bluuebunny/crossref_metadata_2025 huggingface dataset:
Etoposide and Cisplatin Chemotherapy for Metastatic Good-Risk Germ Cell Tumors
Authors: Kondagunta G. Varuni , Bacik Jennifer , Bajorin Dean , Dobrzynski Deborah , Sheinfeld Joel , Motzer Robert J. , Bosl George J.
Published: December 2005

Purpose

To assess response, overall survival, and relapse-free survival of patients with good-risk metastatic germ cell tumor (GCT) by International Germ Cell Consensus Classification Group (IGCCCG) criteria treated with four cycles of etoposide and cisplatin (EP).

Patients and Methods

Two hundred eighty-nine patients with IGCCCG good-risk GCT were treated with four cycles of EP. EP consisted of four cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 to 5 every 21 days.

Results

Two hundred eighty-two of 289 patients (98%) achieved a complete response; 269 (93%) responded to chemotherapy alone and 13 (5%) responded to chemotherapy plus surgical resection of viable disease (GCT other than mature teratoma). Seventeen (6%) experienced relapse, and nine (3%) died as a result of disease at a median follow-up of 7.7 years (range, 0.4 to 21.1 years). Sixty-two of 204 patients (30%) with nonseminoma had findings of teratoma or viable GCT at postchemotherapy surgery.

Conclusion

Four cycles of EP is a highly effective therapy for patients with good-risk GCT, with a high cure rate, low relapse rate, and little evidence of late relapse. Postchemotherapy surgery resection of residual disease remains an important aspect of treatment for these patients. Four cycles of EP is acceptable as a standard regimen for the treatment of good-risk metastatic GCT, and serves as an alternative to three cycles of bleomycin and etoposide before cisplatin.
MYC Amplification and Polysomy 8 in Chondrosarcoma: Array Comparative Genomic Hybridization, Fluorescent In Situ Hybridization, and Association With Outcome
Authors: Morrison Carl , Radmacher Michael , Mohammed Nehad , Suster David , Auer Herbert , Jones Susie , Riggenbach Judy , Kelbick Nicole , Bos Gary , Mayerson Joel
Published: December 2005

Purpose

To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion.

Materials and Methods

Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation.

Results

Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance.

Conclusion

MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.
Should Elderly Non–Small-Cell Lung Cancer Patients Be Offered Elderly-Specific Trials? Results of a Pooled Analysis From the North Central Cancer Treatment Group
Authors: Jatoi Aminah , Hillman Shauna , Stella Philip , Green Erin , Adjei Alex , Nair Suresh , Perez Edith , Amin Bipinkur , Schild Steven E. , Castillo Rene , Jett James R.
Published: December 2005

Purpose

To answer the question, “should elderly non–small-cell lung cancer patients be offered elderly-specific trials?”

Patients and Methods

The North Central Cancer Treatment Group (NCCTG) performed a pooled analysis of elderly patients who participated in elderly-specific trials (required age ≥ 65 years) and age-unspecified trials (required age ≥ 18 years). Between 1998 and 2000, all NCCTG non–small-cell lung cancer (NSCLC) patients with incurable cancer, age ≥ 65 years, and receiving first-line chemotherapy were included. A total of 118 elderly patients participated in elderly-specific trials, and 108, in age-unspecified trials. Demographics and outcomes were compared based on trial type.

Results

The median age of elderly patients in elderly-specific trials was greater: median (range): 73 years (65 to 87) and 70 years (65 to 85), respectively (P < .001), as was the percentage older than 80 years: 17% and 3%, respectively (P = .0008). Median survival times were 232 and 302 days, respectively (P = .08). After adjustment for baseline age, Eastern Cooperative Oncology Group performance score, cancer stage, and body mass index, this survival difference was not statistically significant (hazard ratio = 1.25; P = .16). Grade 3 or worse nonhematologic adverse event rates were greater in age-unspecified trials (81% v 57%, respectively; P < .001), as were grade 3 or worse hematologic events (68% v 10%, respectively; P < .001).

Conclusion

Elderly patients in NSCLC elderly-specific trials suffered lower rates of severe adverse events with no statistically significant differences in survival. It seems that elderly-specific trials are providing quality care and helping to define optimal cancer therapy in the elderly, particularly among the “oldest of the old.”
Individualized Survival Curves Improve Satisfaction With Cancer Risk Management Decisions in Women With BRCA1/2 Mutations
Authors: Armstrong Katrina , Weber Barbara , Ubel Peter A. , Peters Nikki , Holmes John , Schwartz J. Sanford
Published: December 2005

Purpose

Women with BRCA1/2 mutations are faced with complex decisions about breast and ovarian cancer risk management. This study was conducted to determine the effect of a tailored decision support system (DSS) that provides individualized survival and cancer incidence curves specific to expected outcomes of alternative management strategies.

