Uncommon and/or bizarre features of dementia: Part III.

PubMed

Cipriani, Gabriele; Nuti, Angelo; Danti, Sabrina; Picchi, Lucia; Di Fiorino, Mario

2018-06-01

Clinical neurologists have long recognized that dementia can present as atypical or variant syndromes/symptoms. This study aimed at describing uncommon or bizarre symptoms/syndromes observed in patients suffering from dementia. Medline and Google scholar searches were conducted for relevant articles, chapters, and books published before 2018. Search terms used included compulsion, dementia, extracampine hallucination, disordered gambling, humour, and obsession. Publications found through this indexed search were reviewed for further relevant references. The uncommon/bizarre feature of dementia was described as case reports and there were no systematic investigations.

Folded concave penalized learning in identifying multimodal MRI marker for Parkinson’s disease

PubMed Central

Liu, Hongcheng; Du, Guangwei; Zhang, Lijun; Lewis, Mechelle M.; Wang, Xue; Yao, Tao; Li, Runze; Huang, Xuemei

2016-01-01

Background Brain MRI holds promise to gauge different aspects of Parkinson’s disease (PD)-related pathological changes. Its analysis, however, is hindered by the high-dimensional nature of the data. New method This study introduces folded concave penalized (FCP) sparse logistic regression to identify biomarkers for PD from a large number of potential factors. The proposed statistical procedures target the challenges of high-dimensionality with limited data samples acquired. The maximization problem associated with the sparse logistic regression model is solved by local linear approximation. The proposed procedures then are applied to the empirical analysis of multimodal MRI data. Results From 45 features, the proposed approach identified 15 MRI markers and the UPSIT, which are known to be clinically relevant to PD. By combining the MRI and clinical markers, we can enhance substantially the specificity and sensitivity of the model, as indicated by the ROC curves. Comparison to existing methods We compare the folded concave penalized learning scheme with both the Lasso penalized scheme and the principle component analysis-based feature selection (PCA) in the Parkinson’s biomarker identification problem that takes into account both the clinical features and MRI markers. The folded concave penalty method demonstrates a substantially better clinical potential than both the Lasso and PCA in terms of specificity and sensitivity. Conclusions For the first time, we applied the FCP learning method to MRI biomarker discovery in PD. The proposed approach successfully identified MRI markers that are clinically relevant. Combining these biomarkers with clinical features can substantially enhance performance. PMID:27102045

The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical-genomic driver associations.

PubMed

Lee, HoJoon; Palm, Jennifer; Grimes, Susan M; Ji, Hanlee P

2015-10-27

The Cancer Genome Atlas (TCGA) project has generated genomic data sets covering over 20 malignancies. These data provide valuable insights into the underlying genetic and genomic basis of cancer. However, exploring the relationship among TCGA genomic results and clinical phenotype remains a challenge, particularly for individuals lacking formal bioinformatics training. Overcoming this hurdle is an important step toward the wider clinical translation of cancer genomic/proteomic data and implementation of precision cancer medicine. Several websites such as the cBio portal or University of California Santa Cruz genome browser make TCGA data accessible but lack interactive features for querying clinically relevant phenotypic associations with cancer drivers. To enable exploration of the clinical-genomic driver associations from TCGA data, we developed the Cancer Genome Atlas Clinical Explorer. The Cancer Genome Atlas Clinical Explorer interface provides a straightforward platform to query TCGA data using one of the following methods: (1) searching for clinically relevant genes, micro RNAs, and proteins by name, cancer types, or clinical parameters; (2) searching for genomic/proteomic profile changes by clinical parameters in a cancer type; or (3) testing two-hit hypotheses. SQL queries run in the background and results are displayed on our portal in an easy-to-navigate interface according to user's input. To derive these associations, we relied on elastic-net estimates of optimal multiple linear regularized regression and clinical parameters in the space of multiple genomic/proteomic features provided by TCGA data. Moreover, we identified and ranked gene/micro RNA/protein predictors of each clinical parameter for each cancer. The robustness of the results was estimated by bootstrapping. Overall, we identify associations of potential clinical relevance among genes/micro RNAs/proteins using our statistical analysis from 25 cancer types and 18 clinical parameters that include clinical stage or smoking history. The Cancer Genome Atlas Clinical Explorer enables the cancer research community and others to explore clinically relevant associations inferred from TCGA data. With its accessible web and mobile interface, users can examine queries and test hypothesis regarding genomic/proteomic alterations across a broad spectrum of malignancies.

Molecular subgroups of medulloblastoma

PubMed Central

Northcott, Paul A; Dubuc, Adrian M; Pfister, Stefan; Taylor, Michael D

2014-01-01

Recent efforts at stratifying medulloblastomas based on their molecular features have revolutionized our understanding of this morbidity. Collective efforts by multiple independent groups have subdivided medulloblastoma from a single disease into four distinct molecular subgroups characterized by disparate transcriptional signatures, mutational spectra, copy number profiles and, most importantly, clinical features. We present a summary of recent studies that have contributed to our understanding of the core medulloblastoma subgroups, focusing largely on clinically relevant discoveries that have already, and will continue to, shape research. PMID:22853794

A wavelet-based approach for a continuous analysis of phonovibrograms.

PubMed

Unger, Jakob; Meyer, Tobias; Doellinger, Michael; Hecker, Dietmar J; Schick, Bernhard; Lohscheller, Joerg

2012-01-01

Recently, endoscopic high-speed laryngoscopy has been established for commercial use and constitutes a state-of-the-art technique to examine vocal fold dynamics. Despite overcoming many limitations of commonly applied stroboscopy it has not gained widespread clinical application, yet. A major drawback is a missing methodology of extracting valuable features to support visual assessment or computer-aided diagnosis. In this paper a compact and descriptive feature set is presented. The feature extraction routines are based on two-dimensional color graphs called phonovibrograms (PVG). These graphs contain the full spatio-temporal pattern of vocal fold dynamics and are therefore suited to derive features that comprehensively describe the vibration pattern of vocal folds. Within our approach, clinically relevant features such as glottal closure type, symmetry and periodicity are quantified in a set of 10 descriptive features. The suitability for classification tasks is shown using a clinical data set comprising 50 healthy and 50 paralytic subjects. A classification accuracy of 93.2% has been achieved.

How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

PubMed

Wong, Kam Cheong

2016-04-06

Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

Dentin Hypersensitivity: Etiology, Diagnosis and Treatment; A Literature Review

PubMed Central

Davari, AR; Ataei, E; Assarzadeh, H

2013-01-01

The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms “dentin*”, “tooth”, “teeth”, “hypersensit*”, “desensitiz*”. Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used. PMID:24724135

Joint Feature Extraction and Classifier Design for ECG-Based Biometric Recognition.

PubMed

Gutta, Sandeep; Cheng, Qi

2016-03-01

Traditional biometric recognition systems often utilize physiological traits such as fingerprint, face, iris, etc. Recent years have seen a growing interest in electrocardiogram (ECG)-based biometric recognition techniques, especially in the field of clinical medicine. In existing ECG-based biometric recognition methods, feature extraction and classifier design are usually performed separately. In this paper, a multitask learning approach is proposed, in which feature extraction and classifier design are carried out simultaneously. Weights are assigned to the features within the kernel of each task. We decompose the matrix consisting of all the feature weights into sparse and low-rank components. The sparse component determines the features that are relevant to identify each individual, and the low-rank component determines the common feature subspace that is relevant to identify all the subjects. A fast optimization algorithm is developed, which requires only the first-order information. The performance of the proposed approach is demonstrated through experiments using the MIT-BIH Normal Sinus Rhythm database.

Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease Location.

PubMed

Aziz, Danish Abdul; Moin, Maryum; Majeed, Atif; Sadiq, Kamran; Biloo, Abdul Gaffar

2017-01-01

To determine different clinical presentationsand disease location demarcatedby upper and lower gastrointestinal endoscopyand relevant histopathologyin children diagnosed with inflammatory bowel disease (IBD). This is 5 years (2010 to 2015) retrospective studyconducted at the Aga Khan University Hospitalenrolling65admitted children between 6 months to 15years from either gender, diagnosed with IBD on clinical presentation, endoscopy and biopsy. Different clinical presentations at the time of diagnosis were noted in different categories of the disease. All patients underwent upper and lower (up to the terminal ileum) endoscopy with multiple punch biopsies and histologic assessment of mucosal specimens. All endoscopies were done by paediatric gastroenterologists at endoscopy suite of the hospital and all specimens were reported by the pathology department. ESPGHAN revised criteria for the diagnosis of inflammatory bowel disease in children and an adolescent was used to standardize our diagnosis. Extent of disease on endoscopy and relevant histopathology of the biopsy samples were noted at the time of diagnosis. Data was summarized using mean, standard deviation, numbers and percentages for different variables. Total 56 children were enrolled according to inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%) patients were labeled as Indeterminate colitis (IC). Mean age at onset of symptoms was10.03±2.44 and mean age at diagnosis was11.10±2.36. Abdominal pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC. Patients diagnosed with indeterminate colitis(IC) had similar clinical features as in UC patients. Only 7% patients had some extra-intestinal features in the form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 ±12.89) was relatively high in patients withCD in comparison with other categories of IBD. Endoscopic findings and relevant histopathology of biopsy samples in UC showed 65% patient had pan-colitis and 13 % with disease restricted to rectum only whereas in CD 70% patient had disease in ileo-colon and only 10 % had involvement of ileum at the time diagnosis. Patients with UC dominated in our cohort. The most common clinical presentation in UC was bloody diarrhea and rectal bleeding and patients with CDhad abdominal pain and chronic diarrhea as predominant clinical features. Extraintestinal features were uncommon in our cohort. In endoscopic findings, pan-colitis was the mostfrequentfinding in UC and ileo-colonwas common location in CD. IC and UC shared common clinical features and disease location on endoscopy.

Quantitative Ultrasound Using Texture Analysis of Myofascial Pain Syndrome in the Trapezius.

PubMed

Kumbhare, Dinesh A; Ahmed, Sara; Behr, Michael G; Noseworthy, Michael D

2018-01-01

Objective-The objective of this study is to assess the discriminative ability of textural analyses to assist in the differentiation of the myofascial trigger point (MTrP) region from normal regions of skeletal muscle. Also, to measure the ability to reliably differentiate between three clinically relevant groups: healthy asymptomatic, latent MTrPs, and active MTrP. Methods-18 and 19 patients were identified with having active and latent MTrPs in the trapezius muscle, respectively. We included 24 healthy volunteers. Images were obtained by research personnel, who were blinded with respect to the clinical status of the study participant. Histograms provided first-order parameters associated with image grayscale. Haralick, Galloway, and histogram-related features were used in texture analysis. Blob analysis was conducted on the regions of interest (ROIs). Principal component analysis (PCA) was performed followed by multivariate analysis of variance (MANOVA) to determine the statistical significance of the features. Results-92 texture features were analyzed for factorability using Bartlett's test of sphericity, which was significant. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.94. PCA demonstrated rotated eigenvalues of the first eight components (each comprised of multiple texture features) explained 94.92% of the cumulative variance in the ultrasound image characteristics. The 24 features identified by PCA were included in the MANOVA as dependent variables, and the presence of a latent or active MTrP or healthy muscle were independent variables. Conclusion-Texture analysis techniques can discriminate between the three clinically relevant groups.

Appropriateness guidelines and predictive rules to select patients for upper endoscopy: a nationwide multicenter study.

PubMed

Buri, Luigi; Hassan, Cesare; Bersani, Gianluca; Anti, Marcello; Bianco, Maria Antonietta; Cipolletta, Livio; Di Giulio, Emilio; Di Matteo, Giovanni; Familiari, Luigi; Ficano, Leonardo; Loriga, Pietro; Morini, Sergio; Pietropaolo, Vincenzo; Zambelli, Alessandro; Grossi, Enzo; Intraligi, Marco; Buscema, Massimo

2010-06-01

Selecting patients appropriately for upper endoscopy (EGD) is crucial for efficient use of endoscopy. The objective of this study was to compare different clinical strategies and statistical methods to select patients for EGD, namely appropriateness guidelines, age and/or alarm features, and multivariate and artificial neural network (ANN) models. A nationwide, multicenter, prospective study was undertaken in which consecutive patients referred for EGD during a 1-month period were enrolled. Before EGD, the endoscopist assessed referral appropriateness according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, also collecting clinical and demographic variables. Outcomes of the study were detection of relevant findings and new diagnosis of malignancy at EGD. The accuracy of the following clinical strategies and predictive rules was compared: (i) ASGE appropriateness guidelines (indicated vs. not indicated), (ii) simplified rule (>or=45 years or alarm features vs. <45 years without alarm features), (iii) logistic regression model, and (iv) ANN models. A total of 8,252 patients were enrolled in 57 centers. Overall, 3,803 (46%) relevant findings and 132 (1.6%) new malignancies were detected. Sensitivity, specificity, and area under the receiver-operating characteristic curve (AUC) of the simplified rule were similar to that of the ASGE guidelines for both relevant findings (82%/26%/0.55 vs. 88%/27%/0.52) and cancer (97%/22%/0.58 vs. 98%/20%/0.58). Both logistic regression and ANN models seemed to be substantially more accurate in predicting new cases of malignancy, with an AUC of 0.82 and 0.87, respectively. A simple predictive rule based on age and alarm features is similarly effective to the more complex ASGE guidelines in selecting patients for EGD. Regression and ANN models may be useful in identifying a relatively small subgroup of patients at higher risk of cancer.

Anatomy and clinical significance of the uncinate process and uncovertebral joint: A comprehensive review.

PubMed

Hartman, Jeffrey

2014-04-01

The uncinate process and its associated uncovertebral articulation are features unique to the cervical spine. This review examines the morphology of these unique structures with particular emphasis on the regional anatomy, development and clinical significance. Five electronic databases were utilized in the literature search and additional relevant citations were retrieved from the references. A total of 74 citations were included for review. This literature review found that the uncinate processes and uncovertebral articulations are rudimentary at birth and develop and evolve with age. With degeneration they become clinically apparent with compression of related structures; most importantly affecting the spinal nerve root and vertebral artery. The articulations have also been found to precipitate torticollis when edematous and be acutely damaged in severe head and neck injuries. The uncinate processes are also important in providing stability and guiding the motion of the cervical spine. This review is intended to re-examine an often overlooked region of the cervical spine as not only an interesting anatomical feature but also a clinically relevant one. Copyright © 2014 Wiley Periodicals, Inc.

Evaluation of linear classifiers on articles containing pharmacokinetic evidence of drug-drug interactions.

PubMed

Kolchinsky, A; Lourenço, A; Li, L; Rocha, L M

2013-01-01

Drug-drug interaction (DDI) is a major cause of morbidity and mortality. DDI research includes the study of different aspects of drug interactions, from in vitro pharmacology, which deals with drug interaction mechanisms, to pharmaco-epidemiology, which investigates the effects of DDI on drug efficacy and adverse drug reactions. Biomedical literature mining can aid both kinds of approaches by extracting relevant DDI signals from either the published literature or large clinical databases. However, though drug interaction is an ideal area for translational research, the inclusion of literature mining methodologies in DDI workflows is still very preliminary. One area that can benefit from literature mining is the automatic identification of a large number of potential DDIs, whose pharmacological mechanisms and clinical significance can then be studied via in vitro pharmacology and in populo pharmaco-epidemiology. We implemented a set of classifiers for identifying published articles relevant to experimental pharmacokinetic DDI evidence. These documents are important for identifying causal mechanisms behind putative drug-drug interactions, an important step in the extraction of large numbers of potential DDIs. We evaluate performance of several linear classifiers on PubMed abstracts, under different feature transformation and dimensionality reduction methods. In addition, we investigate the performance benefits of including various publicly-available named entity recognition features, as well as a set of internally-developed pharmacokinetic dictionaries. We found that several classifiers performed well in distinguishing relevant and irrelevant abstracts. We found that the combination of unigram and bigram textual features gave better performance than unigram features alone, and also that normalization transforms that adjusted for feature frequency and document length improved classification. For some classifiers, such as linear discriminant analysis (LDA), proper dimensionality reduction had a large impact on performance. Finally, the inclusion of NER features and dictionaries was found not to help classification.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

PubMed

Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji

2017-01-01

Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

Identification of symptom and functional domains that fibromyalgia patients would like to see improved: a cluster analysis.

PubMed

Bennett, Robert M; Russell, Jon; Cappelleri, Joseph C; Bushmakin, Andrew G; Zlateva, Gergana; Sadosky, Alesia

2010-06-28

The purpose of this study was to determine whether some of the clinical features of fibromyalgia (FM) that patients would like to see improved aggregate into definable clusters. Seven hundred and eighty-eight patients with clinically confirmed FM and baseline pain > or =40 mm on a 100 mm visual analogue scale ranked 5 FM clinical features that the subjects would most like to see improved after treatment (one for each priority quintile) from a list of 20 developed during focus groups. For each subject, clinical features were transformed into vectors with rankings assigned values 1-5 (lowest to highest ranking). Logistic analysis was used to create a distance matrix and hierarchical cluster analysis was applied to identify cluster structure. The frequency of cluster selection was determined, and cluster importance was ranked using cluster scores derived from rankings of the clinical features. Multidimensional scaling was used to visualize and conceptualize cluster relationships. Six clinical features clusters were identified and named based on their key characteristics. In order of selection frequency, the clusters were Pain (90%; 4 clinical features), Fatigue (89%; 4 clinical features), Domestic (42%; 4 clinical features), Impairment (29%; 3 functions), Affective (21%; 3 clinical features), and Social (9%; 2 functional). The "Pain Cluster" was ranked of greatest importance by 54% of subjects, followed by Fatigue, which was given the highest ranking by 28% of subjects. Multidimensional scaling mapped these clusters to two dimensions: Status (bounded by Physical and Emotional domains), and Setting (bounded by Individual and Group interactions). Common clinical features of FM could be grouped into 6 clusters (Pain, Fatigue, Domestic, Impairment, Affective, and Social) based on patient perception of relevance to treatment. Furthermore, these 6 clusters could be charted in the 2 dimensions of Status and Setting, thus providing a unique perspective for interpretation of FM symptomatology.

