bluuebunny/crossref_metadata_2025 huggingface dataset:
Patella Eversion Reduces Early Knee Range of Motion and Muscle Torque Recovery after Total Knee Arthroplasty: Comparison between Minimally Invasive Total Knee Arthroplasty and Conventional Total Knee Arthroplasty
Authors: Majima Tokifumi , Nishiike Osamu , Sawaguchi Naohiro , Susuda Kouichi , Minami Akio
Published: December 2010

We hypothesized that patella eversion during total knee arthroplasty (TKA) reduces early return of active knee extension and flexion, quadriceps muscle strength, and postoperative pain. In 100 conventional TKA knees and 100 minimally invasive TKA (MIS TKA) knees, we compared knee range of motion (ROM), postoperative pain, and quadriceps muscle strength at 1 day, 4 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 12 weeks, 1 year, and 5 years after surgery. The differences of surgical approach between MIS TKA and conventional TKA of this study are length of skin incision with subcutaneal flap and patella eversion. In MIS TKA, skin incision is shorter than conventional TKA. Furthermore, patella is not everted in MIS TKA procedure. There were no significant differences in preoperative factors. Postoperative improvement of ROM, postoperative muscle strength recovery, and postoperative improvement of visual analog scale were faster in patients with MIS TKA when compared to that in patients with conventional TKA. On the other hand, no significant difference was observed in complication, 5-year clinical results of subjective knee function score, and the postoperative component angle and lower leg alignment. These results indicate that patella eversion may affect muscle strength recovery and postoperative pain.
Critical Point Theorems and Ekeland Type Variational Principle with Applications
Authors: Lin Lai-Jiu , Wang Sung-Yu , Ansari QamrulHasan
Published: December 2010

We introduce the notion of "Equation missing"-spaces which is much weaker than cone metric spaces defined by Huang and X. Zhang (2007). We establish some critical point theorems in the setting of "Equation missing"-spaces and, in particular, in the setting of complete cone metric spaces. Our results generalize the critical point theorem proposed by Dancs et al. (1983) and the results given by Khanh and Quy (2010) to "Equation missing"-spaces and cone metric spaces. As applications of our results, we characterize the completeness of "Equation missing"-space (cone metric spaces and quasimetric spaces are special cases of "Equation missing"-space) and studying the Ekeland type variational principle for single variable vector-valued functions as well as for multivalued bifunctions in the setting of cone metric spaces.
Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia
Authors: Pan Changyu , Yoo Hyung Joon , Ho Low-Tone
Published: December 2010

Rimonabant, a selective cannabinoid-1 (CB1) receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2or greater without diabetes) from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit) and randomized to rimonabant 20 mg (n=318) or placebo (n=325) for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg,P<.0001). The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp.) (P<.0001). Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P<.0001). This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.
Common Fragile Site Tumor Suppressor Genes and Corresponding MouseModels of Cancer
Authors: Drusco Alessandra , Pekarsky Yuri , Costinean Stefan , Antenucci Anna , Conti Laura , Volinia Stefano , Aqeilan Rami I. , Huebner Kay , Zanesi Nicola
Published: December 2010

Chromosomal common fragile sites (CFSs) are specific mammalian genomic regions that show an increased frequency of gaps and breaks when cells are exposed to replication stress in vitro. CFSs are also consistently involved in chromosomal abnormalities in vivo related to cancer. Interestingly, several CFSs contain one or more tumor suppressor genes whose structure and function are often affected by chromosomal fragility. The two most active fragile sites in the human genome are FRA3B and FRA16D where the tumor suppressor genes FHIT and WWOX are located, respectively. The best approach to study tumorigenic effects of altered tumor suppressors located at CFSs in vivo is to generate mouse models in which these genes are inactivated. This paper summarizes our present knowledge on mouse models of cancer generated by knocking out tumor suppressors of CFS.
MicroRNAs miR-199a-5p and -3p Target the Brm Subunit of SWI/SNF to Generate a Double-Negative Feedback Loop in a Variety of Human Cancers
Authors: Sakurai Kouhei , Furukawa Chihiro , Haraguchi Takeshi , Inada Ken-ichi , Shiogama Kazuya , Tagawa Takanobu , Fujita Shuji , Ueno Yoshihito , Ogata Aya , Ito Mai , Tsutsumi Yutaka , Iba Hideo
Published: December 2010

