bluuebunny/crossref_metadata_2025 huggingface dataset:
c-Src Activation Mediates Erlotinib Resistance in Head and Neck Cancer by Stimulating c-Met
Authors: Stabile Laura P. , He Guoqing , Lui Vivian Wai Yan , Thomas Sufi M. , Henry Cassandra , Gubish Christopher T. , Joyce Sonali , Quesnelle Kelly M. , Siegfried Jill M. , Grandis Jennifer R.
Published: December 2012

Purpose: Strategies to inhibit the EGF receptor (EGFR) using the tyrosine kinase inhibitor erlotinib have been associated with limited clinical efficacy in head and neck squamous cell carcinoma (HNSCC). Co-activation of alternative kinases may contribute to erlotinib resistance.

Experimental Design: We generated HNSCC cells expressing dominant-active c-Src (DA-Src) to determine the contribution of c-Src activation to erlotinib response.

Results: Expression of DA-Src conferred resistance to erlotinib in vitro and in vivo compared with vector-transfected control cells. Phospho-Met was strongly upregulated by DA-Src, and DA-Src cells did not produce hepatocyte growth factor (HGF). Knockdown of c-Met enhanced sensitivity to erlotinib in DA-Src cells in vitro, as did combining a c-Met or c-Src inhibitor with erlotinib. Inhibiting EGFR resulted in minimal reduction of phospho-Met in DA-Src cells, whereas complete phospho-Met inhibition was achieved by inhibiting c-Src. A c-Met inhibitor significantly sensitized DA-Src tumors to erlotinib in vivo, resulting in reduced Ki67 labeling and increased apoptosis. In parental cells, knockdown of endogenous c-Src enhanced sensitivity to erlotinib, whereas treatment with HGF to directly induce phospho-Met resulted in erlotinib resistance. The level of endogenous phospho-c-Src in HNSCC cell lines was also significantly correlated with erlotinib resistance.

Conclusions: Ligand-independent activation of c-Met contributes specifically to erlotinib resistance, not cetuximab resistance, in HNSCC with activated c-Src, where c-Met activation is more dependent on c-Src than on EGFR, providing an alternate survival pathway. Addition of a c-Met or c-Src inhibitor to erlotinib may increase efficacy of EGFR inhibition in patients with activated c-Src. Clin Cancer Res; 19(2); 380–92. ©2012 AACR.
Effect of Exercise on Markers of Inflammation in Breast Cancer Survivors: The Yale Exercise and Survivorship Study
Authors: Jones Sara B. , Thomas Gwendolyn A. , Hesselsweet Sara D. , Alvarez-Reeves Marty , Yu Herbert , Irwin Melinda L.
Published: December 2012

Physical activity is associated with improved breast cancer survival, but the underlying mechanisms, possibly including modification of the inflammatory state, are not well understood. We analyzed changes in interleukin (IL)-6, C-reactive protein (CRP), and TNF-α in a randomized controlled trial of exercise in postmenopausal breast cancer survivors. Seventy-five women, recruited through the Yale-New Haven Hospital Tumor Registry, were randomized to either a six-month aerobic exercise intervention or usual care. Correlations were calculated between baseline cytokines, adiposity, and physical activity measures. Generalized linear models were used to assess the effect of exercise on IL-6, CRP, and TNF-α. At baseline, IL-6 and CRP were positively correlated with body fat and body mass index (BMI) and were inversely correlated with daily pedometer steps (P < 0.001). We found no significant effect of exercise on changes in inflammatory marker concentrations between women randomized to exercise versus usual care, though secondary analyses revealed a significant reduction in IL-6 among exercisers who reached 80% of the intervention goal compared with those who did not. Future studies should examine the effect of different types and doses of exercise and weight loss on inflammatory markers in large-scale trials of women diagnosed with breast cancer. Cancer Prev Res; 6(2); 109–18. ©2012 AACR.
Inositol Hexaphosphate Inhibits Tumor Growth, Vascularity, and Metabolism in TRAMP Mice: A Multiparametric Magnetic Resonance Study
Authors: Raina Komal , Ravichandran Kameswaran , Rajamanickam Subapriya , Huber Kendra M. , Serkova Natalie J. , Agarwal Rajesh
Published: December 2012

Herein, employing anatomical and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), we evaluated noninvasively, the in vivo, chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Male TRAMP mice, beginning at 4 weeks of age, were fed with 1%, 2%, or 4% (w/v) IP6 in drinking water or only drinking water till 28 weeks of age and monitored using MRI over the course of study. Longitudinal assessment of prostate volumes by conventional MRI and tumor vascularity by gadolinium-based DCE-MRI showed a profound reduction in tumor size, partly due to antiangiogenic effects by IP6 treatment. As potential mechanisms of IP6 efficacy, decrease in the expression of glucose transporter GLUT-4 protein together with an increase in levels of phospho-AMP-activated kinase (AMPKTh172) were observed in prostate tissues of mice from IP6 fed-groups, suggesting that IP6 is interfering with the metabolic events occurring in TRAMP prostate. Investigative metabolomics study using quantitative high-resolution 1H-NMR on prostate tissue extracts showed that IP6 significantly decreased glucose metabolism and membrane phospholipid synthesis, in addition to causing an increase in myoinositol levels in the prostate. Together, these findings show that oral IP6 supplement blocks growth and angiogenesis of prostate cancer in the TRAMP model in conjunction with metabolic events involved in tumor sustenance. This results in energy deprivation within the tumor, suggesting a practical and translational potential of IP6 treatment in suppressing growth and progression of prostate cancer in humans. Cancer Prev Res; 6(1); 40–50; ©2012 AACR.
Mixed Hepatocellular Carcinoma and Hepatoblastoma: Cytohistopathologic Findings and Differential Diagnosis
Authors: Canberk Sule , Uludokumaci Atay , Sonmez Ceyda , Cakalir Canser , Gulsen Fatih , Ozbay Gulsen
Published: December 2012