Using classification models for the generation of disease-specific medications from biomedical literature and clinical data repository.

PubMed

Wang, Liqin; Haug, Peter J; Del Fiol, Guilherme

2017-05-01

Mining disease-specific associations from existing knowledge resources can be useful for building disease-specific ontologies and supporting knowledge-based applications. Many association mining techniques have been exploited. However, the challenge remains when those extracted associations contained much noise. It is unreliable to determine the relevance of the association by simply setting up arbitrary cut-off points on multiple scores of relevance; and it would be expensive to ask human experts to manually review a large number of associations. We propose that machine-learning-based classification can be used to separate the signal from the noise, and to provide a feasible approach to create and maintain disease-specific vocabularies. We initially focused on disease-medication associations for the purpose of simplicity. For a disease of interest, we extracted potentially treatment-related drug concepts from biomedical literature citations and from a local clinical data repository. Each concept was associated with multiple measures of relevance (i.e., features) such as frequency of occurrence. For the machine purpose of learning, we formed nine datasets for three diseases with each disease having two single-source datasets and one from the combination of previous two datasets. All the datasets were labeled using existing reference standards. Thereafter, we conducted two experiments: (1) to test if adding features from the clinical data repository would improve the performance of classification achieved using features from the biomedical literature only, and (2) to determine if classifier(s) trained with known medication-disease data sets would be generalizable to new disease(s). Simple logistic regression and LogitBoost were two classifiers identified as the preferred models separately for the biomedical-literature datasets and combined datasets. The performance of the classification using combined features provided significant improvement beyond that using biomedical-literature features alone (p-value<0.001). The performance of the classifier built from known diseases to predict associated concepts for new diseases showed no significant difference from the performance of the classifier built and tested using the new disease's dataset. It is feasible to use classification approaches to automatically predict the relevance of a concept to a disease of interest. It is useful to combine features from disparate sources for the task of classification. Classifiers built from known diseases were generalizable to new diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Infiltrative cervical lesions causing symptomatic occipital neuralgia.

PubMed

Sierra-Hidalgo, F; Ruíz, J; Morales-Cartagena, A; Martínez-Salio, A; Serna, J de la; Hernández-Gallego, J

2011-10-01

Occipital neuralgia is a well-recognized cause of posterior head and neck pain that may associate mild sensory changes in the cutaneous distribution of the occipital nerves, lacking a recognizable local structural aetiology in most cases. Atypical clinical features or an abnormal neurological examination are alerts for a potential underlying cause of pain, although cases of clinically typical occipital neuralgia as isolated manifestation of lesions of the cervical spinal cord, cervical roots, or occipital nerves have been increasingly reported. We describe two cases (one with typical and another one with atypical clinical features) of occipital neuralgia secondary to paravertebral pyomyositis and vertebral relapse of multiple myeloma in patients with relevant medical history that aroused the possibility of an underlying structural lesion. We discuss the need for cranio-cervical magnetic resonance imaging in all patients with occipital neuralgia, even when typical clinical features are present and neurological examination is completely normal.

Supervised learning methods for pathological arterial pulse wave differentiation: A SVM and neural networks approach.

PubMed

Paiva, Joana S; Cardoso, João; Pereira, Tânia

2018-01-01

The main goal of this study was to develop an automatic method based on supervised learning methods, able to distinguish healthy from pathologic arterial pulse wave (APW), and those two from noisy waveforms (non-relevant segments of the signal), from the data acquired during a clinical examination with a novel optical system. The APW dataset analysed was composed by signals acquired in a clinical environment from a total of 213 subjects, including healthy volunteers and non-healthy patients. The signals were parameterised by means of 39pulse features: morphologic, time domain statistics, cross-correlation features, wavelet features. Multiclass Support Vector Machine Recursive Feature Elimination (SVM RFE) method was used to select the most relevant features. A comparative study was performed in order to evaluate the performance of the two classifiers: Support Vector Machine (SVM) and Artificial Neural Network (ANN). SVM achieved a statistically significant better performance for this problem with an average accuracy of 0.9917±0.0024 and a F-Measure of 0.9925±0.0019, in comparison with ANN, which reached the values of 0.9847±0.0032 and 0.9852±0.0031 for Accuracy and F-Measure, respectively. A significant difference was observed between the performances obtained with SVM classifier using a different number of features from the original set available. The comparison between SVM and NN allowed reassert the higher performance of SVM. The results obtained in this study showed the potential of the proposed method to differentiate those three important signal outcomes (healthy, pathologic and noise) and to reduce bias associated with clinical diagnosis of cardiovascular disease using APW. Copyright © 2017 Elsevier B.V. All rights reserved.

EHR based Genetic Testing Knowledge Base (iGTKB) Development

PubMed Central

2015-01-01

Background The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). Methods We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Results Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. Conclusions In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics. PMID:26606281

EHR based Genetic Testing Knowledge Base (iGTKB) Development.

PubMed

Zhu, Qian; Liu, Hongfang; Chute, Christopher G; Ferber, Matthew

2015-01-01

The gap between a large growing number of genetic tests and a suboptimal clinical workflow of incorporating these tests into regular clinical practice poses barriers to effective reliance on advanced genetic technologies to improve quality of healthcare. A promising solution to fill this gap is to develop an intelligent genetic test recommendation system that not only can provide a comprehensive view of genetic tests as education resources, but also can recommend the most appropriate genetic tests to patients based on clinical evidence. In this study, we developed an EHR based Genetic Testing Knowledge Base for Individualized Medicine (iGTKB). We extracted genetic testing information and patient medical records from EHR systems at Mayo Clinic. Clinical features have been semi-automatically annotated from the clinical notes by applying a Natural Language Processing (NLP) tool, MedTagger suite. To prioritize clinical features for each genetic test, we compared odds ratio across four population groups. Genetic tests, genetic disorders and clinical features with their odds ratios have been applied to establish iGTKB, which is to be integrated into the Genetic Testing Ontology (GTO). Overall, there are five genetic tests operated with sample size greater than 100 in 2013 at Mayo Clinic. A total of 1,450 patients who was tested by one of the five genetic tests have been selected. We assembled 243 clinical features from the Human Phenotype Ontology (HPO) for these five genetic tests. There are 60 clinical features with at least one mention in clinical notes of patients taking the test. Twenty-eight clinical features with high odds ratio (greater than 1) have been selected as dominant features and deposited into iGTKB with their associated information about genetic tests and genetic disorders. In this study, we developed an EHR based genetic testing knowledge base, iGTKB. iGTKB will be integrated into the GTO by providing relevant clinical evidence, and ultimately to support development of genetic testing recommendation system, iGenetics.

Changing Concepts and Findings on Autism

ERIC Educational Resources Information Center

Rutter, Michael

2013-01-01

New research findings provide major challenges regarding our understanding of the concept of autism. These are critically discussed in relation to research relevant to classification, genetics, environmental risk factors, gene-environment interplay, animal models, biomarkers, clinical features, neuropathology, pharmacotherapy, behavioral…

Malignant disease and dentistry.

PubMed

Walton, Graham; Seymour, Robin A

2009-11-01

Reports of an ageing population, increasing incidence of malignancy and improved treatments mean that dentists may have an increasing number of patients with, or who have recovered from, a malignancy. Dental professionals are expected to have an understanding of this important disease group so that appropriate dental care can be provided safely. In this first of three articles, we shall describe the important epidemiological and clinical features of the commonest malignancies in the United Kingdom. Dentists should understand the clinical implications of a patient with, or recovering from, a malignancy. This article gives a summary of the relevant features of the commonest malignancies.

Identification of design features to enhance utilization and acceptance of systems for Internet-based decision support at the point of care.

PubMed

Gadd, C S; Baskaran, P; Lobach, D F

1998-01-01

Extensive utilization of point-of-care decision support systems will be largely dependent on the development of user interaction capabilities that make them effective clinical tools in patient care settings. This research identified critical design features of point-of-care decision support systems that are preferred by physicians, through a multi-method formative evaluation of an evolving prototype of an Internet-based clinical decision support system. Clinicians used four versions of the system--each highlighting a different functionality. Surveys and qualitative evaluation methodologies assessed clinicians' perceptions regarding system usability and usefulness. Our analyses identified features that improve perceived usability, such as telegraphic representations of guideline-related information, facile navigation, and a forgiving, flexible interface. Users also preferred features that enhance usefulness and motivate use, such as an encounter documentation tool and the availability of physician instruction and patient education materials. In addition to identifying design features that are relevant to efforts to develop clinical systems for point-of-care decision support, this study demonstrates the value of combining quantitative and qualitative methods of formative evaluation with an iterative system development strategy to implement new information technology in complex clinical settings.

Research training in integrative medicine: how can we make teaching and learning in research methods more sustainable and engaging?

PubMed

Witt, Claudia M; Withers, Shelly Rafferty

2013-01-01

The aim of this project was to identify strategies for increasing learner engagement and knowledge retention in clinical research training of complementary and integrative medicine (CIM) practitioners, and to offer a conceptual framework to address clinical research training for CIM practitioners. In a featured large-group discussion (15min presentation and 30min discussion), two questions (strategies that are recommended to overcome these barriers; relevant aspects for a framework for building sustainable knowledge) were put to the audience. The sample consisted of 43 participants at the International Congress of Educators in Complementary and Alternative Medicine, in Washington, DC, in October 2012. The featured discussion was moderated and detailed notes were taken. Notes were synthesized and discussed by both authors until consensus was reached. Based on the results from the featured discussion session and a focused literature search, a framework for building sustainable knowledge and skills in clinical research for CIM practitioners was developed. Participants' responses to the questions of engagement and sustainability included curricular structures, pedagogical strategies for instruction, the use of digital tools to extend the learning experience, the necessity to ground instruction firmly in the medical literature of the field, and the relevance of mentoring. Key considerations for building sustainable knowledge in clinical research for CIM practitioners are as follows: (1) prioritizing clinical research training, (2) issues of curriculum and pedagogy, (3) technology/digital tools, (4) administrative challenges, (5) supporting the formation of communities of practice, and (6) cultural perspectives of CIM practitioners. © 2013 Elsevier Inc. All rights reserved.

DNA Repair in Prostate Cancer: Biology and Clinical Implications.

PubMed

Mateo, Joaquin; Boysen, Gunther; Barbieri, Christopher E; Bryant, Helen E; Castro, Elena; Nelson, Pete S; Olmos, David; Pritchard, Colin C; Rubin, Mark A; de Bono, Johann S

2017-03-01

For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA damage repair pathway are common in PC, particularly in late-stage disease, and may be relevant for treatment stratification. To review current knowledge on the prevalence and clinical significance of aberrations in DNA repair genes in PC, particularly in metastatic disease. A literature search up to July 2016 was conducted, including clinical trials and preclinical basic research studies. Keywords included DNA repair, BRCA, ATM, CRPC, prostate cancer, PARP, platinum, predictive biomarkers, and hereditary cancer. We review how the DNA repair pathway is relevant to prostate carcinogenesis and progression. Data on how this may be relevant to hereditary cancer and genetic counseling are included, as well as data from clinical trials of PARP inhibitors and platinum therapeutics in PC. Relevant studies have identified genomic defects in DNA repair in PCs in 20-30% of advanced castration-resistant PC cases, a proportion of which are germline aberrations and heritable. Phase 1/2 clinical trial data, and other supporting clinical data, support the development of PARP inhibitors and DNA-damaging agents in this molecularly defined subgroup of PC following success in other cancer types. These studies may be an opportunity to improve patient care with personalized therapeutic strategies. Key literature on how genomic defects in the DNA damage repair pathway are relevant for prostate cancer biology and clinical management is reviewed. Potential implications for future changes in patient care are discussed. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Experts' Views Regarding the Conceptualization of Narcissism.

PubMed

Ackerman, Robert A; Hands, Aaron J; Donnellan, M Brent; Hopwood, Christopher J; Witt, Edward A

2017-06-01

There is debate over the definition of narcissism across social/personality and clinical psychology. The current article aims to quantify the level of disagreement by measuring experts' opinions concerning the attributes most central to narcissism. Accordingly, we developed a comprehensive list of attributes associated with narcissism and had 49 self-identified experts (among them 17 women, 23 psychologists from clinical psychology and 22 from social/personality psychology) rate these characteristics and provide their opinions on several issues related to the conceptualization of narcissism. Experts generally believe that the grandiose features of narcissism are more central than the vulnerable features. However, differences between clinical and social/personality psychologists were evident, especially regarding the relevance of self-esteem. Given the results, we suggest that researchers specify the kind of narcissism being assessed in a given study and consider using assessments of the full range of narcissistic features in future research to provide a more comprehensive perspective on the construct.

Clinical features of olfactory disorders in patients seeking medical consultation

PubMed Central

Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

2013-01-01

Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

PubMed Central

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications. PMID:29867996

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance.

PubMed

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.

A three-dimensional comparison of a morphometric and conventional cephalometric midsagittal planes for craniofacial asymmetry.

PubMed

Damstra, Janalt; Fourie, Zacharias; De Wit, Marnix; Ren, Yijin

2012-02-01

Morphometric methods are used in biology to study object symmetry in living organisms and to determine the true plane of symmetry. The aim of this study was to determine if there are clinical differences between three-dimensional (3D) cephalometric midsagittal planes used to describe craniofacial asymmetry and a true symmetry plane derived from a morphometric method based on visible facial features. The sample consisted of 14 dry skulls (9 symmetric and 5 asymmetric) with metallic markers which were imaged with cone-beam computed tomography. An error study and statistical analysis were performed to validate the morphometric method. The morphometric and conventional cephalometric planes were constructed and compared. The 3D cephalometric planes constructed as perpendiculars to the Frankfort horizontal plane resembled the morphometric plane the most in both the symmetric and asymmetric groups with mean differences of less than 1.00 mm for most variables. However, the standard deviations were often large and clinically significant for these variables. There were clinically relevant differences (>1.00 mm) between the different 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features. The difference between 3D cephalometric midsagittal planes and the true plane of symmetry determined by the visible facial features were clinically relevant. Care has to be taken using cephalometric midsagittal planes for diagnosis and treatment planning of craniofacial asymmetry as they might differ from the true plane of symmetry as determined by morphometrics.

Comparative study between ultrasonography and optical coherence tomography in interventional cardiology

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, Félix; de la Torre-Hernández, José María; Ortega-Quijano, Noé; Zueco-Gil, José Javier; Arce-Diego, José Luis

2009-07-01

In this work, we present clinical images of IVUS and OCT in the evaluation of pharmacological stent endothelization. These preliminary imaging results are analyzed and compared in order to determine the ability of these technologies to visualize relevant intravascular features of interest in interventional cardiology. The results enable to compare the performance of both techniques and to evaluate their potential for clinical purposes.

Deep learning based classification of breast tumors with shear-wave elastography.

PubMed

Zhang, Qi; Xiao, Yang; Dai, Wei; Suo, Jingfeng; Wang, Congzhi; Shi, Jun; Zheng, Hairong

2016-12-01

This study aims to build a deep learning (DL) architecture for automated extraction of learned-from-data image features from the shear-wave elastography (SWE), and to evaluate the DL architecture in differentiation between benign and malignant breast tumors. We construct a two-layer DL architecture for SWE feature extraction, comprised of the point-wise gated Boltzmann machine (PGBM) and the restricted Boltzmann machine (RBM). The PGBM contains task-relevant and task-irrelevant hidden units, and the task-relevant units are connected to the RBM. Experimental evaluation was performed with five-fold cross validation on a set of 227 SWE images, 135 of benign tumors and 92 of malignant tumors, from 121 patients. The features learned with our DL architecture were compared with the statistical features quantifying image intensity and texture. Results showed that the DL features achieved better classification performance with an accuracy of 93.4%, a sensitivity of 88.6%, a specificity of 97.1%, and an area under the receiver operating characteristic curve of 0.947. The DL-based method integrates feature learning with feature selection on SWE. It may be potentially used in clinical computer-aided diagnosis of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Anxiety or agitation in mood disorder with mixed features: A review with a focus on validity as a dimensional criterion.

PubMed

Shim, In Hee; Bae, Dong Sik; Bahk, Won-Myong

2016-08-01

The diagnostic validity of mixed features, excluding anxiety or psychomotor agitation in mood disorders, has not yet been fully examined. PubMed and relevant English-language literature (regardless of year) were searched. Keywords were mixed or mixed state or mixed features or mixed episode and anxious or anxiety or agitation and bipolar disorder or depressive disorder or mood disorder or affective disorder. Most studies on anxiety or psychomotor agitation have included a significant correlation relevant to the "with mixed features" specifier, although it is common in both poles of mood episodes regardless of the predominant polarity. There is some confusion between the characteristic of classical mixed states and the definition of the mixed features specifier with the newly added anxious distress specifier in DSM-5, specifically, whether to include anxiety and agitation as significant characteristics. This change is of concern because a large proportion of patients with mixed features are now unspecified, and this may influence treatment planning and prognosis. The findings of our review suggest that anxiety and psychomotor agitation can be core symptoms in mood episodes with mixed features and important clinical clues for prediction of treatment effects and disease course.