The chromatin remodeling complex SWI/SNF is an important epigenetic regulator that includes one Brm or BRG1 molecule as catalytic subunit. Brm and BRG1 do not function identically, so this complex can regulate gene expression either positively or negatively, depending on the promoter to which it is recruited. Notably, Brm attenuation due to posttranscription suppression occurs often in human tumor cells, in which this event contributes to their oncogenic potential. Here, we report that the 3′-untranslated region of Brm mRNA has two sites that are efficiently targeted by the microRNAs miR-199a-5p and -3p, revealing a novel mechanism for modulation of Brm-type SWI/SNF activity. Computational mapping of the putative promoter region of miR-199a-2 (miPPR-199a-2) has defined it as the major contributing genetic locus for miR-199a-5p and-3p production in these tumor cell lines. We validated this predicted region by direct promoter analysis to confirm that Egr1 is a strong positive regulator of the miR-199a-2 gene. Importantly, we also showed that Egr1, miR-199a-5p, and miR-199a-3p are expressed at high levels in Brm-deficient tumor cell lines but only marginally in Brm-expressing tumor cells. Finally, we also obtained evidence that Brm negatively regulates Egr1. Together, our results reveal that miR-199a and Brm form a double-negative feedback loop through Egr1, leading to the generation of these two distinct cell types during carcinogenesis. This mechanism may offer a partial explanation for why miR-199a-5p and -3p have been reported to be either upregulated or downregulated in a variety of tumors. Cancer Res; 71(5); 1680–9. ©2010 AACR.
TGF-β Promotion of Gli2-Induced Expression of Parathyroid Hormone-Related Protein, an Important Osteolytic Factor in Bone Metastasis, Is Independent of Canonical Hedgehog Signaling
Authors: Johnson Rachelle W. , Nguyen Mai P. , Padalecki Susan S. , Grubbs Barry G. , Merkel Alyssa R. , Oyajobi Babatunde O. , Matrisian Lynn M. , Mundy Gregory R. , Sterling Julie A.
Published: December 2010

Breast cancer frequently metastasizes to bone, in which tumor cells receive signals from the bone marrow microenvironment. One relevant factor is TGF-β, which upregulates expression of the Hedgehog (Hh) signaling molecule, Gli2, which in turn increases secretion of important osteolytic factors such as parathyroid hormone–related protein (PTHrP). PTHrP inhibition can prevent tumor-induced bone destruction, whereas Gli2 overexpression in tumor cells can promote osteolysis. In this study, we tested the hypothesis that Hh inhibition in bone metastatic breast cancer would decrease PTHrP expression and therefore osteolytic bone destruction. However, when mice engrafted with human MDA-MB-231 breast cancer cells were treated with the Hh receptor antagonist cyclopamine, we observed no effect on tumor burden or bone destruction. In vitro analyses revealed that osteolytic tumor cells lack expression of the Hh receptor, Smoothened, suggesting an Hh-independent mechanism of Gli2 regulation. Blocking Gli signaling in metastatic breast cancer cells with a Gli2-repressor gene (Gli2-rep) reduced endogenous and TGF-β–stimulated PTHrP mRNA expression, but did not alter tumor cell proliferation. Furthermore, mice inoculated with Gli2-Rep–expressing cells exhibited a decrease in osteolysis, suggesting that Gli2 inhibition may block TGF-β propagation of a vicious osteolytic cycle in this MDA-MB-231 model of bone metastasis. Accordingly, in the absence of TGF-β signaling, Gli2 expression was downregulated in cells, whereas enforced overexpression of Gli2 restored PTHrP activity. Taken together, our findings suggest that Gli2 is required for TGF-β to stimulate PTHrP expression and that blocking Hh-independent Gli2 activity will inhibit tumor-induced bone destruction. Cancer Res; 71(3); 822–31. ©2010 AACR.
Prevention of Angiotensin II–Mediated Renal Oxidative Stress, Inflammation, and Fibrosis by Angiotensin-Converting Enzyme 2
Authors: Zhong JiuChang , Guo Danny , Chen Christopher B. , Wang Wang , Schuster Manfred , Loibner Hans , Penninger Josef M. , Scholey James W. , Kassiri Zamaneh , Oudit Gavin Y.
Published: December 2010

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase capable of metabolizing angiotensin (Ang) II into Ang 1 to 7. We hypothesized that ACE2 is a negative regulator of Ang II signaling and its adverse effects on the kidneys. Ang II infusion (1.5 mg/kg−1/d−1) for 4 days resulted in higher renal Ang II levels and increased nicotinamide adenine dinucleotide phosphate oxidase activity in ACE2 knockout (Ace2−/y) mice compared to wild-type mice. Expression of proinflammatory cytokines, interleukin-1β and chemokine (C-C motif) ligand 5, were increased in association with greater activation of extracellular-regulated kinase ½ and increase of protein kinase C-α levels. These changes were associated with increased expression of fibrosis-associated genes (α-smooth muscle actin, transforming growth factor-β, procollagen type Iα1) and increased protein levels of collagen I with histological evidence of increased tubulointerstitial fibrosis. Ang II-infused wild-type mice were then treated with recombinant human ACE2 (2 mg/kg−1/d−1, intraperitoneal). Daily treatment with recombinant human ACE2 reduced Ang II-induced pressor response and normalized renal Ang II levels and oxidative stress. These changes were associated with a suppression of Ang II–mediated activation of extracellular-regulated kinase ½ and protein kinase C pathway and Ang II–mediated renal fibrosis and T-lymphocyte-mediated inflammation. We conclude that loss of ACE2 enhances renal Ang II levels and Ang II-induced renal oxidative stress, resulting in greater renal injury, whereas recombinant human ACE2 prevents Ang II-induced hypertension, renal oxidative stress, and tubulointerstitial fibrosis. ACE2 is an important negative regulator of Ang II-induced renal disease and enhancing ACE2 action may have therapeutic potential for patients with kidney disease.
A Historical Analysis of Hip-Hop’s Influence in Dakar from 1984 - 2000
Authors: Herson Ben
Published: December 2010

