bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Gender Differences Exist in the Academic Identification of African American Elementary School-Aged Children?
Authors: McMillian M. Monique , Frierson Henry T. , Campbell Frances A.
Published: April 2010

The disidentification hypothesis predicts that African American boys achieve less in school than African American girls do because boys have less personal investment in doing well academically (i.e., they are disidentified). When do such gender differences emerge? Using self-perception and achievement data from longitudinal studies of children ( N = 113) at high risk for academic problems because they come from low-income families, the authors examined whether elementary school—aged and early adolescent African American boys are more prone to low achievement and disidentification than African American girls. Multiple regression analyses indicated no gender differences in reading or mathematics achievement between boys and girls at age 8 or at age 12. At age 12, African American boys’ self-esteem was predicted by academic performance in ways similar to that of African American girls. Thus, no gender differences emerged in elementary school achievement and no gender-specific disengagement patterns were confirmed among at-risk African American students.
Marriage and Health in the Transition to Adulthood: Evidence for African Americans in the Add Health Study
Authors: Mullan Harris Kathleen , Hedwig Lee  , DeLeone Felicia Yang
Published: April 2010

This article explores the relationships among early marriage (before age 26 years), cohabitation, and health for African Americans and Whites during the transition to adulthood using the National Longitudinal Study of Adolescent Health (Add Health). The study examines three categories of health outcomes relevant to young adulthood: physical health, mental health, and health risk behaviors. Lagged dependent variable models are used to examine the health effects of early marriage and cohabitation accounting for potential health selection into unions. The results indicate that early marriage by young adults does not have protective effects for African Americans; the authors also find more negative effects for African American men than for women. There are mixed results for Whites with some protective effects of marriage for binge drinking. Early marriage for African Americans and Whites is associated with increased body mass index. Cohabitation is uniformly associated with negative health outcomes for all racial and gender groups.
Neuropsychological Lateralization of Brain Dysfunction in Children With Mesial Temporal Sclerosis: A Presurgical Evaluation
Authors: Kar Bhoomika R. , Rao Shobini L. , Chandramouli B.A. , Thennarasu K. , Satishchandra P.
Published: April 2010

Presurgical evaluation of children with mesial temporal sclerosis has shown severe neurocognitive impairments. There is debate about lateralized material-specific deficits in memory in children with mesial temporal sclerosis. The authors examined lateralization of brain dysfunction and age appropriate development of cognitive functions in 17 children (7-15 years) with mesial temporal sclerosis who had histories of uncontrolled epilepsy. The National Institute of Mental Health and Neurosciences (NIMHANS) neuropsychological battery for children was employed and each participant’s performance was compared with the norms. Results showed that the battery was sensitive to deficits in learning and memory associated with mesial temporal sclerosis. However, a lack of clearly lateralized material-specific memory deficits in children with left/right mesial temporal sclerosis was also observed. Performance on tests that assess learning, attention, working memory, and visuospatial functions was found to be below the age appropriate level. Children with mesial temporal sclerosis showed widely distributed neuropsychological deficits.
Autism From a Religious Perspective: A Study of Parental Beliefs in South Asian Muslim Immigrant Families
Authors: Jegatheesan Brinda , Miller Peggy J. , Fowler Susan A.
Published: April 2010

Three multilingual immigrant South Asian Muslim families who have children with autism were interviewed to ascertain their beliefs about autism. Data were drawn from interviews and conversations recorded during 17 months of ethnographic fieldwork in homes and community. Results indicate that families understood the task of raising a child with autism in religious terms. In keeping with the precepts of Islam, their overarching goal was to raise their children as normally as possible, incorporating them into ordinary social, linguistic, and religious practices at home and in the community. Parents strongly contested experts’ understandings of autism, which they believed undermined rather than promoted their children’s development. Findings have implications for multicultural teacher education and enhancing home, community, and school collaboration.
Video Preference Assessment of Students with Autism for Watching Self, Adults, or Peers
Authors: Mechling Linda C. , Moser Sara V.
Published: April 2010

The preferences of students with autism for watching themselves, a familiar adult, or a familiar peer in video recordings were examined. A multi-stimulus video preference assessment was used to evaluate the preferences of five students with autism. Three video options of a preferred activity (e.g., vacuuming) or daily/routine activity (e.g., snack time) were available to students via a computer-based program. Results showed that collectively there was minimal difference between the three video choices across the five students. However, in their individual scores, preferences varied among the students and activities, providing a framework for discussion of individual preference assessments when using video for instructional programs and reinforcement of task performance and behavior.
The Role of the Reflexive-Conditioned Motivating Operation (CMO-R) During Discrete Trial Instruction of Children With Autism
Authors: Carbone Vincent J. , Morgenstern Barry , Zecchin-Tirri Gina , Kolberg Laura
Published: April 2010