Is Dysfunctional Use of the Mobile Phone a Behavioural Addiction? Confronting Symptom-Based Versus Process-Based Approaches.

PubMed

Billieux, Joël; Philippot, Pierre; Schmid, Cécile; Maurage, Pierre; De Mol, Jan; Van der Linden, Martial

2015-01-01

Dysfunctional use of the mobile phone has often been conceptualized as a 'behavioural addiction' that shares most features with drug addictions. In the current article, we challenge the clinical utility of the addiction model as applied to mobile phone overuse. We describe the case of a woman who overuses her mobile phone from two distinct approaches: (1) a symptom-based categorical approach inspired from the addiction model of dysfunctional mobile phone use and (2) a process-based approach resulting from an idiosyncratic clinical case conceptualization. In the case depicted here, the addiction model was shown to lead to standardized and non-relevant treatment, whereas the clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific, empirically based psychological interventions. This finding highlights that conceptualizing excessive behaviours (e.g., gambling and sex) within the addiction model can be a simplification of an individual's psychological functioning, offering only limited clinical relevance. The addiction model, applied to excessive behaviours (e.g., gambling, sex and Internet-related activities) may lead to non-relevant standardized treatments. Clinical case conceptualization allowed identification of specific psychological processes that can be targeted with specific empirically based psychological interventions. The biomedical model might lead to the simplification of an individual's psychological functioning with limited clinical relevance. Copyright © 2014 John Wiley & Sons, Ltd.

Fourier domain image fusion for differential X-ray phase-contrast breast imaging.

PubMed

Coello, Eduardo; Sperl, Jonathan I; Bequé, Dirk; Benz, Tobias; Scherer, Kai; Herzen, Julia; Sztrókay-Gaul, Anikó; Hellerhoff, Karin; Pfeiffer, Franz; Cozzini, Cristina; Grandl, Susanne

2017-04-01

X-Ray Phase-Contrast (XPC) imaging is a novel technology with a great potential for applications in clinical practice, with breast imaging being of special interest. This work introduces an intuitive methodology to combine and visualize relevant diagnostic features, present in the X-ray attenuation, phase shift and scattering information retrieved in XPC imaging, using a Fourier domain fusion algorithm. The method allows to present complementary information from the three acquired signals in one single image, minimizing the noise component and maintaining visual similarity to a conventional X-ray image, but with noticeable enhancement in diagnostic features, details and resolution. Radiologists experienced in mammography applied the image fusion method to XPC measurements of mastectomy samples and evaluated the feature content of each input and the fused image. This assessment validated that the combination of all the relevant diagnostic features, contained in the XPC images, was present in the fused image as well. Copyright © 2017 Elsevier B.V. All rights reserved.

Unsupervised feature relevance analysis applied to improve ECG heartbeat clustering.

PubMed

Rodríguez-Sotelo, J L; Peluffo-Ordoñez, D; Cuesta-Frau, D; Castellanos-Domínguez, G

2012-10-01

The computer-assisted analysis of biomedical records has become an essential tool in clinical settings. However, current devices provide a growing amount of data that often exceeds the processing capacity of normal computers. As this amount of information rises, new demands for more efficient data extracting methods appear. This paper addresses the task of data mining in physiological records using a feature selection scheme. An unsupervised method based on relevance analysis is described. This scheme uses a least-squares optimization of the input feature matrix in a single iteration. The output of the algorithm is a feature weighting vector. The performance of the method was assessed using a heartbeat clustering test on real ECG records. The quantitative cluster validity measures yielded a correctly classified heartbeat rate of 98.69% (specificity), 85.88% (sensitivity) and 95.04% (general clustering performance), which is even higher than the performance achieved by other similar ECG clustering studies. The number of features was reduced on average from 100 to 18, and the temporal cost was a 43% lower than in previous ECG clustering schemes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Automated analysis of free speech predicts psychosis onset in high-risk youths

PubMed Central

Bedi, Gillinder; Carrillo, Facundo; Cecchi, Guillermo A; Slezak, Diego Fernández; Sigman, Mariano; Mota, Natália B; Ribeiro, Sidarta; Javitt, Daniel C; Copelli, Mauro; Corcoran, Cheryl M

2015-01-01

Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry. PMID:27336038

Identification of design features to enhance utilization and acceptance of systems for Internet-based decision support at the point of care.

PubMed Central

Gadd, C. S.; Baskaran, P.; Lobach, D. F.

1998-01-01

Extensive utilization of point-of-care decision support systems will be largely dependent on the development of user interaction capabilities that make them effective clinical tools in patient care settings. This research identified critical design features of point-of-care decision support systems that are preferred by physicians, through a multi-method formative evaluation of an evolving prototype of an Internet-based clinical decision support system. Clinicians used four versions of the system--each highlighting a different functionality. Surveys and qualitative evaluation methodologies assessed clinicians' perceptions regarding system usability and usefulness. Our analyses identified features that improve perceived usability, such as telegraphic representations of guideline-related information, facile navigation, and a forgiving, flexible interface. Users also preferred features that enhance usefulness and motivate use, such as an encounter documentation tool and the availability of physician instruction and patient education materials. In addition to identifying design features that are relevant to efforts to develop clinical systems for point-of-care decision support, this study demonstrates the value of combining quantitative and qualitative methods of formative evaluation with an iterative system development strategy to implement new information technology in complex clinical settings. Images Figure 1 PMID:9929188

Experimental Investigation on Minimum Frame Rate Requirements of High-Speed Videoendoscopy for Clinical Voice Assessment

PubMed Central

Deliyski, Dimitar D; Powell, Maria EG; Zacharias, Stephanie RC; Gerlach, Terri Treman; de Alarcon, Alessandro

2015-01-01

This study investigated the impact of high-speed videoendoscopy (HSV) frame rates on the assessment of nine clinically-relevant vocal-fold vibratory features. Fourteen adult patients with voice disorder and 14 adult normal controls were recorded using monochromatic rigid HSV at a rate of 16000 frames per second (fps) and spatial resolution of 639×639 pixels. The 16000-fps data were downsampled to 16 other rate denominations. Using paired comparisons design, nine common clinical vibratory features were visually compared between the downsampled and the original images. Three raters reported the thresholds at which: (1) a detectable difference between the two videos was first noticed, and (2) differences between the two videos would result in a change of clinical rating. Results indicated that glottal edge, mucosal wave magnitude and extent, aperiodicity, contact and loss of contact of the vocal folds were the vibratory features most sensitive to frame rate. Of these vibratory features, the glottal edge was selected for further analysis, due to its higher rating reliability, universal prevalence and consistent definition. Rates of 8000 fps were found to be free from visually-perceivable feature degradation, and for rates of 5333 fps, degradation was minimal. For rates of 4000 fps and higher, clinical assessments of glottal edge were not affected. Rates of 2000 fps changed the clinical ratings in over 16% of the samples, which could lead to inaccurate functional assessment. PMID:28989342

Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials.

PubMed

Raskob, G; Büller, H; Prins, M; Segers, A; Shi, M; Schwocho, L; van Kranen, R; Mercuri, M

2013-07-01

New oral anticoagulants may simplify long-term therapy by eliminating the need for laboratory monitoring. Edoxaban is an oral, direct inhibitor of factor Xa that is given in a fixed dose once daily. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial low molecular weight heparin (LMWH) followed by edoxaban (60 mg once daily) is non-inferior to LMWH followed by warfarin (International Normalized Ratio of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism (VTE). The primary efficacy outcome is symptomatic recurrent VTE during the 12-month study period. The principal safety outcome is clinically relevant bleeding (major or non-major) occurring during or within 3 days of stopping study treatment. A clinical events committee adjudicates all suspected outcome events. A unique study design feature is the flexible treatment duration of between 3 and 12 months to simulate usual clinical practice, and enabled by: (i) double-blinding to minimize bias that could occur if knowledge of the patient's treatment influenced the duration of therapy; and (ii) follow-up for 12 months of all patients and inclusion in the primary efficacy analysis, regardless of the duration of therapy received. A second innovative design feature is the strategy for achieving an appropriate time in therapeutic range in the warfarin group, with central tracking for each participating center and feedback to the investigators. The standard methods combined with innovative design features should achieve study results that are both scientifically valid and relevant to clinical practice. © 2013 International Society on Thrombosis and Haemostasis.

Classification of suicide attempters in schizophrenia using sociocultural and clinical features: A machine learning approach.

PubMed

Hettige, Nuwan C; Nguyen, Thai Binh; Yuan, Chen; Rajakulendran, Thanara; Baddour, Jermeen; Bhagwat, Nikhil; Bani-Fatemi, Ali; Voineskos, Aristotle N; Mallar Chakravarty, M; De Luca, Vincenzo

2017-07-01

Suicide is a major concern for those afflicted by schizophrenia. Identifying patients at the highest risk for future suicide attempts remains a complex problem for psychiatric interventions. Machine learning models allow for the integration of many risk factors in order to build an algorithm that predicts which patients are likely to attempt suicide. Currently it is unclear how to integrate previously identified risk factors into a clinically relevant predictive tool to estimate the probability of a patient with schizophrenia for attempting suicide. We conducted a cross-sectional assessment on a sample of 345 participants diagnosed with schizophrenia spectrum disorders. Suicide attempters and non-attempters were clearly identified using the Columbia Suicide Severity Rating Scale (C-SSRS) and the Beck Suicide Ideation Scale (BSS). We developed four classification algorithms using a regularized regression, random forest, elastic net and support vector machine models with sociocultural and clinical variables as features to train the models. All classification models performed similarly in identifying suicide attempters and non-attempters. Our regularized logistic regression model demonstrated an accuracy of 67% and an area under the curve (AUC) of 0.71, while the random forest model demonstrated 66% accuracy and an AUC of 0.67. Support vector classifier (SVC) model demonstrated an accuracy of 67% and an AUC of 0.70, and the elastic net model demonstrated and accuracy of 65% and an AUC of 0.71. Machine learning algorithms offer a relatively successful method for incorporating many clinical features to predict individuals at risk for future suicide attempts. Increased performance of these models using clinically relevant variables offers the potential to facilitate early treatment and intervention to prevent future suicide attempts. Copyright © 2017 Elsevier Inc. All rights reserved.

Patient-derived xenografts as preclinical neuroblastoma models.

PubMed

Braekeveldt, Noémie; Bexell, Daniel

2018-05-01

The prognosis for children with high-risk neuroblastoma is often poor and survivors can suffer from severe side effects. Predictive preclinical models and novel therapeutic strategies for high-risk disease are therefore a clinical imperative. However, conventional cancer cell line-derived xenografts can deviate substantially from patient tumors in terms of their molecular and phenotypic features. Patient-derived xenografts (PDXs) recapitulate many biologically and clinically relevant features of human cancers. Importantly, PDXs can closely parallel clinical features and outcome and serve as excellent models for biomarker and preclinical drug development. Here, we review progress in and applications of neuroblastoma PDX models. Neuroblastoma orthotopic PDXs share the molecular characteristics, neuroblastoma markers, invasive properties and tumor stroma of aggressive patient tumors and retain spontaneous metastatic capacity to distant organs including bone marrow. The recent identification of genomic changes in relapsed neuroblastomas opens up opportunities to target treatment-resistant tumors in well-characterized neuroblastoma PDXs. We highlight and discuss the features and various sources of neuroblastoma PDXs, methodological considerations when establishing neuroblastoma PDXs, in vitro 3D models, current limitations of PDX models and their application to preclinical drug testing.

Clinical features and laboratory findings of dengue fever in German travellers: A single-centre, retrospective analysis.

PubMed

Tavakolipoor, Pulad; Schmidt-Chanasit, Jonas; Burchard, Gerd Dieter; Jordan, Sabine

2016-01-01

Dengue fever (DF) is one of the most relevant human arboviral infections worldwide and has become a frequent cause of fever in the returning traveller. This retrospective study aimed to characterize epidemiological and clinical features and laboratory findings of dengue fever in German travellers. This descriptive study analyzed medical records of patients diagnosed with DF presenting at the Section of Tropical Medicine of the University Medical Centre Hamburg-Eppendorf from 2007 to 2011. Data were collected and analyzed retrospectively. In total, data of 119 DF patients (52 female, 67 male) were included in this study. The median age of the patients was 35 (range 15-75 years). DF was most frequently acquired in South-East Asia (n = 65; 54.7%), and in particular in Thailand (n = 23; 19.7%). A considerable percentage of DF infections (n = 14; 11.8%) was imported from Africa. Patients predominantly presented with fever, headache, rash, myalgia and arthralgia but also with gastrointestinal symptoms, i.e. diarrhoea. Nine patients showed signs of minor haemorrhagic manifestations. Neurological complications occurred in 13 patients. Low platelet count, leukopenia and elevated liver enzymes were the most relevant laboratory findings. Twenty patients (17.8%) had to be hospitalized. Overall, the clinical course was mostly mild to moderate, 13 patients (10.9%) showed DF warnings signs, no fatalities occurred. DF presented as a mostly mild to moderate disease in this study cohort. Outpatient treatment was adequate for the majority of patients. Still, detailed knowledge of clinical symptoms and laboratory features is essential for appropriate triage. Copyright © 2016 Elsevier Ltd. All rights reserved.

The hidden Niemann-Pick type C patient: clinical niches for a rare inherited metabolic disease.

PubMed

Hendriksz, Christian J; Anheim, Mathieu; Bauer, Peter; Bonnot, Olivier; Chakrapani, Anupam; Corvol, Jean-Christophe; de Koning, Tom J; Degtyareva, Anna; Dionisi-Vici, Carlo; Doss, Sarah; Duning, Thomas; Giunti, Paola; Iodice, Rosa; Johnston, Tracy; Kelly, Dierdre; Klünemann, Hans-Hermann; Lorenzl, Stefan; Padovani, Alessandro; Pocovi, Miguel; Synofzik, Matthis; Terblanche, Alta; Then Bergh, Florian; Topçu, Meral; Tranchant, Christine; Walterfang, Mark; Velten, Christian; Kolb, Stefan A

2017-05-01

Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Several clinical niches have been identified that harbor patients at increased risk of NP-C.

Warning Signs for Suicide: Theory, Research, and Clinical Applications

ERIC Educational Resources Information Center

Rudd, M. David; Berman, Alan L.; Joiner, Thomas E., Jr.; Nock, Matthew K.; Silverman, Morton M.; Mandrusiak, Michael; Van Orden, Kimberly; Witte, Tracy

2006-01-01

The current article addresses the issue of warning signs for suicide, attempting to differentiate the construct from risk factors. In accordance with the characteristic features discussed, a consensus set of warning signs identified by the American Association of Suicidology working group are presented, along with a discussion of relevant clinical…

Robo-Psychophysics: Extracting Behaviorally Relevant Features from the Output of Sensors on a Prosthetic Finger.

PubMed

Delhaye, Benoit P; Schluter, Erik W; Bensmaia, Sliman J

2016-01-01

Efforts are underway to restore sensorimotor function in amputees and tetraplegic patients using anthropomorphic robotic hands. For this approach to be clinically viable, sensory signals from the hand must be relayed back to the patient. To convey tactile feedback necessary for object manipulation, behaviorally relevant information must be extracted in real time from the output of sensors on the prosthesis. In the present study, we recorded the sensor output from a state-of-the-art bionic finger during the presentation of different tactile stimuli, including punctate indentations and scanned textures. Furthermore, the parameters of stimulus delivery (location, speed, direction, indentation depth, and surface texture) were systematically varied. We developed simple decoders to extract behaviorally relevant variables from the sensor output and assessed the degree to which these algorithms could reliably extract these different types of sensory information across different conditions of stimulus delivery. We then compared the performance of the decoders to that of humans in analogous psychophysical experiments. We show that straightforward decoders can extract behaviorally relevant features accurately from the sensor output and most of them outperform humans.

Version 3 of the historical-clinical-risk management-20 (HCR-20V3): relevance to violence risk assessment and management in forensic conditional release contexts.

PubMed

Douglas, Kevin S

2014-09-01

The conditional release of insanity acquittees requires decisions both about community risk level and the contextual factors that may mitigate or aggravate risk. This article discusses the potential role of the newly revised Historical-Clinical-Risk Management-20 (HCR-20, Version 3) within the conditional release context. A brief review of the structured professional judgment (SPJ) approach to violence risk assessment and management is provided. Version 2 of the HCR-20, which has been broadly adopted and evaluated, is briefly described. New features of Version 3 of the HCR-20 with particular relevance to conditional release decision-making are reviewed, including: item indicators; ratings of the relevance of risk factors to an individual's violence; risk formulation; scenario planning; and risk management planning. Version 3 of the HCR-20 includes a number of features that should assist evaluators and decision-makers to determine risk level, as well as to anticipate and specify community conditions and contexts that may mitigate or aggravate risk. Research on the HCR-20 Version 3 using approximately 800 participants across three settings (forensic psychiatric, civil psychiatric, correctional) and eight countries is reviewed. Copyright © 2014 John Wiley & Sons, Ltd.

Automated interviews on clinical case reports to elicit directed acyclic graphs.

