were eligible (arm A: 51, arm B: 55), 90 males and 16 females, 50 with squamous cell, 16 with large cell, five with adenosquamous, and 35 with adenocarcenoma (median age, 57 years; range, 37 to 71 years). Forty-three patients received PCI as scheduled in arm B. Eleven long-term survivors (arm A: four; arm B: seven) underwent a comprehensive neuropsychological examination. PCI significantly reduced the probability of brain metastases as first site of failure (7.8% at 5 years v 34.7%; P = .02), the overall brain relapse rate was reduced comparably (9.1% at 5 years v 27.2%; P = .04). A slightly reduced neurocognitive performance in comparison with the age-matched normal population was found for patients in both treatment groups. No significant difference between patients who were treated with or without PCI could be noted.

Conclusion

PCI is effective in preventing brain metastases following this aggressive trimodality approach. Neurocognitive late effects are not significantly different between patients treated with or without PCI.
Video-Assisted Thoracic Surgery Lobectomy: Report of CALGB 39802—A Prospective, Multi-Institution Feasibility Study
Authors: Swanson Scott J. , Herndon James E. , D'Amico Thomas A. , Demmy Todd L. , McKenna Robert J. , Green Mark R. , Sugarbaker David J.
Published: October 2007

Purpose

To evaluate the technical feasibility and safety of video-assisted thoracic surgery (VATS) lobectomy for small lung cancers.

Patients and Methods

The Cancer and Leukemia Group B 39802 trial was a prospective, multi-institutional study designed to elucidate the technical feasibility of VATS in early non–small-cell lung cancer (NSCLC) using a standard definition for VATS lobectomy (one 4- to 8-cm access and two 0.5-cm port incisions) that mandated videoscopic guidance and a traditional hilar dissection without rib spreading. Between 1998 and 2001, 128 patients with peripheral lung nodules ≤ 3 cm in size with suspected NSCLC were prospectively registered for VATS lobectomy.

Results

One hundred twenty-seven patients (66 males and 61 females; median age, 66 years; range, 37 to 86 years), with a performance status of 0 (74%) or 1 (26%), underwent surgery. Patients with lymph nodes more than 1 cm by computed tomography scan underwent mediastinal lymph node sampling to rule out N2 disease. One hundred eleven patients (87%) had stage I lung cancer, and 96 (86.5%) of these 111 patients underwent successful VATS lobectomies. The median procedure length was 130 minutes (range, 47 to 428 minutes), and median chest tube duration was 3 days (range, 1 to 14 days). Fifty-eight (60%) of 97 patients underwent diagnostic biopsy at lobectomy. Within 30 days, three (2.7%) of 111 patient deaths occurred, none of which were directly related to VATS technique; seven (7.4%) of 95 patients had grade 3 or greater complications, with only one case of bleeding.

Conclusion

A standardized approach to VATS lobectomy as specifically defined with avoidance of rib spreading is feasible.
Mortality in Acromegaly: A Metaanalysis
Authors: Dekkers O. M. , Biermasz N. R. , Pereira A. M. , Romijn J. A. , Vandenbroucke J. P.
Published: October 2007

Context: Several studies have assessed mortality risk in patients treated for acromegaly. All studies found a mortality that was higher than expected for the general population, but most of these increases were not statistically significant. For this reason, it is not formally established whether mortality in acromegaly is different from the general population.

Objective: The objective of the study was to address the all-cause mortality risk in patients with acromegaly.

Design: The study was a metaanalysis.

Methods: Sixteen studies on mortality in patients with acromegaly were included. The principal outcome of the metaanalysis was the weighted average of the standardized mortality ratio (SMR) of all studies. In addition, we performed a subgroup analysis of studies in which more than 80% of the patients were treated by transsphenoidal approach.

Results: The weighted mean of the SMR from all 16 studies was 1.72 (95% confidence interval 1.62–1.83). In studies with transsphenoidal surgery as the primary therapy, the weighted mean of the SMR was 1.32 (95% confidence interval 1.12–1.56).

