bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Outcomes and Risk Factors in Venous Thrombectomy: An Analysis of the American College of Surgeons NSQIP Dataset
Authors: Davenport Daniel L. , Xenos Eleftherios S.
Published: March 2011

Objectives: Thrombus removal has been shown to improve venous physiology in acute iliofemoral deep-venous thrombosis. Our study focuses on the contemporary application of venous thrombectomy based on data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Methods: Data submitted by over 200 hospitals to the ACS NSQIP participant use file was accessed for the years 2005-2008. The ACS NSQIP protocol provides clinically rigorous preoperative risk and 30-day outcomes for a prospective and systematic sample of vascular surgery patients. Patients were identified who had undergone venous thrombectomy through leg access (Primary procedure CPT 34421 or 34451). Demographic and clinical variables along with 30-day morbidity (1 or more of 21 defined complications) and mortality were evaluated. Secondary/concomitant procedures CPT codes were collected. Univariate analysis between groups was performed using χ 2 or T-tests with P ≤ .05 considered significant. Results: A total of 91 patients were identified who underwent primary venous thrombectomy. The mean age was 62.5 ± 15.8 y and 45 of 91 (49.5%) were female. Thirty-day mortality was 8.8% (8/91). Composite morbidity was 25.3% (23/91). Intraoperative transfusion was required in 18.7% of the patients, lower extremity fasciotomy was performed in 8.8% of the patients and an inferior vena cava (IVC) filter was placed in 2.2% of the patients. An arteriovenous anastomosis was created in only 1 patient; venous angioplasty was performed in 3.3% of the patients. Conclusions: Venous thrombectomy is associated with significant postoperative morbidity and mortality. This is at least partially due to the associated comorbidities of this patient population, approximately 1/5 in our study were ASA class 4. Most frequent causes of morbidity are pulmonary and wound infection complications. Only 2 patients had an IVC filter placed during the operation. Adjunctive procedures to assist vein patency such as arteriovenous fistula creation or venous angioplasty were infrequently performed.
Asymptomatic Carotid Rete Mirabile and Contralateral Carotid Agenesis: A Case Report
Authors: Aburto-Murrieta Yolanda , Dulce Bonifacio-Delgadillo
Published: March 2011

Carotid rete mirabile (CRM) is a physiological network between the external carotid artery (ECA) and internal carotid artery (ICA) in lower mammals. It is a transdural arterial network centered at the parasellar area, in anatomical localization of intracavernous or petrous segment of ICA, associated with hypoplasia or absence of the cervical or petrous segment of ICA. It clinically presents as hemorrhagic or ischemic cerebrovascular disorder. Carotid rete mirabile have an angiographic frequency of 0.01%. The authors present a new case of right ICA agenesis supported by primary collateral channels associated with left hypoplasic ICA and CRM. It is an unusual entity and we highlight the role of CRM in cerebral hemodynamic in this asymptomatic vascular patient. Our aim is detail the angiographic features and diagnosis criteria of CRM.
Environmental Enrichment Facilitates Long-Term Potentiation in Embryonic Striatal Grafts
Authors: Mazzocchi-Jones David , Döbrössy Máté , Dunnett Stephen B.
Published: March 2011

Background. Housing animals in an enriched environment improves motor and cognitive performance and anatomical connectivity in rodent lesion models of Huntington disease and transplantation of embryonic striatal grafts. Objective. The authors evaluate the extent to which environmental enrichment can modify synaptic plasticity in the host-graft neuronal circuitry to try to find a physiological substrate for the observed improvements. Methods. C57BL/6 mice, housed in enriched or standard environments, received unilateral quinolinic acid lesions of the striatum, followed by embryonic striatal grafts. Then, 3 months posttransplantation, synaptic physiology and plasticity were evaluated by extracellular recording from in vitro striatal slices. Results. Environmental enrichment had no effect on the chance of long-term depression (LTD) induction or expression of LTD from either normal or grafted striatum. In contrast, enrichment increased the chance of long-term potentiation (LTP) induction and level of expression associated with increased levels of brain-derived neurotrophic factor within both the intact and grafted striatum compared with levels in the striatum of animals housed in standard environments. Conclusions. Environmental enrichment induces changes in host-graft corticostriatal LTP, thus providing a potential physiological substrate for the enrichment-induced improvement in motor and cognitive performance. The effect may be mediated by modulation of the trophic environment in which the grafted cells develop and integrate.
Rules, Rhetoric, and Genre: Procedural Rhetoric in Persona 3
Authors: Harper Todd
Published: March 2011