PubMed

Luciani, Davide; Stefanini, Federico M

2012-05-01

Setting up clinical reports within hospital information systems makes it possible to record a variety of clinical presentations. Directed acyclic graphs (Dags) offer a useful way of representing causal relations in clinical problem domains and are at the core of many probabilistic models described in the medical literature, like Bayesian networks. However, medical practitioners are not usually trained to elicit Dag features. Part of the difficulty lies in the application of the concept of direct causality before selecting all the causal variables of interest for a specific patient. We designed an automated interview to tutor medical doctors in the development of Dags to represent their understanding of clinical reports. Medical notions were analyzed to find patterns in medical reasoning that can be followed by algorithms supporting the elicitation of causal Dags. Clinical relevance was defined to help formulate only relevant questions by driving an expert's attention towards variables causally related to nodes already inserted in the graph. Key procedural features of the proposed interview are described by four algorithms. The automated interview comprises questions on medical notions, phrased in medical terms. The first elicitation session produces questions concerning the patient's chief complaints and the outcomes related to diseases serving as diagnostic hypotheses, their observable manifestations and risk factors. The second session focuses on questions that refine the initial causal paths by considering syndromes, dysfunctions, pathogenic anomalies, biases and effect modifiers. A case study concerning a gastro-enterological problem and one dealing with an infected patient illustrate the output produced by the algorithms, depending on the answers provided by the doctor. The proposed elicitation framework is characterized by strong consistency with medical background and by a progressive introduction of relevant medical topics. Revision and testing of the subjectively elicited Dag is performed by matching the collected answers with the evidence included in accepted sources of biomedical knowledge. Copyright © 2011 Elsevier B.V. All rights reserved.

[Progress in methodological characteristics of clinical practice guideline for osteoarthritis].

PubMed

Xing, D; Wang, B; Lin, J H

2017-06-01

At present, several clinical practice guidelines for the treatment of osteoarthritis have been developed by institutes or societies. The ultimate purpose of developing clinical practice guidelines is to formulate the process in the treatment of osteoarthritis effectively. However, the methodologies used in developing clinical practice guidelines may place an influence on the transformation and application of that in treating osteoarthritis. The present study summarized the methodological features of individual clinical practice guideline and presented the tools for quality evaluation of clinical practice guideline. The limitations of current osteoarthritis guidelines of China are also indicated. The review article might help relevant institutions improve the quality in developing guide and clinical transformation.

Transient epileptic amnesia: clinical report of a cohort of patients.

PubMed

Lapenta, Leonardo; Brunetti, Valerio; Losurdo, Anna; Testani, Elisa; Giannantoni, Nadia Mariagrazia; Quaranta, Davide; Di Lazzaro, Vincenzo; Della Marca, Giacomo

2014-07-01

Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.

The Incremental Value of Subjective and Quantitative Assessment of 18F-FDG PET for the Prediction of Pathologic Complete Response to Preoperative Chemoradiotherapy in Esophageal Cancer.

PubMed

van Rossum, Peter S N; Fried, David V; Zhang, Lifei; Hofstetter, Wayne L; van Vulpen, Marco; Meijer, Gert J; Court, Laurence E; Lin, Steven H

2016-05-01

A reliable prediction of a pathologic complete response (pathCR) to chemoradiotherapy before surgery for esophageal cancer would enable investigators to study the feasibility and outcome of an organ-preserving strategy after chemoradiotherapy. So far no clinical parameters or diagnostic studies are able to accurately predict which patients will achieve a pathCR. The aim of this study was to determine whether subjective and quantitative assessment of baseline and postchemoradiation (18)F-FDG PET can improve the accuracy of predicting pathCR to preoperative chemoradiotherapy in esophageal cancer beyond clinical predictors. This retrospective study was approved by the institutional review board, and the need for written informed consent was waived. Clinical parameters along with subjective and quantitative parameters from baseline and postchemoradiation (18)F-FDG PET were derived from 217 esophageal adenocarcinoma patients who underwent chemoradiotherapy followed by surgery. The associations between these parameters and pathCR were studied in univariable and multivariable logistic regression analysis. Four prediction models were constructed and internally validated using bootstrapping to study the incremental predictive values of subjective assessment of (18)F-FDG PET, conventional quantitative metabolic features, and comprehensive (18)F-FDG PET texture/geometry features, respectively. The clinical benefit of (18)F-FDG PET was determined using decision-curve analysis. A pathCR was found in 59 (27%) patients. A clinical prediction model (corrected c-index, 0.67) was improved by adding (18)F-FDG PET-based subjective assessment of response (corrected c-index, 0.72). This latter model was slightly improved by the addition of 1 conventional quantitative metabolic feature only (i.e., postchemoradiation total lesion glycolysis; corrected c-index, 0.73), and even more by subsequently adding 4 comprehensive (18)F-FDG PET texture/geometry features (corrected c-index, 0.77). However, at a decision threshold of 0.9 or higher, representing a clinically relevant predictive value for pathCR at which one may be willing to omit surgery, there was no clear incremental value. Subjective and quantitative assessment of (18)F-FDG PET provides statistical incremental value for predicting pathCR after preoperative chemoradiotherapy in esophageal cancer. However, the discriminatory improvement beyond clinical predictors does not translate into a clinically relevant benefit that could change decision making. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Longitudinal MRI assessment: the identification of relevant features in the development of Posterior Fossa Syndrome in children

NASA Astrophysics Data System (ADS)

Spiteri, M.; Lewis, E.; Windridge, D.; Avula, S.

2015-03-01

Up to 25% of children who undergo brain tumour resection surgery in the posterior fossa develop posterior fossa syndrome (PFS). This syndrome is characterised by mutism and disturbance in speech. Our hypothesis is that there is a correlation between PFS and the occurrence of hypertrophic olivary degeneration (HOD) in lobes within the posterior fossa, known as the inferior olivary nuclei (ION). HOD is exhibited as an increase in size and intensity of the ION on an MR image. Intra-operative MRI (IoMRI) is used during surgical procedures at the Alder Hey Children's Hospital, Liver- pool, England, in the treatment of Posterior Fossa tumours and allows visualisation of the brain during surgery. The final MR scan on the IoMRI allows early assessment of the ION immediately after the surgical procedure. The longitudinal MRI data of 28 patients was analysed in a collaborative study with Alder Hey Children's Hospital, in order to identify the most relevant imaging features that relate to the development of PFS, specifically related to HOD. A semi-automated segmentation process was carried out to delineate the ION on each MRI. Feature selection techniques were used to identify the most relevant features amongst the MRI data, demographics and clinical data provided by the hospital. A support vector machine (SVM) was used to analyse the discriminative ability of the selected features. The results indicate the presence of HOD as the most efficient feature that correlates with the development of PFS, followed by the change in intensity and size of the ION and whether HOD occurred bilaterally or unilaterally.

Automatically identifying health- and clinical-related content in wikipedia.

PubMed

Liu, Feifan; Moosavinasab, Soheil; Agarwal, Shashank; Bennett, Andrew S; Yu, Hong

2013-01-01

Physicians are increasingly using the Internet for finding medical information related to patient care. Wikipedia is a valuable online medical resource to be integrated into existing clinical question answering (QA) systems. On the other hand, Wikipedia contains a full spectrum of world's knowledge and therefore comprises a large partition of non-health-related content, which makes disambiguation more challenging and consequently leads to large overhead for existing systems to effectively filter irrelevant information. To overcome this, we have developed both unsupervised and supervised approaches to identify health-related articles as well as clinically relevant articles. Furthermore, we explored novel features by extracting health related hierarchy from the Wikipedia category network, from which a variety of features were derived and evaluated. Our experiments show promising results and also demonstrate that employing the category hierarchy can effectively improve the system performance.

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

New daily persistent headache in the paediatric population.

PubMed

Kung, E; Tepper, S J; Rapoport, A M; Sheftell, F D; Bigal, M E

2009-01-01

We conducted a clinic-based study focusing on the clinical features of new-onset chronic daily headaches (CDH) in children and adolescents. The clinical records and headache diaries of 306 children and adolescents were reviewed, to identify 187 with CDH. Relevant information was transferred to a standardized form that included operational criteria for the diagnoses of the headaches. Since we were interested in describing the clinical features of these headaches, we followed the criteria A and B of the 2nd edn of the International Classification of Headache Disorders (ICHD-2) and refer to them as new daily persistent headaches (NDPH) regardless of the presence of migraine features (therefore, this is a modified version of the ICHD-2 criteria). From the 56 adolescents with NDPH, most (91.8%) did not overuse medications. Nearly half (48.1%) reported they could recall the month when their headaches started. NDPH was more common than chronic tension-type headache in both adolescents overusing and not overusing medication. Individuals with NDPH had headaches fulfilling criteria for migraine on an average of 18.5 days per month. On most days, they had migraine-associated symptoms (one of nausea, photophobia or phonophobia)). NDPH is common in children and adolescents with CDH. Most subjects do not overuse medication. Migraine features are common.

Molecular Heterogeneity in Glioblastoma: Potential Clinical Implications

PubMed Central

Parker, Nicole Renee; Khong, Peter; Parkinson, Jonathon Fergus; Howell, Viive Maarika; Wheeler, Helen Ruth

2015-01-01

Glioblastomas, (grade 4 astrocytomas), are aggressive primary brain tumors characterized by histopathological heterogeneity. High-resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed. PMID:25785247

The Forms and Functions of Impulsive Actions: Implications for Behavioral Assessment and Therapy

ERIC Educational Resources Information Center

Farmer, Richard F.; Golden, Jeannie A.

2009-01-01

Impulsivity is a central defining feature of several psychiatric disorders and a frequent correlate of many forms of psychopathology and maladjustment. Despite recognition of the importance of impulsivity to an understanding of a wide variety of clinically-relevant behaviors, this multifaceted construct remains ill-defined and not well understood.…

Spectrum of Celiac disease in Paediatric population: Experience of Tertiary Care Center from Pakistan.

PubMed

Aziz, Danish Abdul; Kahlid, Misha; Memon, Fozia; Sadiq, Kamran

2017-01-01

To determine clinical features and relevant laboratory investigations of patient with celiac disease (CD) and comparing classical celiac disease (CCD) with Non-diarrheal celiac disease (NDCD). This is a five years retrospective study conducted at The Aga Khan University Hospital Karachi, Pakistan from January 2010 to December 2015, enrolling children from one year to 15 years of either gender diagnosed as celiac disease in accordance with revised ESPGHAN criteria. Biopsy samples with grade 2 or more on Modified Marsh Classification were considered as consistent with celiac disease. Celiac patients were categorized into Classical celiac disease (with Chronic Diarrhea) and non-diarrheal celiac disease (Atypical celiac) and their clinical features and relevant laboratory investigations were documented. Total 66 patients were selected with celiac disease according to inclusion criteria, 39 (59.09%) patients were labeled as CCD and 27 (40.91%) patients were labeled as NDCD. Marsh grading 3a and above were more marked in CCD as compared to NDCD. Mean titer for Tissue transglutaminase antibodies (TTG) were higher in CCD group in comparison to NDCD group. In CCD, the most common clinical presentations were abdominal distension whereas in NDCD, the most remarkable features were recurrent abdominal pain (62.9%). Frequency of failure to thrive is significantly high in CCD (82.05%) but patients merely with short stature were more common in NDCD (33.3%). Refractory anemia was present in 66.6% patients in NDCD group and 41.1% patients in CCD group. 74.3% patients in CCD group were vitamin D deficient whereas 85% patient had vitamin D deficiency in NDCD group (p= 0.03). NDCD is not uncommon in our population. Recurrent abdominal pain, failure to thrive or patients only with short stature and refractory anemia are prominent features in NCDC group whereas abdominal distension, failure to thrive and recurrent abdominal pain were noticeable features in CCD. High grade histopathology and raised antibodies titer is hallmark of CCD. Vitamin D deficiency is almost equally present in both groups.

Animal Models of Alcoholic Liver Disease: Pathogenesis and Clinical Relevance

PubMed Central

Gao, Bin; Xu, Ming-Jiang; Bertola, Adeline; Wang, Hua; Zhou, Zhou; Liangpunsakul, Suthat

2017-01-01

Alcoholic liver disease (ALD), a leading cause of chronic liver injury worldwide, comprises a range of disorders including simple steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. Over the last five decades, many animal models for the study of ALD pathogenesis have been developed. Recently, a chronic-plus-binge ethanol feeding model was reported. This model induces significant steatosis, hepatic neutrophil infiltration, and liver injury. A clinically relevant model of high-fat diet feeding plus binge ethanol was also developed, which highlights the risk of excessive binge drinking in obese/overweight individuals. All of these models recapitulate some features of the different stages of ALD and have been widely used by many investigators to study the pathogenesis of ALD and to test for therapeutic drugs/components. However, these models are somewhat variable, depending on mouse genetic background, ethanol dose, and animal facility environment. This review focuses on these models and discusses these variations and some methods to improve the feeding protocol. The pathogenesis, clinical relevance, and translational studies of these models are also discussed. PMID:28411363

Brain-computer interfaces for EEG neurofeedback: peculiarities and solutions.

PubMed

Huster, René J; Mokom, Zacharais N; Enriquez-Geppert, Stefanie; Herrmann, Christoph S

2014-01-01

Neurofeedback training procedures designed to alter a person's brain activity have been in use for nearly four decades now and represent one of the earliest applications of brain-computer interfaces (BCI). The majority of studies using neurofeedback technology relies on recordings of the electroencephalogram (EEG) and applies neurofeedback in clinical contexts, exploring its potential as treatment for psychopathological syndromes. This clinical focus significantly affects the technology behind neurofeedback BCIs. For example, in contrast to other BCI applications, neurofeedback BCIs usually rely on EEG-derived features with only a minimum of additional processing steps being employed. Here, we highlight the peculiarities of EEG-based neurofeedback BCIs and consider their relevance for software implementations. Having reviewed already existing packages for the implementation of BCIs, we introduce our own solution which specifically considers the relevance of multi-subject handling for experimental and clinical trials, for example by implementing ready-to-use solutions for pseudo-/sham-neurofeedback. © 2013.

Amnesia and crime: a neuropsychiatric response.

PubMed

Wortzel, Hal S; Arciniegas, David B

2008-01-01

Bourget and Whitehurst's "Amnesia and Crime," published in a prior issue of the Journal, addresses a conceptually complex and clinically challenging subject. Their treatment emphasizes psychiatric conditions in which memory disturbances may arise that are relevant to criminal proceedings. However, their consideration of the neurobiology of memory, memory disturbances, and the neurobiological bases of interactions between psychiatric symptoms and memory merit further elaboration. The relevance of memory impairment to criminal matters requires forensic psychiatric experts to possess a basic understanding of the phenomenology and neurobiology of memory. The present authors describe briefly the phenomenology and neuroanatomy of memory, emphasizing first that memory is not a unitary cognitive domain, clinically or neurobiologically. The assertion that psychotic delusions produce memory impairment is challenged, and the description of "organic" amnesia, both semantically and in terms of its clinical features, is reframed. Resources on which to build a neuropsychiatric foundation for forensic psychiatric opinions on memory impairment surrounding criminal behavior are offered.

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections.

PubMed

Bodier-Montagutelli, Elsa; Morello, Eric; L'Hostis, Guillaume; Guillon, Antoine; Dalloneau, Emilie; Respaud, Renaud; Pallaoro, Nikita; Blois, Hélène; Vecellio, Laurent; Gabard, Jérôme; Heuzé-Vourc'h, Nathalie

2017-08-01

Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site. Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation. Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy's clinical positioning in the antimicrobial arsenal against RTIs.

Computed tomographic features of apical infection of equine maxillary cheek teeth: a retrospective study of 49 horses.

PubMed

Bühler, M; Fürst, A; Lewis, F I; Kummer, M; Ohlerth, S

2014-07-01

Computed tomographic (CT) studies evaluating the relevance of individual CT features of apical infection in maxillary cheek teeth are lacking. To study the prevalence and relationship of single CT features in horses with and without clinical evidence of apical infection in maxillary cheek teeth. Retrospective case-control study. Multislice CT scans of the head of 49 horses were evaluated retrospectively. Changes of the infundibulum, pulp, root, lamina dura, periodontal space and alveolar bone in maxillary cheek teeth were recorded. Single CT changes were much more prevalent in the 28 horses with clinical signs. However, infundibular changes and a nondetectable lamina dura were also common in the 21 horses without clinical evidence of apical infection. Computed tomographic abnormalities of the pulp, root, periapical bone and periodontal space and the presence of a tooth fracture were significantly related. Infundibular changes were not associated with other CT signs of apical infection. Although nondetectable lamina dura was the most frequent CT change in all teeth in both studied groups, it was most commonly a solitary feature in otherwise normal teeth. Apical infections, defined as ≥3 CT changes, occurred mainly in the 108/208, 109/209 and 110/210 (Triadan numbers) and were found only in horses with clinical evidence of apical infection, except in one horse without clinical signs that had one affected root. Combined CT changes of the pulp, root, lamina dura, periapical bone and periodontal space and the presence of a tooth fracture appear to be reliable features to diagnose apical infection in maxillary cheek teeth. As a solitary feature, a nondetectable lamina dura should be interpreted cautiously and may even be considered normal due to its minor thickness and/or too low resolution of the imaging modality. © 2013 EVJ Ltd.

[Formula: see text]Official Position of the American Academy of Clinical Neuropsychology (AACN): Guidelines for Practicum Training in Clinical Neuropsychology.