Patients and Methods

This was a double-blind, randomized controlled trial of 32 women with BRCA1/2 mutations. Primary outcome measures were decision satisfaction, cancer anxiety, perceptions of cancer risk given alternative management strategies, and management decisions.

Results

Twenty-seven women completed a 6-week follow-up. Women in the intervention arm (n = 13) reported significantly higher decision satisfaction at follow-up than women in the control arm (n = 14; adjusted mean difference, 9.7; P < .0005). The effect of the DSS was greater among women with low cancer anxiety at baseline than women with high cancer anxiety at baseline (P = .01 for interaction). However, the DSS did not significantly alter cancer anxiety at follow-up, perceptions of cancer risk given alternative management strategies, or management decisions.

Conclusion

The presentation of individualized survival and incidence curves for alternative management options improves satisfaction about cancer risk management decisions among women with BRCA1/2 mutations without increasing anxiety or changing management decisions. The benefit of the DSS is greatest among women with relatively low cancer-related anxiety at baseline.
TGFβ-mediated FGF signaling is crucial for regulating cranial neural crest cell proliferation during frontal bone development
Authors: Sasaki Tomoyo , Ito Yoshihiro , Bringas Pablo , Chou Stanley , Urata Mark M. , Slavkin Harold , Chai Yang
Published: December 2005

The murine frontal bone derives entirely from the cranial neural crest(CNC) and consists of the calvarial (lateral) aspect that covers the frontal lobe of brain and the orbital aspect that forms the roof of bony orbit. TGFβ and FGF signaling have important regulatory roles in postnatal calvarial development. Our previous study has demonstrated that conditional inactivation of Tgfbr2 in the neural crest results in severe defects in calvarial development, although the cellular and molecular mechanisms by which TGFβ signaling regulates the fate of CNC cells during frontal bone development remain unknown. Here, we show that TGFβ IIR is required for proliferation of osteoprogenitor cells in the CNC-derived frontal bone anlagen. FGF acts downstream of TGFβ signaling in regulating CNC cell proliferation, and exogenous FGF2 rescues the cell proliferation defect in the frontal primordium of Tgfbr2 mutant. Furthermore, the CNC-derived frontal primordium requires TGFβ IIR to undergo terminal differentiation. However, this requirement is restricted to the developing calvarial aspect of the frontal bone, whereas the orbital aspect forms despite the ablation of Tgfbr2 gene, implying a differential requirement for TGFβsignaling during the development of various regions of the frontal bone. This study demonstrates the biological significance of TGFβ-mediated FGF signaling cascade in regulating frontal bone development, suggests that TGFβ functions as a morphogen in regulating the fate of the CNC-derived osteoblast and provides a model for investigating abnormal craniofacial development.
The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo
Authors: Chen Canhe , Ware Stephanie M. , Sato Akira , Houston-Hawkins Dianne E. , Habas Raymond , Matzuk Martin M. , Shen Michael M. , Brown Chester W.
Published: December 2005

The formation of the anterior visceral endoderm (AVE) in the pre-gastrulation mouse embryo represents a crucial event in patterning of the anterior-posterior axis. Here, we show that the transforming growth factorβ (Tgfβ) family member Gdf3 (growth-differentiation factor 3), a close relative of Xenopus Vg1, resembles the Tgfβ ligand Nodal in both its signaling activity and its role in AVE formation in vivo. Thus, in cell culture, Gdf3 signaling requires the EGF-CFC co-receptor Cripto and can be inhibited by Lefty antagonists. In Xenopus embryos, Gdf3 misexpression results in secondary axis formation, and induces morphogenetic elongation and mesendoderm formation in animal caps. In mouse embryos, Gdf3 is expressed in the inner cell mass and epiblast, and null mutants frequently exhibit abnormal formation or positioning of the AVE. This phenotype correlates with defects in mesoderm and definitive endoderm formation, as well as abnormal Nodal expression levels. Our findings indicate that Gdf3 acts in a Nodal-like signaling pathway in pre-gastrulation development, and provide evidence for the functional conservation of Vg1 activity in mice.
The Effect of Payoff Feedback and Information Pooling on Reasoning Errors: Evidence from Experimental Markets
Authors: Budescu David V. , Maciejovsky Boris
Published: December 2005

A vast literature shows that individuals frequently violate normative principles in reasoning. In this paper, we report the results of four studies designed to determine if information dissemination in competitive auctions can reduce, or even eliminate, logical errors in the Wason selection task. Our results show that payoff feedback and exposure to the information flow drive the aggregate behavior toward the normative solution. We also found evidence of spillover effects from informed to uninformed traders in one-sided combinatorial auctions, as well as positive transfer effects from competitive to individual settings.
The Effects of Imprecise Probabilities and Outcomes in Evaluating Investment Options
Authors: Du Ning , Budescu David V.
Published: December 2005

