bluuebunny/crossref_metadata_2025 huggingface dataset:
Between Being Cured and Being Healed: The Paradox of Childhood Cancer Survivorship
Authors: Cantrell Mary Ann , Conte Teresa M.
Published: February 2009

In this article, we describe how young adults who are transitioning off treatment for childhood cancer and beginning early survivorship are living in what might be described as a paradox of reality. These survivors' dual reality is their experience of intense frustration with their current state of functioning, and an overwhelming relief that therapy is over and that they survived. They have feelings of fear, trepidation, and anxiety for what experiences lay ahead, but have hope for the future. Finally, they acknowledge the growth they achieved through the experience of cancer treatment, as well as the many missed opportunities to experience normalcy while undergoing therapy. Young adults who are in early cancer survivorship exist in a reality in which they are living disease free, but perceive themselves as having a long road to travel to be healed.
Reframing: Psychological Adjustment of Chinese Women at the Beginning of the Breast Cancer Experience
Authors: Ching Shirley S. Y. , Martinson Ida M. , Wong Thomas K. S.
Published: February 2009

In this article, we present findings from a larger study that explored how Chinese women cope with breast cancer. We report on the process of early psychological adjustment, along with contextual factors and how they influence the women's coping mechanisms at the beginning of the cancer experience. Twenty-four women with diagnoses of breast cancer were interviewed. The grounded theory method was adopted in data collection and analysis. “Reframing” was the core category of the early adjustment process. Focus and approach were the two contextual conditions. Women adopted “fighting,” “following the natural course,” “struggling,” and “bearing” modes in coping with the disease. These findings highlight the significance of focusing on coping and realizing the role of the self in creating a subjective positive interpretation, which subsequently enhances acceptance of the disease at the beginning of the cancer experience. Characteristics of the Chinese people with respect to coping include the collaborative meaning of control and the philosophy of acquiescence to fate.
Patients as Partners in Responsive Research: Methodological Notions for Collaborations in Mixed Research Teams
Authors: Abma Tineke A. , Nierse Christi J. , Widdershoven Guy A. M.
Published: February 2009

Patients are increasingly actively involved in research. We depart from an approach that understands patient participation as dialogue. This idea is grounded in hermeneutic philosophy and responsive research. Patients are engaged in research via dialogues with other stakeholders. New is the inclusion of patients as research partners. Several methodological notions underpin responsive research. In two health research agenda-setting processes (intellectual disability and kidney disease), these notions have been applied and refined for collaboration with research partners in mixed research teams. The findings demonstrate that equal partnerships include involvement in all research activities from beginning to end, a focus on experiential knowledge, mutual learning, openness, and respect. Mutual learning processes help to overcome stereotypes and handle tensions. Other experiences include the financial reimbursement of research partners, and the necessity of an acceptable workload and scheme. The collaboration might then have a surplus value for the research process and for those involved.
The Meaning of Close Relationships and Sexuality: Women's Well-Being Following a Myocardial Infarction
Authors: Sundler Annelie Johansson , Dahlberg Karin , Ekenstam Claes
Published: February 2009

Relationships and sexuality following heart attack (MI) have been studied; nevertheless, little is known about the meaning of social support and relationships to health and well-being after an MI. To our knowledge, no qualitative studies have further investigated the phenomenon. In this study we explore the meaning of close relationships and sexuality to women's health and well-being following MI. Ten women were interviewed using a reflective lifeworld approach and phenomenological epistemology. The meaning of women's close relationships following an MI appears to be closely intertwined with their long-term health process; both health processes and the relationships are affected. Suffering after an MI can be compared to taking a fall in that close relationships can become a safety net. Close relationships and sexuality are integrated into their lived bodies, and in that way have profound influence in their lifeworld experiences. Not all close relationships are intimate; however, all close and meaningful relationships can provide power and strength to the women's health processes. At the same time, these relationships also appear to drain energy and cause suffering.
Defixation as an Intervention Perspective
Authors: Stoppelenburg Annemieke , Vermaak Hans
Published: February 2009

This case study presents reflections on a research intervention conducted at the Dutch Ministry of Foreign Affairs. The subject was the practice of administration. Its objective became to understand its “wicked problems” and to create action principles. It was an analytical research effort as well as a learning intervention. Wicked problems are those that have a large impact on an organization's functioning and that persist regardless of numerous efforts to remedy them. They are characterized both by content and process complexity and are by no means exclusive to the Ministry. This paper focuses not so much on the content of the wicked problems, but on the intervention process which is described from beginning to end. Special attention is paid to intervention paradoxes. At the end of the paper we reflect on different ways to `defixate' intervention progress that seem relevant when dealing with wicked problems.
The Value of CD23 Expression as an Additional Marker in Distinguishing Mediastinal (Thymic) Large B-Cell Lymphoma From Hodgkin Lymphoma
Authors: Salama Mohamed E. , Rajan Mariappan M. , Inamdar Kedar , Tripp Sheryl R. , Perkins Sherrie L.
Published: February 2009