Background: Hepatocellular carcinoma (HCC) accounts for approximately 80% of all the primary malignant tumors of the liver. Hepatoblastoma (HBL) is the most common primary malignant neoplasm of the liver in childhood, and extremely rare in adults. To the best of our knowledge, this is the first report of an adult case with cytopathologic description of a combined HCC and HBL, occurring in a noncirrhotic liver. Case: A 24-year-old male was admitted to the hospital with right-sided abdominal pain. Masses in the liver were detected radiologically. Fine-needle aspiration biopsy and core-needle biopsy revealed a malignant hepatocellular tumor with features of both HCC and HBL. Conclusion: In the present case among the distinct HCC cell groups, areas of smaller and more primitive cells consistent with embryonal type HBL and some other groups of cells with intermediate morphology were observed. These findings suggested the probable single stem cell origin of the tumor with differentiation to both cell groups rather than a combination of two different tumors. Therefore, the term ‘malignant hepatocellular tumor’ could also be considered to define this particular tumor. This case provides support to the previous reports in which HBL areas are described in HCC.
Usefulness of Immunoglobulin Light-Chain Restriction on Immunocytochemical Double Staining for the Cytological Diagnosis of B Cell Non-Hodgkin’s Lymphoma
Authors: Shimoura Yasumasa , Sato Yasuharu , Takata Katsuyoshi , Orita Yorihisa , Nakamura Satoko , Mano Shyouhei , Yoshino Tadashi
Published: December 2012

Objective: We examined the usefulness of light-chain restriction (LCR) on immunocytochemical double staining (IDS) for cytological diagnosis. Study Design: We investigated LCR on IDS in 40 patients with proliferative lymphatic disorders (23 with B cell lymphoma, 13 with reactive lymphoid lesions, 2 with T cell lymphoma and 2 with Hodgkin’s lymphoma). In addition, the results of flow cytometry (FCM) were compared in 34 of these patients. Results: On IDS, LCR was detected in 21 of 23 patients (91.3%) with B cell lymphoma. On FCM, it was detected in 15 of 21 patients (71.4%) with B cell lymphoma. Neither IDS nor FCM showed LCR in any patients with reactive lesions, T cell lymphoma or Hodgkin’s lymphoma. Conclusion: IDS facilitated the detection of LCR with a single specimen under morphological observation. The application of this procedure may improve the accuracy of cytological diagnosis.
Lymphoproliferative Disorders of the Kidney on Fine-Needle Aspiration: Cytomorphology and Radiographic Correlates in 33 Cases
Authors: Subhawong Andrea P. , Subhawong Ty K. , VandenBussche Christopher J. , Siddiqui Momin T. , Ali Syed Z.
Published: December 2012

Background: Unless renal lesions present in the setting of widespread lymphoma, biopsy can be indicated to differentiate from metastases, hypovascular renal cell carcinoma, urothelial carcinoma or infection. We review our experience with lymphoproliferative disorders in the kidney diagnosed by fine-needle aspiration (FNA), and focus on clinicopathologic and radiographic features. Design: All cases of non-Hodgkin lymphoma diagnosed on renal FNA at 2 academic institutions between 1989 and 2011 were reviewed. Clinical history, radiographic and cytomorphologic features, and follow-up were assessed. Results: 33 cases were identified, with 15 primary tumors and 18 recurrences/secondary tumors including 1 acute lymphoblastic lymphoma. The majority were aggressive/high-grade lesions (25/33). 25 cases were substantiated by positive flow cytometry results. Most were detected at follow-up/incidentally. 22 cases showed multiple renal and/or retroperitoneal masses or a significant component of adenopathy; others showed a solitary renal mass. Salient radiologic features included hypodense, infiltrative and ill-defined masses. Cytomorphology showed a monotonous population of large atypical lymphoid cells, often with lymphoglandular bodies. Conclusion: Cytologic diagnosis of renal lymphoma requires analysis of morphological, clinical and immunophenotypic information. Helpful features for diagnosis include: multiple masses on computed tomography, a monotonous population of abnormal cells in a background of lymphoglandular bodies and immunophenotyping demonstrating light chain restriction.
Identification of Atypical Glandular Cells in Pap Smears: Is It a Hit and Miss Scenario?
Authors: Ajit D. , Gavas S. , Joseph S. , Rekhi B. , Deodhar K. , Kane S.
Published: December 2012