Over the past 30 years, hip-hop culture has proliferated globally. One of the most potent examples of Hip-Hop’s effect on global culture can be seen in urban centers throughout Africa. The time period of 1984-2000 were of utmost importance in Senegal where hip-hop culture has had an effect on the cultural, social, and political landscape.
Between Sweet Harmony and a Clash of Cultures: Does a Joint Academic–Practitioner Review Reconcile Rigor and Relevance?
Authors: Nicolai Alexander T. , Schulz Ann-Christine , Göbel Markus
Published: December 2010

A substantial body of literature discusses the so-called rigor—relevance gap in management science and possible ways of overcoming it. A frequently advocated approach, in line with Gibbons, Limoges, Nowotny, Schwartz, and Trow’s “Mode 2” idea of creating “hybrid fora,” is the introduction of joint academic—practitioner review processes in management journals. In an empirical case study of one of the oldest management journals in the world, the authors show that the demands of academic and practitioner reviewers are hardly compatible, and, to some extent, inversely correlated. In contrast to other studies, here the authors show that the reason for the tension between academics and practitioners with regard to this issue does not lie in differences in the evaluation criteria of each group. Rather, the different worldviews of academics and practitioners lead to different interpretations of these criteria and a striking incongruence between the two groups’ ideas of practical relevance.
Glia-Induced Reversible Disruption of Blood–Brain Barrier Integrity and Neuropathological Response of the Neurovascular Unit
Authors: Willis Colin L.
Published: December 2010

The blood–brain barrier (BBB) is the regulated interface that mediates selective transcellular transport of nutrients and essential components from the blood into the brain parenchyma. Many neurodegenerative diseases including stroke, multiple sclerosis, rheumatoid arthritis, and AIDS dementia exhibit loss of BBB integrity. Despite the increasing body of evidence for the involvement of glia in maintaining the BBB, few studies have addressed glial/endothelial/extracellular matrix interactions. A chemically induced astrocyte lesion provides a noninvasive model to study reversible BBB dysfunction in vivo. Blood–brain barrier integrity was assessed with fluorescent dextran tracers (3-70 kDa) and magnetic resonance imaging, in parallel with confocal and electron microscopy imaging of the neurovascular unit. These studies demonstrated modified tight-junction protein expression with loss of vascular integrity. We propose that adherens junction proteins and extracellular matrix remodeling provide a temporary size-selective barrier, whereas astrocyte and microglia activation direct tight-junction proteins to paracellular domains and restore BBB integrity. Morphological comparisons were made with the area postrema, a circumventricular organ with a naturally porous BBB. Further studies into cellular mechanisms of glial/endothelial/extracellular matrix interactions may identify novel glial-based therapeutic targets and innovate therapies for modulating diseases in which gliosis and raised levels of pro-inflammatory mediators are central components.
Proliferative and Nonproliferative Lesions of the Rat and Mouse Hepatobiliary System
Authors: Thoolen Bob , Maronpot Robert R. , Harada Takanori , Nyska Abraham , Rousseaux Colin , Nolte Thomas , Malarkey David E. , Kaufmann Wolfgang , Küttler Karin , Deschl Ulrich , Nakae Dai , Gregson Richard , Vinlove Michael P. , Brix Amy E. , Singh Bhanu , Belpoggi Fiorella , Ward Jerrold M.
Published: December 2010

The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and differential diagnosis for classifying microscopic lesions observed in the hepatobiliary system of laboratory rats and mice, with color microphotographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available for society members electronically on the internet (http://goreni.org). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for lesions of the hepatobiliary system in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
Functional Recovery of the Donor Knee After Autologous Osteochondral Transplantation for Capitellar Osteochondritis Dissecans
Authors: Nishimura Akinobu , Morita Akimasa , Fukuda Aki , Kato Ko , Sudo Akihiro
Published: December 2010

Background: Osteochondral autograft transplantation has been advocated to treat severe osteochondritis dissecans of the humeral capitellum in throwing athletes to reproduce the normal hyaline cartilage and achieve long-term elbow function. Although some authors have reported good outcomes, the current authors are concerned about functional recovery of the donor knee after osteochondral grafts have been harvested.