Released in 2008 for the Playstation 2, Shin Megami Tensei: Persona 3 is a roleplaying game with a diverse genre pedigree. It is a combination of dungeon-crawling RPG and social interaction ‘‘datesim,’’ all wrapped up in the thematic trappings of occult mystery and Japanese popular culture. Using Ian Bogost’s (2007) concept of procedural rhetoric, this article examines how Persona 3’s use of genre conventions and gameplay-based rhetorical frames construct the game’s message, as well as how those structures can inform our understanding of genre for the digital game form.
Flow Experience and Mood States While Playing Body Movement-Controlled Video Games
Authors: Thin Alasdair G. , Hansen Lisa , McEachen Danny
Published: March 2011

Body movement-controlled video games (BMCVGs) are a genre of video gaming utilizing body movement to control game play that is becoming increasingly popular. Despite the popularity and widespread interest in BMCVGs, there is limited information available about the nature of the players’ experiences when they engage in BMCVG play. A total of 14 young adults played 6 different BMCVGs for 6 min each and performed traditional cycling exercise in a randomized order. After two familiarization sessions, on a third occasion, subjects rated their enjoyment and completed the Flow State Scale-2 questionnaire. The BMCVGs were rated more enjoyable than traditional cycling exercise and the Flow dimensions Challenge-Skill Balance and Merging of Action and Awareness scored significantly higher than the norms for exercise activity and instead corresponded more closely to the norms for sporting activity. These findings suggest that BMCVGs could therefore act as a gateway for sedentary individuals to become involved in sporting activities.
More Than Method?: A Discussion of Paradigm Differences Within Mixed Methods Research
Authors: Sommer Harrits Gitte
Published: March 2011

This article challenges the idea that mixed methods research (MMR) constitutes a coherent research paradigm and explores how different research paradigms exist within MMR. Tracing paradigmatic differences at the level of methods, ontology, and epistemology, two MMR strategies are discussed: nested analysis, recently presented by the American political scientist Evan S. Lieberman, and praxeological knowledge, inspired by the French sociologist Pierre Bourdieu. These strategies address two different epistemological problems, namely, the problem of causal inference and the problem of double hermeneutics. Consequently, the research designs as well as the understandings of the “qualitative component” differ noticeably. Realizing such differences at the ontological, epistemological, and methodological level contributes to discussions on how to move forward MMR, embracing differences instead of imposing homogeneity.
Hydration and Medication Use
Authors: Walter Andrea N. , Lenz Thomas L.
Published: March 2011

Hydration is an important part of overall health and also appears to be necessary for the prevention of adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Evidence has shown that this type of medication does little to prevent the onset of muscle soreness and/or damage when used prior to or during physical activity. However, taking this medication while dehydrated may lead to decreased kidney function. Therefore, NSAIDs should be reserved for pain relief and injury treatment. Additionally, an individual’s hydration status can be affected by medications that have the potential to alter thirst sensation, leading to decreased fluid intake, and diuretics, which lead to increased urine output. It is important for individuals taking these medications to be aware of how they may affect hydration status.
Toward a Sociology of Perception: Sight, Sex, and Gender
Authors: Friedman Asia
Published: March 2011

Many theories of social construction make some reference to sight, yet few offer sustained examinations of perception. In light of this, I highlight the visual dimension of the social construction of reality by analyzing visual perception as a process of ‘socio-mental filtration’. Building on theories of social construction — most notably those using the concepts ‘frame’, ‘paradigm’ and ‘schema’ — in which expectations are the organizing force of experience, I focus on how social construction happens. One key effect of expectations is to enact selective attention, which is evocatively captured by the metaphor of a filter. Drawing on the case of sex and gender, I demonstrate that using filter analysis to identify the specific dynamics of ‘socio-optical construction’ — adding a concrete analysis of visual perception to the general idea of social construction — may help scholars to more effectively account for some of the ‘hard problems’ of constructionist theory, such as the body.
Symbolic Use of Decisive Events: Tiananmen as a News Icon in the editorials of the elite U.S. press
Authors: Lee Chin-Chuan , Hongtao Li  , Lee Francis L. F.
Published: March 2011

The Tiananmen crackdown on the pro-democracy movement in 1989 was a decisive event that has provided an enduring prism for the world media to interpret China. This article examines how two of the most preeminent U.S. newspapers— New York Times and Washington Post—editorially invoked Tiananmen as a “news icon” in the past twenty years. We contend that the meanings of Tiananmen were reconstructed over twenty years partly but not completely in line with the changes in the United States’ policy toward China. Specifically, Tiananmen symbolized Communist dictatorship in the initial years after 1989 and then became an example of China’s human rights abuse in the late 1990s. Into the 2000s, the significance of Tiananmen faded away. But it remained as part of United States’ ritualistic memory of China’s repression that invokes the moral bottom line of U.S. foreign policy. In theoretical terms, this study shows how a news icon, in the course of an extended life cycle, may exhibit both continuities and changes in its meanings, and there can also be subtle variations in the relationships between a news icon and the dominant power structure over time.
Organic Nutrition in Pediatrics
Authors: Wilson Diane R.
Published: March 2011