Vagueness attitudes have been used to explain anomalies and irregularities in investment behavior. It is generally assumed (Ellsberg 1961) that decision makers (DMs) dislike vagueness, but this assumption has been challenged by empirical results documenting systematic alternative attitudes to vagueness as a function of its source, the domain of the decisions, and the response mode used. We investigate these three factors in a within-subjects design that was embedded in an investment context. DMs evaluated investment options that varied in terms of their sources of vagueness (probabilities and/or outcomes), in both domains (gains or losses), and employed two response modes (pricing or choice). We confirm that individuals’ vagueness attitudes are malleable, contingent on the dimension salience and the reference domain. In particular, we observed three distinct patterns of “reversals of attitudes” towards vagueness. Our results indicate that the ability of vagueness attitudes to predict investment behavior is limited, as decisions can be systematically influenced by task context and/or perceived gain or loss positions. Economic models may be improved by incorporating more flexible assumptions about individuals’ attitudes toward vagueness.
Investment Decisions and Time Horizon: Risk Perception and Risk Behavior in Repeated Gambles
Authors: Klos Alexander , Weber Elke U. , Weber Martin
Published: December 2005

To investigate the effect of time horizon on investment behavior, this paper reports the results of an experiment in which business graduate students provided certainty equivalents and judged various dimensions of the outcome distribution of simple gambles that were played either once or repeatedly for 5 or 50 times. Systematic mistakes in the ex-ante estimations of the distributions of outcomes after (independent) repeated plays were observed. Despite correctly realizing that outcome standard deviation increases with the number of plays, respondents showed evidence of Samuelson’s (1963) fallacy of large numbers. Perceived risk judgments showed only low correlations with standard deviation estimates, but were instead related to the anticipated probability of a loss (which was overestimated), mean excess loss, and the coefficient of variation. Implications for future research and practical implications for financial advisors are discussed.
The Effect of Asymmetric Bidder Size on an Auction’s Performance: Are More Bidders Always Better?
Authors: Elmaghraby Wedad
Published: December 2005

One commonly held belief in designing auctions is that increasing the number of bidders makes an auction more competitive. Therefore, a buyer who wishes to minimize her procurement costs is better off inviting more suppliers to participate. In this paper, we question the validity of this belief by shedding light on bidders’ behavior when bidders experience economies of scale in production and differ in their production capacity. We consider a setting with two different sized bidders, global and small. We assume that global bidders have a large production capacity (can win in more than one auction) and experience economies of scale in production, whereas small bidders can win in at most one auction. In this new setting, we focus on the impact of allowing both global and small suppliers to compete against each other on the performance of an auction.
Better, Faster, Cheaper: An Experimental Analysis of a Multiattribute Reverse Auction Mechanism with Restricted Information Feedback
Authors: Chen-Ritzo Ching-Hua , Harrison Terry P. , Kwasnica Anthony M. , Thomas Douglas J.
Published: December 2005

The majority of reverse auctions for procurement use a single-attribute (price) format while providing constraints on nonprice attributes such as quality and lead time. Alternatively, a buyer could choose to conduct a multiattribute auction where bidders can specify both a price and levels of nonprice attributes. While such an auction may provide higher theoretical utility to the buyer, it is not clear that this theoretical improvement will be realized given the increased complexity of the auction. In this research, we present an ascending auction mechanism for a buyer whose utility function is known and dependent on three attributes. Motivated by a supply chain procurement problem setting, we consider quality and lead time for the two attributes in addition to price. The auction mechanism provides the bidders with restricted feedback regarding the buyer’s utility function. We explore, experimentally, the performance of this multiattribute auction mechanism as compared to a price-only auction mechanism. Compared with the price-only auction, we find that our mechanism design is effective in increasing both buyer utility and bidder (supplier) profits.
The Effects of Financial Risks on Inventory Policy
Authors: Berling Peter , Rosling Kaj
Published: December 2005

The effect of financial risks on (R, Q) inventory policies is analyzed in a real options framework. Simple adjustments of the usual formulas for R and Q are suggested and tested. Stochastic demand and purchase costs are considered, both with known systematic (business-cycle-related) risk.

The systematic risk of stochastic demand has typically a negligible effect on the optimal values of R and Q, although an improvement may be achieved by a simple adjustment of R.

The systematic risk of the purchase price, c, has a significant effect on R and Q. The capital holding cost should be estimated as r · c, where r is the sum of the risk-free interest rate, the expected price decrease, and the risk premium associated with the systematic risk of c.

For goods quoted on commodity exchanges, r may be estimated directly from the prices on forward contracts. Its size (and sign) varies considerably for different commodities.
Limb alignment in computer-assisted minimally-invasive unicompartmental knee replacement
Authors: Keene G. , Simpson D. , Kalairajah Y.
Published: December 2005

Twenty patients underwent simultaneous bilateral medial unicompartmental knee arthroplasty. Pre-operative hip-knee-ankle alignment and valgus stress radiographs were used to plan the desired post-operative alignment of the limb in accordance with established principles for unicompartmental arthroplasty. In each patient the planned alignment was the same for both knees. Overall, the mean planned post-operative alignment was to 2.3° of varus (0° to 5°).

