bluuebunny/crossref_metadata_2025 huggingface dataset:
Secure Telemedicine: Biometrics for Remote and Continuous Patient Verification
Authors: Agrafioti Foteini , Bui Francis M. , Hatzinakos Dimitrios
Published: November 2012

The technological advancements in the field of remote sensing have resulted in substantial growth of the telemedicine industry. While health care practitioners may now monitor their patients’ well-being from a distance and deliver their services remotely, the lack of physical presence introduces security risks, primarily with regard to the identity of the involved parties. The sensing apparatus, that a patient may employ at home, collects and transmits vital signals to medical centres which respond with treatment decisions despite the lack of solid authentication of the transmitter’s identity. In essence, remote monitoring increases the risks of identity fraud in health care. This paper proposes a biometric identification solution suitable for continuous monitoring environments. The system uses the electrocardiogram (ECG) signal in order to extract unique characteristics which allow to discriminate users. In security, ECG falls under the category ofmedical biometrics, a relatively young but promising field of biometric security solutions. In this work, the authors investigate the idiosyncratic properties of home telemonitoring that may affect the ECG signal and compromise security. The effects of psychological changes on the ECG waveform are taken into consideration for the design of a robust biometric system that can identify users based on cardiac signals despite physical or emotional variations.
Application of Chaos Theory in Trucks' Overloading Enforcement
Authors: Mahmoudabadi Abbas , Abolghasem Arezoo
Published: November 2012

Trucks' overloading is considered as one of the most substantial concerns in road transport due to a possible road surface damage, as well as, are less reliable performance of trucks' braking system. Sufficient human resource and adequate time scheduling are to be planned for surveying trucks' overloading; hence, it seems required to prepare an all-around model to be able to predict the number of overloaded vehicles. In the present research work, the concept of chaos theory has been utilized to predict the ratio of trucks which might be guessed overloaded. The largest Lyapunov exponent is utilized to determine the presence of chaos using experimental data and concluded that the ratio of overloaded trucks reflects chaotic behavior. The prediction based on chaos theory is compared with the results of simple smoothing and moving average methods according to the well-known criterion of mean square errors. The results have also revealed that the chaotic prediction model would act more capably comparing the analogous methods including simple smoothing and moving average to predict the ratio of passing trucks to be possibly overloaded.
Optimization of Carboxymethyl-Xyloglucan-Based Tramadol Matrix Tablets Using Simplex Centroid Mixture Design
Authors: Madgulkar Ashwini R. , Bhalekar Mangesh R. , Padalkar Rahul R. , Shaikh Mohseen Y.
Published: November 2012

The aim was to determine the release-modifying effect of carboxymethyl xyloglucan for oral drug delivery. Sustained release matrix tablets of tramadol HCl were prepared by wet granulation method using carboxymethyl xyloglucan as matrix forming polymer. HPMC K100M was used in a small amount to control the burst effect which is most commonly seen with natural hydrophilic polymers. A simplex centroid design with three independent variables and two dependent variables was employed to systematically optimize drug release profile. Carboxymethyl xyloglucan , HPMC K100M , and dicalcium phosphate were taken as independent variables. The dependent variables selected were percent of drug release at 2nd hour and at 8th hour . Response surface plots were developed, and optimum formulations were selected on the basis of desirability. The formulated tablets showed anomalous release mechanism and followed matrix drug release kinetics, resulting in regulated and complete release from the tablets within 8 to 10 hours. The polymer carboxymethyl xyloglucan and HPMC K100M had significant effect on drug release from the tablet (). Polynomial mathematical models, generated for various response variables using multiple regression analysis, were found to be statistically significant (). The statistical models developed for optimization were found to be valid.
Nonlinear Performance Characteristics of Flux-Switching PM Motors
Authors: Ilhan E. , Kremers M. F. J. , Motoasca T. E. , Paulides J. J. H. , Lomonova E. A.
Published: November 2012

Nonlinear performance characteristics of 3-phase flux-switching permanent magnet motors (FSPM) are overviewed. These machines show advantages of a robust rotor structure and a high energy density. Research on the FSPM is predominated by topics such as modeling and machine comparison, with little emphasis given on its performance and limits. Performance characteristics include phase flux linkage, phase torque, and phase inductance. In the paper, this analysis is done by a cross-correlation of rotor position and armature current. Due to the high amount of processed data, which cannot be handled analytically within an acceptable time period, a multistatic 2D finite element model (FEM) is used. For generalization, the most commonly discussed FSPM topology, 12/10 FSPM, is chosen. Limitations on the motor performance due to the saturation are discussed on each characteristic. Additionally, a focused overview is given on energy conversion loops anddq-axes identification for the FSPM.
Use of the Charge Transfer Reactions for the Spectrophotometric Determination of Risperidone in Pure and in Dosage Forms
Authors: Deepakumari Hemavathi Nagaraju , Revanasiddappa Hosakere Doddarevanna
Published: November 2012