Mediastinal diffuse large B-cell lymphoma (Med-DLBCL) is a subtype of DLBCL that has morphologic and clinical similarities and phenotypic overlaps with classical Hodgkin lymphoma (CHL) involving the mediastinum. CD23 is a marker that has been previously reported in Med-DLBCI and is proposed in the differential diagnosis of M-DLBCL and CHL. A panel of immunostains, including CD45, CD20, CD3, CD30, CD15, CD21, and CD23 as well as Eber was performed on Med-DLBCL and 20CHL. 23/27 Med-DLBCL (85%) were positive for CD23 (membranous) CD30 was negative in 6 and positive in 21 cases. 18 CHL cases were negative for CD23 and only 2 showed rare scattered Reed—Sternberg cells with weak cytoplasmic CD23 staining. CD23 showed a sensitivity of 85% and positive predictive value of 92%. In conclusion CD23 is a useful marker in distinguishing Med-DLBCL and CHL in mediastinal biopsies and may be helpful as an adjunct to histomorphology and other markers in the diagnosis and appropriate clinical management of these lesions.
Intraoperative Consultation for Axillary Sentinel Lymph Node Biopsy: An 8-Year Audit
Authors: Nofech-Mozes Sharon , Hanna Wedad M. , Cil Tulin , Quan May-Lynn , Holloway Claire , Khalifa Mahmoud A.
Published: February 2009

To summarize the authors’ 8-year institutional experience with intraoperative consultation via frozen section (FS) on sentinel lymph node biopsy (SLNB) in breast cancer patients we recorded the, complete operative procedure including additional surgery on the ipsilateral axilla and intraoperative consultation and permanent histopathologic processing for all cases with inoperative consultation on SLNB in breast cancer patients between the groups, χ2 and Fisher’s exact tests were used. Intraoperative consultation was positive in 116/706 cases (16.4%) and final pathology in 158/706 cases (22.4%); the false-negative rate was 26.6%, the false-positive rate was 0%, and the overall accuracy was 94%. False-negative rate was significantly associated with the size of metastasis (micro vs macrometastasis; P < .002) but not significantly associated with the histologic type ( P = 0.76) or pathologist expertise ( P = 0.08). The rate of spared second procedures was 92% when calculated exclusively for patients who ultimately underwent ALND. Intraoperative consultation via FS for SLNB is a safe practice that can reliably save clinically node-negative patients a second surgery.
Interdigitating Dendritic Cell Tumor of the Lymph Node in the Right Submaxillary Region: A Case Report and Review of the Literature
Authors: Zhou Zhi-yi , Sun Rong-chao , Yang Shu-dong , Liang Jia-bei , Jun Rui  , Pan Min-hong
Published: February 2009

Interdigitating dendritic cell tumor/sarcoma is an extremely rare neoplasm that mainly occurs in the lymph node, with only 51 cases reported in the literature to date. The authors report the case of a 41-year-old woman who presented with a 4-month history of a gradually enlarging painless mobile lymphadenopathy in the right submaxillary region. The lymph node mass was completely resected and was treated with 1 cycle of CHOP chemotherapy. After 10 months, she was alive with no evidence of disease. Because interdigitating dendritic cell sarcomas are rare and can show morphologic and immunohistochemical heterogeneity, correct diagnosis requires a high index of suspicion and complete pathological study.
Fuzeon-Induced Collagenophagic Granuloma: A Peculiar Granulomatous Injection Site Reaction to Fuzeon- A Case Report and Review of Literature
Authors: Sidhu Harleen K. , Chaffee Barbara H. , Tvetenstrand Christian D. , Sidhu Jagmohan S.
Published: February 2009

Enfuvirtide (ENF, T-20, or Fuzeon [Hoffman-La Roche Inc, Nutley, NJ, and Trimeris, Inc, Durham, NC]) is an HIV-1 fusion inhibitor and is the only injectable antiretroviral drug available. Injection site reactions (ISRs) are the most frequently reported adverse events, occurring in about 98% of patients. A granuloma annulare—like granulomatous ISR has been reported. We report a granulomatous ISR that is different from granuloma annulare and granuloma annulare—like reaction because it is rich in multinucleated giant cells engulfing altered collagen. We call this type of ISR a collagenophagic granuloma. Most previous reports—with the exception of 1 report—about ISRs with ENF treatment have used punch biopsies, which lack the depth to analyze the reticular dermis and subcutaneous tissue and, therefore, may have missed ISRs, which look like granuloma annulare, and the collagenophagic granulomatous reaction.
“No Matter What Has Been Done Wrong Can Always Be Redone Right”
Authors: Schneider Rachel Zimmer , Feltey Kathryn M.
Published: February 2009