The organic movement is not a recent fad for the environmentally conscious family. The health of children is becoming a driving force for the use of organic foods and beverages. The elimination of foods containing artificial dyes continues to be researched for conditions such as autism and attention deficit/hyperactivity disorders. Concern has been expressed by key pediatric professionals on the exposure of children to endocrine-disrupting chemicals in foods and food packaging and the role they might play in the development of diabetes and childhood obesity. Agricultural scientists continue to investigate the nutritional superiority of organically grown foods, especially their higher content of many antioxidants. Registered dietitians are in a position to aid families in learning about the health benefits of organic foods and ways to make a child’s nutritional environment safer and healthier.
Improving Outcomes Through Quality Improvement
Authors: Charlton Rebecca , Platzker Arnold , Margetis Monique
Published: March 2011

The nutrition quality improvement (QI) program at the Cystic Fibrosis (CF) Center of Childrens Hospital Los Angeles (CHLA)aimed to increase patient body mass index (BMI) through improved clinician (physician, dietitian, and social worker) adherence to nutrition recommendations set forth by the Cystic Fibrosis Foundation (CFF). The QI program used a combination of strategies intended to increase cognitive cues for desired behaviors and to promote environmental change intended to prompt clinicians to adopt nutrition treatment recommendations. Program analysis involved collection of data on clinician behavior, nutrition treatment plans, and patient BMI. Evaluation involved a pretest—posttest design with multiple observations to determine behavior maintenance throughout the 18-month study period. Results indicate that the program produced changes in clinician behavior as evidenced by increased rates of adherence to nutrition recommendations, including the use of BMI/age as the primary nutrition marker and recommending aggressive nutrition treatment, though with noted attrition by the final data collection period. A clear trend toward improvement in BMI/age was evident with statistical significance at the P < .05 level. The QI program demonstrated that simple behavior cues in combination with training can produce changes in clinician behavior, which in turn affects patient outcomes.
Pancreatic Enzyme Products: What’s New?
Authors: Grande Laura
Published: March 2011

A healthy pancreas produces the enzymes lipase, protease, and amylase that assist in the cleaving of food particles and the absorption of nutrients. Patients with pancreatic insufficiency, commonly seen in the cystic fibrosis (CF) population, are unable to produce these enzymes endogenously. Standard treatment for pancreatic insufficiency is pancreatic enzyme replacement therapy administered by mouth. Most endogenous enzymes were developed prior to the Federal Food, Drug, and Cosmetic Act of 1938. As a result, they were marketed by companies and used by patients without the thorough investigation of the Food and Drug Administration (FDA). Enzyme manufacturers were given a deadline of April 28, 2010, by the FDA to conduct safety and efficacy studies and to submit New Drug Applications. Currently, there are only 3 FDA-approved enzyme products on the market: Creon, Zenpep, and Pancreaze. This article discusses the changes to pancreatic enzyme products over the past year and the challenges that CF practitioners have faced as a result of the changes.
Evaluation and Management of Posterior Shoulder Instability
Authors: Tannenbaum Eric , Sekiya Jon K.
Published: March 2011

Context: Posterior shoulder instability is a commonly misdiagnosed disorder in many competitive athletes.

Type of Study: Clinical review.

Evidence Acquisition: Relevant studies on posterior shoulder instability from 1950 to 2010 in PubMed and Cochrane databases were reviewed.

Results: A total of 107 studies were reviewed.

Conclusion: Patients who have undergone at least 6 months of physical therapy and still experience instability symptoms should be considered for surgical stabilization directed at their underlying pathology.
Activity Profile of Members of an Online Health Community After Articular Cartilage Repair of the Knee
Authors: Hambly Karen
Published: March 2011

Background: Articular cartilage repair (ACR) procedures aim to alleviate pain and restore function for individuals with chondral defects. Rehabilitation is lengthy, and there are limited data on return to sports and exercise activities after ACR in non-elite-athlete populations. The Internet is a growing source of health-related information for patients, and it has resulted in the emergence of online health communities.

Purpose: To establish a postoperative activity profile of users of an online health community who have undergone ACR of the knee and to compare this profile with those from the same community who have undergone initial anterior cruciate ligament reconstruction (ACLR).