Objective: Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign. Study Design: A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background. Results: This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%. Conclusions: A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.
Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: Fine-Needle Aspiration with Ultrasound and Histologic Correlation of 41 Cases
Authors: Yang Grace C.H. , Fried Karen , Yakoushina Tatiana V. , Schreiner Andrew M.
Published: December 2012

Objective: The encapsulated follicular variant of papillary carcinoma (FVPC) was recently reported to have genetic alterations and biological behavior closer to follicular adenoma/carcinoma than classic papillary carcinoma and unencapsulated FVPC. The objective of this study is to alert cytologists to this new subtype and to report our experience. Study Design: Cytology of 41 cases of surgery-proven encapsulated FVPC was reviewed and correlated with histopathology and ultrasound findings. These cases were collected over 19 years from 188 aspirates reported as ‘suspicious or atypical, cannot exclude FVPC’ and from 245 aspirates reported as follicular neoplasm. Results: Thirteen aspirates had diffusely atypical nuclei, 20 aspirates had mixed normal and atypical nuclei, and 8 aspirates had no atypical nuclei. On histology, papillary nuclei were distributed focally in the second and third groups. Crowded, oval, clear nuclei occurred in nearly 80% of the cases, nuclear grooves occurred in 12.2%, and nuclear pseudoinclusions occurred in 4.9%. Capsular invasion without angioinvasion was present in 30% of encapsulated FVPCs, with angioinvasion in 17.5% and lymph node metastasis in 7.5%. Most encapsulated FVPCs were benign-appearing on ultrasound with round-to-oval, circumscribed nodules with a hypoechoic rim. Conclusions: Encapsulated FVPC is more difficult to recognize on fine-needle aspiration and ultrasound than unencapsulated FVPC.
Could Alarmingly High Rates of Negative Diagnoses in Remote Rural Areas Be Minimized with Liquid-Based Cytology? Preliminary Results from the RODEO Study Team
Authors: Fregnani José Humberto T.G. , Scapulatempo Cristovam , Haikel Jr Raphael L. , Saccheto Teóclito , Campacci Natália , Mauad Edmundo C. , Longatto-Filho Adhemar
Published: December 2012

Objective: It was the aim of this study to compare diagnostic performances of the BD SurePath™ liquid-based Papanicolaou test (LBC) and the conventional Papanicolaou test (CPT) in cervical samples of women from remote rural areas of Brazil. Study Design: Specimens were collected by mobile units provided by Barretos Cancer Hospital. This report evaluates the manual screening arm of the RODEO study. Of 12,048 women seen between May and December 2010, 6,001 were examined using LBC and 6,047 using CPT. Results: Comparative (LBC vs. CPT) outcomes were: all abnormal tests, 2.1 versus 1.0%; ASC-US (atypical squamous cells of unknown significance), 0.7 versus 0.1%; ASC-H (atypical squamous cells with possible high-grade squamous intraepithelial lesions) and AGC (atypical glandular cells), 0.4 versus 0.3%; LSIL (low-grade squamous intraepithelial lesions), 0.7 versus 0.3%; HSIL (high-grade squamous intraepithelial lesions), 0.4 versus 0.2%, and unsatisfactory, 0.03 versus 0.08%. The LBC arm detected significantly more lesions (ASC-US+) than CPT (p < 0.001); however, when we divided the diagnoses into two groups, ASC-H– (negative/ASC-US/LSIL) and ASC-H+ (ASC-H/AGC/HSIL), the difference was not statistically important (p = 0.213). Conclusions: With inherent difficulties in patient recruitment and patient compliance with cancer screening, best test performance including human papillomavirus test capability are vitally necessary in Brazil’s struggle to reduce cervical cancer.
Oral Anticoagulants – A Frequent Challenge for the Emergency Management of Acute Ischemic Stroke
Authors: Rizos Timolaos , Horstmann Solveig , Jenetzky Ekkehart , Spindler Marcia , Gumbinger Christoph , Möhlenbruch Markus , Ringleb Peter , Hacke Werner , Veltkamp Roland
Published: December 2012