Conclusions: This metaanalysis shows increased all-cause mortality in acromegalic patients, compared with the general population, even after transsphenoidal surgery.
Plasma Amino-Terminal Pro C-Type Natriuretic Peptide in the Neonate: Relation to Gestational Age and Postnatal Linear Growth
Authors: Prickett Timothy C. R. , Dixon Bronwyn , Frampton Chris , Yandle Timothy G. , Richards A. Mark , Espiner Eric A. , Darlow Brian A.
Published: October 2007

Context: C-type natriuretic peptide (CNP) plays an essential role in endochondral bone growth. Insight into CNP’s paracrine actions is possible using plasma measurements of the amino-terminal pro C-type natriuretic peptide (NTproCNP). Whether correlations of NTproCNP with linear growth, as found in children and lambs, apply in neonates is unknown.

Objectives: Our objective was to determine the effects of prematurity, gender, and antenatal steroids on plasma NTproCNP at birth, and serial changes in hormone concentrations, linear growth, and markers of bone turnover in the first month of postnatal life.

Design and Setting: This is a prospective study of newborn infants admitted to an intensive care unit.

Subjects: A total of 48 infants (four gestation groups) were enrolled. Umbilical cord samples were also obtained from 39 healthy term infants.

Main Outcome Measures: Plasma NTproCNP and CNP were measured in cord plasma. In enrolled neonates, serial measurements of hormone concentrations and markers of bone turnover were related to tibial growth velocity as measured by knemometry.

Results: Cord plasma NTproCNP was inversely related to gestational age (r = −0.35; P = 0.003) and was higher in males (P < 0.001). Plasma NTproCNP (P = 0.016) and CNP (P < 0.001) increased within the first week of life, the increase relating inversely to gestational age (r = −0.64; P < 0.001). Plasma NTproCNP at 1 wk was strongly correlated with linear growth velocity (r = 0.49; P < 0.001), and also at 2–4 wk, the relation being stronger than observed between bone turnover markers and growth velocity.

Conclusions: In neonates with diverse disorders affecting growth and nutrition, plasma NTproCNP was strongly correlated with linear growth during the first 4 wk of postnatal life and may prove to be a novel marker of growth plate activity in neonates.
Midkine and LDL-receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells
Authors: Chen Sen , Bu Guojun , Takei Yoshifumi , Sakamoto Kazuma , Ikematsu Shinya , Muramatsu Takashi , Kadomatsu Kenji
Published: October 2007

The growth factor midkine (MK) is highly associated with cancer progression. Knockdown of MK expression strikingly suppresses tumor growth in nude mice. Thus, MK is a candidate target for cancer treatment. LDL-receptor-related protein 1 (LRP1) is a receptor for MK. We found that among the four ligand-binding domains of LRP1, the N-terminal half of the second domain (designated as MK-TRAP) had the strongest affinity to MK. MK-TRAP bound to MK, but not to HB-GAM/pleiotrophin, basic fibroblast growth factor or platelet-derived growth factor (PDGF)-BB. Exogenous MK-TRAP inhibited the binding between MK and LRP1. G401 cells that transiently or stably overexpress MK-TRAP showed decreased cell growth in monolayer culture and reduced colony formation in soft agar, which could be rescued by exogenous MK administration. MK-TRAP collected from conditioned medium also inhibited anchorage-independent growth of G401 cells and CMT-93 cells. Anti-MK antibody also inhibited the anchorage-independent growth. CMT-93 cells stably expressing MK-TRAP formed smaller tumors in a xenograft nude mouse model than control cells. Moreover, GST-RAP, a potent inhibitor of LRP1, inhibited the anchorage-independent growth of control G401 cells but not that of MK-TRAP stable transformants. Collectively, these data demonstrate a crucial role of MK-LRP1 signaling in anchorage-independent cell growth.
Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus
Authors: Yang Feng , Camp David G. , Gritsenko Marina A. , Luo Quanzhou , Kelly Ryan T. , Clauss Therese R. W. , Brinkley William R. , Smith Richard D. , Stenoien David L.
Published: October 2007

