bluuebunny/crossref_metadata_2025 huggingface dataset:
The activity of French Research Ethics Committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study
Authors: Decullier Evelyne , Lhéritier Véronique , Chapuis François
Published: October 2005

Background

Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis.

Methods

Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives.

Results

Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14–17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25–53) and 37 (95% CI: 27–46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise.

Conclusion

The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees.
A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease
Authors: Van der Auwera Ingrid , Wera Stefaan , Van Leuven Fred , Henderson Samuel T
Published: October 2005

Background

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ) deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD.

Results

Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I) were fed either, a standard diet (SD) composed of high carbohydrate/low fat chow, or a ketogenic diet (KD) composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM), compared to SD fed animals (0.29 ± 0.06 mM). In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067). In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures.

Conclusion

Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.
A computational investigation of kinetoplastid trans-splicing
Authors: Gopal Shuba , Awadalla Saria , Gaasterland Terry , Cross George AM
Published: October 2005

Trans-splicing is an unusual process in which two separate RNA strands are spliced together to yield a mature mRNA. We present a novel computational approach which has an overall accuracy of 82% and can predict 92% of known trans-splicing sites. We have applied our method to chromosomes 1 and 3 of Leishmania major, with high-confidence predictions for 85% and 88% of annotated genes respectively. We suggest some extensions of our method to other systems.
Quality of Life and Sexual Functioning in Cervical Cancer Survivors
Authors: Frumovitz Michael , Sun Charlotte C. , Schover Leslie R. , Munsell Mark F. , Jhingran Anuja , Wharton J. Taylor , Eifel Patricia , Bevers Therese B. , Levenback Charles F. , Gershenson David M. , Bodurka Diane C.
Published: October 2005

Purpose

To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy.

Methods

Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer.

Results

One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures.

Conclusion

Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.
Breast Cancer Risk Following Bilateral Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: An International Case-Control Study
Authors: Eisen Andrea , Lubinski Jan , Klijn Jan , Moller Pal , Lynch Henry T. , Offit Kenneth , Weber Barbara , Rebbeck Tim , Neuhausen Susan L. , Ghadirian Parviz , Foulkes William D. , Gershoni-Baruch Ruth , Friedman Eitan , Rennert Gadi , Wagner Teresa , Isaacs Claudine , Kim-Sing Charmaine , Ainsworth Peter , Sun Ping , Narod Steven A.
Published: October 2005

Purpose

The purpose of this study was to estimate the extent of protection offered against breast cancer by prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations and to determine to what extent risk reduction varies with age at oophorectomy, age at diagnosis, and time elapsed since surgery.

Patients and Methods

We analyzed 1,439 patients with breast cancer and 1,866 matched controls derived from a registry of BRCA1 and BRCA2 carriers. We estimated odds ratios (ORs) of breast cancer for having had a bilateral oophorectomy, using conditional logistic regression, matched for parity and for oral contraceptive use.

Results

A previous history of oophorectomy was associated with a significant reduction in breast cancer risk of 56% for BRCA1 carriers (OR = 0.44; 95% CI, 0.29 to 0.66) and of 46% for BRCA2 carriers (OR = 0.57; 95% CI, 0.28 to 1.15). The risk reduction was greater if the oophorectomy was performed before age 40 (OR = 0.36; 95% CI, 0.20 to 0.64 for BRCA1 carriers) than after age 40 (OR = 0.53; 95% CI, 0.30 to 0.91). The protective effect was evident for 15 years post-oophorectomy (OR = 0.39; 95% CI, 0.26 to 0.57).

Conclusion

Oophorectomy is an effective means of reducing the risk of breast cancer in carriers of BRCA1 mutations. The data suggest oophorectomy is protective in BRCA2 carriers as well, but needs to be confirmed in other studies.
Rhabdoid Tumor of the Kidney in The National Wilms' Tumor Study: Age at Diagnosis As a Prognostic Factor
Authors: Tomlinson Gail E. , Breslow Norman E. , Dome Jeffrey , Guthrie Katherine Adams , Norkool Pat , Li Sierra , Thomas Patrick R.M. , Perlman Elizabeth , Beckwith J. Bruce , D'Angio Giulio J. , Green Daniel M.
Published: October 2005

Purpose

The objective of this study is to determine prognostic factors in rhabdoid tumor of the kidney (RTK), including both demographic and treatment variables.

