bluuebunny/crossref_metadata_2025 huggingface dataset:
KLF6-SV1 Drives Breast Cancer Metastasis and Is Associated with Poor Survival
Authors: Hatami Raheleh , Sieuwerts Anieta M. , Izadmehr Sudeh , Yao Zhong , Qiao Rui Fang , Papa Luena , Look Maxime P. , Smid Marcel , Ohlssen Jessica , Levine Alice C. , Germain Doris , Burstein David , Kirschenbaum Alexander , DiFeo Analisa , Foekens John A. , Narla Goutham
Published: January 2013

The KLF6-SV1 splice variant is associated with poor prognosis in early-stage human breast cancer and drives metastasis through the regulation of an EMT-like program in culture and in vivo.
Males Are Overrepresented among Life Science Researchers Committing Scientific Misconduct
Authors: Fang Ferric C. , Bennett Joan W. , Casadevall Arturo
Published: January 2013

A review of the United States Office of Research Integrity annual reports identified 228 individuals who have committed misconduct, of which 94% involved fraud. Analysis of the data by career stage and gender revealed that misconduct occurred across the entire career spectrum from trainee to senior scientist and that two-thirds of the individuals found to have committed misconduct were male. This exceeds the overall proportion of males among life science trainees and faculty. These observations underscore the need for additional efforts to understand scientific misconduct and to ensure the responsible conduct of research.

IMPORTANCEAs many of humanity’s greatest problems require scientific solutions, it is critical for the scientific enterprise to function optimally. Misconduct threatens the scientific enterprise by undermining trust in the validity of scientific findings. We have examined specific demographic characteristics of individuals found to have committed research misconduct in the life sciences. Our finding that misconduct occurs across all stages of career development suggests that attention to ethical aspects of the conduct of science should not be limited to those in training. The observation that males are overrepresented among those who commit misconduct implies a gender difference that needs to be better understood in any effort to promote research integrity.
Symptomatic sclerosing haemangioma: a rare case of solitary pulmonary nodule in a young girl
Authors: Goel Madhu Mati , Kumari Malti , Singh Sushil Kumar , Soren Vijay
Published: January 2013

Sclerosing haemangioma (SH) is a rare benign lung tumour with distinctive variety of histological patterns. SH typically presents as asymptomatic peripheral, solitary well-circumscribed lesion in women with median age at diagnosis in the fifth decade. Preoperative diagnosis of this tumour is difficult, and sometimes even intraoperative frozen sections cannot differentiate it from malignant tumours. Here, we present our experiences in investigating its characteristics. We report a case of a 19-year-old girl who presented with chest pain, cough and sputum and off and on haemoptysis for 6 months. Anti-tubercular treatment was given but provided no relief. CT chest showed a well-defined hypodense solid mass lesion with a soft tissue alternation. Lobectomy was performed. Microscopy revealed a tumour comprising of two distinct populations of cells surface and stromal cells which disposed in papillary, solid, sclerotic and haemorrhagic growth patterns. Histology and immunohistochemistry confirmed the diagnosis of SH of the lung.
Osteogenesis imperfecta and congenital diaphragmatic hernia
Authors: Dholakia Shamik , Cleeve Stuart
Published: January 2013

Osteogenesis imperfecta and congenital diaphragmatic hernia are both conditions that can occur due to genetic mutation. We present the first case to be reported of a child with both osteogenesis imperfecta and congenital diaphragmatic hernias, showing that the incidence of this presentation may be more than chance.
Acute exacerbation of restless legs due to cervical spinal cord ischaemia
Authors: Zwartbol Rachel Theodora , Jellema Korne , Boiten Jelis , Rijsman Roselyne
Published: January 2013

We present a 60-year-old male patient with an acute exacerbation of restless legs due to cervical spinal cord ischaemia. This case supports the hypothesis that interruption of spinal cord pathways are part of the aetiology of restless legs syndrome.
Contiguous haemangioblastomas of the brain and spine in a patient of Von Hippel-Lindau disease
Authors: Rahman Asifur , Hoque Saif Ul , Bhandari Paawan Bahadur , Alam Shamsul
Published: January 2013

Von Hippel-Lindau (VHL) disease is an inherited, autosomal-dominant syndrome caused by heterozygous germline mutations in the VHL gene, and predisposing to the development of benign and malignant tumours and cysts in multiple organ systems involving eyes, kidneys, pancreas, liver and central nervous system. The responsible tumour suppressor gene for VHL disease is in chromosome 3p25. We are presenting a case of a patient with both cerebellar as well as spinal haemangioblastoma in addition to polycystic pancreas. We operated on both the spinal and the cerebellar haemangioblastomas and the patient had made a very good recovery. We present this case for its rarity along with the literature review.
Prosthodontic management of an albinism patient-dental implications and management
Authors: Murthy Varsha , V Yuvraj , Thomas Shaji , Nair Preeti
Published: January 2013