Background: The emergency management of patients with acute ischemic stroke (IS) using oral anticoagulants (OAC) represents a great challenge. Effective anticoagulation predisposes to bleeding and represents a contraindication for systemic thrombolysis. However, patients on OAC can receive intravenous thrombolysis with recombinant tissue-type plasminogen activator if the international normalized ratio (INR) does not exceed 1.7, but data regarding the risk of hemorrhagic complications are highly controversial. Neurointerventional recanalization of intracranial artery occlusion represents an alternative option in OAC patients with acute IS. The proportion of OAC users among consecutive patients who suffer from acute IS or transient ichemic attacks (TIA) is unknown. Methods: A prospective observational study, consecutively enrolling all patients with IS or TIA admitted to our neurological emergency room (ER), was performed between August 2009 and February 2011. Basic demographic variables, present use of OAC, severity of stroke, cardiovascular risk factors, INR values and the symptom onset to presentation time were recorded. In IS patients on OAC presenting within 4.5 h after symptom onset, management was analyzed. In thrombolysed IS patients, bleeding events were documented. Outcome was assessed after 3 months. Results: During the study period, 12,237 patients were admitted to our neurological ER. IS or TIA were diagnosed in 2,074 (16.9%). Complete data were available for 1,914 of these subjects (92.3%); 53.8% were male (median age: 72 years). 69.7% suffered IS, 30.3% TIA. OAC were being used by 8.7% of all patients. OAC patients were older than non-OAC patients (78 vs. 72 years, p < 0.001). Subtherapeutic INR values (<2.0) were found in 67.3% of OAC patients with IS. 54.8% of all OAC IS patients presented at the ER within ≤4.5 h after the event (57/104). An INR ≤1.7 – compatible with systemic thrombolysis – was present in 33/57 patients (57.9%). Recanalization therapy was performed in 21/57 patients (36.8%). No difference in symptomatic or fatal intracerebral bleedings between thrombolysed patients with and without prior OAC use was observed (p = 0.720 and 0.135, respectively). Multivariable analysis of predictors of the 3-month outcome in IS patients revealed that prior medication with OAC was neither associated with an unfavorable clinical outcome after 3 months in the whole population of stroke patients (p = 0.235) nor in patients in whom recanalization approaches were used (n = 306; p = 0.271). Conclusions: Oral anticoagulation represents a frequent challenge for the emergency manangement of IS. A considerable proportion of anticoagulated IS patients appears to be eligible for thrombolysis. Establishing standardized treatment procedures in these patients is warranted.
Mini-Percutaneous Nephrolithotomy with Ureteral Access Sheath in a Transplanted Kidney: Case Report and Literature Review
Authors: Kadlec Adam O. , Ross Michael J. , Milner John E.
Published: December 2012

This is the case of a 69-year-old woman with a history of right iliac fossa living-related kidney transplant that developed acute renal failure due to an obstructing stone in the proximal transplant ureter. She was successfully treated with mini-percutaneous nephrolithotomy wherein a 14-Fr tract was created with serial dilation and a 14-Fr ureteral access sheath was used for access. A flexible ureteroscope with holmium laser and a helical wire basket were used to fragment and extract the stone, respectively. A 10-Fr nephrostomy tube was left for postoperative drainage. There are only a few published reports of mini-percutaneous nephrolithotomy in transplant kidneys, but those reports suggest that the procedure is safe and effective.
Association between Obesity and Dental Caries in Chinese Children
Authors: Wu Ligeng , Chang Rui , Mu Ying , Deng Xiuli , Wu Fei , Zhang Shasha , Zhou Dongyan
Published: December 2012

The study sought to analyze the association between dental caries and obesity in Chinese children, and to investigate the protective and risk factors of dental caries. A total of 280 children aged 7–12 years voluntarily answered the caries examination and questionnaire. Caries was measured using the International Caries Detection and Assessment System. According to the Chinese body mass index, the participants were grouped overweight or normal-weight. The logistic regression model showed no correlation between dental caries and obesity. Drinking yogurt and chewing gum are protective factors, whereas oral breathing and genetic predisposition to caries are risk factors.
Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia: Combined Treatment with Fesoterodine Fumarate Extended-Release and Tamsulosin - A Prospective Study
Authors: Konstantinidis Charalampos , Samarinas Michael , Andreadakis Sotirios , Xanthis Stylianos , Skriapas Konstantinos
Published: December 2012

Objective: To evaluate the efficacy and safety of fesoterodine extended-release (ER) plus tamsulosin in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Patients and Methods: Men aged ≥50 years, with LUTS, prostate volume ≤60 ml and International Prostate Symptom Score (IPSS) ≥13 were enrolled in this study. 173 consecutive patients were treated initially with tamsulosin (0.4 mg) for 1 week. At the second visit, 47 patients out of the sample of 173 who were still experiencing inconvenient LUTS were randomized into two groups. The first group received a therapy with tamsulosin and fesoterodine combination (group 1, n = 24) while the second continued the therapy with the single administration of tamsulosin (group 2, n = 23) for an additional 4-week period. Results: There was no statistically significant difference in age, prostate volume, Qmax, and postvoid residual urine between the two groups. A statistical significance appeared in the combination group regarding the storage and the total IPSS values among the second and third visits (10.5 ± 1.4 to 8.5 ± 1.3 and 16.1 ± 1.8 to 13.7 ± 1.5 respectively). Conclusion: Regarding bothersome LUTS and storage symptoms, fesoterodine ER and tamsulosin combination was significantly more effective than the single administration of tamsulosin.
NIHSS Scores in Ischemic Small Vessel Disease: A Study in CADASIL
Authors: Yao Ming , Hervé Dominique , Allili Nassira , Jouvent Eric , Duering Marco , Dichgans Martin , Chabriat Hugues
Published: December 2012