The principle of motivation has resurfaced as an independent variable in the field of behavior analysis over the past 20 years.The increased interest is the result of refinements of the concept of the motivating operation and its application to the learning needs of persons with developmental disabilities. Notwithstanding the increased emphasis upon modification of motivating operations to reduce problem behavior, there is limited recognition of this important behavioral variable in autism treatment literature. An overview of antecedent-based instructional modifications that lead to a reduction of escape and avoidance behavior of children with autism during instruction is provided. An analysis of these instructional methods as motivating operations is proposed. A conceptually systematic analysis of the influence of instructional methods is offered as a tool for improving the selection and implementation of effective teaching procedures.
Elevated Levels of Cartilage Oligomeric Matrix Protein during In Vitro Cartilage Matrix Generation Decrease Collagen Fibril Diameter
Authors: Bastiaansen-Jenniskens Y.M. , de Bart A.C.W. , Koevoet W. , Jansen K.M.B. , Verhaar J.A.N. , van Osch G.J.V.M. , DeGroot J.
Published: April 2010

Cartilage oligomeric matrix protein (COMP) is a protein present in the cartilage matrix and is expressed more abundantly in osteoarthritis cartilage than in healthy cartilage. The present study was designed to investigate the effect of transforming growth factor β (TGFβ) on COMP deposition and the influence of COMP on collagen biochemistry in a long-term 3-dimensional culture. Bovine chondrocytes in alginate beads were cultured with or without 25 ng/mL TGFβ2 for 21 or 35 days. COMP was overexpressed in bovine chondrocytes using lentiviral transfection. COMP gene expression, COMP protein production, collagen and proteoglycan deposition, and collagen fibril thickness were determined. Addition of TGFβ2 resulted in more COMP mRNA and protein than the control condition without growth factors. Lentiviral transduction with COMP resulted in elevated gene expression of COMP and increased COMP levels in the alginate bead and culture medium compared to untransfected cells. Overexpression of COMP did not affect the deposition of collagen, collagen cross-linking, proteoglycan deposition, or the mechanical properties. Stimulating COMP production by either TGFβ2 or lentivirus resulted in collagen fibrils with a smaller diameter. Taken together, COMP deposition can be modulated in cartilage matrix production by the addition of growth factors or by overexpression of COMP. Inducing COMP protein expression resulted in collagen fibrils with a smaller diameter. Because it has been demonstrated that the collagen fibril diameter is associated with mechanical functioning of the matrix, modulating COMP levels should be taken into account in cartilage regeneration strategies.
Anterior and Posterior Femoral Head-Neck Offset Ratio in the Cam Impingement
Authors: Nemtala Fernando , Mardones Rodrigo M. , Tomic Alexander
Published: April 2010

Purpose: The purpose of this study was to determine if the anterior-posterior offset ratio is altered in patients with symptomatic cam impingement. Study Design: Preoperative radiographs of 15 symptomatic patients with isolated cam-type impingement diagnosed by physical examination and magnetic resonance imaging arthrogram (MRIA) and confirmed by hip arthroscopy findings were assessed. Fifteen asymptomatic volunteers made up the control group. The anterior offset (AO), posterior offset (PO), and AO/PO ratio were calculated. Results: The mean ± SD AO/PO ratio was 0.56 ± 0.1 for the symptomatic group and 0.9 ± 0.2 for the asymptomatic group. This difference was statistically significant. Intra- and interobserver correlation factor for calculating the AO/PO ratio was 0.8 and 0.5, respectively, and differences were not statistically different. Conclusions: The AO/PO ratio in this study was a useful radiological parameter for the assessment of patients with a cam-type impingement.
Dual phase versus CMn strip steels: Comparison of quasi-static and dynamic connection properties for road safety barriers
Authors: Bayton D. A. F. , Fourlaris G.
Published: April 2010

The use of high strength steel grades in automotive applications has been widely recorded. This is due largely to vehicle weight reduction programmes as well as increases in vehicle crash safety legislation. This represents the steel industry's response to the challenge that vehicle components manufactured from steel could get replaced with alternative materials, such as aluminium and polymers. Consequently, new high strength steel grades have been developed to offer credible alternatives. Recently, the UK government has released a new specification, BS EN 1317-1-2-3-4: Road Restraint Systems, to which all new safety barrier designs have to comply. However, much of this development and subsequent usage has been targeted at automotive manufacturers. Road safety barrier technology has not evolved in the same way when compared to vehicle technology. Therefore, a study has been undertaken to assess the outcome of using some of these novel high strength steel grades for the manufacture of road safety barrier components. Quasi-static and dynamic tensile testing at different velocities was undertaken. Representative connection coupons were used to understand the energy absorbing properties of a dual phase steel grade when compared to the current CMn steel grade. The present study presents some initial results as to the increased performance that could be gained from utilising new high strength steel grades for the production of road safety barrier systems.
Sanofi-Aventis and the Complexity of Capitalist Organization
Authors: Leaver Adam , Montalban Matthieu
Published: April 2010