Study Design: Cross-sectional.

Methods: Tegner Activity Scale ratings were collected via a self-reported online questionnaire from 201 participants of an online health community who had undergone tibiofemoral and/or patellofemoral ACR (n = 75) or ACLR (n = 126).

Results: A higher Tegner activity level was significantly correlated to time from surgery for ACR (P < 0.005) and ACLR (P < 0.01). At a minimum of 24 months’ follow-up, the ACR group had a median postoperative Tegner score of 3, compared with 6 for the ACLR group. Tegner score was significantly negatively correlated with age at time of surgery for ACLR (P < 0.05) but not for ACR. Men demonstrated significantly higher Tegner activity levels than did women for both ACLR and ACR (P < 0.05).

Conclusions: Activity levels after ACR in this population increased with postoperative time but remained lower than expected when compared with current published clinical and normative data.

Clinical Relevance: Engagement with an online health community may influence expectations regarding return to sports and exercise activities. Reporting of activity-level data within clinical studies should be differentiated on the basis of sex. Further research is needed to elucidate factors that determine return to sports and exercise activities after ACR.
Subscapularis Strain From Swinging a Baseball Bat in an Adolescent With Closed Physis
Authors: Higgins Brendan T. , Teixeira Rafael P. , Johnson Alan R. , Carrino John A. , McFarland Edward G.
Published: March 2011

A healthy 16-year-old female baseball player was referred by her pediatrician for evaluation of pain in her right, dominant shoulder. The pain had begun insidiously 4 weeks previously after several sessions of batting practice and had worsened until she could not participate in baseball, even with low doses of ibuprofen. She was not participating in any other sports or weight lifting and had had no previous incidents of shoulder pain, but she did have a history of being able to voluntarily subluxate the right shoulder since she was a child. Her voluntary shoulder subluxation and reduction did not reproduce or worsen her pain. Results from her physical examination and radiographs were normal. Magnetic resonance imaging showed edema in the subscapularis muscle consistent with acute muscle strain. She was treated with 6 weeks of rest, ice, and anti-inflammatory medication as needed. She returned to baseball and hitting during the following 6 weeks with no limitations.
The Resource Replenishment Function of Interest
Authors: Thoman Dustin B. , Smith Jessi L. , Silvia Paul J.
Published: March 2011

Interest is a positive emotion associated with increased approach motivation, effort, attention, and persistence. Although experiencing interest promotes behaviors that demand cognitive resources, interest is as a coping resource in frustrating learning situations and is central to self-regulation and sustained motivation. Positive affect, in general, tends to replenish resources, but based on the functions of interest and what interest promotes we suggest that interest, in particular, promotes greater resource replenishment. Across three experiments, experiencing interest during activity engagement (Studies 1 and 2), even when interest is activated via priming (Study 3), caused greater effort and persistence in subsequent tasks than did positive affect. This effect occurred only when participants' psychological resources were previously depleted (Study 1). Paradoxically, engaging an interesting task replenished resources (vs. positive and neutral tasks) even though the interesting task was more complex and required more effort.
A Collaborative Approach to Control Hypertension in Diabetes
Authors: McKee M. Diane , Fletcher Jason , Sigal Irina , Giftos Jonathon , Schechter Clyde , Walker Elizabeth A.
Published: March 2011

We sought to develop and pilot an intervention to improve blood pressure (BP) and other intermediate outcomes (hemoglobin A1c, low-density lipoprotein cholesterol) of diabetes in a low-income, ethnically diverse population. English- or Spanish-speaking primary care patients with BP ≥ 140/90 on 2 visits in the past 12 months and any level of A1c were randomized to usual care (n = 24) or intervention (n = 31). Home health nurses assessed self-management and medication adherence, and they performed health behavior counseling. Participants transmitted daily BP and glucose results using simple home telemetry units to the nurse coordinator; these results were then aggregated and transmitted weekly to primary care providers to facilitate intensified treatment. After controlling for baseline levels, a significantly larger proportion of the intervention group was at goal for BP (adjusted OR = 9.3, P = .006) and A1c (AOR = 4.3, P = .049), but not for low-density lipoprotein cholesterol (AOR = 1.1, P =.86). Clinicians made more BP medication changes in the intervention group compared to the control group (8.3 vs 3.8, approaching significance at P = .06). Self-reported medication adherence and self-care behaviors were not significantly improved. We successfully developed a telephone- and email-based collaboration between home health nurses and primary care clinicians to address poorly controlled hypertension in an ethnically diverse population. The intervention, combining enhanced feedback to patients and their primary care providers and individualized behavior change support by home health nurses, is effective for improving BP and glucose in this setting.
Heme regulates B-cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cells as a ligand of Bach2
Authors: Watanabe-Matsui Miki , Muto Akihiko , Matsui Toshitaka , Itoh-Nakadai Ari , Nakajima Osamu , Murayama Kazutaka , Yamamoto Masayuki , Ikeda-Saito Masao , Igarashi Kazuhiko
Published: March 2011