The side and starting order of surgery were randomised, using conventional instrumentation for one knee and computer-assisted surgery for the opposite side.

The mean variation between the pre-operative plan and the achieved correction in the navigated and the non-navigated limb was 0.9° (sd 1.1; 0° to 4°) and 2.8° (sd 1.4; 1° to 7°), respectively. Using the Wilcoxon signed rank test, we found the difference in variation statistically significant (p < 0.001).

Assessment of lower limb alignment in the non-navigated group revealed that 12 (60%) were within ± 2° of the pre-operative plan, compared to 17 (87%) of the navigated cases.

Computer-assisted surgery significantly improves the post-operative alignment of medial unicompartmental knee arthroplasty compared to conventional techniques in patients undergoing bilateral simultaneous arthroplasty. Improved alignment after arthroplasty is associated with better function and increased longevity.
CT analysis of defects of the cement mantle and alignment of the stem
Authors: Scheerlinck T. , de Mey J. , Deklerck R. , Noble P. C.
Published: December 2005

Using a modern cementing technique, we implanted 22 stereolithographic polymeric replicas of the Charnley-Kerboul stem in 11 pairs of human cadaver femora. On one side, the replicas were cemented line-to-line with the largest broach. On the other, one-size undersized replicas were used (radial difference, 0.89 mm sd 0.13).

CT analysis showed that the line-to-line stems without distal centralisers were at least as well aligned and centered as undersized stems with a centraliser, but were surrounded by less cement and presented more areas of thin (< 2 mm) or deficient (< 1 mm) cement. These areas were located predominantly at the corners and in the middle and distal thirds of the stem. Nevertheless, in line-to-line stems, penetration of cement into cancellous bone resulted in a mean thickness of cement of 3.1 mm (sd 0.6) and only 6.2% of deficient and 26.4% of thin cement. In over 90% of these areas, the cement was directly supported by cortical bone or cortical bone with less than 1 mm of cancellous bone interposed.

When Charnley-Kerboul stems are cemented line-to-line, good clinical results are observed because cement-deficient areas are limited and are frequently supported by cortical bone.
GDC's review of the dental specialist lists
Authors: Mulcahy Mike
Published: December 2005

In January 2004 the education committee of the General Dental Council (GDC) established the Specialist Lists Review Group. In dentistry the concept of a specialist not necessarily becoming a consultant is well established. A whole cadre of specialists exists outside the hospital setting.

The entry and exit of training is quality assured by the Faculty of Dental Surgery (FDS), through the requirement to possess MFDS for entry and through various examinations acting as markers of successful completion of training.
Hospital at Night and the surgical middle grade: An Observational Study from a District General Hospital
Authors: Aspinall SR , Bradburn DM , Mills SJ
Published: December 2005

The cumulative effect of Calmanisation, the New Deal, the European Working Time Directive (EWTD) and the Jaeger and SiMAP rulings has been to reduce trainees' exposure to emergency surgery. The Hospital at Night project has been designed to create a generic team of doctors to maximise the number of doctors available for any task by removing boundaries between teams. This project is currently being piloted in a number of centres around the country, including Wansbeck General Hospital (WGH) a 323-bed district general hospital (DGH) serving a population of 240,000 in Northumberland.
Cancellation of elective surgery – any improvement after ten years?
Authors: Griffin XL , Griffin DR , Berry AR , Hunter DC
Published: December 2005

Cancellation of elective operations represents a waste of resources and a poor standard of service to patients who may already have spent several months on a waiting list. The purpose of this study was to determine the extent of the problem in a typical district general hospital, how it has changed over a period of ten years and whether alterations in resource management in the admission process have led to improvements in service.
The Postgraduate Medical Education and Training Board: a personal view
Authors: Neal David
Published: December 2005

The Postgraduate Medical Education and Training Board (PMETB) is the new official regulator of postgraduate medical education. It aims to be innovative, to improve quality and to work in a collaborative way with the royal colleges, postgraduate deans and others. PMETB intends to introduce some flexibility in curricula and will be asking colleges and specialist advisory committees (SACs) to look at ways of supporting academic surgical careers. PMETB is an opportunity for the colleges to test and introduce innovative ways of assessing competencies in the workplace.
The Specialist Library for Surgery, Theatres and Anaesthesia: An Update
Authors: Homer Kate
Published: December 2005

The web watch article in the June 2005 issue of the Bulletin outlined the background to the specialist library project and introduced the project team and the potential roles of the stakeholders and topic advisers. Since then a great deal has been achieved and this article summarises the major milestones and presents the latest work plan.
Preparing the country for another major terrorist event
Authors: Lloyd David , Yates David , Coats Tim
Published: December 2005

The explosions in London on 7 July 2005 led to scenes of human and structural devastation not experienced since the second world war. The blast injuries that predominated were outside the experience of most contemporary emergency workers. Nevertheless, the general impression is that the response by the various emergency services seems to have been well organised and effective. However, there will no doubt also be lessons to be learned for the future.