Albinism is a congenital hypopigmentary disorder. Albinism is due to the dysfunction of the melanin-producing cells (melanocytes) resulting in defective production of melanin from tyrosine through a complex pathway of metabolic reactions. Little is known about the varied dental features that albinism presents with. This case report summarises the features encountered in albinism, the different oral findings available in the literature and also presents a case of an albinism patient treated with fixed partial denture and the precautions to be exercised for such patients.
Cobb's collar: a rare cause of urinary retention
Authors: Adorisio Ottavio , Bassani Francesca , Silveri Massimiliano
Published: January 2013

Cobb's collar is a membranous stricture of the bulbar urethra, often misdiagnosed, potentially leading to acute urinary retention, upper urinary tract dilations, enuresis, infectious diseases, poor streaming and haematuria. A 14-year-old boy with a history of previous hospitalisations came to our attention. A Cobb's collar was diagnosed and successfully managed with a videoendoscopic one-step approach. Although extremely uncommon, paediatric urologists must be aware of this congenital anomaly. A correct and timely diagnosis and endoscopic management may affect positively the clinical onset of these patients avoiding major urethral surgery and preserving renal and bladder function.
Pleural tuberculosis following lung cancer chemotherapy: a report of two cases proven pathologically by pleural biopsy
Authors: Madan Karan , Singh Navneet , Das Ashim , Behera Digambar
Published: January 2013

Malignancy per se and cytotoxic chemotherapy given for its treatment both are recognised risk factors for the development of tuberculosis (TB). However, individual case descriptions of pleural tuberculosis (TB-PE) following chemotherapy for lung cancer (LC) have not been published previously. We herein report the first two cases of histopathologically proven TB-PE following LC chemotherapy. The first patient was a 38-year-old man with stage IV non-small cell LC (adenocarcinoma) who developed TB-PE following four cycles of chemotherapy (pemetrexed-cisplatin). The second patient was a 49-year-old man with extensive disease small cell LC who developed TB-PE after six cycles of chemotherapy (irinotecan-cisplatin). In both patients, diagnosis of TB-PE was established by demonstration of granulomatous inflammation, caseous necrosis and positive stain for acid-fast bacilli in pleural biopsy specimens. Both cases responded to standard four-drug antitubercular therapy. These cases highlight the importance of carrying out an extensive evaluation for exudative pleural effusions in LC patients receiving chemotherapy, especially in countries with high TB prevalence. Attributing such pleural effusions to disease progression, without histopathological confirmation, may be associated with disastrous consequences.
Massive pulmonary embolism and thrombophilia
Authors: Qureshi Iman , Meshaka Riwa , Donohue Claire , Ali Asad
Published: January 2013

A 32-year-old man presented overnight to the accident and emergency unit with mild breathlessness on exertion. He was found to be hypoxic on room air and his chest x-ray revealed areas of patchy lung consolidation. He was given intravenous antibiotics for presumed community-acquired pneumonia. Unfortunately his condition deteriorated and he remained significantly hypoxic despite high-flow oxygen with ECG evidence of right heart strain. Further questioning revealed a history of protein S deficiency and a strong family history of venous thromboembolic disease. An urgent CT pulmonary angiogram showed an evidence of massive pulmonary embolism and the patient was successfully thrombolysed.
Marcus Gunn jaw winking synkinesis: report of two cases
Authors: Carman Kursat Bora , Ozkan Serhat , Yakut Ayten , Ekici Arzu
Published: January 2013

Marcus Gunn jaw winking synkinesis (MGJWS) is caused by congenital miswiring of a branch of the fifth cranial nerve into the branch of the third cranial nerve supplying the levator muscle. It has been observed in 2–13% of patients with congenital ptosis. Although bilateral cases were reported, most were unilateral and occurred more frequently on the left side than the right. We report two cases of children who presented with ptosis and were diagnosed with MGJWS.
Salmon-mediated nutrient flux in selected streams of the Columbia River basin, USA
Authors: Kohler Andre E. , Kusnierz Paul C. , Copeland Timothy , Venditti David A. , Denny Lytle , Gable Josh , Lewis Bert A. , Kinzer Ryan , Barnett Bruce , Wipfli Mark S.
Published: January 2013

Salmon provide an important resource subsidy and linkage between marine and land-based ecosystems. This flow of energy and nutrients is not unidirectional (i.e., upstream only); in addition to passive nutrient export via stream flow, juvenile emigrants actively export nutrients from freshwater environments. In some cases, nutrient export can exceed import. We evaluated nutrient fluxes in streams across central Idaho, USA, using Chinook salmon (Oncorhynchus tshawytscha) adult escapement and juvenile production data from 1998 to 2008. We found in the majority of stream-years evaluated, adults imported more nutrients than progeny exported; however, in 3% of the years, juveniles exported more nutrients than their parents imported. On average, juvenile emigrants exported 22% ± 3% of the nitrogen and 30% ± 4% of the phosphorus their parents imported. This relationship was density-dependent and nonlinear; during periods of low adult abundance, juveniles were larger and exported up to 194% and 268% of parental nitrogen and phosphorus inputs, respectively. We highlight minimum escapement thresholds that appear to (i) maintain consistently positive net nutrient flux and (ii) reduce the average proportional rate of export across study streams. Our results suggest a state shift occurs when adult spawner abundance falls below a threshold to a point where the probability of juvenile nutrient exports exceeding adult imports becomes increasingly likely.
From cell phenotype to epigenetic mechanisms: new insights into regenerating myocardium
Authors: Romano Simone Lorenzo , Lionetti Vincenzo
Published: January 2013