Background: The National Institutes of Health Stroke Scale (NIHSS) is widely used to measure neurological deficits, evaluate the effectiveness of treatment and predict outcome in acute ischemic stroke. It has also been used to measure the residual neurological deficit at the chronic stage after ischemic events. However, the value of NIHSS in ischemic cerebral small vessel disease has not been specifically evaluated. The purpose of this study was to investigate the link between the NIHSS score and clinical severity in a large population of subjects with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a unique model to investigate the pathophysiology and natural history of ischemic small vessel disease. Methods: Demographic and clinical data of 220 patients with one or more lacunar infarcts confirmed by MRI examination and enrolled from a prospective cohort study were analyzed. Detailed neurological examinations, including evaluation of the NIHSS and modified Rankin Scale score (mRS) for evaluating the clinical severity, were performed in all subjects. The sensitivity, specificity, positive and negative predictive values of various NIHSS thresholds to capture the absence of significant disability (mRS <3) were calculated. General linear models, controlling for age, educational level and different clinical manifestations frequently observed in CADASIL, were used to evaluate the relationships between NIHSS and clinical severity. Results: In the whole cohort, 45 (20.5%) subjects presented with mRS ≥3, but only 16 (7.3%) had NIHSS >5. All but 1 subject with NIHSS >5 showed mRS ≥3. NIHSS ≤5 had an 85.3% positive predictive value for no or slight disability with only 33.3% specificity. The NIHSS, MMSE score and presence or absence of gait disturbances were found to be strongly and independently correlated with disability (all p < 0.001). Altogether, they accounted for 73% of the variance of mRS in contrast with the NIHSS alone accounting for only 50% of this variance. Among patients with NIHSS ≤5, subjects with mRS ≥3 showed a lower MMSE score than those with mRS <3 (p < 0.001). All patients with NIHSS ≤5 but with mRS ≥3 presented either with gait disturbances or MMSE score <25. Conclusions: The present results suggest that the NIHSS cannot reflect the extent of neurological deficit and clinical severity in subjects with lacunar infarctions in the context of a chronic and diffuse small vessel disease. A specific and global neurological scale, including the assessment of cognitive and gait performances, should be developed for ischemic cerebral microangiopathy.
Vulnerable Atherosclerotic Plaque: From the Basic Research Laboratory to the Clinic
Authors: Toutouzas Konstantinos , Stathogiannis Konstantinos , Synetos Andreas , Karanasos Antonios , Stefanadis Christodoulos
Published: December 2012

Coronary heart disease is the commonest cause of death in Western countries, and atherosclerotic plaques that are prone to rupture have been implicated in the pathogenesis of acute coronary syndromes (ACS). Intensive research has been directed at plaque detection, and various invasive methods have been developed thus far that fulfill this purpose and a lot of them are being applied in the clinical setting. Since invasive methods cannot be used for primary prevention, non-invasive imaging modalities are being studied to enhance the diagnostic armory of clinicians in their difficult task of detecting and preventing ACS.
Impact of Ultrasound-Guided Kidney Biopsy Simulation on Trainee Confidence and Biopsy Outcomes
Authors: Dawoud Dalia , Lyndon Will , Mrug Sylvie , Bissler John J. , Mrug Michal
Published: December 2012

Background/Aims: To improve procedural skill competence in real-time ultrasound-guided renal biopsy, we have developed an inexpensive simulation tool (a porcine kidney inserted under a turkey breast) that mimics biopsy conditions in human patients in terms of kidney size, depth, echogenicity and overall structural characteristics. This study investigated the utility of this simulation tool for improving trainees’ confidence in performing renal biopsy and biop- sy-associated bleeding complications. Methods: We have quantitatively assessed the confidence level of renal fellows before and after their initial renal biopsy simulation training. Subsequently, we determined the effect of this simulation training on trainees’ procedural competence by comparing outcomes of clinical renal biopsies performed by fellows that did versus those who did not participate in the simulation training. Results: We show that renal biopsy simulation has improved the confidence level of trainees (23.4 presimulation to 70.3 postsimulation on a 0–100 scale; p = 0.001; η2 = 0.69). The improvement in trainees’ confidence did not vary across their prior experience performing renal biopsies (η2 = 0.23; p = 0.060). Additionally, fellows who participated in the simulation training demonstrated improved competence in performing the renal biopsy procedure in patients. Successful retrieval of renal tissue per pass was 94% (vs. 73% in fellows who did not participate in this simulation training; p = 0.002) and procedure-related blood loss was reduced as indicated by smaller postbiopsy versus prebiopsy hematocrit decline (1.18 vs. 2.68; p = 0.049). Conclusion: Renal biopsy simulation training may improve trainees’ confidence and reduce the severity of biopsy-associated bleeding complications in patients.
Ageing Prisoners' Health Care: Analysing the Legal Settings in Europe and the United States
Authors: Bretschneider Wiebke , Elger Bernice , Wangmo Tenzin
Published: December 2012

Background: Relatively little is known about the current health care situation and the legal rights of ageing prisoners worldwide. To date, only a few studies have investigated their rights to health care. However, elderly prisoners need special attention. Objective: The aim of this article is to critically review the health care situation of older prisoners by analysing the relevant national and international legal frameworks with a particular focus on Switzerland, England and Wales, and the United States (US). Methods: Publications on legal frameworks were searched using Web of Science, PubMed, MEDLINE, HeinOnline, and the National Criminal Justice Reference Service. Searches utilizing combinations of keywords relating to ageing prisoners were performed. Relevant reports and policy documents were obtained in order to understand the legal settings in Switzerland, England and Wales, and the US. All articles, reports, and policy documents published in English and German between 1774 to June 2012 were included for analysis. Using a comparative approach, an outline was completed to distinguish positive policies in this area. Regulatory approaches were investigated through evaluations of soft laws applicable in Europe and US Supreme Court judgements. Results: Even though several documents could be interpreted as guaranteeing adequate health care for ageing prisoners, there is no specific regulation that addresses this issue completely. The Vienna International Plan of Action on Ageing contributes the most by providing an in-depth analysis of the health care needs of older persons. Still, critical analysis of retrieved documents reveals the lack of specific legislation regarding the health care for ageing prisoners. Conclusion: No consistent regulation delineates the provision of health care for ageing prisoners. Neither national nor international institutions have enforceable laws that secure the precarious situation of older adults in prisons. To initiate a change, this work presents critical issues that must be addressed to protect the right to health care and well-being of ageing prisoners. Additionally, it is important to design legal structures and guidelines which acknowledge and accommodate the needs of ageing prisoners.
Obesity and Kidney Transplant Candidates: How Big Is Too Big for Transplantation?
Authors: Lentine Krista L. , Delos Santos Rowena , Axelrod David , Schnitzler Mark A. , Brennan Daniel C. , Tuttle-Newhall Janet E.
Published: December 2012