The aim of study was to develop and validate two simple, sensitive, and extraction-free spectrophotometric methods for the estimation of risperidone in both pure and pharmaceutical preparations. They are based on the charge transfer complexation reactions between risperidone (RSP) as n-electron donor and p-chloranilic acid (p-CA) in method A and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in method B as π-acceptors. In method A, RSP reacts with p-CA in methanol to produce a bright pink-colored chromogen measured at 530 nm whereas, in method B, RSP reacts with DDQ in dichloromethane to form orange-colored complex with a maximum absorption at 460 nm. Beer's law was obeyed in the concentration range of 0–25 and 0–50 μg/mL with molar absorptivity of and L/moL/cm for RSP in methods A and B, respectively. The effects of variables such as reagents, time, and stability of the charge transfer complexes were investigated to optimize the procedures. The proposed methods have been successfully applied to the determination of RSP in pharmaceutical formulations. Results indicate that the methods are accurate, precise, and reproducible (relative standard deviation %).
TeleCyP (Telecytopathology): Real-Time Fine-Needle Aspiration Interpretation
Authors: Goyal Abha , Jhala Nirag , Gupta Prabodh
Published: November 2012

Objective: To assess the application of TeleCyP for real-time fine-needle aspiration interpretation (RFI) necessary for case management and specimen triage. Study Design: Twenty-two endobronchial ultrasound (EBUS)-guided mediastinal and pulmonary cases were included in the learning phase to determine the time and efficiency of TeleCyP. Slides were scanned by a cytopathology fellow in real time, and high-speed transmitted images over a secure network were interpreted by a cytopathologist while maintaining audio communication. In the validation phase, an additional 38 pancreas cases from endoscopic ultrasound (EUS) were evaluated recapitulating the RFI scenario from the learning phase. The cytopathologist was blinded to the results of the diagnosis in both phases. Results: The time to provide assessment of specimen adequacy and a preliminary diagnosis was 53 s in the learning phase and 49 s in the validation phase. There was 100% correlation between RFI and TeleCyP assessment for specimen adequacy. TeleCyP particularly posed challenges in providing definitive interpretation on EUS-fine-needle aspiration of some of the pancreatic solid masses (11%, 4/36). Conclusion: TeleCyP can serve as a powerful alternative, time-efficient strategy to provide RFI, and for specimen triaging which is critical for personalized medicine and patient management.
Role of Fluorescence in situ Hybridization in Lung Cancer Cytology
Authors: Savic Spasenija , Bubendorf Lukas
Published: November 2012

There are several challenges in lung cytology including equivocal cytological findings, lung cancer subclassification, and predictive marker analysis. Fluorescence in situ hybridization (FISH) detects chromosomal alterations that underlie the development and progression of cancer, and pinpoints targets of new anticancer drugs. Detection of such targets by FISH can be of diagnostic utility in morphologically difficult cases. Multitarget FISH with four different chromosomal probes improves the sensitivity of cytology in the diagnosis of lung cancer and clarifies equivocal cytological findings. FISH is becoming increasingly important in the field of predictive marker analysis. FISH is the gold standard to identify ALK rearrangements for treatment with the ALK inhibitor crizotinib (Xalkori). EGFR mutation analysis is the method of choice for selecting patients for therapy with EGFR tyrosine kinase inhibitors (TKIs), whereas the EGFR gene copy number has not been confirmed as a reliable predictive marker. MET amplification is an important mechanism of secondary resistance to EGFR TKIs and a candidate predictive marker for targeted second-line treatment of TKI-resistant non-squamous non-small cell lung cancer. FGFR1 amplification is a promising new marker in squamous cell carcinoma that may predict the response to FGFR1 inhibitors. In conclusion, there are an increasing number of clinically relevant FISH applications in lung cytology. We provide an overview on the current role of FISH in respiratory cytology.
Molecular Diagnostics, Personalized Medicine, and the Evolving Role of the Cytotechnologist: An Institutional Experience
Authors: Kane Lindsey E. , Root Renee R. , Voss Jesse S. , Caudill Jill L. , Sorenson Angela M. , Colborn Lisa K. , Halling Kevin C. , Henry Michael R. , Clayton Amy C. , Kipp Benjamin R.
Published: November 2012

The role of cytotechnologists has focused primarily on the microscopic examination of cytologic specimens for diagnosing disease. Cytotechnologists currently evaluate a wide assortment of both gynecological and nongynecological cytology specimens. However, the Pap test remains the primary test for most cytology laboratories. Recently, human papillomavirus testing and newer cervical cancer screening guidelines have reduced the number of Pap tests, resulting in some anxiety and concern among the cytology community. However, as Pap test volumes continue to decrease, molecular oncology and ancillary testing volumes continue to increase with the advent of new biomarkers and associated personalized therapies. This change in clinical practice has resulted in evolving roles for many cytotechnologists. Cytotechnologists have skills based not only in morphology but also in understanding concepts of disease including neoplasia. These skills allow cytotechnologists to excel in many other types of laboratory testing. This article discusses how the roles of the cytotechnologist have recently expanded at our institution to include involvement in DNA ploidy analysis, quantitative immunohistochemistry, fluorescence in situ hybridization, circulating tumor cells, and molecular oncology testing. Lastly, this article discusses how these newer roles benefit both the cytotechnologist and the clinical laboratory.
Histopathological Work-Up of Resection Specimens, Local Excisions and Biopsies in Colorectal Cancer
Authors: Quirke Philip , Palmer Tim , Hutchins Gordon G.A. , West Nick P.
Published: November 2012