In this article, the authors explore the religious and spiritual experiences and beliefs of incarcerated battered women who killed abusive intimate partners or (step)fathers. Through in-depth interviews with 12 imprisoned battered women, the authors examine the role that religion and spirituality played in the women's lives before and during their incarceration. Regardless of their religious upbringing, most had what they described as spiritual experiences during their time in prison. For them, participation in the support group for battered women and their spiritual experiences “freed them” by giving them a way to reconstruct and reinterpret their victimization, perpetration of violence, and subsequent incarceration.
Opendda: a Novel High-Performance Computational Framework for the Discrete Dipole Approximation
Authors: Donald James Mc , Golden Aaron , Jennings S. Gerard
Published: February 2009

This work presents a highly optimized computational framework for the Discrete Dipole Approximation, a numerical method for calculating the optical properties associated with a target of arbitrary geometry that is widely used in atmospheric, astrophysical and industrial simulations. Core optimizations include the bit-fielding of integer data and iterative methods that complement a new Discrete Fourier Transform (DFT) kernel, which efficiently calculates the matrix— vector products required by these iterative solution schemes. The new kernel performs the requisite 3-D DFTs as ensembles of 1-D transforms, and by doing so, is able to reduce the number of constituent 1-D transforms by 60% and the memory by over 80%. The optimizations also facilitate the use of parallel techniques to further enhance the performance. Complete OpenMP-based shared-memory and MPI-based distributed-memory implementations have been created to take full advantage of the various architectures. Several benchmarks of the new framework indicate extremely favorable performance and scalability.
Performance Modeling and Analysis of a Massively Parallel Direct—Part 1
Authors: Jian He  , Verstak Alex , Watson L.T. , Sosonkina M.
Published: February 2009

Modeling and analysis techniques are used to investigate the performance of a massively parallel version of DIRECT, a global search algorithm widely used in multidisciplinary design optimization applications. Several high-dimensional benchmark functions and real world problems are used to test the design effectiveness under various problem structures. Theoretical and experimental results are compared for two parallel clusters with different system scales and network connectivities. The present work aims at studying the performance sensitivity to important parameters for problem configurations, parallel schemes, and system settings. The performance metrics include the memory usage, load balancing, parallel efficiency, and scalability. An analytical bounding model is constructed to measure the load balancing performance under different schemes. Additionally, linear regression models are used to characterize two major overhead sources, interprocessor communication and processor idleness, and also applied to the isoefficiency functions in scalability analysis. For a variety of high-dimensional problems and large-scale systems, the massively parallel design has achieved reasonable performance. The results of the performance study provide guidance for efficient problem and scheme configuration. More importantly, the generalized design considerations and analysis techniques are beneficial for transforming many global search algorithms into effective large-scale parallel optimization tools.
Performance Modeling and Analysis of a Massively Parallel Direct—Part 2
Authors: Jian He  , Verstak Alex , Sosonkina M. , Watson L.T.
Published: February 2009

Modeling and analysis techniques are used to investigate the performance of a massively parallel version of DIRECT, a global search algorithm widely used in multidisciplinary design optimization applications. Several high-dimensional benchmark functions and real world problems are used to test the design effectiveness under various problem structures. In this second part of a two-part work, theoretical and experimental results are compared for two parallel clusters with different system scales and network connectivities. The first part studied performance sensitivity to important parameters for problem configurations and parallel schemes, using performance metrics such as memory usage, load balancing, and parallel efficiency. Here linear regression models are used to characterize two major overhead sources, interprocessor communication and processor idleness, and also applied to the isoefficiency functions in scalability analysis. For a variety of high-dimensional problems and large-scale systems, the massively parallel design has achieved reasonable performance. The results of the performance study provide guidance for efficient problem and scheme configuration. More importantly, the design considerations and analysis techniques generalize to the transformation of other global search algorithms into effective large-scale parallel optimization tools.
The Problem With the Linpack Benchmark 1.0 Matrix Generator
Authors: Dongarra Jack J. , Langou Julien
Published: February 2009

We characterize the matrix sizes for which the Linpack Benchmark 1.0 matrix generator constructs a matrix with identical columns.
Optimization With High-Cost Objective Function Evaluations in a Computing Grid and an Application To Simulation-Based Design
Authors: Jin Woo Park  , Si Hyong Park  , Seung Jo Kim
Published: February 2009