Obesity impacts many inter-related, and sometimes conflicting, considerations for transplant practice. In this article, we describe an approach for applying available data on the importance of body composition to the kidney transplant population that separates implications for candidate selection, risk stratification among selected candidates, and interventions to optimize health of the individual. Transplant recipients with obesity defined by elevated body mass index (BMI) have been shown in many (but not all) studies to experience an array of adverse outcomes more commonly than normal-weight transplant recipients, including wound infections, delayed graft function, graft failure, cardiac disease, and increased costs. However, current studies have not defined limits of body composition that preclude clinical benefit from transplantation compared with long-term dialysis in patients who have passed a transplant evaluation. Formal cost-effectiveness studies are needed to determine if payers and society should be compensating centers for clinical and financial risks of transplanting obese end-stage renal disease patients. Recent studies also demonstrate the limitations of BMI alone as a measure of adiposity, and further research should be pursued to define practical measures of body composition that refine accuracy for outcomes prediction. Regarding individual management, observational registry studies have not found beneficial associations of pretransplant weight loss with patient or graft survival. However, association studies cannot distinguish purposeful from unintentional weight loss as a result of illness and comorbidity. Prospective evaluations of the impact of targeted risk modification efforts in this population including dietary changes, monitored exercise programs, and bariatric surgery are urgently needed.
Quantification of Chronic Functional Mitral Regurgitation by Automated 3-Dimensional Peak and Integrated Proximal Isovelocity Surface Area and Stroke Volume Techniques Using Real-Time 3-Dimensional Volume Color Doppler Echocardiography
Authors: Thavendiranathan Paaladinesh , Liu Shizhen , Datta Saurabh , Rajagopalan Sanjay , Ryan Thomas , Igo Stephen R. , Jackson Matthew S. , Little Stephen H. , De Michelis Nathalie , Vannan Mani A.
Published: December 2012

Background—

The aim of this study was to test the accuracy of an automated 3-dimensional (3D) proximal isovelocity surface area (PISA) (in vitro and patients) and stroke volume technique (patients) to assess mitral regurgitation (MR) severity using real-time volume color flow Doppler transthoracic echocardiography.

Methods and Results—

Using an in vitro model of MR, the effective regurgitant orifice area and regurgitant volume (RVol) were measured by the PISA technique using 2-dimensional (2D) and 3D (automated true 3D PISA) transthoracic echocardiography. The mean anatomic regurgitant orifice area (0.35±0.10 cm
2
) was underestimated to a greater degree by the 2D (0.12±0.05 cm
2
) than the 3D method (0.25±0.10 cm
2
;
P
<0.001 for both). Compared with the flowmeter (40±14 mL), the RVol by 2D PISA (20±19 mL) was underestimated (
P
<0.001), but the 3D peak (43±16 mL) and integrated PISA-based (38±14 mL) RVol were comparable (
P
>0.05 for both). In patients (n=30, functional MR), 3D effective regurgitant orifice area correlated well with cardiac magnetic resonance imaging RVol
r
=0.84 and regurgitant fraction
r
=0.80. Compared with cardiac magnetic resonance imaging RVol (33±22 mL), the integrated PISA RVol (34±26 mL;
P
=0.42) was not significantly different; however, the peak PISA RVol was higher (48±27 mL;
P
<0.001). In addition, RVol calculated as the difference in automated mitral and aortic stroke volumes by real-time 3D volume color flow Doppler echocardiography was not significantly different from cardiac magnetic resonance imaging (34±21 versus 33±22 mL;
P
=0.33).

Conclusions—

Automated real-time 3D volume color flow Doppler based 3D PISA is more accurate than the 2D PISA method to quantify MR. In patients with functional MR, the 3D RVol by integrated PISA is more accurate than a peak PISA technique. Automated 3D stroke volume measurement can also be used as an adjunctive method to quantify MR severity.
Circulation Research
Most Read: 2010–2011
Authors:   The Editors
Published: December 2012

The following represent a selection of the most read
Circulation Research
articles published between January 2010 and December 2011, presented in reverse order of publication. Articles were selected based on the number of Full Text/PDF downloads, adjusted to compensate for differences in the length of time articles have been available online.