Purpose: The present prospective study analyzed functional recovery of the donor knee after osteochondral graft harvest.

Study Design: Case series; Level of evidence, 4.

Methods: Twelve male patients (average age at surgery, 14.4 years) had severe osteochondritis dissecans of the humeral capitellum treated with osteochondral autograft transplantation from the contralateral knee joint. The donor knee of each patient was assessed for pain (visual analog scale), joint effusion, Lysholm score, radiographic findings, and muscle strength (60 and 180 deg/sec).

Results: At 3 months after surgery, 10 patients were pain-free (visual analog scale score, 0); none had knee joint effusion; and 10 gained 100 points in the Lysholm score. However, muscle power (60 deg/sec) of the knee extensor revealed 8 patients with reduced muscle strength at 3 months compared with the preoperative level, although 11 patients reached preoperative knee extensor muscle strength at 12 months. Radiographic findings at 24 months showed that none of the patients had knee osteoarthritis.

Conclusion: A time lag was evident in recovery between postoperative symptoms and muscle power at 3 months. However, harvesting osteochondral grafts did not exert adverse effects on donor knee function in young athletes at 2 years after undergoing osteochondral autograft transplantation for capitellar osteochondritis dissecans.
Cerebral Volumetric Analysis Over Time in Children With Malformations of Cortical Development: A Quantitative Investigation
Authors: Walker Linsey M. , Poduri Annapurna , Chang Bernard S.
Published: December 2010

Malformations of cortical development are common neurological disorders characterized by disruptions in the normal development of cerebral gray and white matter during fetal life. We performed a quantitative, partly longitudinal investigation of cerebral volumes in a cohort of children with cortical malformations to investigate how their anatomical abnormalities change over time. Cortical malformation subjects showed volumetric curves that were comparable with those reported for healthy individuals, and reached peak cerebral volume, gray matter volume, and white matter volume at ages similar to those reported for healthy children. Volumes of heterotopic gray matter, however, demonstrated increases that were out of proportion to changes in cortical volume or caudate nucleus volume, suggesting that misplaced gray matter can have a unique pattern of maturation. Our findings demonstrate that overall brain growth in children with cortical malformations appears to mirror that of the healthy population, although malformed regions can show distinct growth patterns.
Tracking Without Perceiving
Authors: Spering Miriam , Pomplun Marc , Carrasco Marisa
Published: December 2010

Can people react to objects in their visual field that they do not consciously perceive? We investigated how visual perception and motor action respond to moving objects whose visibility is reduced, and we found a dissociation between motion processing for perception and for action. We compared motion perception and eye movements evoked by two orthogonally drifting gratings, each presented separately to a different eye. The strength of each monocular grating was manipulated by inducing adaptation to one grating prior to the presentation of both gratings. Reflexive eye movements tracked the vector average of both gratings (pattern motion) even though perceptual responses followed one motion direction exclusively (component motion). Observers almost never perceived pattern motion. This dissociation implies the existence of visual-motion signals that guide eye movements in the absence of a corresponding conscious percept.
Provider Characteristics Desired by African American Women in Prenatal Care
Authors: Lori Jody R. , Yi Chin Hwa , Martyn Kristy K.
Published: December 2010

Purpose: The purpose of this study was to describe provider characteristics African American pregnant women identified as important when interacting with their prenatal care providers in an outpatient office setting. Study Design and Method: A descriptive qualitative design was used to explore provider characteristics desired by African American women receiving prenatal care at two inner-city hospital—based obstetric clinics. A total of 22 African American women between the ages of 19 and 28 years participated in the study. Findings: Four major provider characteristic themes emerged from the data: (a) demonstrating quality patient—provider communication, (b) providing continuity of care, (c) treating the women with respect, and (d) delivering compassionate care. Discussion and Conclusion: An overarching theme revealed by the data analysis was the desire by African American women in this study to have their prenatal providers know and remember them. They wanted their providers to understand the context of their lives from their prenatal interactions. Incorporating findings from this study to improve patient—provider interactions during prenatal care could provide an increased understanding of the many complex variables affecting African American women’s lives. Implications for Practice and Research: Prenatal care provides an opportunity for African American women to develop a trusting relationship with a provider. Developing models of prenatal care congruent with the realities of African American women’s lives has the potential to improve patient— provider interactions and potentially affect birth outcomes.
Conducting Transcultural Research: Critical Thinking in Thailand
Authors: Jenkins Sheryl D.
Published: December 2010

Little has been written to help researchers prepare for the unique challenges of conducting transcultural research. The purpose of this article is to discuss issues that arose during the planning and execution of a transcultural study designed to compare critical thinking in Thailand and the United States. The challenges of identifying a research site, selecting participants, incorporating Thai research into the literature review, traveling and living in a foreign culture, overcoming cultural barriers to research, and strengthening internal validity and reliability are addressed.
The Authentic Place in the Amenity Migration Discourse
Authors: Osbaldiston Nick
Published: December 2010