The chromosomal passenger complex (CPC) is a crucial regulator of chromosome, cytoskeleton and membrane dynamics during mitosis. Here, using liquid chromatography coupled to mass spectrometry (LC-MS), we identified phosphopeptides and phosphoprotein complexes recognized by a phosphorylation-specific antibody that labels the CPC. A mitotic phosphorylation motif {PX[G/T/S][L/M]S(P) P or WGLS(P) P} was identified by MS in 11 proteins, including FZR1 (Cdh1) and RIC8A–two proteins with potential links to the CPC. Phosphoprotein complexes contained the known CPC components INCENP, Aurora-B (Aurkb) and TD-60 (Rcc2, RCC1-like), as well as SMAD2, 14-3-3 proteins, PP2A and Cdk1 (Cdc2a), a probable kinase for this motif. Protein sequence analysis identified phosphorylation motifs in additional proteins, including SMAD2, PLK3 and INCENP. Mitotic SMAD2 and PLK3 phosphorylation was confirmed using phosphorylation-specific antibodies, and, in the case of Plk3, phosphorylation correlated with its localization to the mitotic apparatus and the midbody. A mutagenesis approach was used to show that INCENP phosphorylation is required for its localization to the midbody. These results provide evidence for a shared phosphorylation event that regulates localization of crucial proteins during mitosis.
Storage-Space Capacitated Inventory System with (r, Q) Policies
Authors: Zhao Xiaobo , Fan Fan , Liu Xiaoliang , Xie Jinxing
Published: October 2007

We deal with an inventory system with limited storage space for a single item or multiple items. For the single-item system, customers' demand is stochastic. The inventory is controlled by a continuous-review (r, Q) policy. Goods are replenished to the inventory system with a constant lead time. An optimization problem with a storage-space constraint is formulated for computing a single-item (r, Q) policy that minimizes the long-run average system cost. Based on some existing results in the single-item (r, Q) policy without a storage-space constraint in the literature, useful structural properties of the optimization problem are attained. An efficient algorithm with polynomial time computational complexity is then proposed for obtaining the optimal solutions. For the multi-item system, each item possesses its particular customers' demand that is stochastic, its own (r, Q) policy that controls the inventory, and its individual lead time that is constant. An important issue in such inventory systems is the allocation of the storage space to the items and the values of r and Q for each item. We formulate an optimization problem with a storage-space constraint for multi-item (r, Q) policies. Based on the results in the single-item (r, Q) policy with a storage-space constraint, we find useful structural properties of the optimization problem. An efficient algorithm with polynomial time computational complexity is then proposed for obtaining undominated solutions.
Resolution Branch and Bound and an Application: The Maximum Weighted Stable Set Problem
Authors: Avenali Alessandro
Published: October 2007

We propose a new resolution algorithm, called resolution branch and bound (RBB), where a branch-and-bound scheme is empowered by exploiting the information contained in a family of closed subproblems, collected by a full resolution phase. In particular, we use this information to define a new branching rule that seems able to reduce the risk of incurring inappropriate branchings. We apply RBB and the proposed branching rule to the maximum weighted stable set problem, as its features allow us to speed up a time-consuming step in the full resolution phase. To compute upper bounds, we generalize to the weighted case the polynomial time procedure provided by Mannino and Sassano [Mannino, C., A. Sassano. 1994. An exact algorithm for the maximum stable set problem. Computational Optim. Appl. 3 243–258] for the unweighted case. Computational results validate the effectiveness of the provided branching rule and the good performance of RBB on many DIMACS benchmarks.
A New Dantzig-Wolfe Reformulation and Branch-and-Price Algorithm for the Capacitated Lot-Sizing Problem with Setup Times
Authors: Degraeve Zeger , Jans Raf
Published: October 2007

Although the textbook Dantzig-Wolfe decomposition reformulation for the capacitated lot-sizing problem, as already proposed by Manne [Manne, A. S. 1958. Programming of economic lot sizes. Management Sci. 4(2) 115–135], provides a strong lower bound, it also has an important structural deficiency. Imposing integrality constraints on the columns in the master program will not necessarily give the optimal integer programming solution. Manne's model contains only production plans that satisfy the Wagner-Whitin property, and it is well known that the optimal solution to a capacitated lot-sizing problem will not necessarily satisfy this property. The first contribution of this paper answers the following question, unsolved for almost 50 years: If Manne's formulation is not equivalent to the original problem, what is then a correct reformulation? We develop an equivalent mixed-integer programming (MIP) formulation to the original problem and show how this results from applying the Dantzig-Wolfe decomposition to the original MIP formulation. The set of extreme points of the lot-size polytope that are needed for this MIP Dantzig-Wolfe reformulation is much larger than the set of dominant plans used by Manne. We further show how the integrality restrictions on the original setup variables translate into integrality restrictions on the new master variables by separating the setup and production decisions. Our new formulation gives the same lower bound as Manne's reformulation. Second, we develop a branch-and-price algorithm for the problem. Computational experiments are presented on data sets available from the literature. Column generation is accelerated by a combination of simplex and subgradient optimization for finding the dual prices. The results show that branch-and-price is computationally tractable and competitive with other state-of-the-art approaches found in the literature.
Risk Aversion in Inventory Management
Authors: Chen Xin , Sim Melvyn , Simchi-Levi David , Sun Peng
Published: October 2007