Using case study material on French pharmaceutical firm Sanofi-Aventis, this article aims to elaborate on recent criticisms of the varieties of capitalism (VoC) perspective. The article claims that the VoC approach is not so much ‘wrong’ as limited, both by its narrow focus on the national and its exclusive concern with mapping national institutional organization. The article highlights the important role of sectoral and global institutions, and discusses the difficulty of reading firm strategy directly from national institutional change, when ownership and personnel changes often provide senior management with greater autonomy to pursue divergent strategies which are difficult to generalize from the national level. In the case of Sanofi, the article finds that, whilst domestic institutional shifts explain the timing of the company's strategic change, sectoral and global institutions play a more important role in understanding the form and direction of that change. Meanwhile, Sanofi's PDG, Jean-François DeHecq, drew on non-national institutions — notably US- and UK-based institutional shareholders who bought the new share issues, and foreign investment banks which brokered acquisitions — to operationalize a discretionary strategy of expansion in the US market. The article argues that VoC's emphasis on national institutional configurations fails to adequately engage with these complexities. Further, it presents empirics on Sanofi's geographical accumulation and reinvestment of profit, which highlights how funds generated in the US were recycled in France to support well-paid research and manufacturing jobs. The article concludes that Sanofi is better thought of as part of a disorganized but interconnected economic world, where firms operate as a kind of conduit for cross-subsidy between national social settlements. This requires us to question VoC's emphasis on national complementarities and encourages us to think divergently about the degree of separateness between national capitalisms.
Upgrading or Decline? Globalization, Retail Structure, and Labour in the Chilean Textile and Clothing Industry
Authors: Reinecke Gerhard
Published: April 2010

Trade liberalization has plunged the textile and clothing industry in many countries — both in the developed and developing world — into a crisis with important employment losses. Important differences across countries exist regarding the extent of decline, the productivity performance, and the working conditions for the remaining workers in this industry. Based on elements of global commodity chain analysis and the varieties of capitalism (VoC) approach, these different patterns have been explained for developed countries, placing particular emphasis on the scope and effective implementation of industry-wide minimum wages and labour regulations, as well as on retail concentration.

In this article, we apply the above framework to Chile, where the process of downsizing of the industry has followed the least virtuous pattern, with meagre productivity results and precarization of remaining employment. Part of the remaining textile and clothing employment has moved to the informal economy and sweatshop-type enterprises. This outcome is explained by the high degree of retail concentration in Chile, the virtual absence of sectoral collective bargaining and the partial coverage of labour inspection among micro and small enterprises.
Freer Trade, More Regulation? Commercial Regulatory Provisions in Asia-Pacific Free Trade Agreements
Authors: Dent Christopher M
Published: April 2010

Free trade agreements (FTAs) have become a defining feature of the world trade system, expanding rapidly in number since the end of the Cold War and particularly in the Asia-Pacific, a region that was hitherto largely devoid of FTA activity. The nature of FTAs is also changing. Most incorporate a range of ‘trade plus’ measures that extend the reach of these agreements into various realms of commercial regulation, embodying specific rules on intellectual property, investment, government procurement, competition policy, and other areas of commercial practice. With conventional trade barriers (e.g. tariffs) continuing to fall and hence becoming less significant, the commercial regulatory provisions of FTAs have gained greater prominence. This article considers whether ‘freer trade’ in the early twenty-first century is increasingly concerned with setting the appropriate regulatory parameters to foster open market competition, but also competition on the regulatory terms of dominant FTA partners. The analysis centres on seven types of ‘influence effect’ associated with FTA commercial regulation, in broad terms relating to determining the liberalization embodied in agreements, shaping the domestic policy domain of FTA partners, affecting the relationship between FTAs and World Trade Organisation (WTO) accords, conferring regulatory preferences and free-rider advantages to trade partners, exhibiting cross-agreement regulatory influences, and exposing fundamental conflicts of interest on economic and social governance issues.
In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder
Authors: Palmieri Camillo , Falcone Cristina , Iaccino Enrico , Tuccillo Franca Maria , Gaspari Marco , Trimboli Francesca , De Laurentiis Annamaria , Luberto Laura , Pontoriero Marilena , Pisano Antonio , Vecchio Eleonora , Fierro Olga , Panico Maria Rosaria , Larobina Michele , Gargiulo Sara , Costa Nicola , Dal Piaz Fabrizio , Schiavone Marco , Arra Claudio , Giudice Aldo , Palma Giuseppe , Barbieri Antonio , Quinto Ileana , Scala Giuseppe
Published: April 2010