PubMed

Nelson, Aaron P; Roper, Brad L; Slomine, Beth S; Morrison, Chris; Greher, Michael R; Janusz, Jennifer; Larson, Jennifer C; Meadows, Mary-Ellen; Ready, Rebecca E; Rivera Mindt, Monica; Whiteside, Doug M; Willment, Kim; Wodushek, Thomas R

2015-01-01

Practical experience is central to the education and training of neuropsychologists, beginning in graduate school and extending through postdoctoral fellowship. However, historically, little attention has been given to the structure and requirements of practicum training in clinical neuropsychology. A working group of senior-level neuropsychologists, as well as a current postdoctoral fellow, all from a diverse range of settings (The AACN Practicum Guidelines Workgroup), was formed to propose guidelines for practicum training in clinical neuropsychology. The Workgroup reviewed relevant literature and sought input from professional organizations involved in education and training in neuropsychology. The proposed guidelines provide a definition of practicum training in clinical neuropsychology, detail entry and exit criteria across competencies relevant to practicum training in clinical neuropsychology, and discuss the relationship between doctoral training programs and practicum training sites. The proposed guidelines also provide a methodology for competency-based evaluation of clinical neuropsychology practicum trainees and outline characteristics and features that are integral to an effective training environment. Although the guidelines discussed below may not be implemented in their entirety across all clinical neuropsychology practicum training sites, they are consistent with the latest developments in competency-based education.

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Envenomation by Bothrops punctatus in southwestern Colombia.

PubMed

Cañas, Carlos A; Vallejo, Alexandra

2016-12-15

Bothrops punctatus (Chocoan forest lancehead) is a semi-arboreal pitviper species distributed in Panamá, Colombia, and Ecuador, whose human envenomation is poorly characterized. We describe two patients bitten by B. punctatus, whose most relevant clinical feature was the development of a severe coagulopathy with few local manifestations (mild edema without signs of necrosis) at the site of the bite. Patients quickly improved their clinical and laboratory abnormalities after polyvalent antivenom application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medical student appraisal: searching on smartphones.

PubMed

Khalifian, S; Markman, T; Sampognaro, P; Mitchell, S; Weeks, S; Dattilo, J

2013-01-01

The rapidly growing industry for mobile medical applications provides numerous smartphone resources designed for healthcare professionals. However, not all applications are equally useful in addressing the questions of early medical trainees. Three popular, free, mobile healthcare applications were evaluated along with a Google(TM) web search on both Apple(TM) and Android(TM) devices. Six medical students at a large academic hospital evaluated each application for a one-week period while on various clinical rotations. Google(TM) was the most frequently used search method and presented multimedia resources but was inefficient for obtaining clinical management information. Epocrates(TM) Pill ID feature was praised for its clinical utility. Medscape(TM) had the highest satisfaction of search and excelled through interactive educational features. Micromedex(TM) offered both FDA and off-label dosing for drugs. Google(TM) was the preferred search method for questions related to basic disease processes and multimedia resources, but was inadequate for clinical management. Caution should also be exercised when using Google(TM) in front of patients. Medscape(TM) was the most appealing application due to a broad scope of content and educational features relevant to medical trainees. Students should also be cognizant of how mobile technology may be perceived by their evaluators to avoid false impressions.

Features: Real-Time Adaptive Feature and Document Learning for Web Search.

ERIC Educational Resources Information Center

Chen, Zhixiang; Meng, Xiannong; Fowler, Richard H.; Zhu, Binhai

2001-01-01

Describes Features, an intelligent Web search engine that is able to perform real-time adaptive feature (i.e., keyword) and document learning. Explains how Features learns from users' document relevance feedback and automatically extracts and suggests indexing keywords relevant to a search query, and learns from users' keyword relevance feedback…

Analysis of underlying causes of inter-expert disagreement in retinopathy of prematurity diagnosis. Application of machine learning principles.

PubMed

Ataer-Cansizoglu, E; Kalpathy-Cramer, J; You, S; Keck, K; Erdogmus, D; Chiang, M F

2015-01-01

Inter-expert variability in image-based clinical diagnosis has been demonstrated in many diseases including retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and is a major cause of childhood blindness. In order to better understand the underlying causes of variability among experts, we propose a method to quantify the variability of expert decisions and analyze the relationship between expert diagnoses and features computed from the images. Identification of these features is relevant for development of computer-based decision support systems and educational systems in ROP, and these methods may be applicable to other diseases where inter-expert variability is observed. The experiments were carried out on a dataset of 34 retinal images, each with diagnoses provided independently by 22 experts. Analysis was performed using concepts of Mutual Information (MI) and Kernel Density Estimation. A large set of structural features (a total of 66) were extracted from retinal images. Feature selection was utilized to identify the most important features that correlated to actual clinical decisions by the 22 study experts. The best three features for each observer were selected by an exhaustive search on all possible feature subsets and considering joint MI as a relevance criterion. We also compared our results with the results of Cohen's Kappa [36] as an inter-rater reliability measure. The results demonstrate that a group of observers (17 among 22) decide consistently with each other. Mean and second central moment of arteriolar tortuosity is among the reasons of disagreement between this group and the rest of the observers, meaning that the group of experts consider amount of tortuosity as well as the variation of tortuosity in the image. Given a set of image-based features, the proposed analysis method can identify critical image-based features that lead to expert agreement and disagreement in diagnosis of ROP. Although tree-based features and various statistics such as central moment are not popular in the literature, our results suggest that they are important for diagnosis.

Clinical forensic aspects of self-inflicted neck injuries.

PubMed

Govi, Annamaria; Fersini, Federica; Etzold, Saskia; Tsokos, Michael

2018-06-01

The distinction between self-inflicted injuries and other types of injuries is crucial in forensic medicine, and relevant features of wounds should be identified by pathologists, even when they are observed at atypical sites. Herein we report two cases of self-inflicted injuries of the neck involving two young women who had reported being attacked by men.

A review of clinical practice guidelines for lung cancer

PubMed Central

Ball, David; Silvestri, Gerard A.

2013-01-01

Clinical practice guidelines are important evidence-based resources to guide complex clinical decision making. However, it is challenging for health professionals to keep abreast available guidelines and to know how and where to access relevant guidelines. This review examines currently available guidelines for lung cancer published in the English language. Important key features are listed for each identified guideline. The methodology, approaches to dissemination and implementation, and associated resources are summarised. General challenges in the area of guideline development are highlighted. The potential to collaborate more widely across lung cancer guideline developers by sharing literature searches and assessments is discussed. PMID:24163752

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

PubMed Central

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A.; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O.; Tasic, Velibor

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease–causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease–causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology–based diagnosis and improved clinical management. PMID:27151922

Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

PubMed

Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

2018-01-01

With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified the suggested association. Increased homocysteine is thought to be associated with vitamin B12 deficiency - evaluation for potential clinical relevance is suggested. While considerations for clinical metabolic profiling are recommended, including adjustment approaches for clinical confounders, AutoML presents an exciting tool to enhance clinical metabolic profiling and advance translational research endeavors.

Quantification of intra-tumour cell proliferation heterogeneity using imaging descriptors of 18F fluorothymidine-positron emission tomography

NASA Astrophysics Data System (ADS)

Willaime, J. M. Y.; Turkheimer, F. E.; Kenny, L. M.; Aboagye, E. O.

2013-01-01

Intra-tumour heterogeneity is a characteristic shared by all cancers. We explored the use of texture variables derived from images of [18F]fluorothymidine-positron emission tomography (FLT-PET), thus notionally assessing the heterogeneity of proliferation in individual tumours. Our aims were to study the range of textural feature values across tissue types, verify the repeatability of these image descriptors and further, to explore associations with clinical response to chemotherapy in breast cancer patients. The repeatability of 28 textural descriptors was assessed in patients who had two FLT-PET scans prior to therapy using relative differences and the intra-class correlation coefficient (ICC). We tested associations between features at baseline and clinical response measured in 11 patients after three cycles of chemotherapy, and explored changes in FLT-PET at one week after the start of therapy. A subset of eight features was characterized by low variations at baseline (<±30%) and high repeatability (0.7 ≤ ICC ≤ 1). The intensity distribution profile suggested fewer highly proliferating cells in lesions of non-responders compared to responders at baseline. A true increase in CV and homogeneity was measured in four out of six responders one week after the start of therapy. A number of textural features derived from FLT-PET are altered following chemotherapy in breast cancer, and should be evaluated in larger clinical trials for clinical relevance.

Lesion classification using clinical and visual data fusion by multiple kernel learning

NASA Astrophysics Data System (ADS)

Kisilev, Pavel; Hashoul, Sharbell; Walach, Eugene; Tzadok, Asaf

2014-03-01

To overcome operator dependency and to increase diagnosis accuracy in breast ultrasound (US), a lot of effort has been devoted to developing computer-aided diagnosis (CAD) systems for breast cancer detection and classification. Unfortunately, the efficacy of such CAD systems is limited since they rely on correct automatic lesions detection and localization, and on robustness of features computed based on the detected areas. In this paper we propose a new approach to boost the performance of a Machine Learning based CAD system, by combining visual and clinical data from patient files. We compute a set of visual features from breast ultrasound images, and construct the textual descriptor of patients by extracting relevant keywords from patients' clinical data files. We then use the Multiple Kernel Learning (MKL) framework to train SVM based classifier to discriminate between benign and malignant cases. We investigate different types of data fusion methods, namely, early, late, and intermediate (MKL-based) fusion. Our database consists of 408 patient cases, each containing US images, textual description of complaints and symptoms filled by physicians, and confirmed diagnoses. We show experimentally that the proposed MKL-based approach is superior to other classification methods. Even though the clinical data is very sparse and noisy, its MKL-based fusion with visual features yields significant improvement of the classification accuracy, as compared to the image features only based classifier.

Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

PubMed Central

Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

2015-01-01

IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

Autism and Related Disorders

PubMed Central

McPartland, James; Volkmar, Fred R.

2012-01-01

The Pervasive Developmental Disorders are a group of neurodevelopmental disorders that include Autistic Disorder, Asperger’s Disorder, Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS), Childhood Disintegrative Disorder (CDD), and Rett’s Disorder. All feature childhood onset with a constellation of symptoms spanning social interaction and communication and including atypical behavior patterns. The first three disorders (Autistic Disorder, Asperger’s Disorder, and PDD-NOS) are currently referred to as Autism Spectrum Disorders, reflecting divergent phenotypic and etiologic characteristics compared to Rett’s Disorder and CDD. This chapter reviews relevant research and clinical information relevant to appropriate medical diagnosis and treatment. PMID:22608634

Behavioral addictions: a novel challenge for psychopharmacology.

PubMed

Marazziti, Donatella; Presta, Silvio; Baroni, Stefano; Silvestri, Stefano; Dell'Osso, Liliana

2014-12-01

Although addictive syndromes have been traditionally related to substance-use disorders, during the last few decades a novel addictive group, including the so-called "behavioral or no-drug addictions," has been recognized and has attracted increasing attention for its relevant social impact. This group includes pathological gambling, compulsive shopping, TV/Internet/social network/videogame addictions, workaholism, sex and relationship addictions, orthorexia, and overtraining syndrome. Substance and behavioral addictions show similar phenomenological features, such as craving, dependence, tolerance, and abstinence, and perhaps they share a common possible pathophysiology. It is, however, controversial whether all or at least some of them should be considered real disorders or just normal, albeit extreme, behaviors. The aim of this article is to review current data on pharmacological treatment of behavioral addictions. As no specific and validated treatment algorithms are currently available, only an improved knowledge on their psychopathological, clinical, and neurobiological features may have relevant implications for more focused preventive and therapeutic strategies.

A machine learning heuristic to identify biologically relevant and minimal biomarker panels from omics data

PubMed Central

2015-01-01

Background Investigations into novel biomarkers using omics techniques generate large amounts of data. Due to their size and numbers of attributes, these data are suitable for analysis with machine learning methods. A key component of typical machine learning pipelines for omics data is feature selection, which is used to reduce the raw high-dimensional data into a tractable number of features. Feature selection needs to balance the objective of using as few features as possible, while maintaining high predictive power. This balance is crucial when the goal of data analysis is the identification of highly accurate but small panels of biomarkers with potential clinical utility. In this paper we propose a heuristic for the selection of very small feature subsets, via an iterative feature elimination process that is guided by rule-based machine learning, called RGIFE (Rule-guided Iterative Feature Elimination). We use this heuristic to identify putative biomarkers of osteoarthritis (OA), articular cartilage degradation and synovial inflammation, using both proteomic and transcriptomic datasets. Results and discussion Our RGIFE heuristic increased the classification accuracies achieved for all datasets when no feature selection is used, and performed well in a comparison with other feature selection methods. Using this method the datasets were reduced to a smaller number of genes or proteins, including those known to be relevant to OA, cartilage degradation and joint inflammation. The results have shown the RGIFE feature reduction method to be suitable for analysing both proteomic and transcriptomics data. Methods that generate large ‘omics’ datasets are increasingly being used in the area of rheumatology. Conclusions Feature reduction methods are advantageous for the analysis of omics data in the field of rheumatology, as the applications of such techniques are likely to result in improvements in diagnosis, treatment and drug discovery. PMID:25923811

Machine Learning methods for Quantitative Radiomic Biomarkers.

PubMed

Parmar, Chintan; Grossmann, Patrick; Bussink, Johan; Lambin, Philippe; Aerts, Hugo J W L

2015-08-17

Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pre-treatment computed tomography (CT) images of 464 lung cancer patients. To ensure the unbiased evaluation of different machine-learning methods, publicly available implementations along with reported parameter configurations were used. Furthermore, we used two independent radiomic cohorts for training (n = 310 patients) and validation (n = 154 patients). We identified that Wilcoxon test based feature selection method WLCX (stability = 0.84 ± 0.05, AUC = 0.65 ± 0.02) and a classification method random forest RF (RSD = 3.52%, AUC = 0.66 ± 0.03) had highest prognostic performance with high stability against data perturbation. Our variability analysis indicated that the choice of classification method is the most dominant source of performance variation (34.21% of total variance). Identification of optimal machine-learning methods for radiomic applications is a crucial step towards stable and clinically relevant radiomic biomarkers, providing a non-invasive way of quantifying and monitoring tumor-phenotypic characteristics in clinical practice.

Celluloid devils: a research study of male nurses in feature films.

PubMed

Stanley, David

2012-11-01

To report a study of how male nurses are portrayed in feature films. It was hypothesized that male nurses are frequently portrayed negatively or stereotypically in the film media, potentially having a negative impact on male nurse recruitment and the public's perception of male nurses. An interpretive, qualitative methodology guided by insights into hegemonic masculinity and structured around a set of collective case studies (films) was used to examine the portrayal of male nurses in feature films made in the Western world from 1900 to 2007. Over 36,000 feature film synopses were reviewed (via CINAHL, ProQuest and relevant movie-specific literature) for the keyword 'nurse' and 'nursing' with an additional search for films from 1900 to 2010 for the word 'male nurse'. Identified films were labelled as 'cases' and analysed collectively to determine key attributes related to men in nursing and explore them for the emergence of concepts and themes related to the image of male nurses in films. A total of 13 relevant cases (feature films) were identified with 12 being made in the USA. Most films portrayed male nurses negatively and in ways opposed to hegemonic masculinity, as effeminate, homosexual, homicidal, corrupt or incompetent. Few film images of male nurses show them in traditional masculine roles or as clinically competent or self-confident professionals.   Feature films predominantly portray male nurses negatively. Given the popularity of feature films, there may be negative effects on recruitment and on the public's perception of male nurses. © 2012 Blackwell Publishing Ltd.

[Safety evaluation and risk control measures of Cassiae Semen].

PubMed

Zhao, Yi-Meng; Wu, Li; Zhang, Shuo; Zhang, Li; Gao, Xue-Min; Sun, Xiao-Bo; Wang, Chun

2017-11-01

In this study, the authors reviewed domestic and foreign literatures, conducted the textual research on origin and development of Cassia Semen, studied records in ancient books and ancient and modern literatures, clinical adverse reactions and relevant experimental studies in recent years, and summarized the clinical features and influencing factors related to the safety of Cassiae Semen. According to the findings,Cassia Semen's safety risks are mainly liver and kidney system damages, with the main clinical features of fatigue, anorexia, disgusting of oil, yellow urine and gray stool; digestive system injury, with the main clinical features of diarrhea, abdominal distension, nausea and loose stool; reproductive system damage, with the main clinical features of vaginal bleeding. Allergic reactions and clinical adverse events, with the main clinical features for numb mouth, itching skin, nausea and vomiting, diarrhea, wheezing and lip cyanosis were also reported. The toxicological studies on toxic components of Cassiae Semen obtusifolia were carried out through acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. Risk factors might include patients, compatibility and physicians. Physicians should strictly abide by the medication requirements in the Pharmacopoeia, pay attention to rational compatibility, appropriate dosage,correct usage and appropriate processing, control the dosage below 15 g to avoid excessive intake, strictly control the course of treatment to avoid accumulated poisoning caused by long-term administration. At the same time, clinicians should pay attention to the latest research progress, update the knowledge structure, quickly find the latest and useful materials from clinical practice, scientific research and drug information and other literatures, make evaluation and judgment for the materials, establish a traditional Chinese medicine intelligence information library, and strengthen the control over adverse effects with a pre-warning consciousness. The authors suggested standardizing clinical medication of Cassiae Semen, and avoiding misuse or excessive use; clinicians should prescribe it in strict accordance with there commended usage and dosage in the Pharmacopoeia, and focus on the safety signal accumulation in clinic, while strengthening studies for toxic substance basis and toxicity mechanism, in order to give full play to Cassiae Semen's clinical efficacy and reduce its adverse reactions. Copyright© by the Chinese Pharmaceutical Association.