As stated in the past, our motivation in compiling such lists of most read articles is multifarious. By highlighting these articles, we wish to direct the attention of our readers to new information that may be of particular interest to a large fraction of the community of cardiovascular scholars. In addition, a synopsis of the most popular articles can be a useful indicator of burgeoning areas of research that are likely to dominate the landscape for years to come. This “honor roll” is also meant to acknowledge the outstanding work of the authors and their efforts in advancing the frontiers of cardiovascular science. Furthermore, we believe that the articles highlighted below represent paradigms of scientific excellence, particularly with respect to the three criteria that we value most at
Circulation Research
: conceptual and/or mechanistic novelty, scientific impact, and methodological rigor. Finally, we hope that this list will provide tangible evidence of the high (and rising) level of scientific excellence of the work published in
Circulation Research
.
Observations of Thermally Driven Wind Jets at the Exit of Weber Canyon, Utah
Authors: Chrust Morgan F. , Whiteman C. David , Hoch Sebastian W.
Published: December 2012

Thermally driven valley-exit jets were investigated at Utah’s Weber Canyon, a main tributary of the Great Salt Lake basin. An intensive measurement campaign during July–September 2010 supplemented longer-term measurements to characterize the wind and temperature structure in the vicinity of the canyon exit. Exit jets at Weber Canyon are most frequent in late summer or early fall. Strong low-level-wind jets formed at the canyon exit on 75 of 90 nights (83%) during the measurement campaign, with the best-developed winds forming during synoptically undisturbed, clear-sky periods. Winds inside the canyon consisted of a weak down-valley flow layer that occupied most of the 1000-m depth of the canyon. The flow was observed to descend, thin, and accelerate at the valley exit, producing winds that were typically 2.5 times as strong but much more shallow than those inside the canyon. Maximum nighttime jet-axis wind speeds of 15–20 m s−1 are typically found about 80–120 m above the ground at the canyon exit on clear undisturbed nights in the late summer and fall. The jets form 1–3 h after sunset, approach a near-steady state during the late night, and continue until 5–6 h after sunrise, although slowly losing speed after sunrise. The jet is a local modification at the canyon exit of the thermally driven down-valley flow. Its continuation after sunrise is thought to be caused by the nighttime buildup and persistence of a cold-air pool in the Morgan Basin at the east end of the canyon. The potential for utilizing the exit jet for wind power generation is discussed.
Can a Decadal Forecasting System Predict Temperature Extreme Indices?*
Authors: Hanlon Helen M. , Hegerl Gabriele C. , Tett Simon F. B. , Smith Doug M.
Published: December 2012

Daily maximum and minimum summer temperatures have increased throughout the majority of Europe over the past few decades, along with the frequency and intensity of heat waves. It is essential to learn whether this rise is expected to continue in the future for adaptation purposes. A study of predictability of European temperature indices with the Met Office Hadley Centre Decadal Prediction System (DePreSys) has revealed significant skill in predictions of 5- and 10-yr average indices of the summer mean and maximum 5-day average temperatures based on daily maximum and minimum temperatures for a large area of Europe, particularly in the Mediterranean. In contrast, the decadal forecasts of winter mean/minimum 5-day average temperature indices show poorer skill than the summer indices. Significant skill is shown for the United Kingdom in some cases but less than for the European/Mediterranean regions.

Comparison of two parallel ensembles, one initialized with observations and one without initialization, has shown that the skill largely originates from external forcing. However, there were a few cases with hints of additional skill in forecasts of decadal mean indices due to the initialization.

Model realizations of extreme indices can have large biases compared to observations that are different from those of the mean climate indices. Several methods were tested for correcting biases, as well as for testing the significance and quantifying uncertainty of the results to rule out cases of spurious skill. Bias correction of each index individually is required as biases vary across different extremes.
Spatial Patterns of Precipitation Change in CMIP5: Why the Rich Do Not Get Richer in the Tropics
Authors: Chadwick Robin , Boutle Ian , Martin Gill
Published: December 2012

Changes in the patterns of tropical precipitation (P) and circulation are analyzed in Coupled Model Intercomparison Project phase 5 (CMIP5) GCMs under the representative concentration pathway 8.5 (RCP8.5) scenario. A robust weakening of the tropical circulation is seen across models, associated with a divergence feedback that acts to reduce convection most in areas of largest climatological ascent. This is in contrast to the convergence feedback seen in interannual variability of tropical precipitation patterns. The residual pattern of convective mass-flux change is associated with shifts in convergence zones due to mechanisms such as SST gradient change, and this is often locally larger than the weakening due to the divergence feedback.

A simple framework is constructed to separate precipitation change into components based on different mechanisms and to relate it directly to circulation change. While the tropical mean increase in precipitation is due to the residual between the positive thermodynamic change due to increased specific humidity and the decreased convective mass flux due to the weakening of the circulation, the spatial patterns of these two components largely cancel each other out. The rich-get-richer mechanism of greatest precipitation increases in ascent regions is almost negated by this cancellation, explaining why the spatial correlation between climatological P and the climate change anomaly ΔP is only 0.2 over the tropics for the CMIP5 multimodel mean. This leaves the spatial pattern of precipitation change to be dominated by the component associated with shifts in convergence zones, both in the multimodel mean and intermodel uncertainty, with the component due to relative humidity change also becoming important over land.
Adjusting the Wind Stress Drag Coefficient in Storm Surge Forecasting Using an Adjoint Technique
Authors: Peng Shiqiu , Li Yineng , Xie Lian
Published: December 2012