Patients and Methods

A total of 142 patients studied on National Wilms' Tumor Studies 1, 2, 3, 4, and 5 were analyzed. Patients were enrolled between the years 1969 and 2002. Variables examined included sex, age of diagnosis, tumor stage, presence of CNS lesions, as well as treatment variables, including the use of doxorubicin and/or radiotherapy (RT).

Results

No survival differences were observed between males and females, between those treated with or without doxorubicin, or with or without RT. Patients with tumors of lower stage had an overall survival rate of 41.8%, whereas, tumors of higher stage were associated with a 15.9% survival (P < .001). A highly significant difference in survival was noted when patients were stratified according to age of diagnosis. Survival at 4 years in infants under 6 months of age at diagnosis was 8.8%, whereas, survival in patients 2 years of age or older was 41.1% (P < .0001). Stratification into intermediate age brackets demonstrated a strong correlation of increasing survival with increasing age at diagnosis. All patients with a CNS lesion, except one, died.

Conclusion

Age at diagnosis is a highly significant prognostic factor for survival of children with RTK. Infants have a dismal prognosis, whereas, older children have a more favorable outcome. Higher tumor stage and presence of a CNS lesion were both factors predictive of a poor survival rate.
Improved Detection of Second Primary Cancer Using Integrated [18F] Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography for Initial Tumor Staging
Authors: Choi Joon Young , Lee Kyung Soo , Kwon O. Jung , Shim Young Mog , Baek Chung-Hwan , Park Keunchil , Lee Kyung-Han , Kim Byung-Tae
Published: October 2005

Purpose

This study evaluated prospectively the value of integrated whole-body positron emission tomography and computed tomography (PET/CT) using [18F] fluorodeoxyglucose (FDG) in detecting a second primary cancer at the time of the initial staging in comparison with a conventional staging work-up (CSW).

Methods

The participants were 547 patients diagnosed with cancer who underwent FDG PET/CT imaging for the initial staging. An additional diagnostic evaluation was performed when there were abnormal findings indicative of a second primary cancer on either PET/CT or CSW considering the site and the biologic behavior of the alleged primary tumor.

Results

A total of 27 second primary malignant tumors were identified in 26 of the 547 patients (4.8%). FDG PET/CT found 45 lesions indicative of a second primary cancer, of which 24 lesions were proved to be a second primary cancer, seven were clinically unexpected metastases, and 14 lesions were benign. Therefore, sensitivity and positive predictive value of FDG PET/CT in detecting a second primary cancer or an unexpected metastasis were 91% (31 of 34) and 69% (31 of 45), respectively. In contrast, CSW could not identify 16 second primary cancers and one metastatic lesion.

Conclusion

FDG PET/CT at the time of the initial staging is useful for screening a second primary cancer with a high sensitivity. An additional diagnostic work-up is essential when abnormal findings, which are indicative of a second primary cancer, are obtained on PET/CT images to rule out the presence of either a second primary cancer or an unexpected metastasis.
Validation of a Postresection Pancreatic Adenocarcinoma Nomogram for Disease-Specific Survival
Authors: Ferrone Cristina R. , Kattan Michael W. , Tomlinson James S. , Thayer Sarah P. , Brennan Murray F. , Warshaw Andrew L.
Published: October 2005

Purpose

Nomograms are statistically based tools that provide the overall probability of a specific outcome. They have shown better individual discrimination than the current TNM staging system in numerous patient tumor models. The pancreatic nomogram combines individual clinicopathologic and operative data to predict disease-specific survival at 1, 2, and 3 years from initial resection. A single US institution database was used to test the validity of the pancreatic adenocarcinoma nomogram established at Memorial Sloan-Kettering Cancer Center.

Patients and Methods

The nomogram was created from a prospective pancreatic adenocarcinoma database that included 555 consecutive patients between October 1983 and April 2000. The nomogram was validated by an external patient cohort from a retrospective pancreatic adenocarcinoma database at Massachusetts General Hospital that included 424 consecutive patients between January 1985 and December 2003.