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation.
GIBBS MEASURES ON CAYLEY TREES: RESULTS AND OPEN PROBLEMS
Authors: ROZIKOV UTKIR A.
Published: January 2013

The purpose of this review paper is to present systematically all known results on Gibbs measures on Cayley trees (Bethe lattices). There are about 150 papers which contain mathematically rigorous results about Gibbs measures on Cayley trees. This review is mainly based on the recently published mathematical papers. The method used for the description of Gibbs measures on Cayley trees is the method of Markov random field theory and recurrent equations of this theory, but the modern theory of Gibbs measures on trees uses new tools such as group theory, information flows on trees, node-weighted random walks, contour methods on trees and nonlinear analysis. We discuss all the mentioned methods which were developed recently. Thus, the paper informs the reader about what is (mathematically) done in the theory of Gibbs measures on trees and about where the corresponding results were published. We only give proofs which were not published in literature. Moreover, we give several open problems.
ON SPIN-STATISTICS AND BOGOLIUBOV TRANSFORMATIONS IN FLAT SPACE–TIME WITH ACCELERATION CONDITIONS
Authors: GOOD MICHAEL R. R.
Published: January 2013

A single real scalar field of spin zero obeying the Klein–Gordon equation in flat space–time under external conditions is considered in the context of the spin-statistics connection. An imposed accelerated boundary on the field is made to become, in the far future, (1) asymptotically inertial and (2) asymptotically noninertial (with an infinite acceleration). The constant acceleration Unruh effect is also considered. The systems involving nontrivial Bogoliubov transformations contain dynamics which point to commutation relations. Particles described by in-modes obey the same statistics as particles described by out-modes. It is found in the nontrivial systems that the spin-statistics connection can be manifest from the acceleration. The equation of motion for the boundary which forever emits thermal radiation is revealed.
Bianchi Type II, VIII, and IX Perfect Fluid Dark Energy Cosmological Models in Saez-Ballester and General Theory of Gravitation
Authors: Rao V. U. M. , Sireesha K. V. S. , Neelima D.
Published: January 2013

The paper deals with spatially homogeneous anisotropic Bianchi type II, VIII , and IX dark energy cosmological models filled with perfect fluid in the framework of Saez-Ballester (1986) theory, and Einstein's general relativity. Assuming that the two sources interact minimally and therefore their energy momentum tensors are conserved separately, we have considered different cases and presented anisotropic as well as isotropic cosmological models. Some important physical and geometrical features of the models, thus obtained, have been discussed.
Personalized Chemotherapy Profiling Using Cancer Cell Lines from Selectable Mice
Authors: Kamiyama Hirohiko , Rauenzahn Sherri , Shim Joong Sup , Karikari Collins A. , Feldmann Georg , Hua Li , Kamiyama Mihoko , Schuler F. William , Lin Ming-Tseh , Beaty Robert M. , Karanam Balasubramanyam , Liang Hong , Mullendore Michael E. , Mo Guanglan , Hidalgo Manuel , Jaffee Elizabeth , Hruban Ralph H. , Jinnah H.A. , Roden Richard B.S. , Jimeno Antonio , Liu Jun O. , Maitra Anirban , Eshleman James R.
Published: January 2013

Purpose: High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult because contaminating stromal cells overgrow the malignant cells.

Experimental Design: We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts.

Results: Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified 77 U.S. Food and Drug Administration (FDA)–approved drugs with activity, and two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs.

Conclusion: Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. Clin Cancer Res; 19(5); 1139–46. ©2012 AACR.
PD-L1 on Tumor Cells Is Induced in Ascites and Promotes Peritoneal Dissemination of Ovarian Cancer through CTL Dysfunction
Authors: Abiko Kaoru , Mandai Masaki , Hamanishi Junzo , Yoshioka Yumiko , Matsumura Noriomi , Baba Tsukasa , Yamaguchi Ken , Murakami Ryusuke , Yamamoto Ayaka , Kharma Budiman , Kosaka Kenzo , Konishi Ikuo
Published: January 2013

Purpose: Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.

Experimental Design: Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1–overexpression cell line and PD-L1–depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.

Results: Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1–overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.

Conclusion: PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1–targeted therapy is a promising strategy for preventing and treating peritoneal dissemination. Clin Cancer Res; 19(6); 1363–74. ©2012 AACR.
HIC1 Modulates Prostate Cancer Progression by Epigenetic Modification
Authors: Zheng Jianghua , Wang Jinglong , Sun Xueqing , Hao Mingang , Ding Tao , Xiong Dan , Wang Xiumin , Zhu Yu , Xiao Gang , Cheng Guangcun , Zhao Meizhong , Zhang Jian , Wang Jianhua
Published: January 2013

Purpose: Prostate cancer is the second leading cause of cancer deaths among men in Western counties, which has also occurred in Chinese male with markedly increasing incidence in recent years. Although the mechanism underlying its progression still remains unclear, epigenetic modifications are important ethological parameters. The purpose of this study is to determine the methylation status and function of hypermethylatioted in cancer 1 (HIC1) in prostate cancer progression.