The pathological examination of material removed from patients with colorectal neoplasia is important. It provides a wide range of information on, for example, the quality and completeness of excision, the stage and biological aggressiveness, the need for further therapy, and response to therapy. Molecular testing adds valuable information on genetic risk and is required before treatment with anti-EGF-r antibodies. This article highlights the value derived from macroscopic inspection of surgical specimens, careful microscopy and excellent reporting according to national guidelines. Increasing use of a number of preoperative therapies and combinations in rectal cancer change the pathological features found and a standardised approach to the diagnosis of complete response is required. It touches upon the issues with frequent changes in TNM staging and the difficulties these changes are causing. The widespread introduction of bowel cancer screening is changing the stage of presentation of colorectal cancer leading to increasing numbers of local excisions and polyp cancers.
Colorectal Cancer Screening: Practice Guidelines
Authors: Lieberman David
Published: November 2012

Colorectal cancer (CRC) screening has been demonstrated to reduce both incidence and mortality of CRC. There are several different screening options, each with potential benefits and some limitations. Fecal blood tests are primarily early cancer detection tests, which have been shown to reduce CRC mortality. Structural exams of the colon (flexible sigmoidoscopy, colonoscopy and imaging) may identify cancer precursor lesions (adenomas) and early cancer. There is evidence that detection and removal of adenomas may prevent many cancers. New forms of screening using stool DNA, capsule endoscopy and serum testing for genetic mutations are still in evolution, though proof-of-principle studies have been published.
Endoscopic Detection of Colorectal Adenomas: Standards and Sophisticated Methods
Authors: Anders Mario
Published: November 2012

Colorectal cancer represents one of the leading malignancies worldwide. Early endoscopic detection and removal of its precursor lesions, adenomas, and serrated hyperplastic polyps results in a decrease of colon cancer-related death. However, miss rates in adenoma detection up to 26% underline the need for high compliance to basic measures and further improvement in methodology and technology. Basic parameters affecting adenoma detection rates include sufficient training and awareness of the endoscopist, use of high-definition endoscopes, careful examination behind folds, cleansing the colon wall, accurate distention of the colon, and adequate withdrawal time. Advanced imaging techniques, introduced to further improve adenoma detection, have yielded mixed results. These include wide-angle colonoscopes, cap-assisted colonoscopy, and retroscopic methods which may add new obstacles to colonoscopy. Moreover, chromoendoscopy either ‘virtual’ or by topically applied dyes has been suggested to enhance the detection of colonic neoplasia. Yet, studies on patients with average cancer risk have failed to reproduce promising initial results. Similarly, although autofluorescence has not enhanced the diagnostic yield in screening a population at average risk, it may be useful in patients at increased cancer risk. Recently, technical feasibility of molecular imaging employing ‘biomarkers’ has been demonstrated, but needs further evaluation. The newest developments, employing light-scattering spectroscopy, suggest the existence of a ‘field effect’ of colonic carcinogenesis and may enable detection of the earliest neoplastic events and distant adenomas even when applied to normal-appearing mucosa. Upon confirmation, these technologies may result in a substantial change in patient management and risk stratification.
Colorectal Cancer Surgery: What Is Evidence Based and How Should We Do It?
Authors: Bennis Malika , Tiret Emmanuel
Published: November 2012

Evidence-based medicine was first defined by Sackett as ‘the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients’. This requires good quality studies with a high level of proof. However, these studies are often lacking in colorectal surgery. Nevertheless, the topics on which there is general agreement will be discussed. There is now good evidence that the laparoscopic approach is at least equivalent in oncological terms to the conventional open approach in colonic surgery. The question, however, remains unanswered for rectal cancer surgery, which is technically more demanding. Although there are no randomized studies, the introduction of total mesorectal excision for rectal cancer has achieved a major reduction in local recurrence and has been adopted as the gold standard by all colorectal surgeons. Extending this concept to colonic cancer surgery is currently under discussion. The different types of reconstruction in sphincter-preserving surgery which achieve a better functional result than straight anastomosis, including colonic pouch, transverse coloplasty and side-to-end anastomosis, will be discussed. The benefit of temporary fecal diversion in low anastomosis has now been demonstrated with a good level of evidence. The technique of abdominoperineal resection has evolved in the last years and now aims at obtaining a cylindrical specimen, which has resulted in a significant reduction of the local recurrence rate. In early rectal cancer, the technique of local resection has been improved by the introduction of transanal endoscopic microsurgery.
Neoadjuvant Short- or Long-Term Radio(chemo)therapy for Rectal Cancer: How and Who Should Be Treated?
Authors: Rödel Claus , Trojan Jörg , Bechstein Wolf-Otto , Woeste Guido
Published: November 2012

There are two general approaches to preoperative radiotherapy (RT) in rectal cancer: short-course (25 Gy in 5 fractions) radiation with immediate surgery and long-course 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT; 50.4 Gy in 28 fractions) with surgery scheduled 6–8 weeks thereafter. While it is clear that downsizing and downstaging effects are more pronounced with long-course CRT and delayed surgery, a Polish randomized trial and, more recently, an Australian phase III trial demonstrated no significant differences in long-term oncologic outcomes and late toxicity rates between either preoperative concept. Ongoing studies currently address short-course preoperative RT with a longer interval to surgery (Stockholm III trial), and short-course RT with sequential combination chemotherapy in patients with synchronous distant metastasis. With respect to the long-course CRT approach, newer-generation chemotherapeutics as well as molecularly targeted agents have been tested within phase I–III studies, both as induction/adjuvant chemotherapy as well as during concomitant CRT. Evidently, the monolithic approaches to either apply the same schedule of preoperative 5-FU-based CRT to all patients with TNM stage II/III rectal cancer or to give preoperative short-course RT for all patients with resectable rectal cancer irrespective of tumor stage and location need to be questioned. The inclusion of different multimodal treatments into the surgical oncological concept, adapted to tumor location, stage, and individual patient risk factors and preferences is upcoming. Clearly, future developments will aim at identifying and selecting patients for ideal treatment alternatives.
Resectable Rectal Cancer: Which Patient Does Not Need Preoperative Radiotherapy?
Authors: Kulu Yakup , Ulrich Alexis , Büchler Markus W.
Published: November 2012