Results

Of the 424 patients, 375 had all variables documented. At last follow-up, 99 patients were alive, with a median follow-up time of 27 months (range, 2 to 151 months). The 1-, 2-, and 3-year disease-specific survival rates were 68% (95% CI, 63% to 72%), 39% (95% CI, 34% to 44%), and 27% (95% CI, 23% to 32%), respectively. The nomogram concordance index was 0.62 compared with 0.59 with the American Joint Committee on Cancer (AJCC) stage (P = .004). This suggests that the nomogram discriminates disease-specific survival better than the AJCC staging system.

Conclusion

The pancreatic cancer nomogram provides more accurate survival predictions than the AJCC staging system when applied to an external patient cohort. The nomogram may aid in more accurately counseling patients and in better stratifying patients for clinical trials and molecular tumor analysis.
Phase I Study of O6-Benzylguanine and Temozolomide Administered Daily for 5 Days to Pediatric Patients With Solid Tumors
Authors: Warren Katherine E. , Aikin Alberta A. , Libucha Madeleine , Widemann Brigitte C. , Fox Elizabeth , Packer Roger J. , Balis Frank M.
Published: October 2005

Purpose

This pediatric phase I trial of O6-benzylguanine (O6BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O6BG and to define the toxicity profile of the combination in children with solid tumors.

Patients and Methods

Patients ≤ 21 years old with refractory solid tumors were eligible. O6BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O6BG infusion. Starting doses of O6BG and TMZ were 60 mg/m2/d and 28 mg/m2/d, respectively. O6BG was escalated to 90 and 120 mg/m2/d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m2/d. Cycles were repeated every 28 days.

Results

Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O6BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m2/d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m2/d of TMZ combined with 120 mg/m2/d O6BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/m2/d O6BG combined with TMZ doses of 55 mg/m2/d and above.

Conclusion

The recommended doses of O6BG administered with TMZ on a 5-day schedule in children are 120 mg/m2/d of O6BG and 75 mg/m2/d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT.
Pegylated Arginine Deiminase Treatment of Patients With Metastatic Melanoma: Results From Phase I and II Studies
Authors: Ascierto Paolo A. , Scala Stefania , Castello Giuseppe , Daponte Antonio , Simeone Ester , Ottaiano Alessandro , Beneduce Gerardo , De Rosa Vincenzo , Izzo Francesco , Melucci Maria Teresa , Ensor C. Mark , Prestayko Archie W. , Holtsberg Frederick W. , Bomalaski John S. , Clark Mike A. , Savaraj Niramol , Feun Lynn G. , Logan Theodore F.
Published: October 2005

Purpose

Individuals with metastatic melanoma have a poor prognosis. Many human melanomas are auxotrophic for arginine, and arginine is not an essential amino acid in humans. We hypothesized that this auxotrophy may be therapeutically exploited. A novel amino acid–degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma.

Patients and Methods

Two cohort dose-escalation studies were performed. A phase I study in the United States enrolled 15 patients, and a phase I to II study in Italy enrolled 24 patients. The Italian patients also received two subsequent cycles of treatment, each consisting of four once-weekly injections of 160 U/m2. The goals of these studies were to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and the antitumor activity of ADI-SS PEG 20,000 mw.

Results

PK and PD studies indicated that a dose of 160 U/m2lowered plasma arginine from a resting level of approximately 130 μmol/L to less than 2 μmol/L for at least 7 days; nitric oxide levels also were lowered. There were no grade 3 or 4 toxicities directly attributable to the drug. Six of 24 phase I to II patients responded to treatment (five partial responses and one complete response; 25% response rate) and also had prolonged survival.

Conclusion

Elimination of all detectable plasma arginine in patients with metastatic melanoma was well tolerated and may be effective in the treatment of this cancer. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with metastatic melanoma is warranted.
Multifocal and Multicentric Breast Cancer: Does Each Focus Matter?
Authors: Coombs Nathan J. , Boyages John
Published: October 2005

Purpose

The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer.

Methods

The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity.

Results

Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas.