The amenity migration movement has garnered significant interest across the wider academic community. In recent works, the emphasis on the investigation into this phenomenon has centered on the aesthetic attractiveness, both culturally and environmentally, of regional locations. This article follows this theme and explores the role of place in the amenity migration discourse. Using a theoretical framework emerging from the cultural sociology of Smith, it is shown through various metanarratives that authenticity plays a major role in the promotion and protection of amenity migration places. Specifically, natural landscape, cultural heritage, and community are discussed as significant contributors to this aura of authenticity. Maintaining this, however, is somewhat problematic as the phenomenon continues to gather momentum.
Measuring Technical Efficiency in Sports
Authors: Collier Trevor , Johnson Andrew L. , Ruggiero John
Published: December 2010

Standard economic production theory is the basis for measuring technical efficiency in sports. Using programming or regression models, efficiency is defined as the distance of a given team observation from the technology. In this article, the authors show that the standard measures of efficiency using deterministic models are biased downward due to serial correlation with respect to the efficiency measure. In particular, if the number of observed wins for a given team is affected by the team’s inefficiency, it is necessarily true that another team is able to produce outside of the technology. As a result, the observed frontier is not feasible if all inefficiency is eliminated. In this article, the authors propose a correction to this problem and apply new models to estimate efficiency in professional football.
The Construction of News: Energy Crises, Advocacy Messages, and Frames toward Conservation
Authors: Bolsen Toby
Published: December 2010

Much of what people learn about politics comes from the mass media. How media outlets construct their reports have direct consequences for what people think about politics. Scholars and pundits have long debated about the factors that shape media choices. Yet there have been few direct investigations into how three major determinants shape political news: world events, advocacy groups, and the government. This article examines the relative impact of these factors by focusing on the construction of news related to energy conservation in the United States. Specifically, it looks at how events, messages crafted by interest groups, and government-sponsored public service announcements (PSAs) affect news frames and attributions of responsibility for the extant energy situation. It finds that events are the most important factor driving news coverage; advocacy groups are second, followed by PSAs. This suggests that news about conservation is driven more by events than messages supplied by agents seeking to influence public discourse. Thus, groups with specific agendas such as government and advocacy organizations can, at least at times, be limited in terms of their capacity to shape news coverage—which has implications for theories of media choice.
Single-Agent Lenalidomide in the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
Authors: Chen Christine I. , Bergsagel P. Leif , Paul Harminder , Xu Wei , Lau Anthea , Dave Nimisha , Kukreti Vishal , Wei Ellen , Leung-Hagesteijn Chungyee , Li Zhi Hua , Brandwein Joseph , Pantoja Mariela , Johnston James , Gibson Spencer , Hernandez Tiffany , Spaner David , Trudel Suzanne
Published: December 2010

Purpose

Lenalidomide is an oral immunomodulatory drug with multiple effects on the immune system and tumor cell microenvironment leading to inhibition of malignant cell growth. Based on encouraging reports of lenalidomide in relapsed and refractory chronic lymphocytic leukemia (CLL), we investigated the first-line use of single-agent lenalidomide in CLL.

Patients and Methods

Using a starting dose of lenalidomide 10 mg/d for 21 days of a 28-day cycle and weekly 5-mg dose escalations to a target of 25 mg, we encountered severe toxicities (tumor lysis, fatal sepsis) in the first two patients enrolled. The study was halted and the protocol amended to a more conservative regimen: starting dose of lenalidomide 2.5 mg with monthly escalations to a target dose of 10 mg, and extended tumor lysis prophylaxis and monitoring. Gene expression profiles from patient samples before and after 7 days of lenalidomide were performed.

Results

Twenty-five patients were enrolled on the amended protocol. No further tumor lysis events were reported. Tumor flare was common (88%) but mild. Grade 3 to 4 neutropenia occurred in 72% of patients, with only five episodes of febrile neutropenia. The overall response rate was 56% (no complete responses). Although rapid peripheral lymphocyte reductions were observed, rebound lymphocytoses during the week off-therapy were common. Lenalidomide-induced molecular changes enriched for cytoskeletal and immune-related genes were identified.

Conclusion

Lenalidomide is clinically active as first-line CLL therapy and is well-tolerated if a conservative approach with slow dose escalation is used. A lenalidomide-induced molecular signature provides insights into its immunomodulatory mechanisms of action in CLL.
WT1 Mutation and 11P15 Loss of Heterozygosity Predict Relapse in Very Low-Risk Wilms Tumors Treated With Surgery Alone: A Children's Oncology Group Study
Authors: Perlman Elizabeth J. , Grundy Paul E. , Anderson James R. , Jennings Lawrence J. , Green Daniel M. , Dome Jeffrey S. , Shamberger Robert C. , Ruteshouser E. Cristy , Huff Vicki
Published: December 2010

Purpose

Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy.