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: an evidence-based report.

PubMed

Lutgens, Maurice W M D; Meijer, Melanie; Peeters, Babette; Poulsen, Marie-Louise N F; Rutten, Marjet J; Bots, Michiel L; van der Heijden, Geert J M G; Soedamah-Muthu, Sabita S

2008-12-01

Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Clinical metabolomics paves the way towards future healthcare strategies

PubMed Central

Collino, Sebastiano; Martin, François‐Pierre J.; Rezzi, Serge

2013-01-01

Metabolomics is recognized as a powerful top‐down system biological approach to understand genetic‐environment‐health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammalian systems with regard to disease aetiology, diagnostic stratification and, potentially, mechanism of action of therapeutic solutions. A key feature of metabolomics lies in its ability to underpin the complex metabolic interactions of the host with its commensal microbial partners providing a new way to define individual and population phenotypes. This review aims at describing recent applications of metabolomics in clinical fields with insight into diseases, diagnostics/monitoring and improvement of homeostatic metabolic regulation. PMID:22348240

Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Annesley, Thomas M.; Cooks, Robert G.; Herold, David A.

Each year the journal Clinical Chemistry publishes a January special issue on a topic that is relevant to the laboratory medicine community. In January 2016 the topic is mass spectrometry, and the issue is entitled “Clinical Mass Spectrometry: Achieving Prominence in Laboratory Medicine”. One popular feature in our issues is a Q&A on a topic, clearly in this case mass spectrometry. The journal is assembling a panel of 5-6 experts from various areas of mass spectrometry ranging from instrument manufacturing to practicing clinical chemists. Dick Smith is one of the scientist requested to participate in this special issue Q&A onmore » Mass Spectrometry. The Q&A Transcript is attached« less

The high vaginal swab in general practice: clinical correlates of possible pathogens.

PubMed

Dykhuizen, R S; Harvey, G; Gould, I M

1995-06-01

Clinical features, diagnosis and treatment of 286 women whose high vaginal swabs (HVS) submitted by their general practitioners showed pure, heavy growth of Staphylococcus aureus, beta haemolytic streptococci groups A, C or G, Streptococcus milleri, Streptococcus pneumoniae or Haemophilus influenzae were analysed. Women with group A, C and G streptococci frequently had clinical vulvovaginitis and although the numbers were too small for statistical confirmation, S. pneumoniae and H. influenzae appeared to cause clinical disease as well. The association of S. aureus or S. milleri with clinical vulvovaginitis was much less convincing. It seems relevant for laboratories to report sensitivities for group A, C and G streptococci. Further research is needed to determine the pathogenicity of S. pneumoniae and H. influenzae.

Bipolar disorder and ADHD: comorbidity and diagnostic distinctions.

PubMed

Marangoni, Ciro; De Chiara, Lavinia; Faedda, Gianni L

2015-08-01

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) are neurodevelopmental disorders with onset in childhood and early adolescence, and common persistence in adulthood. Both disorders are often undiagnosed, misdiagnosed, and sometimes over diagnosed, leading to high rates of morbidity and disability. The differentiation of these conditions is based on their clinical features, comorbidity, psychiatric family history course of illness, and response to treatment. We review recent relevant findings and highlight epidemiological, clinical, family history, course, and treatment-response differences that can aid the differential diagnosis of these conditions in an outpatient pediatric setting.

Free-living monitoring of Parkinson's disease: Lessons from the field.

PubMed

Del Din, Silvia; Godfrey, Alan; Mazzà, Claudia; Lord, Sue; Rochester, Lynn

2016-09-01

Wearable technology comprises miniaturized sensors (eg, accelerometers) worn on the body and/or paired with mobile devices (eg, smart phones) allowing continuous patient monitoring in unsupervised, habitual environments (termed free-living). Wearable technologies are revolutionizing approaches to health care as a result of their utility, accessibility, and affordability. They are positioned to transform Parkinson's disease (PD) management through the provision of individualized, comprehensive, and representative data. This is particularly relevant in PD where symptoms are often triggered by task and free-living environmental challenges that cannot be replicated with sufficient veracity elsewhere. This review concerns use of wearable technology in free-living environments for people with PD. It outlines the potential advantages of wearable technologies and evidence for these to accurately detect and measure clinically relevant features including motor symptoms, falls risk, freezing of gait, gait, functional mobility, and physical activity. Technological limitations and challenges are highlighted, and advances concerning broader aspects are discussed. Recommendations to overcome key challenges are made. To date there is no fully validated system to monitor clinical features or activities in free-living environments. Robust accuracy and validity metrics for some features have been reported, and wearable technology may be used in these cases with a degree of confidence. Utility and acceptability appears reasonable, although testing has largely been informal. Key recommendations include adopting a multidisciplinary approach for standardizing definitions, protocols, and outcomes. Robust validation of developed algorithms and sensor-based metrics is required along with testing of utility. These advances are required before widespread clinical adoption of wearable technology can be realized. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

The role of boldness in psychopathy: A study of academic and clinical perceptions.

PubMed

Berg, Joanna M; Lilienfeld, Scott O; Sellbom, Martin

2017-10-01

The relevance of boldness to psychopathy has recently become a major flashpoint of scientific controversy. Although some authors have contended that boldness is a necessary (although insufficient) component of psychopathy, others have asserted that it is largely or entirely irrelevant to psychopathy. We addressed this issue by examining clinical perceptions of the relevance of the 3 triarchic dimensions (boldness, disinhibition, and meanness) to psychopathy among a sample of mental health professionals and graduate students (N = 228) using a vignette-based, person-centered methodology. A vignette comprising boldness descriptors afforded statistically significant and moderate to large (Cohen's ds ranged from .47 to .99) increases in perceived resemblance to overall psychopathy above and beyond the other triarchic dimensions, both singly and jointly; these findings extended largely to clinical perceptions of Factor 1 (i.e., interpersonal and affective aspects of psychopathy) but not Factor 2 (i.e., impulsive and antisocial aspects of psychopathy) resemblance. Contrary to the claims of some recent authors, boldness alone was perceived as being as relevant to psychopathy as was disinhibition, although both dimensions were perceived as less relevant to psychopathy than was meanness. These findings offer strong support for the contention that boldness is regarded as a key feature of classical psychopathy and are broadly consistent with interpersonal models of psychopathy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The co-occurrence of driver mutations in chronic myeloproliferative neoplasms.

PubMed

Boddu, Prajwal; Chihara, Dai; Masarova, Lucia; Pemmaraju, Naveen; Patel, Keyur P; Verstovsek, Srdan

2018-06-27

Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by proliferation of one or more elements of the myeloid lineage. Key genetic aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in Philadelphia chromosome-negative MPNs. While thought to be mutually exclusive, occasional isolated reports of coexistence of BCR-ABL1 and JAK2, and JAK2 with MPL or CALR aberrations have been described. Given the paucity of data, clinical characteristics and outcome of patients harboring concurrent Philadelphia-positive and Philadelphia-negative mutations or dual Philadelphia-negative driver mutations have not been systematically evaluated, and their clinical relevance is largely unknown. It is difficult to determine the true relevance of co-existing driver mutations on outcomes given the rarity of its occurrence. In this case series, we describe those patients who had dual driver mutations detected at any point during the course of their disease and characterized their clinical and laboratory features, bone marrow pathology, and overall disease course.

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract.

PubMed

Vivante, Asaf; Hwang, Daw-Yang; Kohl, Stefan; Chen, Jing; Shril, Shirlee; Schulz, Julian; van der Ven, Amelie; Daouk, Ghaleb; Soliman, Neveen A; Kumar, Aravind Selvin; Senguttuvan, Prabha; Kehinde, Elijah O; Tasic, Velibor; Hildebrandt, Friedhelm

2017-01-01

Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by whole-exome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1 Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management. Copyright © 2016 by the American Society of Nephrology.

Perceived Pain Extent is Not Associated With Widespread Pressure Pain Sensitivity, Clinical Features, Related Disability, Anxiety, or Depression in Women With Episodic Migraine.

PubMed

Fernández-de-Las-Peñas, Cesar; Falla, Deborah; Palacios-Ceña, María; Fuensalida-Novo, Stella; Arias-Buría, Jose L; Schneebeli, Alessandro; Arend-Nielsen, Lars; Barbero, Marco

2018-03-01

People with migraine present with varying pain extent and an expanded distribution of perceived pain may reflect central sensitization. The relationship between pain extent and clinical features, psychological outcomes, related disability, and pressure pain sensitivity in migraine has been poorly investigated. Our aim was to investigate whether the perceived pain extent, assessed from pain drawings, relates to measures of pressure pain sensitivity, clinical, psychological outcomes, and related disability in women with episodic migraine. A total of 72 women with episodic migraine completed pain drawings, which were subsequently digitized allowing pain extent to be calculated utilising novel software. Pressure pain thresholds were assessed bilaterally over the temporalis muscle (trigeminal area), the cervical spine (extratrigeminal area), and tibialis anterior muscle (distant pain-free area). Clinical features of migraine, migraine-related disability (migraine disability assessment questionnaire [MIDAS]), and anxiety and depression (Hospital Anxiety-Depression Scale [HADS]) were also assessed. Spearman ρ correlation coefficients were computed to reveal correlations between pain extent and the remaining outcomes. No significant associations were observed between pain extent and pressure pain thresholds in trigeminal, extratrigeminal or distant pain-free areas, migraine pain features, or psychological variables including anxiety or depression, and migraine-related disability. Pain extent within the trigeminocervical area was not associated with any of the measured clinical outcomes and not related to the degree of pressure pain sensitization in women with episodic migraine. Further research is needed to determine if the presence of expanded pain areas outside of the trigeminal area can play a relevant role in the sensitization processes in migraine.

Clinical and histologic features of acute-onset erythroderma in dogs with gastrointestinal disease: 18 cases (2005-2015).

PubMed

Cain, Christine L; Bradley, Charles W; Mauldin, Elizabeth A

2017-12-15

OBJECTIVE To describe the clinical and histologic features of acute erythroderma in dogs with gastrointestinal disease. DESIGN Retrospective case series. ANIMALS 18 dogs with erythroderma and gastrointestinal disease. PROCEDURES Medical records and biopsy specimens were reviewed. Information collected from medical records included signalment, clinical signs, physical examination and diagnostic test results, treatment, and outcome. The Naranjo algorithm was used to estimate the probability of an adverse drug reaction for each dog. RESULTS All dogs had an acute onset of erythematous macules or generalized erythroderma. Histologic features of skin biopsy specimens had 3 patterns representing a progressive spectrum of inflammation. Most dogs had vomiting (n = 17) and hematochezia (10). Signs of gastrointestinal disease became evident before, after, or concurrent with the onset of skin lesions in 10, 3, and 5 dogs, respectively. Inflammatory bowel disease, pancreatitis, and adverse food reaction were diagnosed in 5, 3, and 3 dogs, respectively. The cause of the gastrointestinal signs was not identified for 8 dogs. Eight dogs had a Naranjo score consistent with a possible adverse drug reaction. Treatment of skin lesions included drug withdrawal (n = 15), antihistamines (16), and corticosteroids (14). Signs of gastrointestinal disease and skin lesions resolved at a mean of 4.6 days and 20.8 days, respectively, after onset. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated acute erythroderma may be associated with > 1 gastrointestinal disease or an adverse drug reaction in some dogs. Recognition of the clinical and histologic features of this syndrome is essential for accurate diagnosis.

DISSECT: a new mnemonic-based approach to the categorization of aortic dissection.

PubMed

Dake, M D; Thompson, M; van Sambeek, M; Vermassen, F; Morales, J P

2013-08-01

Classification systems for aortic dissection provide important guides to clinical decision-making, but the relevance of traditional categorization schemes is being questioned in an era when endovascular techniques are assuming a growing role in the management of this frequently complex and catastrophic entity. In recognition of the expanding range of interventional therapies now used as alternatives to conventional treatment approaches, the Working Group on Aortic Diseases of the DEFINE Project developed a categorization system that features the specific anatomic and clinical manifestations of the disease process that are most relevant to contemporary decision-making. The DISSECT classification system is a mnemonic-based approach to the evaluation of aortic dissection. It guides clinicians through an assessment of six critical characteristics that facilitate optimal communication of the most salient details that currently influence the selection of a therapeutic option, including those findings that are key when considering an endovascular procedure, but are not taken into account by the DeBakey or Stanford categorization schemes. The six features of aortic dissection include: duration of disease; intimal tear location; size of the dissected aorta; segmental extent of aortic involvement; clinical complications of the dissection, and thrombus within the aortic false lumen. In current clinical practice, endovascular therapy is increasingly considered as an alternative to medical management or open surgical repair in select cases of type B aortic dissection. Currently, endovascular aortic repair is not used for patients with type A aortic dissection, but catheter-based techniques directed at peripheral branch vessel ischemia that may complicate type A dissection are considered valuable adjunctive interventions, when indicated. The use of a new system for categorization of aortic dissection, DISSECT, addresses the shortcomings of well-known established schemes devised more than 40 years ago, before the introduction of endovascular techniques. It will serve as a guide to support a critical analysis of contemporary therapeutic options and inform management decisions based on specific features of the disease process. Copyright © 2013 European Society for Vascular Surgery. All rights reserved.

Where to find information about drugs

PubMed Central

Day, Richard O; Snowden, Leone

2016-01-01

SUMMARY Good medicines information is critical to medical practice. Choose high-quality, pre-appraised sources first and make sure they are current. Select the information that is most relevant to the needs of your particular patient. Take the time to become familiar with the features of the resources you use. Australian Medicines Handbook, Therapeutic Guidelines, Australian Prescriber and NPS MedicineWise cover most routine clinical practice needs. PMID:27346917

Assessment of surveys for the management of hospital clinical pharmacy services.

PubMed

Čufar, Andreja; Mrhar, Aleš; Robnik-Šikonja, Marko

2015-06-01

Survey data sets are important sources of data, and their successful exploitation is of key importance for informed policy decision-making. We present how a survey analysis approach initially developed for customer satisfaction research in marketing can be adapted for an introduction of clinical pharmacy services into a hospital. We use a data mining analytical approach to extract relevant managerial consequences. We evaluate the importance of competences for users of a clinical pharmacy with the OrdEval algorithm and determine their nature according to the users' expectations. For this, we need substantially fewer questions than are required by the Kano approach. From 52 clinical pharmacy activities we were able to identify seven activities with a substantial negative impact (i.e., negative reinforcement) on the overall satisfaction of clinical pharmacy services, and two activities with a strong positive impact (upward reinforcement). Using analysis of individual feature values, we identified six performance, 10 excitement, and one basic clinical pharmacists' activity. We show how the OrdEval algorithm can exploit the information hidden in the ordering of class and attribute values, and their inherent correlation using a small sample of highly relevant respondents. The visualization of the outputs turns out highly useful in our clinical pharmacy research case study. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model.

PubMed

Ay, Hakan; Arsava, E Murat; Johnston, S Claiborne; Vangel, Mark; Schwamm, Lee H; Furie, Karen L; Koroshetz, Walter J; Sorensen, A Gregory

2009-01-01

Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >/=4) as covariates. Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >/=4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.

The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

PubMed

Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca

2016-01-01

The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance

PubMed Central

Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M. H.; Brandt, Kristian K.; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik

2015-01-01

The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. PMID:26482314

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan.

PubMed

Teede, H; Deeks, A; Moran, L

2010-06-30

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

PubMed Central

2010-01-01

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS. PMID:20591140

Development and initial evaluation of an instrument to assess physiotherapists' clinical reasoning focused on clients' behavior change.

PubMed

Elvén, Maria; Hochwälder, Jacek; Dean, Elizabeth; Söderlund, Anne

2018-05-01

A systematically developed and evaluated instrument is needed to support investigations of physiotherapists' clinical reasoning integrated with the process of clients' behavior change. This study's aim was to develop an instrument to assess physiotherapy students' and physiotherapists' clinical reasoning focused on clients' activity-related behavior and behavior change, and initiate its evaluation, including feasibility and content validity. The study was conducted in three phases: 1) determination of instrument structure and item generation, based on a model, guidelines for assessing clinical reasoning, and existing measures; 2) cognitive interviews with five physiotherapy students to evaluate item understanding and feasibility; and 3) a Delphi process with 18 experts to evaluate content relevance. Phase 1 resulted in an instrument with four domains: Physiotherapist; Input from client; Functional behavioral analysis; and Strategies for behavior change. The instrument consists of case scenarios followed by items in which key features are identified, prioritized, or interpreted. Phase 2 resulted in revisions of problems and approval of feasibility. Phase 3 demonstrated high level of consensus regarding the instrument's content relevance. This feasible and content-validated instrument shows potential for use in investigations of physiotherapy students' and physiotherapists' clinical reasoning, however continued development and testing are needed.

Perceptual learning: toward a comprehensive theory.