Conclusion

The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.
New Treatment Options Have Changed the Survival of Patients With Follicular Lymphoma
Authors: Fisher Richard I. , LeBlanc Michael , Press Oliver W. , Maloney David G. , Unger Joseph M. , Miller Thomas P.
Published: October 2005

Background

The natural history of follicular lymphoma is believed not to have changed over the last 30 years. Median survivals have ranged from 7 to 10 years, and the disease is considered incurable. However, multiple new treatment options have been developed in the last decade, and their impact on survival of follicular lymphoma remains unknown.

Patients and Methods

In the current analysis, we identified all previously untreated, advanced-stage, follicular lymphoma patients treated with the following three sequential treatment approaches: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy ± nonspecific immunostimulants (Southwest Oncology Group [SWOG] 7426 and 7713: 1974 to 1983); prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide (ProMACE) plus mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) ± interferon (SWOG 8809: 1988 to 1994); and CHOP followed by monoclonal antibody (MoAb) therapy (SWOG 9800 and 9911: 1998 to 2000). We assessed the patients' progression-free survival (PFS) and overall survival (OS). The MoAb trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by 131I-tositumomab (SWOG 9911).

Results

The PFS curves for the CHOP and ProMACE-MOPP studies are overlapping, with 4-year PFS estimates of 46% and 48%, respectively. However, the PFS rate of the CHOP + MoAb studies is significantly improved at 61% (P = .005). The OS curves show improvement with each succeeding study. The 4-year estimate of OS is 69% for the CHOP regimens, 79% for the ProMACE-MOPP study, and 91% for the CHOP + MoAb regimens (P < .001). These conclusions were retained after adjusting for differences in prognostic factors between the study groups.

Conclusion

The results of this study suggest that OS for patients with follicular lymphoma has improved over time and that the choice of initial therapy may matter.
Oxaliplatin, Fluorouracil, and Leucovorin for Patients With Unresectable Liver-Only Metastases From Colorectal Cancer: A North Central Cancer Treatment Group Phase II Study
Authors: Alberts Steven R. , Horvath William L. , Sternfeld William C. , Goldberg Richard M. , Mahoney Michelle R. , Dakhil Shaker R. , Levitt Ralph , Rowland Kendrith , Nair Suresh , Sargent Daniel J. , Donohue John H.
Published: October 2005

Purpose

Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied.

Patients and Methods

Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate.

Results

Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months.

Conclusion

Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.
Secondary Amenorrhea After Hodgkin’s Lymphoma Is Influenced by Age at Treatment, Stage of Disease, Chemotherapy Regimen, and the Use of Oral Contraceptives During Therapy: A Report From the German Hodgkin’s Lymphoma Study Group
Authors: Behringer Karolin , Breuer Kai , Reineke Thorsten , May Michael , Nogova Lucia , Klimm Beate , Schmitz Tatiana , Wildt Ludwig , Diehl Volker , Engert Andreas
Published: October 2005

Purpose

Long-term survivors of successfully treated Hodgkin’s lymphoma (HL) are at risk for late complications. Among these, infertility for female patients is of major importance. The subject of this analysis is to evaluate the menstrual status after HL therapy.

Patients and Methods

From 1994 to 1998, the German Hodgkin’s Lymphoma Study Group conducted clinical trials for early-, intermediate-, and advanced-stage HL (trials HD7 to HD9) involving a total of 3,186 patients. A survey was carried out to evaluate the menstrual status after therapy. The following factors were assessed concerning their influence on amenorrhea: age, treatment, stage, and the use of oral contraceptives during chemotherapy.

Results

A total of 405 women aged younger than 40 years answered the study questions. After a median follow-up of 3.2 years, 51.4% of the women receiving eight cycles of dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) had continuous amenorrhea. Amenorrhea was significantly more frequent after dose-escalated BEACOPP compared with doxorubicin, bleomycin, vinblastine, and dacarbazine; cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine; or standard BEACOPP (P = .0066). Amenorrhea after therapy was most pronounced in women with advanced-stage HL (P < .0001), in women older than 30 years at treatment (P = .0065), and in women who did not take oral contraceptives during chemotherapy (P = .0002).