This successful response can be attributed to the level of disaster preparedness that has been developed in London (as in other parts of the country) following previous terrorist attacks and transport accidents; in addition, in the case of the emergency care of the injured there was the availability of medical expertise and facilities.
A surgeon, but not as we know it…
Authors: Freudmann Matt
Published: December 2005

This month Matt Freudmann, the BOTA president writes an update on how the Modernising Medical Careers (MMC) proposals are progressing. A few months ago we were being assured that the Certificate of Completion of Training would be no different from the Certificate of Completion of Specialist Training in terms of standards and eligibility for posts. The new MMC structure for progression would appear to be far more subtle and complex than a simple 'run-through' now, with more avenues out of programmes into service posts. Mr Freudmann is nervous…
The future of surgical research in the age of MMC
Authors: Mundy Tony
Published: December 2005

Although it would be nice to believe that all surgical research is conducted by individuals dedicated to the academic ideal, in reality many trainees go into research in order to make themselves more competitive when applying for a national training number (NTN). Undoubtedly, many of these people enjoy the research they do and benefit from it but many lose their interest when an NTN has been secured. This is a tremendous waste of resources which could otherwise be made available for those who truly wish to pursue research.
Metal-catalyzed routes to rings, chains, and macromolecules based on inorganic elements
Authors: Bartole-Scott Alexandra , Jaska Cory A. , Manners Ian
Published: December 2005

In this perspective article, some of our recent work directed at the development of new catalytic routes to rings, chains, and macromolecules based on main group and transition elements will be discussed.
Synthesis, structure, and chemistry of selenium-containing four-membered rings
Authors: Block Eric , Dikarev Evgeny V. , Jin Jin , Li Bo , Petrukhina Marina A. , Zhang Shao-Zhong
Published: December 2005

Recent chemistry of four-membered ring selenium compounds is reviewed followed by a summary of work in our laboratories in this area. 2-Thia-6-selenaspiro[3.3]heptane has been synthesized for the first time. X-ray structures for the latter compound as well as for 2,6-dithiaspiro[3.3]heptane and 2,6-diselenaspiro[3.3]heptane have been determined. These compounds are useful as "rigid-rod" ligands for coordination to transition-metal complexes.
Oxacycle synthesis via radical cyclization of β-alkoxyacrylates
Authors: Lee Eun
Published: December 2005

Oxolane and oxane units in oxacyclic natural products were prepared via radical cyclization reaction of β-alkoxyacrylates, β-alkoxymethacrylates, and β-alkoxyvinyl ketones.
New Territories for Anthropologists
Authors: DAGG ANNE INNIS
Published: December 2005

Genetic Nature/Culture: Anthropology and Science beyond the Two‐Culture Divide. Alan H. Goodman, Deborah Heath, M. Susan Lindee, eds. Berkeley: University of California Press, 2003. 328 pp.

Evolution's Rainbow: Diversity, Gender, and Sexuality in Nature and People. Joan Roughgarden. Berkeley: University of California Press, 2004. 474 pp.
Yali's Question: Sugar, Culture, and History
Authors: SCAGLION RICHARD
Published: December 2005

Yali's Question: Sugar, Culture, and History. Frederick Errington and Deborah Gewertz. Chicago: University of Chicago Press, 2004. 319 pp.
Migration, Modernity and Social Transformation in South Asia
Authors: LEONARD KAREN
Published: December 2005

Migration, Modernity and Social Transformation in South Asia. Filippo Osella and Katy Gardner, eds. Thousand Oaks, CA: Sage Publications, 2004. 380 pp.
Violence in War and Peace: An Anthology
Authors: STRATHERN ANDREW , STEWART PAMELA J.
Published: December 2005

Violence in War and Peace: An Anthology. Nancy Scheper‐Hughes and Philippe Bourgois, eds. Malden, MA: Blackwell Publishers, 2004. 496 pp.
Musqueam Reference Grammar
Authors: THOM BRIAN
Published: December 2005

Musqueam Reference Grammar. Wayne Suttles. Vancouver: University of British Columbia Press, 2004. 632 pp.
Areca-Nut Abuse and Neonatal Withdrawal Syndrome
Authors: López-Vilchez Maria Angeles , Seidel Veronica , Farré MagÍ , García-Algar Oscár , Pichini Simona , Mur Antonio
Published: December 2005

Areca-nut chewing occurs widely in South Asia and the Indian subcontinent. Here we present a case of neonatal withdrawal syndrome in an infant born to a woman who was a chronic areca-nut user. Arecoline, the principal neuroactive alkaloid in areca nuts, was found in the mother's placenta.
Relationship of Surgical Approach to Neurodevelopmental Outcomes in Hypoplastic Left Heart Syndrome
Authors: Mahle William T. , Visconti Karen J. , Freier M. Catherin , Kanne Stephen M. , Hamilton William G. , Sharkey Angela M. , Chinnock Richard E. , Jenkins Kathy J. , Isquith Peter K. , Burns Thomas G. , Jenkins Pamela C.
Published: December 2005

OBJECTIVE. Two strategies for surgical management are used for infants with hypoplastic left heart syndrome (HLHS), primary heart transplantation and the Norwood procedure. We sought to determine how these 2 surgical approaches influence neurodevelopmental outcomes at school age.