The emerging grid computing technologies are aimed at the creation of virtual supercomputers to conduct huge scale scientific computations by harvesting computing resources on the Internet. This paper introduces a grid-enabled implementation of an optimization program for large-scale optimization problems requiring high-cost, black-box objective function evaluations. Adopting grid computing can be particularly beneficial for building surrogates such as response surfaces and carrying out large-scale optimizations using stochastic optimization algorithms. However, several problems have to be resolved for effective utilization of grid resources because of heterogeneity in computer capacity among grid resources and limited network conditions inherent in grid systems. This paper identifies some of the problems and introduces algorithms to effectively carry out large-scale optimizations on a grid. Specifically, asynchronous genetic and particle swarm optimization algorithms are developed for grid computing environments. The performance and characteristics of the grid-enabled implementations are assessed via extensive numerical tests. Finally, structural design based on high-fidelity simulations is carried out using the proposed algorithm in a computing grid system.
Social inequality in adolescent daily smoking: Has it changed over time?
Authors: Rasmussen Mette , Due Pernille , Damsgaard Mogens T. , Holstein Bjørn E.
Published: February 2009

Background and aim: In most northern European countries adolescent smoking is most prevalent in lower social classes but there is little information about time trends in social inequality. This paper describes trends in social inequality in daily smoking among adolescents from 1991 to 2006 by both absolute social inequality (prevalence difference between low and high social class) and relative social inequality (prevalence ratio). Methods: We analysed 15-year-olds from the Health Behaviour in School-aged Children (HBSC) study in Denmark in 1991, 1994, 1998, 2002 and 2006, total n = 6703. The surveys were comparable because of similar procedures for sampling, data collection, and measurements of smoking and parents' occupational social class. Findings: From 1991 to 2006 the prevalence of daily smoking decreased from 15.9% to 10.9% among boys and from 20.1% to 10.6% among girls. The social inequality fluctuated over time and was different for boys and for girls. The prevalence difference between boys from low and high social class was 5.2% in 1991 and 9.3% in 2006, corresponding figures for girls were 4.8% and 7.0%. The prevalence ratio among boys was 1.38 (in 1991) and 2.19 (in 2006), among girls 1.28 and 1.95. Conclusions: Daily smoking was most prevalent among students from lower social classes and the level of inequality fluctuated over time. Conclusions on social inequality in adolescent smoking may appear differently when described by absolute and relative measures. The absolute and relative social inequality in adolescent smoking was higher in 2006 than in 1991.
Surgical Treatment of an Extrarenal Pseudoaneurysm After Kidney Transplantation
Authors: Sharron Jennifer A. , Esterl Robert M. , Washburn William K. , Abrahamian Greg A.
Published: February 2009

A 69-year-old man who underwent a kidney transplantation developed a large pseudoaneurysm at the anastomosis between the right external iliac artery and renal transplant artery. After an unsuccessful attempt using percutaneous thrombin injection, the patient underwent open exploratory laparotomy and surgical ligation of the pseudoaneurysm with preservation of renal graft function.
Microstructure and mechanical properties of novel rail steels
Authors: Panda B. , Balasubramaniam R. , Moon A.
Published: February 2009

Four new rail steels, alloyed with Cu, Cr, Ni and Si, were designed to improve the corrosion resistance of conventional C–Mn rail steel. The mechanical behaviour of these four rail steels were tested and compared qualitatively with C–Mn, Cu–Mo and Cr–Mn rail steels. While the strengths of Cu–Mo, Cr–Mn, Cr–Cu–Ni and Cr–Cu–Ni–Si rail steels were comparable; the strengths of Cu–Ni and Cu–Si steels were relatively low. The ductility of Cu–Mo and Cu–Ni rail steels were higher compared to C–Mn and Cr–Mn rail steels. The optimum combination of strength and ductility was realised in the case of Cu–Mo rail steel, followed by Cr–Cu–Ni and Cr–Cu–Ni–Si rail steels. The tensile properties have been understood by considering microstructural (notably, lamellar spacing of pearlite) and fracture surface features. The effect of alloying elements on hardness and tensile properties has been explained based on their effect in shifting the continuous cooling transformation curves as well as austenite stability region, in addition to solid solution strengthening and strengthening by carbide formation.
Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study
Authors: Schmiegelow Kjeld , Al-Modhwahi Ibrahim , Andersen Mette Klarskov , Behrendtz Mikael , Forestier Erik , Hasle Henrik , Heyman Mats , Kristinsson Jon , Nersting Jacob , Nygaard Randi , Svendsen Anne Louise , Vettenranta Kim , Weinshilboum Richard
Published: February 2009

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.
Cloning, characterization and expression analysis of porcine microRNAs
Authors: Reddy Alavala Matta , Zheng Yun , Jagadeeswaran Guru , Macmil Simone L , Graham Wiley B , Roe Bruce A , Desilva Udaya , Zhang Weixiong , Sunkar Ramanjulu
Published: February 2009

Background

MicroRNAs (miRNAs) are small ~22-nt regulatory RNAs that can silence target genes, by blocking their protein production or degrading the mRNAs. Pig is an important animal in the agriculture industry because of its utility in the meat production. Besides, pig has tremendous biomedical importance as a model organism because of its closer proximity to humans than the mouse model. Several hundreds of miRNAs have been identified from mammals, humans, mice and rats, but little is known about the miRNA component in the pig genome. Here, we adopted an experimental approach to identify conserved and unique miRNAs and characterize their expression patterns in diverse tissues of pig.