Conclusion

Most women who are treated for advanced-stage HL experience amenorrhea after therapy. Amenorrhea is significantly more frequent in women with advanced-stage HL receiving eight cycles of dose-escalated BEACOPP and in women older than 30 years at first treatment. Furthermore, the data show a statistical association between the use of oral contraceptives and return of menstrual cycle, which is subject to further investigation.
Biology of Progesterone Receptor Loss in Breast Cancer and Its Implications for Endocrine Therapy
Authors: Cui Xiaojiang , Schiff Rachel , Arpino Grazia , Osborne C. Kent , Lee Adrian V.
Published: October 2005

The response to endocrine therapy in breast cancer correlates with estrogen receptor (ER) and progesterone receptor (PR) status. ER-positive/PR-negative breast cancers respond less well to selective ER modulator (SERM) therapy than ER-positive/PR-positive tumors. The predictive value of PR has long been attributed to the dependence of PR expression on ER activity, with the absence of PR reflecting a nonfunctional ER and resistance to hormonal therapy. However, recent clinical and laboratory evidence suggests that ER-positive/PR-negative breast cancers may be specifically resistant to SERMs, whereas they may be less resistant to estrogen withdrawal therapy with aromatase inhibitors, which is a result inconsistent with the nonfunctional ER theory. Novel alternative molecular mechanisms potentially explaining SERM resistance in ER-positive/PR-negative tumors have been suggested by recent experimental indications that growth factors may downregulate PR levels. Thus, the absence of PR may not simply indicate a lack of ER activity, but rather may reflect hyperactive cross talk between ER and growth factor signaling pathways that downregulate PR even as they activate other ER functions. Therefore, ER-positive/PR-negative breast tumors might best be treated by completely blocking ER action via estrogen withdrawal with aromatase inhibitors, by targeted ER degradation, or by combined therapy targeting both ER and growth factor signaling pathways. In this review, we will discuss the biology and etiology of ER-positive/PR-negative breast cancer, highlighting recent data on molecular cross talk between ER and growth factor signaling pathways and demonstrating how PR might be a useful marker of these activities. Finally, we will consider the clinical implications of these observations.
Multiagent Chemotherapy and Deferred Radiotherapy in Infants With Malignant Brain Tumors: A Report From the Children’s Cancer Group
Authors: Geyer J. Russell , Sposto Richard , Jennings Mark , Boyett James M. , Axtell Richard A. , Breiger David , Broxson Emmett , Donahue Bernadine , Finlay Jonathan L. , Goldwein Joel W. , Heier Linda A. , Johnson Dennis , Mazewski Claire , Miller Douglas C. , Packer Roger , Puccetti Diane , Radcliffe Jerilynn , Tao May Lin , Shiminski-Maher Tania
Published: October 2005

Purpose

To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis.

Patients and Methods

Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed.

Results

Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% ± 3%, and the survival rate was 43% ± 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% ± 5%, 17% ± 6%, and 32% ± 6%, and 14% ± 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy.

Conclusion

Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.
Binuclear complexes as tectons in designing supramolecular solid-state architectures
Authors: Andruh Marius
Published: October 2005

Oligonuclear complexes as well as coordination polymers with various network topologies can be obtained by using homo- or heterobinuclear complexes as starting materials. These building blocks are stable complexes, where the metal ions are held together by compartmental ligands, or alkoxo-bridged Cu(II) species. The binuclear nodes can be connected through appropriate exo-dentate ligands, or through metal-containing anions (e.g., [M(CN)6]3-, M = CrIII, FeIII, CoIII). A rich variety of 3d-3d and 3d-4f heterometallic complexes, with interesting architectures and topologies of the spin carriers, has been obtained. A particular case is the one concerning the 3d-4f binuclear nodes. Following this strategy, we were able to obtain coordination polymers containing three different spin carriers (2p-3d-4f; 3d-3d'-4f).
Photodegradation of pesticides and application of bioanalytical methods for their detection
Authors: Franko Mladen , Sarakha Mohamed , Čibej Anja , Boškin Aleš , Bavcon Mojca , Trebše Polonca
Published: October 2005

Photodegradation of coumaphos and azinphos-methyl in the air, in oxygen, and in nitrogen atmosphere (quartz reactor equipped with six 18-W lamps with the maximum emission intensity at 310 nm) was studied. The fastest reaction occurred with coumaphos in nitrogen atmosphere (complete decomposition in 10 min), where the formation of a new compound was also detected by high-performance liquid chromatography (HPLC). In the case of azinphos-methyl, no additional signals in HPLC chromatogram were observed. The rearrangement mechanism, involving a triplet-state activation complex and the formation of an acetylcholinesterase (AChE)-inhibiting oxo analog of coumaphos was verified and confirmed by laser flash photolysis.