Heme binds to proteins to modulate their function, thereby functioning as a signaling molecule in a variety of biologic events. We found that heme bound to Bach2, a transcription factor essential for humoral immunity, including antibody class switch. Heme inhibited the DNA binding activity of Bach2 in vitro and reduced its half-life in B cells. When added to B-cell primary cultures, heme enhanced the transcription of Blimp-1, the master regulator of plasma cells, and skewed plasma cell differentiation toward the IgM isotype, decreasing the IgG levels in vitro. Intraperitoneal injection of heme in mice inhibited the production of antigen-specific IgM when heme was administered simultaneously with the antigen but not when it was administered after antigen exposure, suggesting that heme also modulates the early phase of B-cell responses to antigen. Heme oxygenase-1, which is known to be regulated by heme, was repressed by both Bach2 and Bach1 in B cells. Furthermore, the expression of genes for heme uptake changed in response to B-cell activation and heme administration. Our results reveal a new function for heme as a ligand of Bach2 and as a modulatory signal involved in plasma cell differentiation.
Epitope characterization and crystal structure of GA101 provide insights into the molecular basis for type I/II distinction of CD20 antibodies
Authors: Niederfellner Gerhard , Lammens Alfred , Mundigl Olaf , Georges Guy J. , Schaefer Wolfgang , Schwaiger Manfred , Franke Andreas , Wiechmann Kornelius , Jenewein Stefan , Slootstra Jerry W. , Timmerman Peter , Brännström Annika , Lindstrom Frida , Mössner Ekkehard , Umana Pablo , Hopfner Karl-Peter , Klein Christian
Published: March 2011

CD20 is a cell-surface marker of normal and malignant B cells. Rituximab, a monoclonal antibody targeting CD20, has improved the treatment of malignant lymphomas. Therapeutic CD20 antibodies are classified as either type I or II based on different mechanisms of killing malignant B cells. To reveal the molecular basis of this distinction, we fine-mapped the epitopes recognized by both types. We also determined the first X-ray structure of a type II antibody by crystallizing the obinutuzumab (GA101) Fab fragment alone and in complex with a CD20 cyclopeptide. Despite recognizing an overlapping epitope, GA101 binds CD20 in a completely different orientation than type I antibodies. Moreover, the elbow angle of GA101 is almost 30° wider than in type I antibodies, potentially resulting in different spatial arrangements of 2 CD20 molecules bound to a single GA101 or rituximab molecule. Using protein tomography, different CD20 complexes were found to be associated with the 2 antibodies, and confocal microscopy showed different membrane compartmentalization of these subpopulations of the cellular CD20 pool. Our findings offer a possible molecular explanation for the different cellular responses elicited by type I and II antibodies.
Initiatives to shorten duration of untreated psychosis: systematic review
Authors: Lloyd-Evans Brynmor , Crosby Michelle , Stockton Sarah , Pilling Stephen , Hobbs Lorna , Hinton Mark , Johnson Sonia
Published: March 2011

Background

Long duration of untreated psychosis (DUP) is common and associated with poor outcomes. Strategies to enhance early detection of first-episode psychosis have been advocated.

Aims

To evaluate initiatives for early detection of psychosis.

Method

Systematic review of available evidence on the effectiveness of early detection initiatives to reduce the DUP.

Results

The review included 11 studies which evaluated 8 early detection initiatives. Evidence suggests that general practitioner education campaigns and dedicated early intervention services do not by themselves reduce DUP or generate more treated cases. Evidence for multifocus initiatives is mixed: intensive campaigns targeting the general public as well as relevant professionals may be needed. No studies evaluated initiatives targeting young people or professionals from non-health organisations.

Conclusions

How early detection can be achieved is not clear. Evidence is most promising for intensive public awareness campaigns: these require organisation and resourcing at a regional or national level. More good-quality studies are needed to address gaps in knowledge.
Childhood eating disorders: British national surveillance study
Authors: Nicholls Dasha E. , Lynn Richard , Viner Russell M.
Published: March 2011

Background

The incidence of eating disorders appears stable overall, but may be increasing in younger age groups. Data on incidence, clinical features and outcome of early-onset eating disorders are sparse.

Aims

To identify new cases of early-onset eating disorders (<13 years) presenting to secondary care over 1 year and to describe clinical features, management and 1-year outcomes.