Results

By sequencing a small RNA library generated using pooled RNA from the pig heart, liver and thymus; we identified a total of 120 conserved miRNA homologs in pig. Expression analysis of conserved miRNAs in 14 different tissue types revealed heart-specific expression of miR-499 and miR-208 and liver-specific expression of miR-122. Additionally, miR-1 and miR-133 in the heart, miR-181a and miR-142-3p in the thymus, miR-194 in the liver, and miR-143 in the stomach showed the highest levels of expression. miR-22, miR-26b, miR-29c and miR-30c showed ubiquitous expression in diverse tissues. The expression patterns of pig-specific miRNAs also varied among the tissues examined.

Conclusion

Identification of 120 miRNAs and determination of the spatial expression patterns of a sub-set of these in the pig is a valuable resource for molecular biologists, breeders, and biomedical investigators interested in post-transcriptional gene regulation in pig and in related mammals, including humans.
A community based field research project investigating anaemia amongst young children living in rural Karnataka, India: a cross sectional study
Authors: Pasricha Sant-Rayn , Vijaykumar Varalaxmi , Prashanth NS , Sudarshan H , Biggs Beverley-Ann , Black Jim , Shet Arun
Published: February 2009

Background

Anaemia is an important problem amongst young children living in rural India. However, there has not previously been a detailed study of the biological aetiology of this anaemia, exploring the relative contributions of iron, vitamin B12, folate and Vitamin A deficiency, inflammation, genetic haemoglobinopathy, hookworm and malaria. Nor have studies related these aetiologic biological factors to household food security, standard of living and child feeding practices. Barriers to conducting such work have included perceived reluctance of village communities to permit their children to undergo venipuncture, and logistical issues. We have successfully completed a community based, cross sectional field study exploring in detail the causes of anaemia amongst young children in a rural setting.

Methods and design

A cross sectional, community based study. We engaged in extensive community consultation and tailored our study design to the outcomes of these discussions. We utilised local women as field workers, harnessing the capacity of local health workers to assist with the study. We adopted a programmatic approach with a census rather than random sampling strategy in the village, incorporating appropriate case management for children identified to have anaemia. We developed a questionnaire based on existing standard measurement tools for standard of living, food security and nutrition. Specimen processing was conducted at the Primary Health Centre laboratory prior to transport to an urban research laboratory.

Discussion

Adopting this study design, we have recruited 415 of 470 potentially eligible children who were living in the selected villages. We achieved support from the community and cooperation of local health workers. Our results will improve the understanding into anaemia amongst young children in rural India. However, many further studies are required to understand the health problems of the population of rural India, and our study design and technique provide a useful demonstration of a successful strategy.
Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity
Authors: Freeburg Elizabeth M , Goyeneche Alicia A , Seidel Erin E , Telleria Carlos M
Published: February 2009

Background

The prototypical antiprogestin mifepristone exhibits potent growth inhibition activity towards ovarian cancer cells in vitro and in vivo. The aim of this research was to establish whether mifepristone is capable of inhibiting cell proliferation and inducing apoptotic cell death regardless of the degree of sensitivity ovarian cancer cells exhibit to cisplatin.

Methods

OV2008, OV2008/C13, A2780, A2780/CP70, Caov-3, and SK-OV-3 cell lines exhibiting a range of sensitivities to cisplatin were used. Growth inhibition, cell viability, and sub-diploid DNA content in response to treatment with escalating doses of either mifepristone or cisplatin were assessed by microcapillary cytometry. Apoptotic cell death was evaluated by measuring genomic DNA fragmentation and cleavage of caspase-3 and poly (ADP ribose) polymerase (PARP).

Results

The sensitivities to cisplatin manifested by the cell lines were OV2008 > A2780 > Caov-3 > SK-OV-3 > OV2008/C13 > A2780/CP70. Mifepristone inhibited the growth of all six cell lines in a dose-related manner with IC50s ranging from ~6–12 μM and without significant correlation with the relative sensitivities the cells displayed for cisplatin. Moreover, at the highest concentration studied, mifepristone triggered apoptotic death in all six cell lines as evidenced by the increase in sub-diploid fragmented DNA content and cleavage of caspase-3 and of its downstream substrate PARP.