The suitability of bioanalytical flow-injection analysis (FIA) systems, based on AChE inhibition and spectrophotometric or thermal lens spectrometric detection for rapid and sensitive screening in food quality control was demonstrated. Owing to the high sensitivity of thermal lens spectrometry (TLS), several steps in sample preparation can be avoided (preconcentration, purification, isolation) and incubation times reduced. High sample throughputs (10 h-1) are, however, also achievable for medium toxic oxo organophosphorus (OP) pesticides using spectrophotometric detection providing limits of detection (LODs) at the level of 10 ppb malaoxon equivalents, which is still about 50 times below maximal residue levels. Testing of the method for practical application on a set of 60 samples gave no false negative results and a level of 1.7 % false positives.
Hazardous industrial waste stabilization using inorganic phosphates: Investigation of possible mechanisms
Authors: Ioannidis Themistoklis A. , Zouboulis Anastasios I.
Published: October 2005

The present study focuses on the use of phosphate-containing compounds, such as apatites, as stabilization additives for solid industrial wastes. The examined highly toxic waste contained mainly lead, iron, and bromides. Phosphates (synthetic or natural), when used as additives, were found to diminish the release of lead from the stabilized waste below the respective legislative concentration limits, following the application of DIN 38414 standard leaching method and within the range of pH values 7.5-10.5. The respective synthetic compounds of lead, PbO and Pb(OH)Br, existing also in the solid waste, were additionally studied during simulation experiments, in order to examine the possible mechanisms of waste stabilization, by using the same additives (phosphates). The obtained results showed the possibility of another parallel mechanism, different from that proposed in the literature, which is the sorption of aqueous lead ions onto the apatite surface. It was suggested that lead can be also transformed into the less soluble solid phases through the interaction (surface crystallization) of exposed lead surface with the aqueous environment. The formation of new crystals onto the surface of lead phase was sufficiently fast, especially in the case of natural phosphate mineral additive, most probably due to the presence of calcite, which supplies part of its carbonate content for the formation of respective lead carbonate solid phases.
Notes toward a Queer History of Naturalization
Authors: Somerville Siobhan B
Published: October 2005

Studies of sexuality and U.S. citizenship have offered rich and transformative insights about the ways in which ideologies of the nation both shape and are shaped by questions of sexuality. But existing scholarship has less frequently and consistently attended to the ways that the state itself might be understood as sexualized. This article begins to trace a queer history of the formal mechanisms that the state uses to produce new citizens by focusing on the earliest federal law on naturalization, passed in 1790, as well as contemporaneous commentaries on immigration and acquired citizenship in the early national period.
I argue that we should be more skeptical of the distinction typically drawn between birthright citizenship and naturalization Ð ascriptive vs. consensual. Instead, I show how the opposition between the two models actually serves to mask the ways that both birthright citizenship and naturalization have historically been embedded within (hetero)sexualized understandings of production. Rather than breaking with a model of citizenship based on bloodline, the very language of naturalization has been encumbered with assumptions about a reproductive subject, and so tends to reinforce the model of an organic, sexually reproduced citizenry. Despite its potential to make good on the liberal promise of consent, even naturalization cannot escape a logic of belonging that depends upon the transmission of citizenship through biological reproduction. This is not simply because legislation has tended to instantiate exclusionary ideologies of identity (race, gender, class, sexual orientation) that have "spoiled" the liberal promise of citizenship in the U.S., but also, and perhaps more stubbornly, because this blood logic is embedded within the very metaphors through which such a form of producing citizenship is imagined.
Remembering the USS Chesapeake : The Politics of Maritime Death and Impressment
Authors: Cray Robert E
Published: October 2005