Traditional inventory models focus on risk-neutral decision makers, i.e., characterizing replenishment strategies that maximize expected total profit, or equivalently, minimize expected total cost over a planning horizon. In this paper, we propose a framework for incorporating risk aversion in multiperiod inventory models as well as multiperiod models that coordinate inventory and pricing strategies. We show that the structure of the optimal policy for a decision maker with exponential utility functions is almost identical to the structure of the optimal risk-neutral inventory (and pricing) policies. These structural results are extended to models in which the decision maker has access to a (partially) complete financial market and can hedge its operational risk through trading financial securities. Computational results demonstrate that the optimal policy is relatively insensitive to small changes in the decision-maker's level of risk aversion.
Using EPECs to Model Bilevel Games in Restructured Electricity Markets with Locational Prices
Authors: Hu Xinmin , Ralph Daniel
Published: October 2007

We study a bilevel noncooperative game-theoretic model of restructured electricity markets, with locational marginal prices. Each player in this game faces a bilevel optimization problem that we model as a mathematical program with equilibrium constraints (MPEC). The corresponding game is an example of an equilibrium program with equilibrium constraints (EPEC). We establish sufficient conditions for the existence of pure-strategy Nash equilibria for this class of bilevel games and give some applications. We show by examples the effect of network transmission limits, i.e., congestion, on the existence of equilibria. Then we study, for more general equilibrium programs with equilibrium constraints, the weaker pure-strategy concepts of local Nash and Nash stationary equilibria. We pose the latter as solutions of complementarity problems (CPs) and show their equivalence with the former in some cases. Finally, we present numerical examples of methods that attempt to find local Nash equilibria or Nash stationary points of randomly generated electricity market games.
Balancing Terrorism and Natural Disasters—Defensive Strategy with Endogenous Attacker Effort
Authors: Zhuang Jun , Bier Vicki M.
Published: October 2007

In this paper, we apply game theory to identify equilibrium strategies for both attacker and defender in a fully endogenous model of resource allocation for countering terrorism and natural disasters. The key features of our model include balancing protection from terrorism and natural disasters, and describing the attacker choice by a continuous level of effort rather than a discrete choice (i.e., attack or not). Interestingly, in a sequential game, increased defensive investment can lead an attacker to either increase his level of effort (to help compensate for the reduced probability of damage from an attack), or decrease his level of effort (because attacking has become less profitable). This can either reduce or increase the effectiveness of investments in protection from intentional attack, and can therefore affect the relative desirability of investing in protection from natural disasters.
Minimizing the Worst Slowdown: Offline, Online
Authors: Moulin Hervé
Published: October 2007

We look for protocols (service disciplines) setting an upper bound on the slowdown (expected sojourn time divided by job size) a job may face, irrespective of the processing times of other jobs. We call this worst slowdown the liability of a job. In a scheduling problem with identical release dates, allowing the server to randomize the order of service cuts almost in half the liability profiles feasible under deterministic protocols. The same is true if cash transfers are feasible and users have linear waiting costs. When release times are arbitrary, we characterize liability functions implementable by a deterministic online protocol, where the liability depends on the number of jobs in the queue upon release of the job. In an M/D/1 queue with a given arrival rate, the liability of a job is at least its slowdown when all other jobs are of the same size. We conjecture that this liability is feasible online, and identify a probabilistic protocol exceeding it by at most 130%.
A Comparison of the Optimal Costs of Two Canonical Inventory Systems
Authors: Janakiraman Ganesh , Seshadri Sridhar , Shanthikumar J. George
Published: October 2007