PubMed

Watanabe, Takeo; Sasaki, Yuka

2015-01-03

Visual perceptual learning (VPL) is long-term performance increase resulting from visual perceptual experience. Task-relevant VPL of a feature results from training of a task on the feature relevant to the task. Task-irrelevant VPL arises as a result of exposure to the feature irrelevant to the trained task. At least two serious problems exist. First, there is the controversy over which stage of information processing is changed in association with task-relevant VPL. Second, no model has ever explained both task-relevant and task-irrelevant VPL. Here we propose a dual plasticity model in which feature-based plasticity is a change in a representation of the learned feature, and task-based plasticity is a change in processing of the trained task. Although the two types of plasticity underlie task-relevant VPL, only feature-based plasticity underlies task-irrelevant VPL. This model provides a new comprehensive framework in which apparently contradictory results could be explained.

Magnetic resonance imaging features of Great Danes with and without clinical signs of cervical spondylomyelopathy

PubMed Central

Martin-Vaquero, Paula; da Costa, Ronaldo C.

2014-01-01

Objective To characterize and compare the MRI morphological features of the cervical vertebral column of Great Danes with and without clinical signs of cervical spondylomyelopathy (CSM). Design Prospective cohort study. Animals 30 Great Danes (15 clinically normal and 15 CSM-affected). Procedures All dogs underwent MRI of the cervical vertebral column (C2–3 through T1–2). Features evaluated included sites of subarachnoid space compression, spinal cord compression, or both; degree, cause, and direction of compression; MRI signal changes of the spinal cord; articular process (facet) joint characteristics; internal vertebral venous plexus visibility; and presence of extradural synovial cysts as well as presence and degree of intervertebral disk degeneration and foraminal stenosis. Results Clinically normal and CSM-affected dogs had 11 and 61 compressive sites, respectively, detected with MRI. All CSM-affected dogs had ≥ 1 site of spinal cord compression. No signal changes were observed in spinal cords of normal dogs, whereas 14 sites of hyperintensity were found in 9 CSM-affected dogs. Foraminal stenosis was present in 11 clinically normal and all CSM-affected dogs. The number of stenotic foraminal sites was significantly greater in the CSM-affected group, and severe stenosis appeared to be more common in this group than in the clinically normal group. Significant differences were identified between clinically normal and CSM-affected dogs with regard to amount of synovial fluid evident, regularity of articular surfaces, degree of articular process joint proliferation, and internal vertebral venous plexus visibility. Conclusions and Clinical Relevance Abnormalities were detected with MRI in several clinically normal Great Danes. Severe spinal cord compression, number of stenotic foraminal sites, and signal changes within the spinal cord distinguished CSM-affected from clinically normal Great Danes. PMID:25075822

MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia

PubMed Central

Trino, Stefania; Caivano, Antonella; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Del Vecchio, Luigi; Musto, Pellegrino; De Luca, Luciana

2018-01-01

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets. PMID:29401684

Leap motion evaluation for assessment of upper limb motor skills in Parkinson's disease.

PubMed

Butt, A H; Rovini, E; Dolciotti, C; Bongioanni, P; De Petris, G; Cavallo, F

2017-07-01

The main goal of this study is to investigate the potential of the Leap Motion Controller (LMC) for the objective assessment of motor dysfunctioning in patients with Parkinson's disease (PwPD). The most relevant clinical signs in Parkinson's Disease (PD), such as slowness of movements, frequency variation, amplitude variation, and speed, were extracted from the recorded LMC data. Data were clinically quantified using the LMC software development kit (SDK). In this study, 16 PwPD subjects and 12 control healthy subjects were involved. A neurologist assessed the subjects during the task execution, assigning them a score according to the MDS/UPDRS-Section III items. Features of motor performance from both subject groups (patients and healthy controls) were extracted with dedicated algorithms. Furthermore, to find out the significance of such features from the clinical point of view, machine learning based methods were used. Overall, our findings showed the moderate potential of LMC to extract the motor performance of PwPD.

Understanding adolescent personality pathology from growth trajectories of childhood oddity.

PubMed

De Clercq, Barbara; Verbeke, Lize; De Caluwé, Elien; Vercruysse, Tom; Hofmans, Joeri

2017-10-01

Research on developmental trajectories of early maladaptive features for understanding later personality disorders (PDs) is increasingly recognized as an important study area. The course of early odd features is highly relevant in this regard, as only a few researchers have addressed childhood oddity in the context of emerging PDs. Using latent growth modeling, the current study explores growth parameters of odd features in a mixed sample of Flemish community and referred children (N = 485) across three measurement waves with 1-year time intervals. Personality pathology was assessed at a fourth assessment point in adolescence. Beyond a general declining trend in oddity characteristics, the results demonstrated that both an early onset and an increasing trend of oddity-related characteristics over time are independent predictors of adolescent PDs. Childhood oddity tends to be the most manifest precursor for PDs with a core oddity feature (i.e., the schizotypal and borderline PD), but also appears to predict most of the other DSM-5 PDs. Results are discussed from an overarching developmental framework on PDs (Cicchetti, 2014), specifically focusing on the principle of multifinality. From a clinical perspective, the significance of increasing or steady-high childhood oddity trajectories for adolescent PDs highlights the relevance of systematic screening processes across time.

Rough-Fuzzy Clustering and Unsupervised Feature Selection for Wavelet Based MR Image Segmentation

PubMed Central

Maji, Pradipta; Roy, Shaswati

2015-01-01

Image segmentation is an indispensable process in the visualization of human tissues, particularly during clinical analysis of brain magnetic resonance (MR) images. For many human experts, manual segmentation is a difficult and time consuming task, which makes an automated brain MR image segmentation method desirable. In this regard, this paper presents a new segmentation method for brain MR images, integrating judiciously the merits of rough-fuzzy computing and multiresolution image analysis technique. The proposed method assumes that the major brain tissues, namely, gray matter, white matter, and cerebrospinal fluid from the MR images are considered to have different textural properties. The dyadic wavelet analysis is used to extract the scale-space feature vector for each pixel, while the rough-fuzzy clustering is used to address the uncertainty problem of brain MR image segmentation. An unsupervised feature selection method is introduced, based on maximum relevance-maximum significance criterion, to select relevant and significant textural features for segmentation problem, while the mathematical morphology based skull stripping preprocessing step is proposed to remove the non-cerebral tissues like skull. The performance of the proposed method, along with a comparison with related approaches, is demonstrated on a set of synthetic and real brain MR images using standard validity indices. PMID:25848961

Oculomotor selection underlies feature retention in visual working memory.

PubMed

Hanning, Nina M; Jonikaitis, Donatas; Deubel, Heiner; Szinte, Martin

2016-02-01

Oculomotor selection, spatial task relevance, and visual working memory (WM) are described as three processes highly intertwined and sustained by similar cortical structures. However, because task-relevant locations always constitute potential saccade targets, no study so far has been able to distinguish between oculomotor selection and spatial task relevance. We designed an experiment that allowed us to dissociate in humans the contribution of task relevance, oculomotor selection, and oculomotor execution to the retention of feature representations in WM. We report that task relevance and oculomotor selection lead to dissociable effects on feature WM maintenance. In a first task, in which an object's location was encoded as a saccade target, its feature representations were successfully maintained in WM, whereas they declined at nonsaccade target locations. Likewise, we observed a similar WM benefit at the target of saccades that were prepared but never executed. In a second task, when an object's location was marked as task relevant but constituted a nonsaccade target (a location to avoid), feature representations maintained at that location did not benefit. Combined, our results demonstrate that oculomotor selection is consistently associated with WM, whereas task relevance is not. This provides evidence for an overlapping circuitry serving saccade target selection and feature-based WM that can be dissociated from processes encoding task-relevant locations. Copyright © 2016 the American Physiological Society.

Task-relevant perceptual features can define categories in visual memory too.

PubMed

Antonelli, Karla B; Williams, Carrick C

2017-11-01

Although Konkle, Brady, Alvarez, and Oliva (2010, Journal of Experimental Psychology: General, 139(3), 558) claim that visual long-term memory (VLTM) is organized on underlying conceptual, not perceptual, information, visual memory results from visual search tasks are not well explained by this theory. We hypothesized that when viewing an object, any task-relevant visual information is critical to the organizational structure of VLTM. In two experiments, we examined the organization of VLTM by measuring the amount of retroactive interference created by objects possessing different combinations of task-relevant features. Based on task instructions, only the conceptual category was task relevant or both the conceptual category and a perceptual object feature were task relevant. Findings indicated that when made task relevant, perceptual object feature information, along with conceptual category information, could affect memory organization for objects in VLTM. However, when perceptual object feature information was task irrelevant, it did not contribute to memory organization; instead, memory defaulted to being organized around conceptual category information. These findings support the theory that a task-defined organizational structure is created in VLTM based on the relevance of particular object features and information.

Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance.

PubMed

Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali

2017-06-01

The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

Sexual behavior that is "out of control": a theoretical conceptual approach.

PubMed

Bancroft, John

2008-12-01

At this stage of our knowledge, it seems reasonable to assume that out-of-control sexual behavior results from a variety of etiological mechanisms associated with different behavioral patterns that share Goodman's two key features of addictive behavior: (1) a recurrent failure to control the sexual behavior; and (2) continuation of the behavior despite harmful consequences. Any overriding definition relevant to clinical management seems premature until we better understand the various patterns and their likely determinants. The concepts of "compulsivity" and "addiction" may have explanatory value in some cases, but are not helpful when used as general terms for this class of behavior problem. Stein and colleagues suggested that, in these circumstances, we use the term "hypersexuality." In my opinion, out-of-control sexual behavior or "impulse control disorders" as proposed by Barth and Kinder are more appropriate nonspecific terms because they focus on the issue of control rather than on high levels of sexuality. A number of clinically relevant and researchable hypotheses need to be addressed in further research, which hopefully will lead to more etiologically or therapeutically relevant subcategories of out-of-control sexual behavior.

Mirror neurons and their clinical relevance.

PubMed

Rizzolatti, Giacomo; Fabbri-Destro, Maddalena; Cattaneo, Luigi

2009-01-01

One of the most exciting events in neurosciences over the past few years has been the discovery of a mechanism that unifies action perception and action execution. The essence of this 'mirror' mechanism is as follows: whenever individuals observe an action being done by someone else, a set of neurons that code for that action is activated in the observers' motor system. Since the observers are aware of the outcome of their motor acts, they also understand what the other individual is doing without the need for intermediate cognitive mediation. In this Review, after discussing the most pertinent data concerning the mirror mechanism, we examine the clinical relevance of this mechanism. We first discuss the relationship between mirror mechanism impairment and some core symptoms of autism. We then outline the theoretical principles of neurorehabilitation strategies based on the mirror mechanism. We conclude by examining the relationship between the mirror mechanism and some features of the environmental dependency syndromes.

Amnesia and crime.

PubMed

Bourget, Dominique; Whitehurst, Laurie

2007-01-01

Amnesia for serious offenses has important legal implications, particularly regarding its relevance in the contexts of competency to stand trial and criminal responsibility. Forensic psychiatrists and other mental health professionals are often required to provide expert testimony regarding amnesia in defendants. However, the diagnosis of amnesia presents a challenge, as claims of memory impairment may stem from organic disease, dissociative amnesia, amnesia due to a psychotic episode, or malingered amnesia. We review the theoretical, clinical, and legal perspectives on amnesia in relation to crime and present relevant cases that demonstrate several types of crime-related amnesia and their legal repercussions. Consideration of the presenting clinical features of crime-related amnesia may enable a fuller understanding of the different types of amnesia and assist clinicians in the medico-legal assessment and diagnosis of the claimed memory impairment. The development of a profile of aspects characteristic of crime-related amnesia would build toward establishing guidelines for the assessment of amnesia in legal contexts.

MYC immunohistochemical and cytogenetic analysis are required for identification of clinically relevant aggressive B cell lymphoma subtypes.

PubMed

Raess, Philipp W; Moore, Stephen R; Cascio, Michael J; Dunlap, Jennifer; Fan, Guang; Gatter, Ken; Olson, Susan B; Braziel, Rita M

2018-06-01

Accurate subclassification of aggressive B cell lymphomas (ABCLs) requires integration of morphologic, immunohistochemical (IHC), and cytogenetic information. Optimal strategies have not been well defined for diagnosis of high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (HGBLwR) and double expressor lymphomas with MYC and BCL2 protein overexpression. One hundred and eighty seven ABCLs were investigated with complete IHC and FISH analysis. Morphologic and IHC analysis was insufficient to identify clinically relevant HGBLwR. Approximately, 75% of cases classified as HGBLwR showed conventional DLBCL morphologic features. Fourteen percent of MYC-rearranged cases were negative by IHC. Conversely, 60% of cases positive for MYC by IHC did not demonstrate a MYC rearrangement. Analysis by FISH without MYC and BCL2 IHC would miss 41 cases of double expressor lymphoma. Complete IHC and FISH analysis is recommended in the evaluation of all ABCLs.

Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists.

PubMed

Lee, Hwajeong; Westerhoff, Maria; Shen, Bo; Liu, Xiuli

2016-05-01

-Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. -To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. -The literature was reviewed. -Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.

Pragmatic characteristics of patient-reported outcome measures are important for use in clinical practice.

PubMed

Kroenke, Kurt; Monahan, Patrick O; Kean, Jacob

2015-09-01

Measures for assessing patient-reported outcomes (PROs) that may have initially been developed for research are increasingly being recommended for use in clinical practice as well. Although psychometric rigor is essential, this article focuses on pragmatic characteristics of PROs that may enhance uptake into clinical practice. Three sources were drawn on in identifying pragmatic criteria for PROs: (1) selected literature review including recommendations by other expert groups; (2) key features of several model public domain PROs; and (3) the authors' experience in developing practical PROs. Eight characteristics of a practical PRO include: (1) actionability (i.e., scores guide diagnostic or therapeutic actions/decision making); (2) appropriateness for the relevant clinical setting; (3) universality (i.e., for screening, severity assessment, and monitoring across multiple conditions); (4) self-administration; (5) item features (number of items and bundling issues); (6) response options (option number and dimensions, uniform vs. varying options, time frame, intervals between options); (7) scoring (simplicity and interpretability); and (8) accessibility (nonproprietary, downloadable, available in different languages and for vulnerable groups, and incorporated into electronic health records). Balancing psychometric and pragmatic factors in the development of PROs is important for accelerating the incorporation of PROs into clinical practice. Published by Elsevier Inc.

'Mind the gap' between the development of therapeutic innovations and the clinical practice in oncology: A proposal of the European Organisation for Research and Treatment of Cancer (EORTC) to optimise cancer clinical research.

PubMed

Kempf, Emmanuelle; Bogaerts, Jan; Lacombe, Denis; Liu, Lifang

2017-11-01

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current 'innovation-centred' system to a truly 'patient-centred' paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does expert knowledge improve automatic probabilistic classification of gait joint motion patterns in children with cerebral palsy?

PubMed Central

Papageorgiou, Eirini; Nieuwenhuys, Angela; Desloovere, Kaat

2017-01-01

Background This study aimed to improve the automatic probabilistic classification of joint motion gait patterns in children with cerebral palsy by using the expert knowledge available via a recently developed Delphi-consensus study. To this end, this study applied both Naïve Bayes and Logistic Regression classification with varying degrees of usage of the expert knowledge (expert-defined and discretized features). A database of 356 patients and 1719 gait trials was used to validate the classification performance of eleven joint motions. Hypotheses Two main hypotheses stated that: (1) Joint motion patterns in children with CP, obtained through a Delphi-consensus study, can be automatically classified following a probabilistic approach, with an accuracy similar to clinical expert classification, and (2) The inclusion of clinical expert knowledge in the selection of relevant gait features and the discretization of continuous features increases the performance of automatic probabilistic joint motion classification. Findings This study provided objective evidence supporting the first hypothesis. Automatic probabilistic gait classification using the expert knowledge available from the Delphi-consensus study resulted in accuracy (91%) similar to that obtained with two expert raters (90%), and higher accuracy than that obtained with non-expert raters (78%). Regarding the second hypothesis, this study demonstrated that the use of more advanced machine learning techniques such as automatic feature selection and discretization instead of expert-defined and discretized features can result in slightly higher joint motion classification performance. However, the increase in performance is limited and does not outweigh the additional computational cost and the higher risk of loss of clinical interpretability, which threatens the clinical acceptance and applicability. PMID:28570616

[Alienation: Differential Psychopathology of Ego-Disturbances].

PubMed

Bodatsch, M; Kuhn, J

2016-11-01

Alienation, i. e. disorders of the inner experience of integrity, continuity, and agency, represents a feature of both psychotic and non-psychotic disorders. Thereby, ego disturbances are thought to be specific for schizophrenia. Depersonalisation, in contrast, has been reported in schizophrenia as well as a neurotic, probably distinct syndrome. The differentiation of psychotic vs. non-psychotic alienation is often all but trivial. The present paper provides an overview of the historical roots and the psychopathological conceptualizations of alienation. Clinically relevant features of psychotic alienation are highlighted. Experience of passivity, loss of authenticity and disturbances of striving and volition appear as psychotic characteristics. © Georg Thieme Verlag KG Stuttgart · New York.

KERATOACANTHOMA OF THE INFERIOR LIP: REVIEW AND REPORT OF CASE WITH SPONTANEOUS REGRESSION

PubMed Central

Ramos, Lara Maria A.; Cardoso, Sérgio V.; Loyola, Adriano M.; Rocha, Marcus A.; Durighetto, Antônio Francisco

2009-01-01

Keratoacanthoma (KA) is a self-limited benign epithelial proliferative lesion that eventually presents with very similar clinical features to squamous cell carcinoma. Many KA appear in the vermilion border of the lips and therefore dental professionals must be familiar of the disease. This article reports the case of a 40-year-old female patient presenting with an exophytic ulcerative tumor in her lower lip that resolved after incisional biopsy. Photographic documentation of the case is presented and topics that are relevant to the clinical management of the disease are addressed. PMID:19466263

Aortic Valve Endocarditis Complicated by ST-Elevation Myocardial Infarction

PubMed Central

Jenny, Benjamin E.