METHODS. A multicenter, cross-sectional study of neurodevelopmental outcomes among school-aged children (>8 years of age) with HLHS was undertaken between July 2003 and September 2004. Four centers enrolled 48 subjects, of whom 47 completed neuropsychologic testing. Twenty-six subjects (55%) had undergone the Norwood procedure and 21 (45%) had undergone transplantation, with an intention-to-treat analysis. The mean age at testing was 12.4 ± 2.5 years. Evaluations included the Wechsler Abbreviated Scale of Intelligence, Clinical Evaluation of Language Fundamentals, Wechsler Individual Achievement Test, and Beery-Buktenica Developmental Test of Visual-Motor Integration.

RESULTS. The mean neurocognitive test results were significantly below population normative values. The mean full-scale IQ for the entire cohort was 86 ± 14. In a multivariate model, there was no association of surgical strategy with any measure of developmental outcome. A longer hospital stay, however, was associated significantly with lower verbal, performance, and full-scale IQ scores. Aortic valve atresia was associated with lower math achievement test scores.

CONCLUSIONS. Neurodevelopmental deficits are prevalent among school-aged children with HLHS, regardless of surgical approach. Complications that result in prolonged hospitalization at the time of the initial operation are associated with neurodevelopmental status at school age.
Comparison of White Sucker Age Estimates from Scales, Pectoral Fin Rays, and Otoliths
Authors: Sylvester Ryan M. , Berry Charles R.
Published: December 2005

The ages of 229 white suckers Catostomus commersonii from six drainages in the upper Missouri River basin were estimated from scales, pectoral fin ray sections, and lapilli otolith sections to evaluate the potential bias of age estimates between structures. Age estimates were compared by calculating the coefficient of variation, average percent error, percent agreement, and percent agreement within 1 year, as well as by constructing age bias plots. Overall, the relative precision of age estimates from pectoral fin rays and otoliths was higher than that of age estimates from scales and otoliths, but neither pair differed in precision from scales and fin rays. The relative precision of age estimates between pairs of structures was variable both within and among drainages, and few trends could be detected. The percent agreement between structures ranged from 50.0% to 93.8% among drainages, but 9 of 18 pairs had agreement rates greater than 70.0%. Percent agreement within 1 year was greater than 85.0% for all pairs of structures in all drainages. Age estimates from scales underestimated the age estimates from pectoral fin rays and otoliths beyond age 3, while pectoral fin rays only slightly underestimated ages from otoliths of fish older than age 6. We recommend sectioned lapilli otoliths for estimating the age of white suckers, especially if mature individuals are present in the population and lethal collection techniques are allowed. Pectoral fin ray sections are the best nonlethal structure for estimating the age of white suckers but may underestimate the ages of fish older than 5 years. Scales remain suitable for estimating the ages of immature fish, but their use is not recommended for mature fish. This information will allow fisheries managers and researchers to select the most appropriate structure for use in future age assessment studies of white suckers and other catostomid species.
Predicting Crappie Recruitment in Ohio Reservoirs with Spawning Stock Size, Larval Density, and Chlorophyll Concentrations
Authors: Bunnell David B. , Hale R. Scott , Vanni Michael J. , Stein Roy A.
Published: December 2005

Stock–recruit models typically use only spawning stock size as a predictor of recruitment to a fishery. In this paper, however, we used spawning stock size as well as larval density and key environmental variables to predict recruitment of white crappies Pomoxis annularis and black crappies P. nigromaculatus, a genus notorious for variable recruitment. We sampled adults and recruits from 11 Ohio reservoirs and larvae from 9 reservoirs during 1998–2001. We sampled chlorophyll as an index of reservoir productivity and obtained daily estimates of water elevation to determine the impact of hydrology on recruitment. Akaike's information criterion (AIC) revealed that Ricker and Beverton–Holt stock–recruit models that included chlorophyll best explained the variation in larval density and age-2 recruits. Specifically, spawning stock catch per effort (CPE) and chlorophyll explained 63–64% of the variation in larval density. In turn, larval density and chlorophyll explained 43–49% of the variation in age-2 recruit CPE. Finally, spawning stock CPE and chlorophyll were the best predictors of recruit CPE (i.e., 74–86%). Although larval density and recruitment increased with chlorophyll, neither was related to seasonal water elevation. Also, the AIC generally did not distinguish between Ricker and Beverton–Holt models. From these relationships, we concluded that crappie recruitment can be limited by spawning stock CPE and larval production when spawning stock sizes are low (i.e., CPE < 5 crappies/net-night). At higher levels of spawning stock sizes, spawning stock CPE and recruitment were less clearly related. To predict recruitment in Ohio reservoirs, managers should assess spawning stock CPE with trap nets and estimate chlorophyll concentrations. To increase crappie recruitment in reservoirs where recruitment is consistently poor, managers should use regulations to increase spawning stock size, which, in turn, should increase larval production and recruits to the fishery.
Extending Survival with Chemotherapy in Metastatic Breast Cancer
Authors: O'Shaughnessy Joyce
Published: December 2005