We compare two inventory systems, one in which excess demand is lost and the other in which excess demand is backordered. Both systems are reviewed periodically. They experience the same sequence of identically and independently distributed random demands. Holding and shortage costs are considered. The holding cost parameter is identical; however, the cost of a lost sale could be different from the per-period cost of backlogging a unit sale. When these costs are equal, we prove that the optimal expected cost for managing the system with lost sales is lower. When the cost of a lost sale is greater, we establish a relationship between these parameters that ensures that the reverse inequality is true. These results are useful for designing inventory systems. We also introduce a new stochastic comparison technique in this paper.
Book Reviews
Authors: Frey Mattias , de Seife Ethan
Published: October 2007

Screening the Past: Memory and Nostalgia in Cinema, Pam Cook (2005) London, New York: Routledge, 224 pp., ISBN: 0415183758, paperback, 17.99, 31.95

Dudley Murphy: Hollywood Wild Card, Susan Delson, (2006) Minneapolis: University of Min-nesota Press, 272 pp., ISBN 0816646546 (hbk),
27.95
Increased serum S100B protein in chronic schizophrenic patients in Korea
Authors: Ryoun Kim Hye , Kyung Lee Mi , Park Doo-Byung
Published: October 2007

No Abstract available
The systemic inflammatory response syndrome C-reactive protein and transthyretin conundrum
Authors: Bernstein Larry H.
Published: October 2007

No Abstract available
Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons via PKCε: A Novel Pathway for Heat Hyperalgesia
Authors: Zhang Hua , Cang Chun-Lei , Kawasaki Yasuhiko , Liang Ling-Li , Zhang Yu-Qiu , Ji Ru-Rong , Zhao Zhi-Qi
Published: October 2007

The neuropeptide substance P (SP) is expressed in unmyelinated primary sensory neurons and represents the best known “pain” neurotransmitter. It is generally believed that SP regulates pain transmission and sensitization by acting on neurokinin-1 receptor (NK-1), which is expressed in postsynaptic dorsal horn neurons. However, the expression and role of NK-1 in primary sensory neurons are not clearly characterized. Our data showed that NK-1 was expressed in both intact and dissociated dorsal root ganglion (DRG) neurons. In particular, NK-1 was mainly coexpressed with the capsaicin receptor TRPV1 (transient receptor potential vanilloid subtype 1), a critical receptor for the generation of heat hyperalgesia. NK-1 agonist [Sar9, Met(O2)11]–substance P (Sar-SP) significantly potentiated capsaicin-induced currents and increase of [Ca2+]iin dissociated DRG neurons. NK-1 antagonist blocked not only the potentiation of TRPV1 currents but also heat hyperalgesia induced by intraplantar Sar-SP. NK-1 antagonist also inhibited capsaicin-induced spontaneous pain, and this inhibition was enhanced after inflammation. To analyze intracellular cross talking of NK-1 and TRPV1, we examined downstream signal pathways of G-protein-coupled NK-1 activation. Sar-SP-induced potentiation of TRPV1 was blocked by inhibition of G-protein, PLCβ (phospholipase C-β), or PKC but not by inhibition of PKA (protein kinase A). In particular, PKCε inhibitor completely blocked both Sar-SP-induced TRPV1 potentiation and heat hyperalgesia. Sar-SP also induced membrane translocation of PKCε in a portion of small DRG neurons. These results reveal a novel mechanism of NK-1 in primary sensory neurons via a possible autocrine and paracrine action of SP. Activation of NK-1 in these neurons induces heat hyperalgesia via PKCε-mediated potentiation of TRPV1.
Different Effects of Voluntary and Involuntary Attention on EEG Activity in the Gamma Band
Authors: Landau Ayelet N. , Esterman Michael , Robertson Lynn C. , Bentin Shlomo , Prinzmetal William
Published: October 2007

Previous studies have shown that EEG activity in the gamma range can be modulated by attention. Here, we compared this activity for voluntary and involuntary spatial attention in a spatial-cueing paradigm with faces as targets. The stimuli and trial timing were kept constant across attention conditions with only the predictive value of the cue changing. Gamma-band response was linked to voluntary shifts of attention, but not to the involuntary capture of attention. The presence of increased gamma responses for the voluntary allocation of attention, and its absence in cases of involuntary capture suggests that the neural mechanisms governing these two types of attention are different. Moreover, these data allow a description of the temporal dynamics contributing to the dissociation between voluntary and involuntary attention. The distribution of this correlate of voluntary attention is consistent with a top-down process involving contralateral anterior and posterior regions.