B-cell lymphoma is a clonal expansion of neoplastic cells that may result in fatal outcomes. Here, we report the in vivo targeting and growth inhibition of aggressive A20 murine B-cell lymphoma by idiotype-specific peptide pA20-36. pA20-36 was selected from random peptide libraries and bound specifically to the B-cell receptor (BCR) of A20 cells in mice engrafted with A20 lymphoma, as shown by histology and positron emission tomographic analysis. BCR cross-linking of A20 cells with pA20-36 resulted in massive apoptosis of targeted tumor cells and in an increased survival of the diseased animals without any detectable evidence of toxicity. The pA20-36 treatment reverted the immune suppression of the tumor microenvironment as shown by reduced expression of vascular endothelial growth factor, interleukin-10, and transforming growth factor-β cytokines together with a lower number of CD11b+Gr-1+ inhibitor myeloid-derived suppressor cells and Foxp3+CD4+ Treg cells. Furthermore, pA20-36 treatment was associated with an increased number of tumor-infiltrating, activated CD8+ T cells that exerted a tumor-specific cytolytic activity. These findings show that a short peptide that binds specifically to the complementarity-determining regions of the A20 BCR allows in vivo detection of neoplastic cells together with significant inhibition of tumor growth in vivo.
WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system
Authors: Hou Hsin-An , Huang Tai-Chung , Lin Liang-In , Liu Chieh-Yu , Chen Chien-Yuan , Chou Wen-Chien , Tang Jih-Luh , Tseng Mei-Hsuan , Huang Chi-Fei , Chiang Ying-Chieh , Lee Fen-Yu , Liu Ming-Chih , Yao Ming , Huang Shang-Yi , Ko Bor-Sheng , Hsu Szu-Chun , Wu Shang-Ju , Tsay Woei , Chen Yao-Chang , Tien Hwei-Fang
Published: April 2010

The impact of WT1 mutations in acute myeloid leukemia (AML) is not completely settled. We aimed to determine the clinical implication of WT1 mutation in 470 de novo non-M3 AML patients and its stability during the clinical course. WT1 mutations were identified in 6.8% of total patients and 8.3% of younger patients with normal karyotype (CN-AML). The WT1 mutation was closely associated with younger age (P < .001), French-American-British M6 subtype (P = .006), and t(7;11)(p15;p15) (P = .003). Multivariate analysis demonstrated that the WT1 mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and the CN-AML group. A scoring system incorporating WT1 mutation, NPM1/FLT3-ITD, CEBPA mutations, and age into survival analysis proved to be very useful to stratify CN-AML patients into different prognostic groups (P < .001). Sequential analyses were performed on 133 patients. WT1 mutations disappeared at complete remission in all WT1-mutated patients studied. At relapse, 3 of the 16 WT1-mutated patients who had paired samples lost the mutation and 2 acquired additional mutations, whereas 3 of 110 WT1-wild patients acquired novel mutations. In conclusion, WT1 mutations are correlated with poor prognosis in AML patients. The mutation status may be changed in some patients during AML progression.
Drug target prediction and prioritization: using orthology to predict essentiality in parasite genomes
Authors: Doyle Maria A , Gasser Robin B , Woodcroft Ben J , Hall Ross S , Ralph Stuart A
Published: April 2010

Background

New drug targets are urgently needed for parasites of socio-economic importance. Genes that are essential for parasite survival are highly desirable targets, but information on these genes is lacking, as gene knockouts or knockdowns are difficult to perform in many species of parasites. We examined the applicability of large-scale essentiality information from four model eukaryotes,Caenorhabditis elegans, Drosophila melanogaster, Mus musculusandSaccharomyces cerevisiae, to discover essential genes in each of their genomes. Parasite genes that lack orthologues in their host are desirable as selective targets, so we also examined prediction of essential genes within this subset.

Results

Cross-species analyses showed that the evolutionary conservation of genes and the presence of essential orthologues are each strong predictors of essentiality in eukaryotes. Absence of paralogues was also found to be a general predictor of increased relative essentiality. By combining several orthology and essentiality criteria one can select gene sets with up to a five-fold enrichment in essential genes compared with a random selection. We show how quantitative application of such criteria can be used to predict a ranked list of potential drug targets fromAncylostoma caninumandHaemonchus contortus- two blood-feeding strongylid nematodes, for which there are presently limited sequence data but no functional genomic tools.