Conclusion

Mifepristone is cytotoxic towards ovarian cancer cells independent of the sensitivity exhibited by the cells to cisplatin, displaying cytostatic effects at lower concentrations and lethal effects at higher concentrations. Mifepristone monotherapy emerges as a valuable therapeutic alternative for platinum-resistant ovarian cancers.
Simultaneous multifrequency inversion of full-waveform seismic data
Authors: Hu Wenyi , Abubakar Aria , Habashy Tarek M.
Published: February 2009

We present a simultaneous multifrequency inversion approach for seismic data interpretation. This algorithm inverts all frequency data components simultaneously. A data-weighting scheme balances the contributions from different frequency data components so the inversion process does not become dominated by high-frequency data components, which produce a velocity image with many artifacts. A Gauss-Newton minimization approach achieves a high convergence rate and an accurate reconstructed velocity image. By introducing a modified adjoint formulation, we can calculate the Jacobian matrix efficiently, allowing the material properties in the perfectly matched layers (PMLs) to be updated automatically during the inversion process. This feature ensures the correct behavior of the inversion and implies that the algorithm is appropriate for realistic applications where a priori information of the background medium is unavailable. Two different regularization schemes, an [Formula: see text]-norm and a weighted [Formula: see text]-norm function, are used in this algorithm for smooth profiles and profiles with sharp boundaries, respectively. The regularization parameter is determined automatically and adaptively by the so-called multiplicative regularization technique. To test the algorithm, we implement the inversion to reconstruct the Marmousi velocity model using synthetic data generated by the finite-difference time-domain code. These numerical simulation results indicate that this inversion algorithm is robust in terms of starting model and noise suppression. Under some circumstances, it is more robust than a traditional sequential inversion approach.
Intellectual Property
Authors: Walker David A.
Published: February 2009

The Intellectual Property department in each issue of Geophysics provides U.S. patent abstracts, published patent abstracts of U.S. patent applications, and published abstracts filed under the Patent Cooperation Treaty (PCT).
Gene Expression Profiles Differentiating Between Breast Cancers Clinically Responsive or Resistant to Letrozole
Authors: Miller William R. , Larionov Alexey , Renshaw Lorna , Anderson Thomas J. , Walker John R. , Krause Andreas , Sing Tobias , Evans Dean B. , Dixon J. Michael
Published: February 2009

Purpose

Endocrine agents, such as letrozole, are established in the treatment of hormone-dependent breast cancer. However, response rates are only 50% to 70% in the neoadjuvant setting and lower in advanced disease. Thus there is a need to identify novel markers predicting for response and to understand molecular mechanisms of resistance.

Patients and Methods

Sequential tumor biopsies were taken before and after 10 to 14 days of neoadjuvant treatment with letrozole in patients with estrogen receptor–rich breast cancer. Expression profiles on high-density microarray chips were then related to clinical responses as assessed from tumor volume measurements after 3 months of treatment.

Results

Of 52 patients, 37 (71%) were classified as having a clinical response to letrozole and 15 being clinically resistant. Bioinformatic analysis identified 205 covariables (69 baseline expression, 45 day 14 expression, and 91 change in expression with treatment) which differentiated between clinical responders and nonresponders. Hierarchical clustering using the variables separated responders and nonresponders into two distinct groups. Ontological assessment indicated that discriminating genes were enriched toward cellular biosynthetic processes. In particular, functional gene assessment showed ribosomal protein probes to have higher baseline expression in tumors responsive to letrozole and increased expression with treatment in nonresponding cases.

Conclusion

To our knowledge, this is the first study to describe genetic covariables and molecular processes discriminating between tumors clinically responsive and resistant to an aromatase inhibitor. The understanding of such molecular phenotypes will be important in optimizing the clinical use of aromatase inhibitors, both in terms of identifying responsive breast cancers and developing new agents to target resistance pathways.
Characteristics Associated With Important Clinical End Points in Patients With Chronic Lymphocytic Leukemia at Initial Treatment
Authors: Wierda William G. , O'Brien Susan , Wang Xuemei , Faderl Stefan , Ferrajoli Alessandra , Do Kim-Anh , Garcia-Manero Guillermo , Cortes Jorge , Thomas Deborah , Koller Charles , Burger Jan , Lerner Susan , Kantarjian Hagop , Keating Michael
Published: February 2009

Purpose

Response to front-line treatment and subsequent clinical course for patients with chronic lymphocytic leukemia (CLL) are heterogeneous. Identifying pretreatment patient characteristics or prognostic factors associated with clinical outcomes is important for counseling patients, conducting clinical research, and evaluating trial results.

Patients and Methods

We evaluated the pretreatment characteristics of 595 previously untreated patients who had National Cancer Institute Working Group indications to initiate front-line therapy for predictors of complete response (CR), time to treatment failure (TTF), and overall survival (OS). Multivariable models were developed for all three end points.

Results

CR is an important treatment end point correlated with longer TTF and OS. In this retrospective analysis, front-line treatment regimen was a significant independent predictive factor for all three end points; chemoimmunotherapy was the superior treatment regimen. Considering front-line treatment regimen, other independent patient characteristics associated with CR included age and β2-microglobulin (β-2M). TTF was independently associated with age, β-2M, percent lymphocytes in bone marrow, and treatment regimen. Improved OS was independently associated with younger age, lower β-2M, and treatment regimen. Two weighted prognostic models or nomograms, one including and one excluding treatment regimen, were constructed using significant characteristics to predict 5- and 10-year survival probability and estimate median survival time.