Learning Objectives

After completing this course, the reader will be able to: Identify trials that have demonstrated a survival benefit with a modern chemotherapeutic agent or regimen in MBC.Summarize recent findings of randomized trials showing survival benefits with targeted therapy–chemotherapy combinations in MBC.Discuss quality-of-life findings and their implications in clinical practice.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Metastatic breast cancer (MBC) remains essentially incurable, and goals of therapy include the palliation of symptoms, delay of disease progression, and prolongation of overall survival time without negatively impacting quality of life. Anthracycline and taxane-based therapies have traditionally shown the highest degree of activity in MBC. Though numerous randomized clinical trials have shown improvements in overall response rates, few have found clear survival benefits. In recent years, however, there has been a small but growing series of clinical trials demonstrating modest, but meaningful survival advantages in metastatic disease. A common feature in many of these trials has been the use of a taxane, and more recently, a taxane combined with an antimetabolite. In addition, the development of targeted biologic agents active against MBC, such as trastuzumab and bevacizumab, has demonstrated great potential for enhancing the effects of chemotherapy and producing meaningful survival improvements. The role of the taxanes, antimetabolites, and biologics in extending survival in MBC is discussed.
Achieving Treatment Goals for Hormone-Refractory Prostate Cancer with Chemotherapy
Authors: Berry William , Eisenberger Mario
Published: December 2005

Learning Objectives

After completing this course, the reader will be able to: Describe the efficacy and toxicity results of two phase III trials that evaluated a docetaxel-based regimen for the treatment of HRPC.Discuss the utility of PSA as a survival marker in HRPC trials.List agents under investigation for the second-line treatment of HRPC.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

The belief that hormone-refractory prostate cancer (HRPC) is a chemotherapy-resistant disease has been effectively refuted by the results of two recent randomized phase III trials. The TAX327 trial compared weekly docetaxel, every-3-weeks (Q3W) docetaxel, and Q3W mitoxantrone plus prednisone in 1,006 patients with HRPC, and results demonstrated that survival was significantly longer with a docetaxel-based regimen than with mitoxantrone. That trial demonstrated that only Q3W docetaxel was significantly superior to mitoxantrone with respect to overall survival. Quality of life was also superior in the docetaxel groups. In the Southwest Oncology Group (SWOG) 9916 trial, 674 men with progressive HRPC were randomized to 3-week cycles of docetaxel plus estramustine or mitoxantrone plus prednisone. Overall and disease-free survival times were significantly longer in the docetaxel arm. Collectively, the results of these trials demonstrate that survival can be significantly improved with chemotherapy in patients with HRPC to an extent that is comparable with the survival benefits seen in other cancers considered sensitive to chemotherapy such as breast cancer. Among various research tasks in HRPC is the definition of potential surrogate end points for survival, which will facilitate the conduct of pivotal trials. Prostate-specific antigen (PSA) response rate and changes in PSA constructs (i.e., PSA doubling time and PSA velocity) are promising potential surrogate end points for future trials and are being actively evaluated at the present time. Until there is clear demonstration of a surrogate role for these alternative end points, survival remains the appropriate end point for phase III trials in HRPC. There is a need for safe and effective second- and third-line regimens for patients progressing after docetaxel, and these patients should enter clinical trials designed for this population. Mitoxantrone, vinorelbine, the platinum analogue satraplatin, and epothilone are among compounds that require careful testing in this setting. The addition of targeted therapies, such as the endothelin receptor antagonist, atrasentan, and angiogenesis inhibitors, such as thalidomide and bevacizumab, to docetaxel-based therapy is being evaluated. High-dose calcitriol may also be an effective addition to docetaxel. The extensive effort devoted to the evaluation of chemotherapy and other systemic modalities of treatment of HRPC is likely to yield additional clinical benefit for patients, making HRPC a more manageable, less lethal, and less debilitating disease.
Advances in the Treatment of Metastatic Colorectal Cancer
Authors: Goldberg Richard M.
Published: December 2005