Patients and Methods

Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation.

Results

11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors.

Conclusion

WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.
Intravenous Calcium and Magnesium for Oxaliplatin-Induced Sensory Neurotoxicity in Adjuvant Colon Cancer: NCCTG N04C7
Authors: Grothey Axel , Nikcevich Daniel A. , Sloan Jeff A. , Kugler John W. , Silberstein Peter T. , Dentchev Todor , Wender Donald B. , Novotny Paul J. , Chitaley Umesh , Alberts Steven R. , Loprinzi Charles L.
Published: December 2010

Purpose

Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT.

Methods

Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect.

Results

Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo.

Conclusion

Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.
Second Primary Cancers After an Index Head and Neck Cancer: Subsite-Specific Trends in the Era of Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Morris Luc G.T. , Sikora Andrew G. , Patel Snehal G. , Hayes Richard B. , Ganly Ian
Published: December 2010

Purpose

Patients with head and neck squamous cell carcinoma (HNSCC) are at elevated risk of second primary malignancies (SPM), most commonly of the head and neck (HN), lung, and esophagus. Our objectives were to identify HNSCC subsite-specific differences in SPM risk and distribution and to describe trends in risk over 3 decades, before and during the era of human papillomavirus (HPV) –associated oropharyngeal SCC.

Methods

Population-based cohort study of 75,087 patients with HNSCC in the Surveillance, Epidemiology, and End Results (SEER) program. SPM risk was quantified by using standardized incidence ratios (SIRs), excess absolute risk (EAR) per 10,000 person-years at risk (PYR), and number needed to observe. Trends in SPM risk were analyzed by using joinpoint log-linear regression.

Results

In patients with HNSCC, the SIR of second primary solid tumor was 2.2 (95% CI, 2.1 to 2.2), and the EAR was 167.7 cancers per 10,000 PYR. The risk of SPM was highest for hypopharyngeal SCC (SIR, 3.5; EAR, 307.1 per 10,000 PYR) and lowest for laryngeal SCC (SIR, 1.9; EAR, 147.8 per 10,000 PYR). The most common SPM site for patients with oral cavity and oropharynx SCC was HN; for patients with laryngeal and hypopharyngeal cancer, it was the lung. Since 1991, SPM risk has decreased significantly among patients with oropharyngeal SCC (annual percentage change in EAR, −4.6%; P = .03).

Conclusion

In patients with HNSCC, the risk and distribution of SPM differ significantly according to subsite of the index cancer. Before the 1990s, hypopharynx and oropharynx cancers carried the highest excess risk of SPM. Since then, during the HPV era, SPM risk associated with oropharyngeal SCC has declined to the lowest risk level of any subsite.
WT1 Synonymous Single Nucleotide Polymorphism rs16754 Correlates With Higher mRNA Expression and Predicts Significantly Improved Outcome in Favorable-Risk Pediatric Acute Myeloid Leukemia: A Report From the Children's Oncology Group
Authors: Ho Phoenix A. , Kuhn Julia , Gerbing Robert B. , Pollard Jessica A. , Zeng Rong , Miller Kristen L. , Heerema Nyla A. , Raimondi Susana C. , Hirsch Betsy A. , Franklin Janet L. , Lange Beverly , Gamis Alan S. , Alonzo Todd A. , Meshinchi Soheil
Published: December 2010

Purpose

To analyze the prevalence and clinical implications of Wilms' tumor 1 (WT1) single nucleotide polymorphism (SNP) rs16754 in the context of other prognostic markers in pediatric acute myeloid leukemia (AML).

Patients and Methods

Available diagnostic marrow specimens (n = 790) from 1,328 patients enrolled in three consecutive Children's Cancer Group/Children's Oncology Group trials were analyzed for the presence of SNP rs16754. SNP status was correlated with disease characteristics, WT1 expression level, and clinical outcome.

Results

SNP rs16754 was present in 229 (29%) of 790 patients. The SNP was significantly more common in Asian and Hispanic patients and less common in white patients (P < .001). SNP rs16754 was also less common in patients with inv(16) (P = .043) and more common in patients with −5/del(5q) (P = .047). WT1 expression levels were significantly higher in patients with rs16754 or with WT1 mutations compared with WT1 wild-type patients (P = .021). Five-year overall survival (OS) for patients with and without the SNP was 60% and 50%, respectively (P = .031). Prognostic assessment by risk group demonstrated that in patients with low-risk disease, OS for those with and without SNP rs16754 was 90% versus 64% (P < .001) with a corresponding disease-free survival of 72% versus 53% (P = .041).