Conclusions

The present study demonstrates the utility of using orthology information from multiple, diverse eukaryotes to predict essential genes. The data also emphasize the challenge of identifying essential genes among those in a parasite that are absent from its host.
Students' perceptions about the transition to the clinical phase of a medical curriculum with preclinical patient contacts; a focus group study
Authors: Godefrooij Merijn B , Diemers Agnes D , Scherpbier Albert JJA
Published: April 2010

Background

Studies have shown that medical students experience the transition between preclinical and clinical training as a stressful period. They are generally frustrated by their inability to apply their knowledge to solve clinical problems in practice. Preclinical patient contacts may offer a solution to this 'shock of practice.' We studied how students who have had preclinical patient contacts perceive the transition from preclinical to clinical training and, more specifically, how they value these early patient contacts as preparation for learning in clinical practice.

Methods

A purposive sample of 21 students participated in three focus groups which met twice during their first weeks of clinical clerkships. The interviews were recorded and transcribed literally. Qualitative content analysis of the transcriptions was performed.

Results

According to the students, working in clinical practice was enjoyable, motivated them to study and helped them to develop non-analytical reasoning skills. The students experienced stress due to increased working hours and work load, uncertainty as to what was expected of them and self-perceived lack of knowledge. They did not experience a major gap between the preclinical and clinical phase and felt well prepared for the clerkships. The preclinical patient contacts were considered to be instrumental in this.

Conclusions

Early patient contacts seem to ameliorate the shock of practice and prepare students for clinical work. The problems mentioned by the students in this study are mainly related to the socialisation process. The results of this study have to be validated by quantitative research.
Changes in the accessibility of the HIV-1 Integrase C-terminus in the presence of cellular proteins
Authors: Benkhelifa-Ziyyat Sofia , Bucher Stéphanie , Zanta-Boussif Maria-Antonietta , Pasquet Julie , Danos Olivier
Published: April 2010

Background

Following entry, uncoating, and reverse transcription, a number of cellular proteins become associated with the Human Immunodeficiency Virus type 1 (HIV-1) pre-integration complex (PIC). With the goal of obtaining reagents for the analysis of the HIV-1 PIC composition and localisation, we have constructed functional integrase (IN) and matrix (MA) proteins that can be biotinylated during virus production and captured using streptavidin-coated beads.

Results

Although the labelled C-terminus allows for the sensitive detection of virion-associated IN, it becomes inaccessible in the presence of cellular proteins. This masking is not dependent on the nature of the tag and does not occur with the tagged MA. It was not observed either with an IN mutant unable to interact with LEDGF/p75, or when LEDGF/p75 was depleted from cells.

Conclusion

Our observation suggests that a structural rearrangement or oligomerization of the IN protein occurs during the early steps of infection and that this process is related to the presence of LEDGF/p75.
An outbreak of aseptic meningitis caused by coxsackievirus A9 in Gansu, the People's Republic of China
Authors: Cui Aili , Yu Deshan , Zhu Zhen , Meng Lei , Li Hui , Liu Jianfeng , Liu Guiyan , Mao Naiying , Xu Wenbo
Published: April 2010

Background

An outbreak of aseptic meningitis occurred in Tianshui city of Gansu Province, the People's Republic of China, from March to June 2005. A total of 85 patients were clinical confirmed as aseptic meningitis in this outbreak.

Results

CVA9 was mainly responsible for this outbreak supported by the clinical manifestations of the patients, epidemiological data of the outbreak, the results of RT-PCR and complete VP1 sequence determination, conventional neutralization assays, IgM serological assays, viral isolation and phylogenetics analysis. Through phylogenetic analysis and homogeneity analysis for partial VP1 gene, the nucleotide and amino acid homologies between Gansu isolates and former Chinese CVA9 strains were 88.2%-96.1% and 97.2%-99.2%, respectively. Multiple transmission chains of CVA9 occurred in different provinces or years in China. Moreover, in order to clarify the genotype of CVA9, Gansu CVA9 strains isolated in this outbreak were compared with other CVA9 isolates based on VP1/2A junction regions (genotyping region) and they might belong to a new genotype of CVA9, which could be assigned for genotype XIII,

Conclusions

CVA9 was confirmed as the pathogen responsible for this outbreak. The phylogenetic analysis indicated that the CVA9 strains isolated in this outbreak might belong to a new genotype.
Surveillance of FAP: a prospective blinded comparison of capsule endoscopy and other GI imaging to detect small bowel polyps
Authors: Tescher Paul , Macrae Finlay A , Speer Tony , Stella Damien , Gibson Robert , Tye-Din Jason A , Srivatsa Geeta , Jones Ian T , Marion Kaye
Published: April 2010

Background

Familial adenomatous polyposis (FAP) is a hereditary disorder characterized by polyposis along the gastrointestinal tract. Information on adenoma status below the duodenum has previously been restricted due to its inaccessibility in vivo. Capsule Endoscopy (CE) may provide a useful adjunct in screening for polyposis in the small bowel in FAP patients. This study aims to evaluate the effectiveness of CE in the assessment of patients with FAP, compared to other imaging modalities for the detection of small bowel polyps.