Method

Surveillance over 14 months through the established British Paediatric Surveillance System, and a novel child and adolescent psychiatry surveillance system set up for this purpose.

Results

Overall incidence was 3.01/100 000 (208 individuals). In total, 37% met criteria for anorexia nervosa; 1.4% for bulimia nervosa; and 43% for eating disorder not otherwise specified. Nineteen per cent showed determined food avoidance and underweight without weight/shape concerns. Rates of comorbidity were 41%; family history of psychiatric disorder 44%; and early feeding difficulties 21%. Time to presentation was >8 months. A total of 50% were admitted to hospital, typically soon after diagnosis. Outcome data were available for 76% of individuals. At 1 year, 73% were reported improved, 6% worse and 10% unchanged (11% unknown). Most were still in treatment, and seven were hospital in-patients for most of the year.

Conclusions

Childhood eating disorders represent a significant clinical burden to paediatric and mental health services. Efforts to improve early detection are needed. These data provide a baseline to monitor changing trends in incidence.
The Madrid Declaration: why we need a coordinated Europe-wide effort in mental health research
Authors: Ayuso-Mateos José L. , Wykes Til , Arango Celso
Published: March 2011

The Madrid Declaration is being promoted by representatives from seven nationally funded mental health research networks, along with leaders of ongoing European Union-funded mental health projects. It advocates the creation of a Network of Excellent Networks, based on a dynamic and adaptive cross-European network of distinctly qualified research centres.
Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix
Authors: Dueñas-González Alfonso , Zarbá Juan J. , Patel Firuza , Alcedo Juan C. , Beslija Semir , Casanova Luis , Pattaranutaporn Pittayapoom , Hameed Shahid , Blair Julie M. , Barraclough Helen , Orlando Mauro
Published: March 2011

Purpose

To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.

Patients and Methods

Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).

Results

Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.

Conclusion

Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.
Prospective Study of Breast Cancer Incidence in Women With a BRCA1 or BRCA2 Mutation Under Surveillance With and Without Magnetic Resonance Imaging
Authors: Warner Ellen , Hill Kimberley , Causer Petrina , Plewes Donald , Jong Roberta , Yaffe Martin , Foulkes William D. , Ghadirian Parviz , Lynch Henry , Couch Fergus , Wong John , Wright Frances , Sun Ping , Narod Steven A.
Published: March 2011

Purpose

The sensitivity of magnetic resonance imaging (MRI) for breast cancer screening exceeds that of mammography. If MRI screening reduces mortality in women with a BRCA1 or BRCA2 mutation, it is expected that the incidence of advanced-stage breast cancers should be reduced in women undergoing MRI screening compared with those undergoing conventional screening.

Patients and Methods

We followed 1,275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years. In total, 445 women were enrolled in an MRI screening trial in Toronto, Ontario, Canada, and 830 were in the comparison group. The cumulative incidences of ductal carcinoma in situ (DCIS), early-stage, and late-stage breast cancers were estimated at 6 years in the cohorts.

Results

There were 41 cases of breast cancer in the MRI-screened cohort (9.2%) and 76 cases in the comparison group (9.2%). The cumulative incidence of DCIS or stage I breast cancer at 6 years was 13.8% (95% CI, 9.1% to 18.5%) in the MRI-screened cohort and 7.2% (95% CI, 4.5% to 9.9%) in the comparison group (P = .01). The cumulative incidence of stages II to IV breast cancers was 1.9% (95% CI, 0.2% to 3.7%) in the MRI-screened cohort and 6.6% (95% CI, 3.8% to 9.3%) in the comparison group (P = .02). The adjusted hazard ratio for the development of stages II to IV breast cancer associated with MRI screening was 0.30 (95% CI, 0.12 to 0.72; P = .008).

Conclusion

Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced-stage breast cancer in BRCA1 and BRCA2 carriers.
Phase I Trials of Molecularly Targeted Agents: Should We Pay More Attention to Late Toxicities?
Authors: Postel-Vinay Sophie , Gomez-Roca Carlos , Molife L. Rhoda , Anghan Bhavesh , Levy Antonin , Judson Ian , De Bono Johann , Soria Jean-Charles , Kaye Stan , Paoletti Xavier
Published: March 2011

Purpose

Phase I trials traditionally aim at determining the recommended phase II dose (RP2D) using grade ≥ 3 toxicity data from cycle 1 (C1) only. This design dates from the era of conventional chemotherapy and may not be relevant for new molecularly targeted agents (MTAs) usually administered in a chronic fashion and for which late or moderate toxicities may deserve particular attention.