Conclusion

The presence of SNP rs16754 was an independent predictor of improved OS; outcome differences were most pronounced in the low-risk subgroup. The high prevalence of WT1 SNP rs16754, and its correlation with improved outcome, identifies WT1 SNP rs16754 as a potentially important molecular marker of prognosis in pediatric AML.
Pediatric End-of-Life Care for Taiwanese Children Who Died As a Result of Cancer From 2001 Through 2006
Authors: Tzuh Tang Siew , Hung Yen-Ni , Liu Tsang-Wu , Lin Dong-Tsamn , Chen Yueh-Chih , Wu Shiao-Chi , Hsia Hsu Tsui
Published: December 2010

Purpose

Patterns of aggressive end-of-life (EOL) care have not been extensively explored in a pediatric cancer population, especially outside Western countries. The purpose of this population-based study was to examine trends in aggressive pediatric EOL cancer care in Taiwan.

Methods

Retrospective cohort study that used administrative data among 1,208 pediatric cancer decedents from 2001 through 2006.

Results

Taiwanese pediatric cancer patients who died in 2001 through 2006 received aggressive EOL care. The majority of these patients in their last month of life continued to receive chemotherapy (52.5%), used intensive care (57.0%), underwent intubation (40.9%), underwent mechanical ventilation (48.2%), or spent greater than 14 days (69.5%) in hospital, and they died in an acute care hospital (78.8%). Of these pediatric cancer patients, one in four received cardiopulmonary resuscitation in the month before they died, and only 7.2% received hospice care. Among those who received hospice care, 21.8% started such care within the last 3 days of life. This pattern of aggressive EOL care did not change over the study period except for significantly decreased intubation in the last month of life.

Conclusion

Continued chemotherapy and heavy use of life-sustaining treatments in the last month of life coupled with lack of hospice care to support Taiwanese pediatric cancer patients dying at home may lead to multiple unplanned health care encounters, prolonged hospitalization at EOL, and eventual death in an acute care hospital for the majority of these patients. Future research should design interventions that enable Taiwanese pediatric cancer patients to receive EOL care that best meets the individual or the parental needs and preferences.
Randomized Phase II Trial of Adjuvant Hepatic Arterial Infusion and Systemic Chemotherapy With or Without Bevacizumab in Patients With Resected Hepatic Metastases From Colorectal Cancer
Authors: Kemeny Nancy E. , Jarnagin William R. , Capanu Marinela , Fong Yuman , Gewirtz Alexandra N. , DeMatteo Ronald P. , D'Angelica Michael I.
Published: December 2010

Purpose

Add systemic bevacizumab (Bev) to adjuvant hepatic arterial infusion (HAI) plus systemic therapy after liver resection to increase recurrence-free survival (RFS).

Patients and Methods

Patients were randomly assigned to HAI plus systemic therapy with or without Bev. If 1-year RFS of ≥ 80% was obtained in Bev arm, then the regimen would be studied further. HAI with fluorodeoxyuridine plus dexamethasone was given on days 1 to 14 of a 5-week cycle. Systemic therapy and Bev 5 mg/kg was delivered on days 15 and 29: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2,000 mg/m2 infusion for 2 days (if patients received prior oxaliplatin, then irinotecan 150 mg/m2 was used). RFS and survival were estimated by using the Kaplan-Meier method and compared by using the log-rank test.

Results

The two arms had similar characteristics: synchronous disease (66% v 63%), more than one metastasis (84% v 74%), and clinical risk score ≥ 3 (50% v 46%) for no Bev versus Bev arms, respectively. With a median follow-up of 30 months, 4-year survival was 85% and 81% (P = .5), and 4-year RFS was 46% versus 37%; 1-year RFS was 83% and 71% (P = .4) for no Bev versus Bev arms. Bilirubin > 3 mg/dL was seen in zero of 38 versus five of 35 patients (P = .02) and biliary stents were placed in zero versus four patients (P = .05) in no Bev versus Bev arms.

Conclusion

The addition of Bev to adjuvant HAI plus systemic therapy after liver resection did not seem to increase RFS or survival but appeared to increase biliary toxicity. Four-year survival was 85% and 81% for no Bev and Bev arms, respectively.
Psychiatry and the Social Sciences, 1940–2009
Authors: Scull Andrew
Published: December 2010

This paper examines the changing relationship between psychiatry and three major social sciences, psychology, sociology, and economics, in the period between the outbreak of the Second World War and the end of the twentieth century. That interaction varied across the different disciplines and over time. The most sustained impact was on the discipline of psychology, where size and the shape of the discipline were radically transformed, beginning with the mental health crisis of the war years. In sociology, the initial cooperation with psychiatry that marked the late 1940s and 1950s was soon transformed into an adversarial relationship, before the two disciplines largely went their separate ways, beginning in the mid-1980s. At about the same time, mental health economics began to emerge as a subspecialty, though, for reasons the article explores, it has remained a marginal enterprise in the eyes of most professional economists.
Poverty in Cold War America: A Problem That Has No Name? The Invisible Network of Poverty Experts in the 1950s and 1960s
Authors: Huret Romain
Published: December 2010