Conclusion

Identifying pretreatment patient characteristics associated with CR, TTF, and OS establishes a baseline to compare and incorporate new prognostic factors. Treatment had an impact on the significance of these factors. Prognostic models may help patients and clinicians in decision making as well as facilitate clinical research through design and analyses of clinical trials.
Bendamustine: Rebirth of an Old Drug
Authors: Cheson Bruce D. , Rummel Mathias J.
Published: February 2009

Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non–cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab. Superiority over chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL) led to its recent approval for this disease in the United States. Bendamustine is approved in Germany for the treatment of patients with indolent NHL, CLL, and multiple myeloma. Activity has also been noted in patients with breast cancer and small-cell lung cancer. Questions related to the optimization of bendamustine therapy, including dose and schedule, role relative to other available agents, and management of toxicities, are being investigated. However, the availability of bendamustine provides another effective treatment option for patients with lymphoid malignancies.
First-Line Gefitinib for Patients With Advanced Non–Small-Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations Without Indication for Chemotherapy
Authors: Inoue Akira , Kobayashi Kunihiko , Usui Kazuhiro , Maemondo Makoto , Okinaga Shoji , Mikami Iwao , Ando Masahiro , Yamazaki Koichi , Saijo Yasuo , Gemma Akihiko , Miyazawa Hitoshi , Tanaka Tomoaki , Ikebuchi Kenji , Nukiwa Toshihiro , Morita Satoshi , Hagiwara Koichi
Published: February 2009

Purpose

This multicenter phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for patients with advanced non–small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations without indication for chemotherapy as a result of poor performance status (PS).

Patients and Methods

Chemotherapy-naïve patients with poor PS (patients 20 to 74 years of age with Eastern Cooperative Oncology Group PS 3 to 4, 75 to 79 years of age with PS 2 to 4, and ≥ 80 years of age with PS 1 to 4) who had EGFR mutations examined by the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method were enrolled and received gefitinib (250 mg/d) alone.

Results

Between February 2006 and May 2007, 30 patients with NSCLC and poor PS, including 22 patients with PS 3 to 4, were enrolled. The overall response rate was 66% (90% CI, 51% to 80%), and the disease control rate was 90%. PS improvement rate was 79% (P < .00005); in particular, 68% of the 22 patients improved from ≥ PS 3 at baseline to ≤ PS 1. The median progression-free survival, median survival time, and 1-year survival rate were 6.5 months, 17.8 months, and 63%, respectively. No treatment-related deaths were observed.

Conclusion

This is the first report indicating that EGFR mutation-positive patients with extremely poor PS benefit from first-line gefitinib. Because there previously has been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations as a biomarker is recommended in this patient population.
Phase II Study of Weekly Gemcitabine and Vinorelbine for Children With Recurrent or Refractory Hodgkin's Disease: A Children's Oncology Group Report
Authors: Cole Peter D. , Schwartz Cindy L. , Drachtman Richard A. , de Alarcon Pedro A. , Chen Lu , Trippett Tanya M.
Published: February 2009

Purpose

The Children's Oncology Group conducted this phase II study to assess the efficacy and toxicity of gemcitabine and vinorelbine (GV) in pediatric patients with heavily pretreated relapsed/refractory Hodgkin's disease. Both agents have significant single-agent response rates in this setting.

Methods

GV was given on days 1 and 8 of each 21-day treatment cycle: vinorelbine 25 mg/m2/dose administered via intravenous (IV) push before gemcitabine 1,000 mg/m2/dose IV over 100 minutes. Any patients who demonstrated a measurable response (complete response [CR], very good partial response [VGPR], or partial response [PR]) were considered to have experienced a response to GV. Response was evaluated after every two cycles. A two-stage minimax rule was used to test the null hypothesis that the response rate is ≤ 40% against an alternative hypothesis of a response rate more than 65%.

Results

Thirty eligible patients with a median age of 17.7 years (range, 10.7 to 29.4 years) were enrolled. All patients had received at least two prior chemotherapy regimens, and 17 patients had undergone prior autologous stem-cell transplantation. Hematologic toxicity was predominant in all treatment cycles. Nonhematologic grade 3 to 4 toxicity, including elevated hepatic enzymes and hyperbilirubinemia, was less common. Pericardial and pleural effusions developed in one patient after cycles 4 and 5 of GV, consistent with gemcitabine-induced radiation recall. There were no toxic deaths. Measurable responses were seen in 19 (76%) of 25 assessable patients (95% exact binomial CI, 55% to 91%), including six CRs, 11 VGPRs, and two PRs.