A three-dimensional ocean model and its adjoint model are used to adjust the drag coefficient in the calculation of wind stress for storm surge forecasting. A number of identical twin experiments (ITEs) with different error sources imposed are designed and performed. The results indicate that when the errors come from the wind speed, the drag coefficient is adjusted to an “optimal value” to compensate for the wind errors, resulting in significant improvements of the specific storm surge forecasting. In practice, the “true” drag coefficient is unknown and the wind field, which is usually calculated by an empirical parameter model or a numerical weather prediction model, may contain large errors. In addition, forecasting errors may also come from imperfect model physics and numerics, such as insufficient resolution and inaccurate physical parameterizations. The results demonstrate that storm surge forecasting errors can be reduced through data assimilation by adjusting the drag coefficient regardless of the error sources. Therefore, although data assimilation may not fix model imperfection, it is effective in improving storm surge forecasting by adjusting the wind stress drag coefficient using the adjoint technique.
State-Sponsored Precarious Work in Indonesia
Authors: Tjandraningsih Indrasari
Published: December 2012

This article discusses labor outsourcing as the main form of precarious work in Indonesia. It is argued that demands for labor flexibility and the expansion of precarious work show that the state’s role in protecting workers is being cast aside as Indonesia’s peripheral position in global capitalism sees the state sponsoring a “labor flexibility regime.” Labor outsourcing was legalized in 2003 with the enactment of Labor Law No. 13/2003. That law came from an agreement between the government and the International Monetary Fund. Labor outsourcing is now widespread and has detrimental effects for workers and unions. Labor outsourcing practices have created a new actor in industrial relations: the labor agency. It has also created a highly complicated and difficult labor relations situation, fragmenting workers by work status and bringing harsh confrontations between labor unions and community members. Labor outsourcing practices have also presented tough challenges for the Indonesian labor movement in developing alternative strategies for organizing.
Seduced and surrounded by security: A post-structuralist take on Norwegian High North securitizing discourses
Authors: Jensen Leif C
Published: December 2012

Combining elements of the Copenhagen school’s securitization theory with a Foucauldian discourse analysis, this article examines certain discursive processes that emerged in the wake of Norway’s 2005 High North Initiative. The Norwegian government’s explicit politicization of energy issues appears to have acted as door opener, letting ‘security’ in to colonize the High North discourses once more. Russia is again firmly positioned as the ‘radical other’, leaving the discursive field open to various forms of securitizing discourses. The post-2005 discursive field of the Northern areas is, in many ways, more open-ended, complex and confusing than ever. The opening up and expansion of the concept of High North security means that ‘everything’ is seen as having a security potential. What does seem clear is the increasing presence of security in primary texts and the media debate: entry to and credibility in the discourse depends on ‘security speak’ across an ever-widening array of thematic contexts. The article also argues that a combination of securitization theory and discourse analysis seems a fruitful way forward in shifting more focus towards the active and important role of the audience in securitizing processes.
Vocational Interventions with Offenders
Authors: Varghese Femina P.
Published: December 2012

Vocational interventions for criminal justice populations have existed for years in various forms, but have traditionally not used an interdisciplinary approach and have shown significant limitations in effectiveness. This article informs scholars and practitioners of interdisciplinary research on vocational interventions and how knowledge from criminal justice literature and career theory can be combined so that relevant and effective theory-based vocational interventions for offenders and ex-offenders can be developed. Such an integrative approach would address the limitations of existing approaches and would foster the development of vocational interventions that go beyond what is offered currently. A model summarizing this integrative approach is provided. This article concludes by presenting understudied areas in offender career development, such as offenders’ willingness to work, illegal employment as a form of work, and the implications of a criminal record on career development. Continued research in these areas can promote effective rehabilitative efforts that meet the vocational needs of this marginalized population.
A Review of Human Factors Challenges of Complex Adaptive Systems
Authors: Karwowski Waldemar
Published: December 2012

Objective:

In this paper, the author explores a need for a greater understanding of the true nature of human–system interactions from the perspective of the theory of complex adaptive systems, including the essence of complexity, emergent properties of system behavior, nonlinear systems dynamics, and deterministic chaos.

Background:

Human performance, more often than not, constitutes complex adaptive phenomena with emergent properties that exhibit nonlinear dynamical (chaotic) behaviors.

Methods:

The complexity challenges in the design and management of contemporary work systems, including service systems, are explored. Examples of selected applications of the concepts of nonlinear dynamics to the study of human physical performance are provided.

Results:

Understanding and applications of the concepts of theory of complex adaptive and dynamical systems should significantly improve the effectiveness of human-centered design efforts of a large system of systems.

Conclusion:

Performance of many contemporary work systems and environments may be sensitive to the initial conditions and may exhibit dynamic nonlinear properties and chaotic system behaviors. Human-centered design of emergent human–system interactions requires application of the theories of nonlinear dynamics and complex adaptive system.

Application:

The success of future human–systems integration efforts requires the fusion of paradigms, knowledge, design principles, and methodologies of human factors and ergonomics with those of the science of complex adaptive systems as well as modern systems engineering.