The bombardment of the USS Chesapeake by the HMS Leopard on June 22, 1807, outraged citizens of the young republic. Not only had three sailors been killed and eighteen more wounded, but the British had forcibly removed four other men that they claimed belonged to them. Angry Americans condemned the incident, demanded satisfaction, and prepared for war. Although the crisis abated, diplomatic negotiations failed to resolve the issue until late 1811, and the surviving sailors were not returned until the start of the War of 1812. How Americans recalled the Chesapeake disaster has never been satisfactory examined. The episode was, to be sure, a diplomatic cause celebre, suggesting that the U.S. flag afforded no protection against a British navy intent upon impressment. Yet the memory of the incident also reveals the contours and limits of American compassion toward sailors. If mariners received praise for economic contributions and wartime heroism, they nonetheless attracted suspicion when ashore. While concerned about issues of trade and neutral rights, Americans proved less interested in protecting and retrieving sailors seized by the British. The four impressed men from the ChesapeakeÐJenkin Ratford, David Martin, John Strachan, and William WareÐillustrate this social phenomenon. If Ratford received publicity because of his 1807 execution, the other three men, two of whom were persons of color, generally remained unnamed and ignored, not unlike other impressed sailors. As such, the Chesapeake episode illuminates American ambivalence toward the sailors of the young republic. Class and race rendered sailors anonymous in the public memory.
The Details of Desire: From Dolores on the Dotted Line to Dotted Dolores
Authors: Bouchet Marie
Published: October 2005

Lolita is an ambiguous object of desire, whose "twofold nature," halfway between woman and child, constantly escapes Humbert's attempts to "fix once for all the perilous magic of nymphets." Trying to fix the unfixable in words, Humbert develops different strategies to articulate his desire. Unable to provide a complete and stable picture of his beloved, he relies highly on metonymy, rehearsing body fragments and playing on ellipses. The nymphet's body is even semiotized, as Humbert repeatedly focuses on signs, markings inscribed onto her flesh. These signs dot her body and establish it as a text in an utterly original manner: Lolita and Lolita are indeed the same.
Today's Children, Tomorrow's Leaders: Are We Neglecting the Agents of Change?
Authors: HaileMariam Assegedetch
Published: October 2005

There is an abundant body of knowledge suggesting that early experience influences later human behavior. Based on the literature, this article suggests that human development at the individual level has far-reaching consequences for the social, economic, and political development of a people. For instance, education, one measure of human development, has been inaccessible to more than 50 percent of school age children in Ethiopia. To effect fundamental change in Ethiopia, attention and resources must be dedicated to children's well-being and potential. The article also discusses the role that current environmental conditions may play in the development of learned helplessness in Ethiopian children. Because of the country's limited resources, nonformal education that taps traditional Ethiopian resources for fostering children's development is proposed.
Beyond EBM: new directions for evidence-based public health
Authors: McGuire Wendy L
Published: October 2005

Public health researchers, policy makers, and practitioners agree that health is the outcome of interactions between biological, behavioral, and social determinants. Nonetheless, institutional patterns of research funding and practice remain obstacles to generating research at and between each of these levels. These practices are embedded in historic assumptions about the nature of reality and how it can best be understood. Current debates over the criteria for evaluating public health research have centered on the applicability of the clinical evidence-based medicine (EBM) model to the field of public health. The EBM hierarchy, which is based on traditional scientific assumptions about causality, is insufficient and potentially harmful as the basis for evaluating research on the determinants of health. Yet those who have put forward a critique of EBM have failed to develop a plausible alternative. Critical realism, based on the philosophy of Roy Bhaskar, may provide a way out of the current stalemate, enabling public health researchers from various disciplines and research paradigms to work together, bringing the full weight of scientific knowledge to bear on increasingly complex and global public health problems.
Evidence-Based Alternative Medicine?
Authors: Borgerson Kirstin
Published: October 2005

The validity of evidence-based medicine (EBM) is the subject of ongoing controversy. The EBM movement has proposed a "hierarchy of evidence," according to which randomized controlled trials (RCTs) and meta-analyses of RCTs provide the most reliable evidence concerning the efficacy of medical interventions. The evaluation of alternative medicine therapies highlights problems with the EBM hierarchy. Alternative medical researchers—like those in mainstream medicine—wish to evaluate their therapies using methods that are rigorous and that are consistent with their philosophies of medicine and healing. These investigators have three ways to relate their work to EBM. They can accept the EBM hierarchy and carry out RCTs when possible; they can accept the EBM standards but argue that the special characteristics of alternative medicine warrant the acceptance of "lower" forms of evidence; or they can challenge the EBM approach and work to develop new research designs and new standards of evidence that reflect their approach to medical care. For several reasons, this last option is preferable. First, it will best meet the needs of alternative medicine practitioners. Moreover, because similar problems beset the evaluation of mainstream medical therapies, reevaluation of standards of evidence will benefit everyone in the medical community—including, most importantly, patients.
Looking for Rules in a World of Exceptions: reflections on evidence-based practice
Authors: Upshur Ross
Published: October 2005