Experimental Design: The methylation status of HIC1 promoter was assayed in cell lines, tissues, and plasma of patients with prostate cancer by using methylation-specific PCR and bisulfate sequencing PCR. The ability of HIC1 to regulate proliferation, migration, and invasion was assessed by MTT, scratch-healing assay, and reconstituted extracellular matrices in porous culture chambers. Tumorigenesis, metastases, and bone destruction were analyzed in mice bearing prostate cancer cells restoring HIC1 by using Xenogen IVIS with radiographic system and small-animal positron emission tomography computed tomographic images. Microarrays were searched for genes that had correlated expression with HIC1 mRNA. Reporter gene assays were used to determine whether HIC1 affected the expression of CXCR7, and chromatin immunoprecipitation was used to determine whether HIC1 bound to CXCR7 promoters. All P values were determined using 2-sided tests.

Results: The methylation status of 11 CpG sites within HIC1 promoter was abundantly methylated in cell lines, tissues, and plasma of patients with prostate cancer compared with those of respective normal controls. Restoring HIC1 expression in prostate cancer cells markedly inhibited proliferation, migration, and invasion and induced the apoptosis in these cells. Moreover, mice bearing prostate cancer–restoring HIC1 cells had a marked effect on reducing tumor growth, multiple tissue metastases, and bone destruction. Notably, we also identified that the chemokine receptor CXCR7 is a direct downstream target gene of HIC1. Finally, we showed that CXCR7 promoter in prostate cancer cells is negatively regulated by HIC1, which may be responsible for prostate cancer progression.

Conclusions: Our data show for the first time that hypermethylation of HIC1 promoter results in loss of its repressive function, responsible for prostate cancer progression and invasion. These findings suggest that therapies targeting epigenetic events regulating HIC1 expression may provide a more effective strategy for prostate cancer treatment. Clin Cancer Res; 19(6); 1400–10. ©2012 AACR.
Establishment and Validation of Circulating Tumor Cell–Based Prognostic Nomograms in First-Line Metastatic Breast Cancer Patients
Authors: Giordano Antonio , Egleston Brian L. , Hajage David , Bland Joseph , Hortobagyi Gabriel N. , Reuben James M. , Pierga Jean-Yves , Cristofanilli Massimo , Bidard Francois-Clement
Published: January 2013

Purpose: Circulating tumor cells (CTC) represent a new outcome-associated biomarker independent from known prognostic factors in metastatic breast cancer (MBC). The objective here was to develop and validate nomograms that combined baseline CTC counts and the other prognostic factors to assess the outcome of individual patients starting first-line treatment for MBC.

Experimental Design: We used a training set of 236 patients with MBCs starting a first-line treatment from the M.D. Anderson Cancer Center (Houston, TX) to establish nomograms that calculated the predicted probability of survival at different time points: 1, 2, and 5 years for overall survival (OS) and 6 months and 1 and 2 years for progression-free survival (PFS).The covariates computed in the model were age, disease subtype, visceral metastases, performance status, and CTC counts by CellSearch. Nomograms were independently validated with 210 patients with MBCs from the Institut Curie (Paris, France) who underwent first-line chemotherapy. The discriminatory ability and accuracy of the models were assessed using Harrell c-statistic and calibration plots at different time points in both training and validation datasets.

Results: Median follow-up was of 23 and 29 months in the MD Anderson and Institut Curie cohorts, respectively. Nomograms showed good c-statistics: 0.74 for OS and 0.65 for PFS and discriminated OS prediction at 1, 2, and 5 years, and PFS prediction at 6 months and 1 and 2 years.

Conclusions: Nomograms, which relied on CTC counts as a continuous covariate, easily facilitated the use of a web-based tool for estimating survival, supporting treatment decisions and clinical trial stratification in first-line MBCs. Clin Cancer Res; 19(6); 1596–602. ©2013 AACR.
Personalized Immune-Interception of Cancer and the Battle of Two Adaptive Systems—When Is the Time Right?
Authors: Dhodapkar Madhav V.
Published: January 2013

A growing body of evidence points to a coevolutionary model of cancer, wherein the cross-talk between tumor cells (or their subclones) and the host determine the malignant potential of individual tumors. Most of this natural history is clinically invisible and includes preneoplastic states. The capacity of the immune system to recognize these incipient lesions provides the basis for targeting them immunologically to arrest the development of preneoplasia toward clinical cancer. Kimura and colleagues provide evidence of immunogenicity of a potential cancer vaccine in patients with a history of advanced colon adenomas. These studies provide proof-of-principle or feasibility of such an approach in the clinic. Here, we discuss emerging opportunities and challenges in harnessing the immune system to “intercept” the precursor or preneoplastic lesions. Both cancer cells as well as the immune system represent independent and complex systems with plasticity and adaptive potential. It is therefore likely that specific aspects of the cross-talk between tumor cells and host may differ between individual tumors and determine the evolution of both tumors and the host response. We try to make the case to consider individualized approaches based on the genetic make-up of tumor cells and properties of the host response. Such strategies may be needed to optimally position the immune system to prevent cancers. Cancer Prev Res; 6(3); 173–6. ©2013 AACR.
Preinfarction Angina Reduces Infarct Size in ST-Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention
Authors: Reiter Ronald , Henry Timothy D. , Traverse Jay H.
Published: January 2013