It is well known that some patients with resectable rectal cancer benefit from preoperative radiotherapy in combination with or without chemotherapy. In order to reduce local recurrence and improve long-term survival, current guidelines advocate such neoadjuvant treatment in UICC (Union for International Cancer Control) stage II and III patients. However, the vast majority of patients may be adequately treated by rectal resection with total mesorectal excision (TME) alone. Recent evidence suggests an overtreatment of patients leading to unnecessary exposure to acute and long-term toxicity of radiation therapy. The question which consequently arises is which patient does not need preoperative radiotherapy. Improvements in MRI combined with better understanding of prognostic indicators suggest that patients with UICC stage I tumors, with tumors more than 12 cm proximal the anal verge can and patients with a circumferential resection margin ≥2 mm as assessed by preoperative MRI might be managed by radical surgery with adequate TME alone.
Surgical Strategies to Synchronous Colorectal Liver Metastases
Authors: Brouquet Antoine , Nordlinger Bernard
Published: November 2012

Synchronous colorectal liver metastases include a wide variety of clinical presentation depending on the location and the extent of the primary tumor, the extent of metastatic disease in the liver, and the presence of extrahepatic disease. Only a minority of patients with synchronous colorectal liver metastases and an intact primary tumor can be candidates for a curative treatment approach. In the past two decades, considerable progress with both antitumor agents and surgical strategies has contributed to increase the number of patients that can achieve complete resection of primary tumor and liver metastases. Optimal treatment of colorectal resectable liver metastases includes preoperative chemotherapy that can be administered after resection of the primary tumor and before resection of liver metastases in a ‘classical’ fashion, before combined resection of the primary tumor and liver metastases, and before liver resection of liver metastases followed by resection of the primary tumor in the reverse strategy. With regard to the large variety of clinical presentations in patients with synchronous colorectal liver metastases, none of these treatment strategies can be recommended in all patients. The complexity and the multiplicity of available treatment options underline the need for a multidisciplinary approach to this disease.
Neuromuscular Blockade and Lung Function during Resuscitation of Infants with Congenital Diaphragmatic Hernia
Authors: Murthy Vadivelam , D’Costa Walton , Nicolaides Kypros , Davenport Mark , Fox Grenville , Milner Anthony D. , Campbell Morag , Greenough Anne
Published: November 2012

Background: There is no consensus or evidence as to whether a neuromuscular blocking agent should be used during the initial resuscitation of infants with congenital diaphragmatic hernia (CDH) in the labour ward. Objective: To determine if administration of a neuromuscular blocking agent affected the lung function of infants with CDH during their initial resuscitation in the labour ward. Methods: Fifteen infants with CDH were studied (median gestational age 38 weeks, range 34–41; birth weight 2,790 g, range 1,780–3,976). Six infants had undergone feto-endotracheal occlusion (FETO). Flow, airway pressure, tidal volume and dynamic lung compliance changes were recorded using a respiratory function monitor (NM3, Respironics). Twenty inflations immediately before, immediately after and 5 min after administration of a neuromuscular blocking agent (pancuronium bromide) were analysed. Results: The median dynamic lung compliance of the 15 infants was 0.22 ml/cm H2O/kg (range 0.1–0.4) before and 0.16 ml/cm H2O/kg (range 0.1–0.3) immediately after pancuronium bromide administration (p < 0.001) and remained at a similar low level 5 min after pancuronium bromide administration. The FETO compared to the non-FETO infants had a lower median dynamic compliance both before (p < 0.0001) and 5 min after pancuronium administration (p < 0.001) and required significantly longer durations of ventilation (p = 0.004), supplementary oxygen (p = 0.003) and hospitalisation (p = 0.007). Conclusions: Infants with CDH, particularly those who have undergone FETO, have a low lung compliance at birth, and this is further reduced by administration of a neuromuscular blocking agent.
The Utility of Fine-Needle Aspiration in the Diagnosis of Primary and Metastatic Tumors to the Lung: a Retrospective Examination of 1,032 Cases
Authors: Adams Julia , Wu Howard H.
Published: November 2012