Method

20 consecutive patients with previously diagnosed FAP and duodenal polyps, presenting for routine surveillance of polyps at The Royal Melbourne Hospital were recruited. Each fasted patient initially underwent a magnetic resonance image (MRI) of the abdomen, and a barium small bowel follow-through study. Capsule Endoscopy was performed four weeks later on the fasted patient. An upper gastrointestinal side-viewing endoscopy was done one (1) to two (2) weeks after this. Endoscopists and investigators were blinded to results of other investigations and patient history.

Results

Within the stomach, upper gastrointestinal endoscopy found more polyps than other forms of imaging. SBFT and MRI generally performed poorly, identifying fewer polyps than both upper gastrointestinal and capsule endoscopy. CE was the only form of imaging that identified polyps in all segments of the small bowel as well as the only form of imaging able to provide multiple findings outside the stomach/duodenum.

Conclusion

CE provides important information on possible polyp development distal to the duodenum, which may lead to surgical intervention. The place of CE as an adjunct in surveillance of FAP for a specific subset needs consideration and confirmation in replication studies.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12608000616370
Development of a Multimarker Assay for Early Detection of Ovarian Cancer
Authors: Yurkovetsky Zoya , Skates Steven , Lomakin Aleksey , Nolen Brian , Pulsipher Trenton , Modugno Francesmary , Marks Jeffrey , Godwin Andrew , Gorelik Elieser , Jacobs Ian , Menon Usha , Lu Karen , Badgwell Donna , Bast Robert C. , Lokshin Anna E.
Published: April 2010

Purpose

Early detection of ovarian cancer has great promise to improve clinical outcome.

Patients and Methods

Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.

Results

A training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer.

Conclusion

A panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.
Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine Combination Treatment for Patients With Waldenström Macroglobulinemia: Clinical and Biologic Results of a Phase II Multicenter Study
Authors: Laszlo Daniele , Andreola Giovanna , Rigacci Luigi , Fabbri Alberto , Rabascio Cristina , Mancuso Patrizia , Pruneri Giancarlo , Radice Davide , Pinto Antonello , Frigeri Ferdinando , Calabrese Liliana , Billio Atto , Bertolini Francesco , Martinelli Giovanni
Published: April 2010

Purpose

To assess the efficacy of 2-chloro-2′-deoxyadenosine (2-CdA) given subcutaneously (SC) in combination with rituximab in the treatment of newly diagnosed/pretreated patients with Waldenström macroglobulinemia (WM) and to correlate the response to treatment with biologic findings (immunophenotypic and pharmacogenomic analysis).

Patients and Methods

From December 2003 to February 2007, 29 patients were enrolled. Intended therapy consisted of a combination of rituximab (375 mg/m2) on day 1 followed by 2-CdA 0.1 mg/kg (SC injection) for 5 consecutive days, administered monthly for four cycles. Anemia (n = 16), neurologic symptoms (n = 6), symptomatic cryoglobulinemia (n = 4), and thrombocytopenia (n = 3) represented the reasons for starting treatment. The expression of ζ chain–associated protein kinase 70 (Zap-70) and of seven genes involved in 2-CdA metabolism as markers of response to the combination treatment was evaluated.

Results

With a median follow-up of 43 months, the overall response rate observed was 89.6%, with seven complete responses (CR), 16 partial responses, and three minor response, without any difference between newly or pretreated patients (P = .522). The therapy was well tolerated, except for transitory cardiac toxicity (n = 2) and intolerance to rituximab (n = 2). No major infections were observed despite the lack of antimicrobial prophylaxis. No patients developed transformation to high-grade non-Hodgkin's lymphoma nor myelodysplasia. Low expression levels of human concentrative nucleoside transporter 1 (hCNT1) were correlated with the failure to achieve a CR (P = .024), whereas no association with Zap-70 expression was found.