After more than a decade, evidence-based medicine (EBM) is well established as an important influence in health care. EBM has engendered a wide range of responses from near-evangelical fervor to angered rejection, with supporters convinced of its scientific superiority and detractors of its needless reductionism. EBM is not a philosophical doctrine, and its originators and proponents have, for the most part, ignored critics and foresworn theorizing. However, EBM claims to be a normative guide to being a better physician. The theoretical, practical, and philosophical dimensions of EBM are intimately intertwined. This essay is a sustained reflection on the issues raised by EBM as experienced by a clinician/teacher who has tried to apply the tenets of EBM in clinical care and teaching over the past decade, and who has sought to expand the borders of EBM from a philosophical point of view.
Fellow Traveler: The Cinematic-Political Consciousness of Judd Ne'eman
Authors: Ben-Shaul Nitzan S
Published: October 2005

The peculiar trajectory followed by Ne'eman in his post-1977 political films reveals the characteristics of the political consciousness of a large group of Israeli artists, academics, and left-oriented activists. Their passive political resentment at the Israeli occupation of the West Bank and Gaza strip that followed the 1967 War took a radical shift following the political overturn in the 1977 elections, which brought to power the right-wing Likud party, leading the group to politicize Israeli culture and to denounce the Israeli occupation and the repression of the Palestinian people. However, this altruistic stand was based upon a dead-end, pessimistic, and ultimately ethnocentric viewpoint. We find in the films of Ne'eman and other Israeli filmmakers after 1977 a contradiction between an explicit moral critique of Israeli politics and the aesthetic grounding of this critique within a cinematic reality of persecution and hopelessness. Ne'eman, however, in his last film, Streets of Yesterday, brings to light the conflict submerged in his prior films and in all the films produced by the group. Having revealed the futility of the group's political consciousness Ne'eman abandoned his cinematic political activism in favor of research and teaching.
Blind Space: Roadblock Movies in the Contemporary Israeli Film
Authors: Zanger Anat
Published: October 2005

The border is a special space that is neither "ours" nor "theirs" but, rather, a third, "in-between" space. In this paper I examine the ways in which the checkpoints are situated along the Israeli borders and scrutinize the function of the movie camera vis-à-vis these checkpoints. A reading of four contemporary Israeli recent films, Ben-Gurion (Gr'aad & Levenberg, 1997), Borders (Riklis & Kaydar, 2001) Close, Closed, Closure (Levi, 2002) and Checkpoints (Shamir, 2003), allows me to expose the transition sites at different places along the border during the last few years. Tracing the border spatiality, I will examine the performative dimension (Butler) that replaced the dialogic one (Martin Buber) between the authorities in the position of control and the subordinated transients that pass under the watchful eye of that control. Through the camera, these sites of transition in films are exposed as heterogeneous meeting points, located in the indeterminate space between surveillance, prejudices, and fears.
Marketing Trauma and the Theatre of War in Northern Uganda
Authors: Edmondson Laura
Published: October 2005

This essay explores the ways in which theatre and performance are used to market trauma and humanitarianism in northern Uganda, where a civil war has been waging between the Lord's Resistance Army (LRA) and the Ugandan government since the late 1980s. Specifically, the article focuses on the dynamics of performance in a rehabilitation center for former child soldiers sponsored by World Vision. I draw upon my observations and personal experiences at the center to suggest that drama is valued primarily as a marketing tool to reach international and national audiences. In addressing specific variations upon the narrative of war, however, I find that theoretical frameworks of globalization and marketing do not satisfactorily explain the fierce investment in a linear story and the trappings of realism. The final section argues that former LRA captives use indigenous dances to carve out a space in which cultural memory and globalization intersect.