Conclusion

GV is an effective and well-tolerated reinduction regimen for children with relapsed or refractory Hodgkin's disease.
Risk for Hospitalization With Depression After a Cancer Diagnosis: A Nationwide, Population-Based Study of Cancer Patients in Denmark From 1973 to 2003
Authors: Dalton Susanne O. , Laursen Thomas Munk , Ross Lone , Mortensen Preben Bo , Johansen Christoffer
Published: February 2009

Purpose

As more people survive cancer, it is necessary to understand the long-term impact of cancer. We investigated whether cancer survivors are at increased risk for hospitalization for depression.

Methods

We linked data on all 5,703,754 persons living in Denmark on January 1, 1973, or born thereafter to the Danish Cancer Registry and identified 608,591 adults with a diagnosis of cancer. Follow-up for hospitalization for depression in the Danish Psychiatric Central Register from 1973 through 2003 yielded 121,227,396 person-years and 121,304 hospitalizations for depression. The relative risk (RR) for depression among cancer survivors relative to the cancer-free population was estimated by Poisson regression analysis with adjustment for age and period and stratified by sex, site of cancer, and extent of disease.

Results

The risk for depression in the first year after a cancer diagnosis was increased, with RRs ranging from 1.16 (95% CI, 0.90 to 1.51) in women with colorectal cancer to 3.08 (95% CI, 1.88 to 5.02) in men with brain cancer. Decreasing but still significant excess risks during subsequent years were observed for most specific cancers. The risk remained increased throughout the study period for both men and women surviving hormone-related cancers, for women surviving smoking-related cancers, and for men surviving virus- and immune-related cancers.

Conclusion

This study confirms an increased risk for depression in patients facing a disruptive event like cancer. Early recognition and effective treatment are needed to prevent admission of cancer survivors for depression.
Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005
Authors: Altekruse Sean F. , McGlynn Katherine A. , Reichman Marsha E.
Published: February 2009

Purpose

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Incidence rates are increasing in the United States. Monitoring incidence, survival, and mortality rates within at-risk populations can facilitate control efforts.

Methods

Age-adjusted incidence trends for HCC were examined in the Surveillance, Epidemiology, and End Results (SEER) registries from 1975 to 2005. Age-specific rates were examined for birth cohorts born between 1900 and 1959. Age-adjusted incidence and cause-specific survival rates from 1992 to 2005 were examined in the SEER 13 registries by race/ethnicity, stage, and treatment. United States liver cancer mortality rates were also examined.

Results

Age-adjusted HCC incidence rates tripled between 1975 and 2005. Incidence rates increased in each 10-year birth cohort from 1900 through the 1950s. Asians/Pacific Islanders had higher incidence and mortality rates than other racial/ethnic groups, but experienced a significant decrease in mortality rates over time. From 2000 to 2005, marked increases in incidence rates occurred among Hispanic, black, and white middle-aged men. Between 1992 and 2004, 2- to 4-year HCC survival rates doubled, as more patients were diagnosed with localized and regional HCC and prognosis improved, particularly for patients with reported treatment. Recent 1-year survival rates remained, however, less than 50%.

Conclusion

HCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men. Screening of at-risk groups and treatment of localized-stage tumors may contribute to increasing HCC survival rates in the United States. More progress is needed.
Surgical Treatment of Low- and Intermediate-Risk Papillary Thyroid Cancer with Minimally Invasive Video-Assisted Thyroidectomy
Authors: Miccoli Paolo , Pinchera Aldo , Materazzi Gabriele , Biagini Agnese , Berti Piero , Faviana Pinuccia , Molinaro Eleonora , Viola David , Elisei Rossella
Published: February 2009

Background: Minimally invasive video-assisted thyroidectomy (MIVAT) was introduced in the clinical practice to treat small benign thyroid nodules. This method has recently been demonstrated to produce the same completeness as a conventional thyroidectomy in patients with papillary thyroid cancer (PTC). The low number of treated cases and the limited follow-up of these patients represent the major limitations of these studies.

Objective: The aim of the study was to compare the outcome of two groups of PTC patients, one treated with MIVAT and the other with conventional thyroidectomy, after a median follow-up of 5 yr.

Study Group: A total of 221 PTC patients were enrolled in this study according to the following criteria: 171 were treated with MIVAT (group A), and 50 were treated with conventional thyroidectomy (group B).

Results: The outcome and the cumulative 131I activity administered to achieve curative status were compared. After a mean follow-up of 3.6 ± 1.5 yr (range, 1–8 yr; median, 5 yr), no differences were found between group A and group B. A similar rate of permanent hypoparathyroidism and/or nerve cord palsy was found in both groups.

Conclusion: We demonstrated that PTC patients operated on with MIVAT had a good outcome after 5 yr. This was similar to the outcome of patients treated with conventional thyroidectomy and the same degree of exposure to 131I. These results, together with the evidence of a similar degree of completeness and rate of complications between the two surgical techniques, show that MIVAT is a valid option to treat low- and intermediate-risk PTC patients.