Background: With the emergence of improved treatment strategies for patients with malignant lung tumors, it has become increasingly important to adequately diagnose and subclassify lung lesions. In our large retrospective study, we assessed the utility of fine-needle aspiration (FNA) in the diagnosis of primary and metastatic tumors to the lung. Methods: A computerized search of our laboratory informatics system was performed to identify cases from FNA of the lung and FNA of metastatic lung cancers to other sites. All of the corresponding surgical pathology reports were also reviewed. All of the cases were categorized as atypical (A), benign (B), malignant (M), nondiagnostic (ND), or suspicious (S) for data analysis purposes. Results: A total of 1,032 FNA cases were categorized as follows: 34 (3.3%) A, 142 (13.8%) B, 717 (69.5%) M, 121 (11.7%) ND, and 18 (1.7%) S. Of the 717 cases of malignant FNA, a specific tumor type was able to be rendered on cytomorphology alone or with the help of immunostains in 99% as follows: adenocarcinoma (296 cases, 41%), squamous cell carcinoma (158 cases, 22%), metastatic tumors (123 cases, 17%), small cell carcinoma (56 cases, 8%), non-small cell lung carcinoma (NSCLC) (58 cases, 8%), neuroendocrine carcinoma (15 cases, 2%), and poorly differentiated carcinoma (4 cases, 1%). Out of all NSCLC cases, 89% were able to be subclassified as either adenocarcinoma or squamous carcinoma. The most frequent origins of metastatic tumors to the lung were renal cell carcinoma (n = 22), melanoma (n = 17), colon (n = 15), breast (n = 14), and urothelial carcinoma (n = 10). There was also metastasis from 18 other organs with fewer than 5 cases each. There were 333 correlated histologic specimens including 191 small biopsies and 142 resection specimens. Diagnostic sensitivity and specificity for malignancy were 96 and 100%, respectively. Diagnostic accuracy was 97%. Sampling error resulted in 8 false-negative cases on FNA. Conclusions: FNA is both sensitive and specific in the diagnosis and subclassification of both primary and metastatic lung tumors. Eighty-nine percent of NSCLC cases were able to be further subclassified as adenocarcinoma or squamous cell carcinoma by FNA.
Semiautomated Laser Capture Microdissection of Lung Adenocarcinoma Cytology Samples
Authors: Roy Chowdhuri Sinchita , Hanson Jeffrey , Cheng Jerome , Rodriguez-Canales Jaime , Fetsch Patricia , Balis Ulysses , Filie Armando C. , Giaccone Giuseppe , Emmert-Buck Michael R. , Hipp Jason D.
Published: November 2012

Objective: In the past decade molecular diagnostics has changed the clinical management of lung adenocarcinoma patients. Molecular diagnostics, however, is largely dependent on the quantity and quality of the tumor DNA that is retrieved from the tissue or cytology samples. Frequently, patients are diagnosed on cytology specimens where the tumor cells are scattered within the cell block, making selecting for tumor enrichment difficult. In the past we have used laser capture microdissection (LCM) to select for pure populations of tumor cells to increase the sensitivity of molecular assays. This study explores several methods for semiautomated computer-guided LCM. Study Design: Hematoxylin and eosin- or TTF-1-immunostained slides from a pleural effusion cell block with metastatic lung adenocarcinoma were used for LCM with either AutoScan or a recently described pattern-matching algorithm, spatially invariant vector quantization (SIVQ), to define morphologic predicates (vectors) to select cells of interest. Results: We retrieved pure populations of tumor cells using both algorithm-guided LCM approaches with slight variations in cellular retrievals. Both methods were semiautomated, requiring minimum technical supervision. Conclusion: In this study we demonstrate the first semiautomated, computer-guided LCM of a cytology specimen using SIVQ and AutoScan, a first step towards the long-term goal of integrating LCM into the clinical cytology-molecular workflow.
MicroRNA Profiling in Lung Cancer Reveals New Molecular Markers for Diagnosis
Authors: Solomides Charalambos C. , Evans Barry J. , Navenot Jean-Marc , Vadigepalli Rajanikanth , Peiper Stephen C. , Wang Zi-xuan
Published: November 2012

Objective: To identify new molecular diagnostic markers for non-small cell lung carcinoma (NSCLC) by analyzing microRNA (miRNA) expression profile differences in samples from NSCLC patients and adults with nonneoplastic diseases. Study Design: miRNA expression was studied in archival formalin-fixed, paraffin-embedded tissues by microarray and confirmed by real-time PCR analysis of NSCLC and normal lung tissues. An algorithm for discriminating normal, squamous cell carcinoma (SQCC), and adenocarcinoma (ADC) tissue was derived from miRNA expression studies and applied towards characterization of poorly differentiated NSCLC samples. Results: Microarray data from a genome-wide scan revealed 34 differentially expressed miRNAs, 5 of which enabled algorithmic discrimination of normal tissue from carcinoma (SQCC or ADC), as well as SQCC from ADC. Expression of miR-21 was significantly increased in both tumor types, whereas levels of miR-451 and miR-486-5p were reduced. SQCC was distinguished from normal tissue and ADC by high-level miR-205 expression and decreased miR-26b. Comparison of miRNA profiles to histological and immunohistochemical findings in 19 poorly differentiated specimens demonstrated the potential clinical utility of miRNA profiling to provide important insights into the classification of SQCC and ADC. Conclusion: This study presents a novel algorithm for specimen classification in cases of poorly differentiated NSCLC.
Antimicrobial Resistance Genotype Trend and Its Association with Host Clinical Characteristics in Respiratory Isolates of Haemophilus influenzae
Authors: Hagiwara Eri , Baba Tomohisa , Shinohara Takeshi , Nishihira Ryuichi , Komatsu Shigeru , Ogura Takashi
Published: November 2012