Conclusion

The combination of rituximab and SC 2-CdA is safe and effective in patients with WM requiring treatment. The pharmacogenomic analysis associated with the study suggests hCNT1 might be beneficial in predicting clinical response to such a combination treatment.
Testis Cancer Survivors' Health Behaviors: Comparison With Age-Matched Relative and Demographically Matched Population Controls
Authors: Shinn Eileen H. , Swartz Richard J. , Thornton Bob B. , Spiess Philippe E. , Pisters Louis L. , Basen-Engquist Karen M.
Published: April 2010

Purpose

To determine the prevalence rate of health behaviors in testis cancer survivors and to determine whether the rate of health behaviors in survivors was significantly different than those of their age-matched relative controls and a population-based control group matched for age, sex, education, and income.

Patients and Methods

The health behaviors of 162 testis cancer survivors were compared with their age-matched relative controls (n = 74) and an age-, sex-, education-, and income-matched population-based control group (n ranged from 1,123 to 9,775). Health behaviors were assessed with the telephone-administered Behavioral Risk Factor and Surveillance Survey.

Results

Nearly one in five testis cancer survivors reported current smoking and one third reported problem drinking. Only 11% reported having at least five servings of fruits and vegetables per day. Compared with their relative controls, the survivors were more likely to engage in regular exercise. For those participants who drank, survivors were twice as likely to engage in problem drinking and averaged a higher number of drinks compared to their Centers for Disease Control (CDC) controls. Survivors were also half as likely to have at least five servings of fruits and vegetables per day compared with the CDC controls.

Conclusion

The overall picture regarding testis cancer survivors' health behaviors was mixed compared with the relative and CDC control groups. Our results suggest that reduced alcohol use and increased fruit and vegetable consumption may be important targets for future disease prevention in testis cancer survivors.
Population-Based Study of the Risk of Second Primary Contralateral Breast Cancer Associated With Carrying a Mutation inBRCA1orBRCA2
Authors: Malone Kathleen E. , Begg Colin B. , Haile Robert W. , Borg Ake , Concannon Patrick , Tellhed Lina , Xue Shanyan , Teraoka Sharon , Bernstein Leslie , Capanu Marinela , Reiner Anne S. , Riedel Elyn R. , Thomas Duncan C. , Mellemkjær Lene , Lynch Charles F. , Boice John D. , Anton-Culver Hoda , Bernstein Jonine L.
Published: April 2010

Purpose

Women with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation.

Patients and Methods

In this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed.

Results

Compared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance.

Conclusion

The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
High-Dose Therapy and Autologous Stem-Cell Transplantation in Waldenström Macroglobulinemia: The Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Kyriakou Charalampia , Canals Carmen , Sibon David , Cahn Jean Yves , Kazmi Majid , Arcese William , Kolbe Karin , Gorin Norbert Claude , Thomson Kristy , Milpied Noel , Niederwieser Dietger , Indrák Karel , Corradini Paolo , Sureda Anna , Schmitz Norbert
Published: April 2010

Purpose

The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome.

Patients and Methods

We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation–based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years).

Results

Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years.

Conclusion

ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.
Prognostic Accuracy of Computed Tomography Findings for Patients With Laryngeal Cancer Undergoing Laryngectomy
Authors: Beitler Jonathan J. , Muller Susan , Grist William J. , Corey Amanda , Klein Adam M. , Johns Michael M. , Perkins Charles L. , Davis Lawrence W. , Udayasanker Unni , Landry Jerome C. , Shin Dong M. , Hudgins Patricia A.
Published: April 2010

Purpose

The indications for upfront laryngectomy in the management of laryngeal cancer are a functionless larynx and extralaryngeal extension. Practically, clinicians rely on imaging to predict which patients will have T4 disease. Our goal was to review the accuracy of preoperative computed tomography (CT) scanning in determining the necessity for initial laryngectomy for advanced laryngeal cancer.

Patients and Methods

In total, 107 consecutive untreated laryngectomy specimens with high-quality, preoperative CT imaging interpreted by our neuroradiologists were reviewed. Radiographic findings, including sclerosis, invasion, penetration, extralaryngeal spread, and subglottic extension were correlated with pathologic findings. CT images were not reinterpreted, since our purpose was to assess the original interpretations.

Results

CT imaging reported 23 cases of thyroid cartilage penetration and 27 cases of extralaryngeal spread. Pathology reported 12 cases of thyroid cartilage invasion, 29 cases of penetration, and 45 cases of extralaryngeal disease. CT imaging identified 17 (59%) of 29 cases of pathologically documented thyroid cartilage penetration and 22 (49%) of 45 cases of pathologically documented extralaryngeal spread. Pathologically proven extralaryngeal spread without thyroid cartilage penetration occurred in 18 (40%) of 45 cases. The positive predictive values for thyroid cartilage penetration and extralaryngeal spread were 74% and 81%. Sclerosis was of limited value in predicting thyroid cartilage invasion or penetration. Cricoid or arytenoid destruction predicted for thyroid cartilage penetration at rates of 57% and 63%.