Patients and Methods

All consecutive patients treated in phase I trials of MTAs at the Royal Marsden Hospital and Institut Gustave Roussy between January 2005 and July 2008 were included. Gastrointestinal, skin, and clinical renal toxicities of any grade and grades 3 to 4 toxic events of any type occurring at any cycle on treatment were recorded. Doses administered, treatment interruptions, dose modifications, and prescription of comedications were analyzed.

Results

A total of 445 patients (1,566 cycles; median treatment duration, 55 days) were included in 36 eligible trials; 790 toxicities (590, grade 1; 176, grade, 2; 24 grades, 3 to 4) and 1,819 toxicities (1,521, grade 1; 265, grade 2; 33, grades 3 to 4) were recorded during and after C1, respectively; 57% of the grades 3 to 4 toxicities occurred after C1; 50% of patients presented their worst-grade toxicity after C1. The risk of grades 3 to 4 toxicity was 3% in cycles 1 to 6 and was almost null afterwards. No cumulative toxicities were observed. Median toxicity duration was 15 days, with comedication administered in 68% of events.

Conclusion

Moderate and severe toxicities occur regularly after the first cycle in phase I trials of MTAs and may deserve increased attention in the RP2D process for these agents.
Bilateral Negative Sentinel Nodes Accurately Predict Absence of Lymph Node Metastasis in Early Cervical Cancer: Results of the SENTICOL Study
Authors: Lécuru Fabrice , Mathevet Patrice , Querleu Denis , Leblanc Eric , Morice Philipe , Daraï Emile , Marret Henri , Magaud Laurent , Gillaizeau Florence , Chatellier Gilles , Dargent Daniel
Published: March 2011

Purpose

Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy.

Patients and Methods

Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes.

Results

One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally.

Conclusion

Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.
Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial
Authors: Mikkelsen Torben S. , Sparreboom Alex , Cheng Cheng , Zhou Yinmei , Boyett James M. , Raimondi Susana C. , Panetta John C. , Bowman W. Paul , Sandlund John T. , Pui Ching-Hon , Relling Mary V. , Evans William E.
Published: March 2011

Purpose

To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m2) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG1-7) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes.

Methods

From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m2) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG1-7in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells).

Results

The 24-hour infusion resulted in significantly higher amounts of MTXPG1-7in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/109cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG1-7accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/109cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG1-7but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG1-7accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation.

Conclusion

Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes.
Conventional-Dose Versus High-Dose Chemotherapy As First Salvage Treatment in Male Patients With Metastatic Germ Cell Tumors: Evidence From a Large International Database
Authors: Lorch Anja , Bascoul-Mollevi Caroline , Kramar Andrew , Einhorn Lawrence , Necchi Andrea , Massard Christophe , De Giorgi Ugo , Fléchon Aude , Margolin Kim , Lotz Jean-Pierre , Germà-Lluch Jose Ramon , Powles Thomas , Kollmannsberger Christian , Beyer Jörg
Published: March 2011

Purpose

Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience progression with first-line treatment.

Patients and Methods

Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables.

Results

Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups.

Conclusion

This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population.
Mah Laqa Bai and Gender: The Language, Poetry, and Performance of a Courtesan in Hyderabad
Authors: Kugle Scott
Published: March 2011

Shi`i devotion and Urdu poetry both flourished in unique ways in the Deccan region, but did these cultural phenomena allow new creativity for women? This question can be addressed by examining the courtesan Mah Laqa Bai (AH 1181–1240/1768–1824), one of the most powerful figures in the court of the second Nizam of Hyderabad, Nizam `Ali Khan (r. 1762–1803), and the third Nizam, Sikandar Jah (r. 1803–29), as well as being mistress to their prime ministers of Iranian descent. She was one of the first women poets to compile a full divan of Urdu ghazals and was adept at music and dance. This essay examines the issue of gender in her poetry and personality. It argues that she wrote as a woman but in the poetic male voice. She wrote at a time when Urdu in the Deccan region was being altered to conform to Mogul standards with heavy “Persianization” of its diction. The essay asks whether Deccani Urdu was a feminine language before this reform, as argued by some literary historians of the Deccan. It then asks whether Mah Laqa Bai had a feminist agenda as a women poet of the eighteenth century, as charged by some feminist scholars of the Deccan. The essay concludes that Mah Laqa Bai's concept of the feminine was shaped by her role as a dancing female devotee of Imam `Ali, rather than by linguistic structures or political ideologies.
May Fatimah Gather Our Tears: The Mystical and Intercessory Powers of Fatimah al-Zahra in Indo-Persian, Shi`i Devotional Literature and Performance
Authors: Ruffle Karen G.
Published: March 2011