Background: β-Lactam resistance genotype trends in clinical isolates of Haemophilus influenzae and their correlation with the clinical background were analyzed. Methods: Five hundred and ten respiratory isolates of H. influenzae collected during the period 2002–2009 were classified by PCR into gBLNAS (genotype for β-lactamase-negative ampicillin-susceptible), gBLNAR (genotype for β-lactamase-negative ampicillin-resistant) and 3 other genotypes. The associations with host clinical data and antimicrobial susceptibility were analyzed in all 144 isolates between 2008 and 2009. Results: The 8-year trend analysis detected an increase in gBLNAR with a decrease in gBLNAS. The probability of being a causative pathogen did not differ between genotypes. Host clinical characteristics such as age and gender did not differ with gBLNAR or gBLNAS, but the underlying respiratory diseases did differ. gBLNAR was found at the highest rate in 83% of isolates from patients with nontuberculous mycobacteriosis. In contrast, gBLNAR accounted for as little as 33% of isolates from chronic obstructive pulmonary disease. Conclusions: There were no differences in the pathogenicity of gBLNAR and gBLNAS. The underlying respiratory diseases may be related to the resistance genotype.
Exercise Limitations by the Oxygen Delivery and Utilization Systems in Aging and Disease: Coordinated Adaptation and Deadaptation of the Lung-Heart Muscle Axis - A Mini-Review
Authors: Burtscher Martin
Published: November 2012

Cardiorespiratory fitness (aerobic exercise capacity) is one of the most important prerequisites for successful aging in human beings and depends on adequate oxygen transport by the respiratory and circulatory systems from environmental air to the working muscles and the efficient utilization of oxygen by the mitochondria. A linear dose-response relation between aerobic exercise capacity, morbidity, mortality, and quality of life is well documented. The process of normal aging is associated with a variable reduction in functional capacity of the main organs involved in oxygen delivery and utilization. Integrated changes of the heart-lung muscle axis are termed here ‘coordinated deadaptation', e.g. due to aging and disease, in contrast to the beneficial effects of ‘coordinated adaptation', e.g. resulting from exercise training. Physical inactivity in aging persons initiates a circulus vitiosus resulting in coordinated deadaptation of the oxygen delivery and utilization systems mainly affecting the heart-muscle axis. Whereas in the healthy elderly the deadaptation process starts from inactive locomotor muscles, the lung or the heart represent the origin in patients suffering from respiratory or cardiovascular diseases. Specific exercise training programs, considering the state of cardiorespiratory health and physical activity, are the most important and almost the only effective intervention to avoid or to break the circulus vitiosus, thereby promoting quality and expectancy of life in aging humans.
The Interventional Radiologist’s Perspective on Lung Biopsy
Authors: Elnekave Eldad , Thornton Raymond
Published: November 2012

Percutaneous image-guided lung biopsies are commonly performed by radiologists. Here, we review common indications and contraindications for the procedure, image guidance and tissue retrieval options, and other special considerations.
Bone Mineral Density as a Predictor of Atherosclerosis and Arterial Wall Stiffness in Obese African-American Women
Authors: McFarlane Samy I. , Qureshi Ghazanfar , Singh Gagandeep , Venner-Jones Kinda , Salciccioli Louis , Lazar Jason
Published: November 2012

Bone demineralization is associated with higher cardiovascular event rates, possibly due to vascular calcification and accelerated atherosclerosis. African-Americans have less bone loss and less calcium content within atherosclerotic plaques. However, whether loss of bone mass is related to atherosclerosis has not been examined in African-Americans. The objective of this study was to evaluate possible associations between bone mineral density (BMD), carotid intimal-medial thickness (CIMT), and arterial stiffness. We studied 100 obese African-American women (BMI: 26.6 ± 6.2; age: 63 ± 14 years) referred for BMD estimation by dual-energy X-ray absorptiometry scan. BMD (g/cm2) was obtained at the lumbar spine (L1–L4), femoral neck, and total hip. Arterial stiffness was evaluated by the heart rate-corrected augmentation index (AI@75) and pulse wave velocity (PWV) using applanation tonometry. CIMT was measured by vascular ultrasound. Mean CIMT, AI@75, and PWV were 0.72 ± 0.14 mm, 28.8 ± 9.0%, and 8.9 ± 1.6 m/s, respectively. Mean BMD values at the lumbar spine, femoral neck, and hip were 0.96 ± 0.19, 0.80 ± 0.16, and 0.91 ± 0.17 g/cm2. Older subjects had higher CIMT (r = 0.61, p < 0.001) and AI@75 (r = 0.42, p < 0.001). There was a significant correlation between AI@75 and CIMT (r = 0.45, p < 0.001). BMD was negatively correlated with AI@75 (lumbar: r = –0.22, p = 0.03; femoral neck: r = –0.24, p = 0.01; hip: r = –0.21, p = 0.03). BMD was unrelated to CIMT (lumbar: r = –0.09, p = 0.42; femoral neck: r = –0.15, p = 0.17; hip: r = –0.13, p = 0.23). On multivariate analysis, age (p < 0.001), hypertension (p = 0.02), and lumbar BMD (p = 0.01, R2 = 0.30) were independent predictors of increased AI@75 after adjusting for age, height, and cardiovascular risk factors. These findings were unchanged upon substitution of femoral neck BMD (p = 0.05, R2 = 0.28) into the model. There was a trend with hip BMD (p = 0.06, R2 = 0.28) in the regression model. Age-matched comparison between normal BMD (n = 25) and osteoporotic patients (n = 34) demonstrated a significant difference in AI@75 (26.6 ± 8.9 vs. 31.6 ± 9.1%, p = 0.04). In summary, women with lower BMD had increased arterial stiffness. There was no relationship between BMD and atherosclerosis. In conclusion, age, hypertension, and BMD are independent predictors of higher arterial stiffness. Vascular changes are related to bone mineral loss, suggesting lower BMD may increase cardiovascular risk in African-Americans.
Decreased Autonomic Modulation of Heart Rate and Altered Cardiac Sympathovagal Balance in Patients with Cushing's Syndrome: Role of Endogenous Hypercortisolism
Authors: Chandran Dinu S. , Ali Naseer , Jaryal Ashok Kumar , Jyotsna Viveka P. , Deepak Kishore Kumar
Published: November 2012