Background—

Preinfarction angina may act as a clinical surrogate of ischemic preconditioning that may reduce infarct size and improve mortality in the setting of thrombolytic therapy for ST-elevation myocardial infarction. However, the benefits of preinfarction angina in the setting of primary percutaneous coronary intervention with stenting is inconclusive because of the greater achievement of infarct artery patency and speed of reperfusion.

Methods and Results—

To identify a homogeneous population, we performed a retrospective analysis of 1031 patients admitted with a first ST-elevation myocardial infarction with ischemic times between 1 and 6 hours who received primary percutaneous coronary intervention. We identified 245 patients who had occluded arteries on presentation, of which 79 patients had documented preinfarction angina defined as chest pain within 24 hours of infarction. Infarct size was measured as the peak creatine kinase level, a metric supported in a subgroup by late enhancement on cardiac magnetic resonance imaging. Patients with preinfarction angina (n=79) had a 50% reduction in infarct size compared with those patients without preinfarction angina (n=166) by both peak creatine kinase (1094±75 IU/L versus 2270±102 IU/L;
P
<0.0001) and creatine kinase area under curve (18 420±18 941 versus 36 810±21 741 IU/h per liter;
P
<0.0001) despite having identical ischemic times (185±8 minutes versus 181±5 minutes;
P
=0.67) and angiographic area at risk (24.1±1.2% versus 25.3±0.9%;
P
=0.43). There was an absolute 4% improvement in left ventricular ejection fraction before discharge in those patients with preinfarction angina (
P
<0.02).

Conclusions—

The occurrence of preinfarction angina is associated with significant myocardial protection in the setting of primary percutaneous coronary intervention with stenting during ST-elevation myocardial infarction. Because preinfarction angina is relatively common, it is important that these patients be identified in clinical trials investigating therapies designed to reduce reperfusion injury and infarct size.
Amino Terminal Pro–B-Type Natriuretic Peptide, Secondary Stroke Prevention, and Choice of Antithrombotic Therapy
Authors: Longstreth W.T. , Kronmal Richard A. , Thompson John L.P. , Christenson Robert H. , Levine Steven R. , Gross Rebecca , Brey Robin L. , Buchsbaum Richard , Elkind Mitchell S.V. , Tirschwell David L. , Seliger Stephen L. , Mohr J.P. , deFilippi Christopher R.
Published: January 2013

Background and Purpose—

Because of its association with atrial fibrillation and heart failure, we hypothesized that amino terminal pro–B-type natriuretic peptide (NT-proBNP) would identify a subgroup of patients from the Warfarin–Aspirin Recurrent Stroke Study, diagnosed with inferred noncardioembolic ischemic strokes, where anticoagulation would be more effective than antiplatelet agents in reducing risk of subsequent events.

Methods—

NT-proBNP was measured in stored serum collected at baseline from participants enrolled in Warfarin–Aspirin Recurrent Stroke Study, a previously reported randomized trial. Relative effectiveness of warfarin and aspirin in preventing recurrent ischemic stroke or death over 2 years was compared based on NT-proBNP concentrations.

Results—

About 95% of 1028 patients with assays had NT-proBNP below 750 pg/mL, and among them, no evidence for treatment effect modification was evident. For 49 patients with NT-proBNP >750 pg/mL, the 2-year rate of events per 100 person-years was 45.9 for the aspirin group and 16.6 for the warfarin group, whereas for 979 patients with NT-proBNP ≤750 pg/mL, rates were similar for both treatments. For those with NT-proBNP >750 pg/mL, the hazard ratio was 0.30 (95% confidence interval: 0.12–0.84;
P
=0.021) significantly favoring warfarin over aspirin. A formal test for interaction of NT-proBNP with treatment was significant (
P
=0.01).

Conclusions—

For secondary stroke prevention, elevated NT-proBNP concentrations may identify a subgroup of ischemic stroke patients without known atrial fibrillation, about 5% based on the current study, who may benefit more from anticoagulants than antiplatelet agents.

Clinical Trial Registration—

This trial was not registered because enrollment began before 2005.
The developmental and social history of repetitively aggressive mental health patients
Authors: Grenyer Brin FS , Lewis Kate L , Ilkiw-Lavalle Olga , Deane Rebecca , Milicevic Denise , Pai Nagesh
Published: January 2013

Objective:

A small subgroup of patients is primarily responsible for the large number of aggressive and violent incidents in psychiatric inpatient units. This study aims to identify the developmental, social and interpersonal histories of repeatedly aggressive patients in order to better understand their treatment needs.