Conclusion

CT imaging has clear limitations when deciding whether there is thyroid cartilage penetration or extralaryngeal spread of advanced laryngeal cancer. Extralaryngeal spread without thyroid cartilage penetration was more common than expected. Alternate methods of pretreatment assessment are needed.
Phase II Clinical Trial of Sorafenib in Metastatic Medullary Thyroid Cancer
Authors: Lam Elaine T. , Ringel Matthew D. , Kloos Richard T. , Prior Thomas W. , Knopp Michael V. , Liang Jiachao , Sammet Steffen , Hall Nathan C. , Wakely Paul E. , Vasko Vasyl V. , Saji Motoyasu , Snyder Pamela J. , Wei Lai , Arbogast Daria , Collamore Minden , Wright John J. , Moley Jeffrey F. , Villalona-Calero Miguel A. , Shah Manisha H.
Published: April 2010

Purpose

Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret and VEGFR, showed antitumor activity in preclinical studies of MTC.

Patients and Methods

In this phase II trial of sorafenib in patients with advanced MTC, the primary end point was objective response. Secondary end points included toxicity assessment and response correlation with tumor markers, functional imaging, and RET mutations. Using a two-stage design, 16 or 25 patients were to be enrolled onto arms A (hereditary) and B (sporadic). Patients received sorafenib 400 mg orally twice daily.

Results

Of 16 patients treated in arm B, one achieved partial response (PR; 6.3%; 95% CI, 0.2% to 30.2%), 14 had stable disease (SD; 87.5%; 95% CI, 61.7% to 99.5%), and one was nonevaluable. In a post hoc analysis of 10 arm B patients with progressive disease (PD) before study, one patient had PR of 21+ months, four patients had SD ≥ 15 months, four patients had SD ≤ 6 months, and one patient had clinical PD. Median progression-free survival was 17.9 months. Arm A was prematurely terminated because of slow accrual. Common adverse events (AEs) included diarrhea, hand-foot-skin reaction, rash, and hypertension. Although serious AEs were rare, one death was seen. Tumor markers decreased in the majority of patients, and RET mutations were detected in 10 of 12 sporadic MTCs analyzed.

Conclusion

Sorafenib is reasonably well tolerated, with suggestion of clinical benefit for patients with sporadic MTC. Caution should be taken because of the rare but fatal toxicity potentially associated with sorafenib.
BCL-2/IgH Polymerase Chain Reaction Status at the End of Induction Treatment Is Not Predictive for Progression-Free Survival in Relapsed/Resistant Follicular Lymphoma: Results of a Prospective Randomized EORTC 20981 Phase III Intergroup Study
Authors: van Oers Marinus H.J. , Tönnissen Evelyn , Van Glabbeke Martine , Giurgea Livia , Jansen Joop H. , Klasa Richard , Marcus Robert E. , Wolf Max , Kimby Eva , Vranovsky Andrej , Holte Harald , Hagenbeek Anton , van der Reijden Bert A.
Published: April 2010

Purpose

The prognostic value of residual BCL2/immunoglobulin heavy chain (BCL2/IgH) –positive cells in peripheral blood (PB) or bone marrow (BM) after induction treatment in follicular lymphoma (FL) is still controversial. In a prospective randomized phase III intergroup trial of 465 patients with relapsed/resistant follicular lymphoma (FL), we showed that addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone induction results in increased overall and complete response rates, and that rituximab maintenance strongly improves median progression-free survival (PFS) as well as overall survival. Here, we studied whether BCL2/IgH major break point levels in PB/BM correlated with response rates/quality for the induction phase and PFS for the maintenance phase.

Patients and Methods

Samples were obtained before and after induction therapy and at the end of the 2 years maintenance/observation period. BCL2/IgH major break point–positive cells were quantified by genomic quantitative polymerase chain reaction in 792 samples from 238 patients.

Results

Pretreatment BCL2/IgH levels had no significant prognostic value for overall response or complete remission rates after induction treatment, but pretreatment positive BM results had an adverse prognostic value for PFS from first randomization (P = .023). Importantly, BCL2/IgH levels at the end of induction treatment had no prognostic value for PFS from second randomization. The highly significant improved PFS by rituximab maintenance was observed in both BCL2/IgH PB/BM–positive and –negative groups.

Conclusion

Postinduction BCL2/IgH major break point status in BM/PB is not useful for decisions on subsequent therapy for patients with relapsed/resistant FL.