“The Mistress of Two Worlds” explores the ways that Fatimah al-Zahra's mystical and intercessory powers construct a temporal devotional world for the Shia. of the Deccan in south-central India, projecting individual loyalty to the imams and remembrance of their sacrifices into an eschatological framework in which Fatimah is transformed from a gatherer of the tears of the mourners into the judge and intercessory authority of Muslim loyalty to the Ahl-e Bait on the Day of Judgment. This essay focuses on four aspects of Fatimah's mystical and intercessory powers in Indo-Persian Shiism: (1) Fatimah's pre-eternal light that generates prophecy and the imamate, illuminating heaven on the Day of Judgment; (2) the imitable, worldly model that Fatimah's poverty and faith provide for the Shia to integrate into their daily lives; (3) the role of relics and other ritual objects endowed with Fatimah's intercessory grace (baraka) in Hyderabadi Shii devotion; and (4) Fatimah's role as the ultimate intercessor and arbitrator on the Day of Judgment in Hyderabadi Shiism.
The Road That Never Was: The Silk Road and Trans-Eurasian Exchange
Authors: Rezakhani Khodadad
Published: March 2011

The Silk Road is commonly used as a convenient blanket term to describe the many trade routes and points of contact that criss-crossed Central Asia. The term is generally overused, to the point that everything in the history of the region is conceptualized within the confines of the Silk Road(s). By reading Greco-Roman and particularly Chinese sources on the contacts between the eastern and western termini of the Eurasian continent, this article demonstrates that the Silk Road is not only a nineteenth-century name but, indeed, a modern historiographical invention, serving to lump together individual histories and creating long-distance connections where they never existed. It is proposed that for a more productive study of Central Asian history, we must do away with the notion of the Silk Road and notice the realities, to consider individual socioeconomic systems and their peculiarities.
Children of Cain in the Land of Error: A Central Asian Merchant's Treatise on Government and Society in Ming China
Authors: Hemmat Kaveh Louis
Published: March 2011

The Khatay'namah, or Book of China, a description of Chinese government and society in the mid-Ming period, written by a Central Asian merchant and presented to the Ottoman court in 1516, is evidence that the advent of more rationalized, centralized, and bureaucratic forms of governance in Ming China played a significant role in political developments in the Islamic world. The political ideology of the Ming founder, combining bureaucratic absolutism with a kind of populism that emphasized a direct connection between ruler and subjects, would see a close parallel in the Ottoman Empire in the reign of Suleyman I (1520–66). The Chinese near contemporary of Suleyman, the Zhengde emperor (1505–21), promoted his reign as a continuation of the Mongol Empire, called himself by the title Sheikh `Alam, and took other measures that engendered speculation of his conversion to Islam. This and other developments in China, including construction of the Great Wall in the late fifteenth century, resonated with millenarian beliefs in the Islamic world. The Khatay'namah's description of China evokes millenarian, utopian ideals but also demystifies China's prosperity, which it attributes to the Chinese people's assiduous adherence to law and system, or qanun. This account of China reflects the importance of cross-border trade, the military, and Muslim Chinese communities as sites of encounter between the Islamic world and the Chinese state. The text's rhetorical strategy of emphasizing similarities between China and the Ottoman Empire may be a reflection of early attempts by Muslim Chinese to negotiate a distinct Chinese Islamic identity.
The Imaginary Realm: Europe's Enlightenment Image of Early Modern Iran
Authors: Matthee Rudi
Published: March 2011

This essay explores the historical roots of the enigma that Iran perpetually presents to the outside world—a bleak and forbidding, deeply religious place that is also welcoming, poetic, and remarkably secular—by tracing the image European Enlightenment thinkers constructed of the country and its inhabitants. They were inspired by the lived experience of famous seventeenth-century travelers such as Jean Chardin and Jean-Baptiste Tavernier, but, writing after the fall of the Safavids, at a time when Iran had dissolved into chaos and despotism and when Westerners no longer visited the country, they ended up constructing an imaginary realm. Iranians simultaneously appear as stoics and epicureans; they are spiritually inclined but also crassly materialistic; they are often amazingly tolerant but as often fanatical, and though refined, they can also be unspeakably cruel. The resulting contradictory imagery—from which we still borrow—shows us Iran as the complex place that it was but also as a reflection of Europe's own foibles and anxieties, as the self seen through the other. Enlightenment thinkers, grappling with questions about human nature and the essence of power, juxtaposed the glories of the country's old civilization and its rich cultural legacy to its ruined melancholy presence, using this fallen state as a mirror and a morality tale about the laws of nature and the frailty of the human condition.