Methods:

A total of 1269 consecutive inpatients were studied over 18 months, identifying 64 who were repeatedly aggressive; 128 non-aggressive patients were randomly matched to the aggressive patients by age, sex and diagnosis. Developmental, social, interpersonal and familial histories were obtained from a chart review.

Results:

Repeatedly aggressive patients were significantly more likely to have had a history of aggression, physical and sexual abuse, and experienced interpersonal problems and parental divorce.

Conclusions:

Aggressive patients do not just need short-term skills training, but interventions that target interpersonal and personality disorder deficits associated with their developmental histories.
Determination of non-uniform residual stresses in laminated composites using integral hole drilling method: Experimental evaluation
Authors: Ghasemi AR , Taheri-Behrooz F , Shokrieh MM
Published: January 2013

In this article, the integral hole drilling method, developed in the first part of this research, has been employed to calculate the non-uniform residual stresses trapped within various composite laminates. Test specimens were fabricated using hand layup assisted with vacuum bagging technique. In order to study the capability of the model in predicting the residual stresses in different layups, three different ply configurations are used in this article as: symmetric cross-ply ([0°2/90°2] S), unsymmetric cross-ply ([0°4/90°4]), and symmetric quasi-isotropic ([0°/±45°/90°] S) specimens. Using the developed method in the present research, calculated residual stresses in each layer of the laminates showed good agreements in comparison with the theoretical values.
Occlusal Effects on Longitudinal Bone Alterations of the Temporomandibular Joint
Authors: Zhang J. , Jiao K. , Zhang M. , Zhou T. , Liu X.-D. , Yu S.-B. , Lu L. , Jing L. , Yang T. , Zhang Y. , Chen D. , Wang M.-Q.
Published: January 2013

The pathological changes of subchondral bone during osteoarthritis (OA) development in the temporomandibular joint (TMJ) are poorly understood. In the present study, we investigated the longitudinal alterations of subchondral bone using a rat TMJ-OA model developed in our laboratory. Changes in bone mass were examined by micro-CT, and changes in osteoblast and osteoclast activities were analyzed by real-time PCR, immunohistochemistry, and TRAP staining. Subchondral bone loss was detected from 8 weeks after dental occlusion alteration and reached the maximum at 12 weeks, followed by a repair phase until 32 weeks. Although bone mass increased at late stages, poor mechanical structure and lower bone mineral density (BMD) were found in these rats. The numbers of TRAP-positive cells were increased at 12 weeks, while the numbers of osteocalcin-expressing cells were increased at both 12 and 32 weeks. Levels of mRNA expression of TRAP and cathepsin K were increased at 12 weeks, while levels of ALP and osteocalcin were increased at both 12 and 32 weeks. These findings demonstrated that there is an active bone remodeling in subchondral bone in TMJs in response to alteration in occlusion, although new bone was formed with lower BMD and poor mechanical properties.
Effect of polymer modifiers on the properties of bitumen
Authors: Bulatović Vesna Ocelić , Rek Vesna , Marković Kristina Jurkaš
Published: January 2013

This article presents an investigation about the polymer-modified bitumens (PMBs) containing styrene–butadiene–styrene (SBS) block copolymers with different structures, linear (SBS-L) and radial (SBS-R), semicrystalline copolymer ethylene–vinyl acetate (EVA), and terpolymer ethylene–butyl acrylate–glycidyl methacrylate, Elvaloy AM and Elvaloy 4170. The aim of the study was to establish the influence of the polymer type and content on the properties of PMBs for engineering applications and to evaluate the effectiveness of polymer modifiers. The results indicated that the polymer modification improved the rheological properties of bitumen, increased critical temperature, that is better resistance to permanent deformation was achieved as well as a wider temperature range in service. The degree of improvement generally increased with the polymer content but varied with the polymer type.
Transition from higher education to National Health Service for visually impaired physiotherapists: An interpretative phenomenological exploration
Authors: Atkinson Karen , Hutchinson Jane Owen
Published: January 2013

This idiographic study aims to hear the voices of a small group of visually impaired physiotherapists to explore their lived experience 1 of transition from higher education (HE) into employment. The findings are based on six semi-structured interviews analysed using an interpretative phenomenological approach. Participants were visually impaired physiotherapists who are either working, or have worked, in the National Health Service (NHS). A number of interrelated themes emerged concerning the work of the disabled self, compensation, stigma and passing, disclosure, barriers, disempowerment, and positive experiences. These appear to be linked to a reluctance by participants to engage with their disability identity. The experiences and perceptions of participants do not provide evidence of a commitment to disability-related support for disabled health-care professionals. The results of this study indicate that a wide range of both personal and institutional barriers still exist in the NHS.
An overview of a UK paediatric visual impaired population and low vision aid provision
Authors: Theodorou Nana , Shipman Tracey
Published: January 2013