Background/Aims: Endogenous Cushing's syndrome is associated with a higher risk of cardiovascular morbidity and mortality. Previous literature suggested multiple possible links by which hypercortisolism may alter the autonomic control of cardiovascular functions. We investigated the impact of chronic endogenous hypercortisolism on the autonomic regulation of cardiac functions by short-term heart rate variability analysis. Methods: Eighteen patients with endogenous Cushing's syndrome and 20 age-, gender- and BMI-matched controls participated in the study. ECG signal was acquired in lead II configuration for 5 min and heart rate variability assessment was made in both time and frequency domain using the extracted RR interval data. Results: All time and frequency domain measures of heart rate variability were significantly (p < 0.05) lower in the patient group compared to the control group. The patient group had an altered sympathovagal balance with low frequency/high frequency band ratio significantly higher than the control group [1.857 (0.6747-2.610) vs. 0.8581 (0.4779-1.352); p = 0.0253]. A significant negative correlation was obtained between normalized high frequency power of heart rate variability and basal cortisol levels (r = -0.6594; p = 0.0029). Multiple linear regression analysis identified age, disease duration (in months), basal cortisol levels and systolic blood pressure as independent predictors of normalized high frequency power. Conclusion: Findings of the study clearly portrayed the diminished autonomic modulation of heart rate in endogenous Cushing's syndrome and its possible relationship with hypercortisolism as the main causative factor. Diminished heart rate variability may be an indicator of the increased risk of cardiac mortality in these patients.
Treatment of Metastatic Neuroendocrine Tumors of the Thymus with Capecitabine and Temozolomide: A Case Series
Authors: Saranga-Perry Vita , Morse Brian , Centeno Barbara , Kvols Larry , Strosberg Jonathan
Published: November 2012

Background: Metastatic neuroendocrine tumors of the thymus are exceedingly rare with an annual incidence of approximately 0.2 per 1,000,000. They are highly resistant to therapy and there have been no reports of an objective radiographic response to treatment. Materials and Methods: The authors retrospectively evaluated 3 patients with progressive, metastatic neuroendocrine tumors of the thymus who were treated with a combination of capecitabine and temozolomide. Radiographic scans were evaluated and response assessed using RECIST criteria. Results: One patient experienced a partial radiographic response, another patient experienced a minor response and the third patient experienced stable disease as the best response to treatment. Conclusion: The combination of capecitabine and temozolomide appears to be active in a rare neuroendocrine malignancy that is generally refractory to systemic therapy. Prospective multicenter trials are needed to validate this strategy.
The influence of thrombophilia on the long-term survival of patients with a history of venous thromboembolism
Authors: Reitter-Pfoertner Sylvia , Waldhoer Thomas , Mayerhofer Michaela , Eigenbauer Ernst , Ay Cihan , Mannhalter Christine , Kyrle Paul Alexander , Pabinger Ingrid
Published: November 2012

Data on the long-term survival following venous thromboembolism (VTE) are rare,and the influence of thrombophilia has not been evaluated thus far. Our aim was to assess thrombophilia-parameters as predictors for long-term survival of patients with VTE. Overall, 1,905 outpatients (99 with antithrombin-, protein C or protein S deficiency, 517 with factor V Leiden, 381 with elevated factor VIII and 160 with elevated homocysteine levels, of these 202 had a combination and 961 had none of these risk factors) were included in the study between September 1, 1994 and December 31, 2007. Retrospective survival analysis showed that a total of 78 patients (4.1%) had died during the analysis period, among those four of definite or possible pulmonary embolism and four of bleeding. In multivariable analysis including age and sex an association with increased mortality was found for hyperhomocysteinemia (hazard ratio 2.0 [1.1.-3.5]) whereas this was not the case for all other investigated parameters. We conclude that the classical hereditary thrombophilia risk factors did not have an impact on the long-term survival of patients with a history of VTE. Thus our study supports the current concept that thrombophilia should not be a determinant for decision on long term anticoagulation. However, hyperhomocysteinaemia, known as a risk factor for recurrent VTE and arterial disease, might impact survival.
Characterisation of mutations and molecular studies of type 2 von Willebrand disease
Authors: Jan Rifat , Kannan Meganathan , Obser Tobias , Hassan Md Imtaiyaz , Oyen Florian , Budde Ulrich , Saxena Renu , Ahmad Firdos , Schneppenheim Reinhard
Published: November 2012