This essay analyzes the network of social experts who launched the War on Poverty in the Kennedy and Johnson administrations from 1963 to 1968. If they are often neglected in historical accounts, which are focused on public intellectuals and presidential advisers, these experts played a major role in the process of defining poverty in the affluent society. From World War II to the 1960s, their work remained largely invisible since it was made in bureaucratic and academic circles. If experts had free rein to carry out research on income distribution and the establishment of a poverty line, they proved to be less powerful when poverty gained national and political attention. Paradoxically, the War on Poverty was a pyrrhic victory for this generation of experts, who tried to reinvigorate the liberal social contract of the postwar years in the United States.
Rebellions across the (Rice) Fields: Social Scientists and Indochina, 1965–1975
Authors: Rangil Teresa Tomás
Published: December 2010

This essay presents how, during the Indochinese revolutionary wars of the 1960s and 1970s, the traditional image of rebels inspired by moral causes or socioeconomic grievances was superseded by an image of purely materialistic, rational insurgents. Economists studied revolutions from two different traditions: the systems analysis perspective of the RAND Corporation and the rational choice analysis from the public choice school of Virginia. We situate their views with reference to explanations offered by other social scientists, especially modernization and relative deprivation theorists, as well as Marxist scholars to show how, from 1965 to 1975, economists' approach to revolutions gained momentum among social scientists.
Ground between Two Stones: Melville Herskovits and the Fate of Economic Anthropology
Authors: Pearson Heath
Published: December 2010

Melville Herskovits's work in economic anthropology, published between 1926 and 1952, sought to give the subdiscipline both a name and a characteristic mode of inquiry. The name stuck, but his methodological proposals were ultimately rejected by nearly all researchers in the field. Practitioners with an allegiance to economic theory took exception to Herskovits's insistence that culture be accepted as a primary determinant of human behavior; those with a commitment to anthropology proved equally resistant to his premise that all economic action be understood as “economizing,” that is, maximizing an objective subject to constraints. The fate of Herskovits's ideas over the past seventy years is distinctive: rejection was followed by caricature, then outright misrepresentation, and finally near-oblivion. This essay is offered not as a vindication of the Herskovits program for economic anthropology, but as a case study in how methodological exclusivity can result in flawed scholarship and in the stunting of interdisciplinary initiatives.
Marginal to the Revolution: The Curious Relationship between Economics and the Behavioral Sciences Movement in Mid-Twentieth-Century America
Authors: Pooley Jefferson , Solovey Mark
Published: December 2010

American economics largely ignored the behavioral sciences movement in the decade after World War II. The social scientists who adopted the “behavioral sciences” moniker were self-consciously nomothetic, fond of mathematics and statistical analysis, and eager to stand close to the natural sciences. The same was true of leading postwar economists, and yet they alone opted out, with only a few exceptions. We explore this divide as it emerged in the early development of the Ford Foundation's Behavioral Sciences Program (BSP). We describe early efforts to incorporate economics into the BSP in a substantial manner, premised on the belief that economic analysis could be greatly strengthened by the behavioral science orientation, with its emphasis on rigorous empirical study of actual human behavior. Yet these efforts failed, in large part because economists, especially those commonly labeled “neoclassical,” were uninterested, skeptical, and even dismissive of what they took to be an immature and faddish initiative. Gaps in postwar prestige and clashing models of social science contributed to the Ford Foundation's decision to fund economics on a separate track from the other social sciences. In our account, the adoption of the “behavioral sciences” terminology in tandem with the movement's institutional anchoring at the Ford Foundation thus reflected and widened the split between economists and their counterparts in the other social sciences.
Specializing in Interdisciplinarity: The Committee on Social Thought as the University of Chicago's Antidote to Compartmentalization in the Social Sciences
Authors: Emmett Ross B.
Published: December 2010

The social sciences at the University of Chicago are renowned for their leadership in the development of empirical investigation in their respective disciplines. The postwar Chicago school of economics is only the best known of the efforts at that university to entrench specialized competencies in the faculty and students practicing a social scientific discipline. During the same period, the Committee on Social Thought emerged as an academic interdisciplinary unit in the humanities and social sciences. Ironically, the committee became the place in which one honed the competencies required for a particular type of interdisciplinarity.
Economics and Sociology: From Complementary to Competing Perspectives
Authors: Geary Daniel
Published: December 2010

This article offers a case study of how social scientific disciplines differentiate themselves from one another, focusing on the relationship of economics to sociology. It presents four categories to describe common ways that economists and sociologists understood the relationship between the two disciplines. It argues that perceptions of the disciplines' relationship to one another shifted from complementary to competing in the post-1945 period.