A retrospective study was carried out to evaluate the paediatric visual impaired population attending the Low Vision Clinic at Sheffield Teaching Hospitals NHS Foundation Trust, over a period of 14 years. Data were collected and analysed for children less than 17 years for prevalence, demographics, registration status, aetiologies, and types of low vision aids issued. The total number of children identified was 204. Of these, 19 percent of the children were registered blind, 45 percent were registered partially sighted, and 36 percent were not registered. The four diagnostic groups were genetic (29%), prenatal (36%), perinatal (23%), and childhood (12%). Describing local characteristics of paediatric visual impairment is a useful measure of current low vision service provision. This information can further inform educational, social, and health needs for the visually impaired children to ensure adequate service provision.
In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation
Authors: Mulla H , Lawson G , von Anrep C , Burke M D , Upton D U , Firmin R K , Killer H
Published: January 2013

Sedative agents are routinely administered to critically ill patients, both on and off extracorporeal membrane oxygenation (ECMO), to enable patients to be comfortable and facilitate patient management. It has been observed empirically in our paediatric intensive care unit that doses of sedative drugs required to achieve desired levels of sedation in ECMO patients are far greater than those used in non-ECMO patients. These differences could not simply be accounted for by differences in patient types, clinical status or sedation levels. We therefore undertook an in vitro evaluation of drug binding in ECMO circuits.

This study investigated how the polyvinyl chloride (PVC) and silicone rubber components of neonatal ECMO circuits affect drug delivery in patients through drug sorption. Phase 1 investigated drug uptake by the two polymers in static solutions of known concentrations of four commonly used sedative drugs: lorazepam, midazolam, diazepam and propofol. Phase 2 involved the setting up of a complete neonatal ECMO circuit, injecting the drug solutions pre-reservoir at a flow rate of 350 ml/min and collecting samples post-oxygenator for analysis.

Phase 1 results revealed significant uptake of drugs with losses in the range 40-98% and in the order propofol • diazepam • midazolam • lorazepam. Phase 2 results were similar and in the first 40 min of running an ECMO circuit only 10% of propofol passed through the circuit. These results may help to explain observed clinical phenomena and raise important issues regarding drug dosing in ECMO patients.
The hazardous effects of alveolar hypocapnia on lung mechanics during weaning from cardiopulmonary bypass
Authors: Bayindir Osman , Akpinar Belhhan , Özbek Ug'ur , Cakali Emine , Pekcan Ülkü , Bulutçu Füsun , Sönmez Bingür
Published: January 2013

The bronchoconstrictive effects of alveolar hypocapnia during weaning from cardiopulmonary bypass (CPB) were investigated in patients undergoing elective coronary artery revascularization. Thirty patients were randomly assigned into two equal groups. In both groups, mechanical ventilation was initiated for 3 min prior to weaning from CPB with the venous pressure low. This kept the pulmonary vascular bed empty, resulting in alveolar hypocapnia (ETCO2 < 2 kPa). Peak airway pressure ( Ppeak) and plateau pressures ( Pplateau) were recorded. In group 1, 5% CO2 was added to the inspiratory gas mixture and the ETCO2 allowed to rise (ETCO2 > 3.3 kPa). The ventilation pressure measurements were recorded again after 3 min stabilization. In group 2, the venous pressure was increased to allow the pulmonary venous bed to fill and the ventilation pressures recorded after a 3 min period of stabilization.

In group 1, the ventilatory pressures dropped significantly ( p < 0.001) when the alveolar hypocapnia was reversed with added CO2 ( Ppeak 19.71 ± 5.7 to 12.31 ± 2.8 cmH2O and Pplateau 13.15 ± 3.28 to 9.15 ± 2.23 cmH2O). In group 2, a similar effect was achieved by allowing filling of the pulmonary vascular bed ( Ppeak 17.46 ± 4.72 to 11.92 ± 3.03 cmH2O and Pplateau 13.93 ± 4.10 to 9.37 ± 3.00 cmH2O).

These results suggest that filling the pulmonary vascular bed prior to initiating ventilation, when weaning from CPB, prevents the otherwise deleterious effects of alveolar hypocapnia, resulting in raised bronchomotor tonus and raised airway pressures.
An in vitro evaluation of a new cannula tip design compared with two clinically established cannula-tip designs regarding aortic arch vessel perfusion characteristics
Authors: Joubert-Huebner E , Gerdes A , Sievers H-H
Published: January 2013

We investigated in vitro aortic arch vessel perfusion characteristics of single and multiple jet-stream cannulae and a new dispersion stream tip aortic cannula. Pressures and flows of all arch vessels were measured while directing cannulae jets at the different arch vessels using 6 l/min pump flow. The highest increase in pressure above the set systemic level of 80 mmHg and increase in flow above the set normal flow distribution in the arch vessels occurred in the jet-streamed arch vessels with the single stream cannula. The values were as follows: 29 mmHg and 118 ml/min for the innominate artery, 28 mmHg and 42 ml/min for the left common carotid artery, and 25 mmHg and 54 ml/min for the left subclavian artery. The dispersion stream cannula showed increases in pressure and flow, followed by the multiple stream cannula. Aortic cannula tips and the orientation of jets are potential sources of imbalances of arch vessel perfusion with possible clinical implications regarding perfusion of arch vessels during extracorporeal circulation.
Affinity pump system: a new peristaltic blood pump for cardiopulmonary bypass
Authors: Jaggy C , Lachat M , Leskosek B , Zünd G , Turina M
Published: January 2013