Type 2 von Willebrand disease (VWD) is characterised by qualitative defects in von Willebrand factor (VWF). Exon 28 of the VWF gene is known to be a hot spot for type 2 VWD mutations. The goal of this study was to characterise the mutations in VWF exon 28 and understand the molecular basis of phenotypes through in vitro and in silico studies. Mutation screening was performed in 56 type 2 VWD patients through direct sequencing. Expression vectors for five mutations were transiently expressed in 293-EBNA cells to understand the mutations pathology. Furthermore, in silico structure analysis was performed for 13 missense mutations.A total of 16 including eight novel mutations were detected in 23 (41%) patients. Of these, 15 were missense (including seven V1439M, A1464P, M1495L, I1509V, R1527Q, N1635I and A1647D novel ones) and one was a novel gene conversion. Expression studies and characterisation of recombinant VWF suggested the loss of VWF function for mutants P1266Q, V1439M and N1635I and gain of function for mutant R1308C. No apparent defect was seen in mutant N1231S. In silico structure analysis suggested the probable gain or loss of hydrogen/van der Waals interactions in 10 mutant proteins. In conclusion, type 2A mutations and gene conversion were found to be a common cause of type 2 VWD. Expression studies suggest the mutations N1635I for type 2A(II), P1266Q and V1439M for type 2M, R1308C for type 2B VWD and N1231S as a non-causative variant. Moreover, in silico studies of the mutants show the probable cause of respective phenotypes.
Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss
Authors: Su Mei-Tsz , Lin Sheng-Hsiang , Chen Yi-Chi , Kuo Pao-Lin
Published: November 2012

A fine balance between coagulation and fibrinolysis is critical in early pregnancy. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) are involved in the fibrinolytic process, and several studies have reported the association between their gene polymorphisms and recurrent pregnancy loss (RPL). This study was conducted to investigate the association between PAI-1 and ACE polymorphisms and idiopathic RPL, using meta-analyses. A systematic review of the published literature from the MEDLINE and EMBASE databases before April 2012 was conducted. Of 209 potentially relevant studies, 22 case-control studies comprising a total of 2,820 RPL patients and 3,009 controls were included. Among these studies were 11 reports of PAI-1 4G/5G and 11 of ACE I/D polymorphisms in patients with RPL. A significant association was found withthe ACE I/D polymorphism [summary odds ratio 1.29 (95% confidence interval 1.02–1.62)] in studies including more than two recurrent abortions. Subgroup analysis did not show significant associations with RPL in Caucasian and non-Caucasian patients. Meta-analyses of PAI-1 4G/5G polymorphism were not found associations with RPL in studies including more than two or three recurrent abortions, and in studies of Caucasian and non-Caucasian patients. In conclusion, meta-analyses showed a significant association between the ACE I/D polymorphism and idiopathic RPL. High clinical heterogeneity existed among studies of PAI-1 4G/5G, and the aggregated data failed to confer higher susceptibility to idiopathic RPL. More well-designed studies with different ethnic populations are required for future integration.
Extensive White Matter Hyperintensities May Increase Brain Volume in Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy
Authors: Yao Ming , Jouvent Eric , During Marco , Godin Ophélia , Hervé Dominique , Guichard Jean Pierre , Zhu Yi-Cheng , Gschwendtner Andreas , Opherk Christian , Dichgans Martin , Chabriat Hugues
Published: November 2012

Background and Purpose—

The extent of white matter hyperintensities (WMH) is associated with cerebral atrophy in elderly people. WMH is a radiological hallmark of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), but their relationship with brain volume remains poorly understood. The association between WMH and brain volume was analyzed in a large population of patients with CADASIL.

Methods—

Demographic and MRI data of 278 patients recruited from a prospective cohort study were analyzed. Volumes of WMH and lacunar infarcts, number of cerebral microbleeds, and brain parenchymal fraction were measured. Multivariate analysis was used to study the impact of WMH on brain volume at baseline.

Results—

In univariate analyses, brain parenchymal fraction was negatively associated with age, male sex, and all MRI markers. Multiple regression modeling showed that brain parenchymal fraction was inversely related to age, number of cerebral microbleeds, and normalized volume of lacunar infarcts but positively related to normalized volume of WMH (
P
<0.001). This positive relationship was independent of the presence/absence of lacunar infarcts or of cerebral microbleeds. Subgroup analysis showed that this association was significant in subjects having normalized volume of WMH ≥6.13 or brain parenchymal fraction ≥86.37% (median values, both
P
≤0.001).

Conclusion—

The results of the present study suggest that extensive WMH may be associated with increase of brain volume in CADASIL. In this disorder, WMH may be related not only to loss of white matter components, but also to a global increase of water content in the cerebral tissue.
Do Charters Retain Teachers Differently? Evidence from Elementary Schools in Florida
Authors: Cowen Joshua M. , Winters Marcus A.
Published: November 2012

We analyze patterns of teacher attrition from charter schools and schools in the traditional public sector. Using rich data on students, teachers, and schools in Florida, we estimate teacher effectiveness based on repeated test scores reported at the student level for each teacher over time. Among all teachers, those in charter schools appear more likely to exit the profession than those in the traditional public sector, and in both sectors the least effective teachers are more likely to exit than their more effective counterparts. Few of these relationships appear evident for within- or between-district transfers, and there are no differential relationships between effectiveness and attrition in the charter sector. We interpret these results as indicating that whatever administrative or organizational differences may exist in charter schools, they do not necessarily translate into a discernible difference in the ability to dismiss poorly performing teachers.