Learning Objectives

After completing this course, the reader will be able to: Identify the advantages and disadvantages of the various chemotherapeutic regimens used to treat metastatic colorectal cancer.Discuss the emerging role of new agents for the treatment of metastatic colorectal cancer.Discuss the current status of trials of new combination therapies in the treatment of metastatic colorectal cancer.Describe quality of life data for combination chemotherapy for metastatic colorectal cancer and the influence of quality of life on treatment decisions.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

The overall 5-year survival rate for patients with metastatic colorectal cancer (CRC) is less than 10%. Median survival with 5-fluorouracil (5-FU)/leucovorin (LV) therapy is approximately 12 months. Recent additions to the chemotherapy armamentarium for this disease have begun to prolong median survival times. In trials in which patients are exposed to all three approved chemotherapy agents, oxaliplatin, irinotecan, and 5-FU/LV, or capecitabine during the course of their disease, median survival has reached 20 months. The addition of oxaliplatin and irinotecan to 5-FU/LV regimens has also led to the maintenance of quality of life for longer intervals than were traditionally observed with 5-FU/LV alone. Current standard first-line regimens for metastatic CRC are FOLFOX (infusional 5-FU/LV with oxaliplatin) and FOLFIRI (infusional 5-FU/LV with irinotecan). The addition of bevacizumab to a two-drug regimen (irinotecan with 5-FU/LV) prolongs median survival to 20 months, with a modest amount of additional toxicity. Improvements in this median survival have not yet been realized with modifications to the current standard regimens; however, the oral agent capecitabine appears to be a reasonable substitute for infusional 5-FU/LV in combination regimens or as a single agent, with the advantage of reducing the inconvenience of the long infusion time. Ongoing investigations will identify a place for capecitabine, epidermal growth factor inhibitors, and new cytotoxics in the treatment of metastatic CRC.
Evolving Chemotherapy for Advanced Gastric Cancer
Authors: Ajani Jaffer A.
Published: December 2005

Learning Objectives

After completing this course, the reader will be able to: Identify the current standard of care and new chemotherapy options for patients with advanced gastric cancer.Discuss recently reported results of phase II and phase III randomized trials of chemotherapy for the treatment of advanced gastric cancer.Outline the clinical implications of recent clinical trial findings and future treatment strategies.Describe regimens that have quality-of-life benefits for patients with advanced gastric cancer and how patients should be selected and managed appropriately.

Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com

Gastric cancer is the fourth most commonly diagnosed cancer and is the second leading cause of cancer death worldwide. More than 50% of patients undergo surgery, but even after a curative resection, 60% of patients relapse locally or with distant metastases. Despite the fact that many advances have occurred in the management of gastric cancer, it continues to carry a poor prognosis, amplifying the importance of palliative chemotherapy. When compared with best supportive care alone, combination chemotherapy yields a significant advantage in the management of advanced gastric cancer. However, no single regimen has emerged or been accepted as clearly superior over another. Numerous phase II studies have demonstrated promising results with newer agents including irinotecan, docetaxel, capecitabine, S-1, and oxaliplatin. Recently reported phase III results with these agents now demonstrate positive developments in the treatment options for patients with advanced gastric cancer.
Inverse Dual‐Permeability Modeling of Preferential Water Flow in a Soil Column and Implications for Field‐Scale Solute Transport
Authors: Köhne J. Maximilian , Mohanty Binayak P. , Šimůnek Jirka
Published: December 2005

The question of whether or not soil hydraulic parameters of dual‐permeability models (DPM) can be properly identified by inverse analysis of preferential water flow data has not been resolved to date. We applied a DPM based on two coupled Richards' equations to compare the performance of inverse and forward simulations of laboratory preferential flow data. Infiltration and drainage experiments were conducted using a repacked loam soil column (80 cm long, 24‐cm diameter) containing a cylindrical sand region (2.4‐cm diameter) as the preferential flow path (PFP) along its central axis. The forward DPM water flow simulations relied on hydraulic parameters for the matrix and the PFP as determined by means of separate infiltration and drainage experiments on loam and sand columns, respectively. One inverse DPM approach relied on standard (lumped) observations of infiltration and outflow, while the other included outflow through the matrix and the PFP. Both inverse approaches provided accurate matches of bulk infiltration and outflow, but the outflow out of the matrix and the PFP could only be described when fitting the DPM to region‐specific outflow data. The practical implication of this finding for predicting solute transport in natural soils was evaluated. An observed tile‐drainage hydrograph was used for inverse hydraulic DPM parameter estimation, followed by fitting the solute transfer coefficient and the dispersivity for simulating Br− tracer concentrations. This sequential fitting procedure was successful for hydrograph simulation but unsuccessful for Br− breakthrough simulation. Simultaneous hydraulic and transport parameter estimation considerably improved the approximation of Br− concentrations. This study shows that a hydrograph alone is not sufficient for inverse identification of soil hydraulic DPM parameters. Simultaneously employing hydrograph and solute breakthrough data may facilitate identification of hydraulic and transport DPM parameters to characterize preferential flow and solute transport.