An in vitro study has been carried out to assess the pump performance of a new peristaltic, extracorporeal displacement pump (Affinity) for cardiopulmonary bypass. The pump system consists of a pump rotor (0-110 rpm), a pump chamber, a venous reservoir with a 5/8″ connecting tube and the Affinity console. The polyurethane chamber is connected to the venous reservoir by a 5/8″ tube and fills passively due to the hydrostatic pressure exhibited by the fluid height in the venous reservoir. The implementation of an occlusive segment in the pump chamber, which collapses in low filling states, should prevent significant negative pressures. An in vitro circuit was filled with bovine blood (37°C, hematocrit 35%) and the pump flow was measured by an ultrasonic transit time flow probe with respect to pre-load, diameter and length of attached tubing in the venous line, pump speed (rpm) and size of the connecting tube (3/8″ and 5/8″).

At 108 rpm and a preload equal to 10 mmHg, the flow was 8.6 ± 0.42 l/min for an afterload of 80 mmHg. The reduction of the inlet connector to 3/8″ diminished the pump flow significantly to 5.2 ± 0.31 l/min ( p < 0.0001). The pump flow decreased linearly with respect to the length of the attached tube in the venous line and for a 2 m long 5/8″ silicon tube, the rpm-optimized flow was still 6.0 ± 0.28 l/min at a preload of 10 mmHg. In case of low filling state or too high rpm, the occlusive segment collapsed and no cavitation bubbles could be detected.

Our in vitro measurements yield a nomogram for rpm-optimized blood flow with respect to the pre-load in the venous reservoir. The delivered 5/8″ connecting tube facilitates optimum filling of the pump chamber for high blood flow, but limits the use of venous reservoirs to Affinity products. The pump yields a high blood flow even when long tubing in the venous line is used. This makes the pump a candidate for a ventricular assist device. In hypovolemia or high rpm, the occlusive segment collapses and no negative pressure is generated at the inflow site of the pump chamber.
Comparison of two doses of aprotinin in patients receiving aspirin before coronary bypass surgery
Authors: Moran Sergio V , Lema Guillermo , Medel Jessica , Irarrazaval Manuel J , Zalaquett Ricardo , Garayar Bernardita , Flaskamp Renate
Published: January 2013

This study was designed to evaluate efficacy and tolerability of two different doses of aprotinin in patients receiving aspirin before undergoing coronary artery bypass grafting. Forty-two patients were randomized to receive either placebo (group I), or aprotinin in doses of 4 000 000 KIU (group II) or 6 000 000 KIU (group III). Drug efficacy was determined by measuring postoperative blood loss and transfusion of blood products. Both doses were effective in reducing blood loss and transfusion requirements. Blood loss through thoracotomy drainage was 450 ± 224, 182 ± 144, 142 ± 98 ml, respectively, for control and treatment groups II and III ( p = 0.0001). The numbers of patients with blood transfusions were seven (50%), two (17%) and two (17%) for group I and treatment groups II and III, respectively ( p = 0.10). Tolerability was excellent and complications few and reversible.

In conclusion, high and medium doses of aprotinin were well tolerated and reduced bleeding and transfusion requirements in patients submitted to coronary bypass surgery under the effects of aspirin.
Impact of membrane oxygenators on pulsatile versus nonpulsatile perfusion in a neonatal model
Authors: Ündar Akif , Koenig Karl M , Frazier O H , Fraser Charles D
Published: January 2013

We investigated the effects of two new hollow-fiber membrane oxygenators, the Capiox SX10 and the Lilliput 901, on pulsatile versus nonpulsatile perfusion in an in vitro model designed to simulate a 3 kg infant. The experiments were divided into eight groups (six pulsatile and two nonpulsatile), according to the equipment and settings used. Each group included six tests. In all experiments, the pseudo-patient’s mean arterial pressure was 40 mmHg, and the pump flow rate was 550 ml/min. During pulsatile cardiopulmonary bypass, the pump’s base flow was set at 30%, and the pump rate was set at 80, 100, 120, 140, or 150 beats/min. The PUMP START and PUMP STOP timing points were adjusted to produce different pulse-width settings. We were especially interested in evaluating the pre- and postoxygenator extracorporeal circuit pressure (ECP), the oxygenator pressure drop, and the precannula ECP.

When used with a pulsatile roller pump, the Capiox produced a significantly lower preoxygenator ECP than the Lilliput ( p < 0.001); moreover, the Capiox yielded a significantly lower oxygenator pressure drop ( p < 0.001). During nonpulsatile perfusion, the Capiox again produced a lower preoxygenator ECP than the Lilliput ( p < 0.001). These results suggest that the Capiox may be more suitable than the Lilliput when the pulsatile flow is employed, and pulsatile flow does not increase the ECP with either oxygenator.