2014-01-01

Infective endocarditis complicated by abscess formation and coronary artery compression is a rare clinical event with a high mortality rate, and diagnosis requires a heightened degree of suspicion. We present the clinical, angiographic, and echocardiographic features of a 73-year-old woman who presented with dyspnea and was found to have right coronary artery compression that was secondary to abscess formation resulting from diffuse infectious endocarditis. We discuss the patient's case and briefly review the relevant medical literature. To our knowledge, this is the first reported case of abscess formation involving a native aortic valve and the right coronary artery. PMID:25593539

Enhancing interpretability of automatically extracted machine learning features: application to a RBM-Random Forest system on brain lesion segmentation.

PubMed

Pereira, Sérgio; Meier, Raphael; McKinley, Richard; Wiest, Roland; Alves, Victor; Silva, Carlos A; Reyes, Mauricio

2018-02-01

Machine learning systems are achieving better performances at the cost of becoming increasingly complex. However, because of that, they become less interpretable, which may cause some distrust by the end-user of the system. This is especially important as these systems are pervasively being introduced to critical domains, such as the medical field. Representation Learning techniques are general methods for automatic feature computation. Nevertheless, these techniques are regarded as uninterpretable "black boxes". In this paper, we propose a methodology to enhance the interpretability of automatically extracted machine learning features. The proposed system is composed of a Restricted Boltzmann Machine for unsupervised feature learning, and a Random Forest classifier, which are combined to jointly consider existing correlations between imaging data, features, and target variables. We define two levels of interpretation: global and local. The former is devoted to understanding if the system learned the relevant relations in the data correctly, while the later is focused on predictions performed on a voxel- and patient-level. In addition, we propose a novel feature importance strategy that considers both imaging data and target variables, and we demonstrate the ability of the approach to leverage the interpretability of the obtained representation for the task at hand. We evaluated the proposed methodology in brain tumor segmentation and penumbra estimation in ischemic stroke lesions. We show the ability of the proposed methodology to unveil information regarding relationships between imaging modalities and extracted features and their usefulness for the task at hand. In both clinical scenarios, we demonstrate that the proposed methodology enhances the interpretability of automatically learned features, highlighting specific learning patterns that resemble how an expert extracts relevant data from medical images. Copyright © 2017 Elsevier B.V. All rights reserved.

Dorsal hippocampus is necessary for visual categorization in rats.

PubMed

Kim, Jangjin; Castro, Leyre; Wasserman, Edward A; Freeman, John H

2018-02-23

The hippocampus may play a role in categorization because of the need to differentiate stimulus categories (pattern separation) and to recognize category membership of stimuli from partial information (pattern completion). We hypothesized that the hippocampus would be more crucial for categorization of low-density (few relevant features) stimuli-due to the higher demand on pattern separation and pattern completion-than for categorization of high-density (many relevant features) stimuli. Using a touchscreen apparatus, rats were trained to categorize multiple abstract stimuli into two different categories. Each stimulus was a pentagonal configuration of five visual features; some of the visual features were relevant for defining the category whereas others were irrelevant. Two groups of rats were trained with either a high (dense, n = 8) or low (sparse, n = 8) number of category-relevant features. Upon reaching criterion discrimination (≥75% correct, on 2 consecutive days), bilateral cannulas were implanted in the dorsal hippocampus. The rats were then given either vehicle or muscimol infusions into the hippocampus just prior to various testing sessions. They were tested with: the previously trained stimuli (trained), novel stimuli involving new irrelevant features (novel), stimuli involving relocated features (relocation), and a single relevant feature (singleton). In training, the dense group reached criterion faster than the sparse group, indicating that the sparse task was more difficult than the dense task. In testing, accuracy of both groups was equally high for trained and novel stimuli. However, both groups showed impaired accuracy in the relocation and singleton conditions, with a greater deficit in the sparse group. The testing data indicate that rats encode both the relevant features and the spatial locations of the features. Hippocampal inactivation impaired visual categorization regardless of the density of the category-relevant features for the trained, novel, relocation, and singleton stimuli. Hippocampus-mediated pattern completion and pattern separation mechanisms may be necessary for visual categorization involving overlapping irrelevant features. © 2018 Wiley Periodicals, Inc.

Attentional Selection Can Be Predicted by Reinforcement Learning of Task-relevant Stimulus Features Weighted by Value-independent Stickiness.

PubMed

Balcarras, Matthew; Ardid, Salva; Kaping, Daniel; Everling, Stefan; Womelsdorf, Thilo

2016-02-01

Attention includes processes that evaluate stimuli relevance, select the most relevant stimulus against less relevant stimuli, and bias choice behavior toward the selected information. It is not clear how these processes interact. Here, we captured these processes in a reinforcement learning framework applied to a feature-based attention task that required macaques to learn and update the value of stimulus features while ignoring nonrelevant sensory features, locations, and action plans. We found that value-based reinforcement learning mechanisms could account for feature-based attentional selection and choice behavior but required a value-independent stickiness selection process to explain selection errors while at asymptotic behavior. By comparing different reinforcement learning schemes, we found that trial-by-trial selections were best predicted by a model that only represents expected values for the task-relevant feature dimension, with nonrelevant stimulus features and action plans having only a marginal influence on covert selections. These findings show that attentional control subprocesses can be described by (1) the reinforcement learning of feature values within a restricted feature space that excludes irrelevant feature dimensions, (2) a stochastic selection process on feature-specific value representations, and (3) value-independent stickiness toward previous feature selections akin to perseveration in the motor domain. We speculate that these three mechanisms are implemented by distinct but interacting brain circuits and that the proposed formal account of feature-based stimulus selection will be important to understand how attentional subprocesses are implemented in primate brain networks.

Multi-centre diagnostic classification of individual structural neuroimaging scans from patients with major depressive disorder.

PubMed

Mwangi, Benson; Ebmeier, Klaus P; Matthews, Keith; Steele, J Douglas

2012-05-01

Quantitative abnormalities of brain structure in patients with major depressive disorder have been reported at a group level for decades. However, these structural differences appear subtle in comparison with conventional radiologically defined abnormalities, with considerable inter-subject variability. Consequently, it has not been possible to readily identify scans from patients with major depressive disorder at an individual level. Recently, machine learning techniques such as relevance vector machines and support vector machines have been applied to predictive classification of individual scans with variable success. Here we describe a novel hybrid method, which combines machine learning with feature selection and characterization, with the latter aimed at maximizing the accuracy of machine learning prediction. The method was tested using a multi-centre dataset of T(1)-weighted 'structural' scans. A total of 62 patients with major depressive disorder and matched controls were recruited from referred secondary care clinical populations in Aberdeen and Edinburgh, UK. The generalization ability and predictive accuracy of the classifiers was tested using data left out of the training process. High prediction accuracy was achieved (~90%). While feature selection was important for maximizing high predictive accuracy with machine learning, feature characterization contributed only a modest improvement to relevance vector machine-based prediction (~5%). Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity. These results indicate that machine learning techniques have the potential to inform clinical practice and research, as they can make accurate predictions about brain scan data from individual subjects. Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure.

The Effects of Goal Relevance and Perceptual Features on Emotional Items and Associative Memory

PubMed Central

Mao, Wei B.; An, Shu; Yang, Xiao F.

2017-01-01

Showing an emotional item in a neutral background scene often leads to enhanced memory for the emotional item and impaired associative memory for background details. Meanwhile, both top–down goal relevance and bottom–up perceptual features played important roles in memory binding. We conducted two experiments and aimed to further examine the effects of goal relevance and perceptual features on emotional items and associative memory. By manipulating goal relevance (asking participants to categorize only each item image as living or non-living or to categorize each whole composite picture consisted of item image and background scene as natural scene or manufactured scene) and perceptual features (controlling visual contrast and visual familiarity) in two experiments, we found that both high goal relevance and salient perceptual features (high salience of items vs. high familiarity of items) could promote emotional item memory, but they had different effects on associative memory for emotional items and neutral backgrounds. Specifically, high goal relevance and high perceptual-salience of items could jointly impair the associative memory for emotional items and neutral backgrounds, while the effect of item familiarity on associative memory for emotional items would be modulated by goal relevance. High familiarity of items could increase associative memory for negative items and neutral backgrounds only in the low goal relevance condition. These findings suggest the effect of emotion on associative memory is not only related to attentional capture elicited by emotion, but also can be affected by goal relevance and perceptual features of stimulus. PMID:28790943

The Effects of Goal Relevance and Perceptual Features on Emotional Items and Associative Memory.

PubMed

Mao, Wei B; An, Shu; Yang, Xiao F

2017-01-01

Showing an emotional item in a neutral background scene often leads to enhanced memory for the emotional item and impaired associative memory for background details. Meanwhile, both top-down goal relevance and bottom-up perceptual features played important roles in memory binding. We conducted two experiments and aimed to further examine the effects of goal relevance and perceptual features on emotional items and associative memory. By manipulating goal relevance (asking participants to categorize only each item image as living or non-living or to categorize each whole composite picture consisted of item image and background scene as natural scene or manufactured scene) and perceptual features (controlling visual contrast and visual familiarity) in two experiments, we found that both high goal relevance and salient perceptual features (high salience of items vs. high familiarity of items) could promote emotional item memory, but they had different effects on associative memory for emotional items and neutral backgrounds. Specifically, high goal relevance and high perceptual-salience of items could jointly impair the associative memory for emotional items and neutral backgrounds, while the effect of item familiarity on associative memory for emotional items would be modulated by goal relevance. High familiarity of items could increase associative memory for negative items and neutral backgrounds only in the low goal relevance condition. These findings suggest the effect of emotion on associative memory is not only related to attentional capture elicited by emotion, but also can be affected by goal relevance and perceptual features of stimulus.

Stabilizing l1-norm prediction models by supervised feature grouping.

PubMed

Kamkar, Iman; Gupta, Sunil Kumar; Phung, Dinh; Venkatesh, Svetha

2016-02-01

Emerging Electronic Medical Records (EMRs) have reformed the modern healthcare. These records have great potential to be used for building clinical prediction models. However, a problem in using them is their high dimensionality. Since a lot of information may not be relevant for prediction, the underlying complexity of the prediction models may not be high. A popular way to deal with this problem is to employ feature selection. Lasso and l1-norm based feature selection methods have shown promising results. But, in presence of correlated features, these methods select features that change considerably with small changes in data. This prevents clinicians to obtain a stable feature set, which is crucial for clinical decision making. Grouping correlated variables together can improve the stability of feature selection, however, such grouping is usually not known and needs to be estimated for optimal performance. Addressing this problem, we propose a new model that can simultaneously learn the grouping of correlated features and perform stable feature selection. We formulate the model as a constrained optimization problem and provide an efficient solution with guaranteed convergence. Our experiments with both synthetic and real-world datasets show that the proposed model is significantly more stable than Lasso and many existing state-of-the-art shrinkage and classification methods. We further show that in terms of prediction performance, the proposed method consistently outperforms Lasso and other baselines. Our model can be used for selecting stable risk factors for a variety of healthcare problems, so it can assist clinicians toward accurate decision making. Copyright © 2015 Elsevier Inc. All rights reserved.

One Year of Glaucoma Research in Review: 2013 to 2014

PubMed Central

Van Tassel, Sarah H.; Radcliffe, Nathan M.; Demetriades, Anna M.

2015-01-01

Purpose The purpose of this study was to provide the practicing clinical ophthalmologist with an update of relevant glaucoma literature published from 2013 to 2014. Design Literature review. Methods The authors conducted a 1-year (October 1, 2013, to September 30, 2014) English-language glaucoma literature search on PubMed of articles containing “glaucoma” or “glaucomatous” with title/abstract as a filter. Medical Subject Headings (MeSH) filtered searching was not performed because of the newness of the reviewed material. Results Literature review yielded 2,314 articles, after which we excluded reviews and letters to the editor. We highlighted articles featuring new or updated approaches to the pathophysiology, diagnosis, or treatment of glaucoma and gave preference to human research. Conclusions This review features literature that is of interest to ophthalmologists in practice and also highlights studies that may provide insight to future developments applicable to clinical ophthalmology. PMID:26197218

Integrating query of relational and textual data in clinical databases: a case study.

PubMed

Fisk, John M; Mutalik, Pradeep; Levin, Forrest W; Erdos, Joseph; Taylor, Caroline; Nadkarni, Prakash

2003-01-01

The authors designed and implemented a clinical data mart composed of an integrated information retrieval (IR) and relational database management system (RDBMS). Using commodity software, which supports interactive, attribute-centric text and relational searches, the mart houses 2.8 million documents that span a five-year period and supports basic IR features such as Boolean searches, stemming, and proximity and fuzzy searching. Results are relevance-ranked using either "total documents per patient" or "report type weighting." Non-curated medical text has a significant degree of malformation with respect to spelling and punctuation, which creates difficulties for text indexing and searching. Presently, the IR facilities of RDBMS packages lack the features necessary to handle such malformed text adequately. A robust IR+RDBMS system can be developed, but it requires integrating RDBMSs with third-party IR software. RDBMS vendors need to make their IR offerings more accessible to non-programmers.

Primary sternum diffuse large B-cell lymphoma: A case report and review of the literature

PubMed Central

TONG, MENG-YING; ZHANG, XIAN; YU, ZHE; SUN, XIU-HUA; LI, SHUANG; ZHANG, YANG

2015-01-01

Primary bone lymphoma (PBL) is a rare disease, accounting for >1% of all cases of malignant lymphoma. Diffuse large B-cell lymphoma (DLBCL) is the most common histological type of PBL. The present study reported the case of a 68-year-old male with primary bone DLBCL, originally occurred in the sternum, which is a rare form of presentation. Computed tomography (CT), magnetic resonance imaging and bone emission CT were performed, followed by immunohistochemical analysis of a biopsy specimen, and the results were used to establish the diagnosis. At the time of diagnosis, no osseous involvement was observed. The clinical, radiological and histological features of PBL can mimic other medical conditions, thereby making the diagnosis difficult, and frequently leading to delays in treatment. The present study investigated the clinical features, management and prognosis of PBL, and reviewed previous relevant cases. PMID:26137117

Morphological evaluation of clefts of the lip, palate, or both in dogs.

PubMed

Peralta, Santiago; Fiani, Nadine; Kan-Rohrer, Kimi H; Verstraete, Frank J M

2017-08-01

OBJECTIVE To systematically characterize the morphology of cleft lip, cleft palate, and cleft lip and palate in dogs. ANIMALS 32 client-owned dogs with clefts of the lip (n = 5), palate (23), or both (4) that had undergone a CT or cone-beam CT scan of the head prior to any surgical procedures involving the oral cavity or face. PROCEDURES Dog signalment and skull type were recorded. The anatomic form of each defect was characterized by use of a widely used human oral-cleft classification system on the basis of CT findings and clinical images. Other defect morphological features, including shape, relative size, facial symmetry, and vomer involvement, were also recorded. RESULTS 9 anatomic forms of cleft were identified. Two anatomic forms were identified in the 23 dogs with cleft palate, in which differences in defect shape and size as well as vomer abnormalities were also evident. Seven anatomic forms were observed in 9 dogs with cleft lip or cleft lip and palate, and most of these dogs had incisive bone abnormalities and facial asymmetry. CONCLUSIONS AND CLINICAL RELEVANCE The morphological features of congenitally acquired cleft lip, cleft palate, and cleft lip and palate were complex and varied among dogs. The features identified here may be useful for surgical planning, developing of clinical coding schemes, or informing genetic, embryological, or clinical research into birth defects in dogs and other species.

Irrelevant reward and selection histories have different influences on task-relevant attentional selection.

PubMed

MacLean, Mary H; Giesbrecht, Barry

2015-07-01

Task-relevant and physically salient features influence visual selective attention. In the present study, we investigated the influence of task-irrelevant and physically nonsalient reward-associated features on visual selective attention. Two hypotheses were tested: One predicts that the effects of target-defining task-relevant and task-irrelevant features interact to modulate visual selection; the other predicts that visual selection is determined by the independent combination of relevant and irrelevant feature effects. These alternatives were tested using a visual search task that contained multiple targets, placing a high demand on the need for selectivity, and that was data-limited and required unspeeded responses, emphasizing early perceptual selection processes. One week prior to the visual search task, participants completed a training task in which they learned to associate particular colors with a specific reward value. In the search task, the reward-associated colors were presented surrounding targets and distractors, but were neither physically salient nor task-relevant. In two experiments, the irrelevant reward-associated features influenced performance, but only when they were presented in a task-relevant location. The costs induced by the irrelevant reward-associated features were greater when they oriented attention to a target than to a distractor. In a third experiment, we examined the effects of selection history in the absence of reward history and found that the interaction between task relevance and selection history differed, relative to when the features had previously been associated with reward. The results indicate that under conditions that demand highly efficient perceptual selection, physically nonsalient task-irrelevant and task-relevant factors interact to influence visual selective attention.

Health System Features That Enhance Access to Comprehensive Primary Care for Women Living with HIV in High-Income Settings: A Systematic Mixed Studies Review.

PubMed

O'Brien, Nadia; Hong, Quan Nha; Law, Susan; Massoud, Sarah; Carter, Allison; Kaida, Angela; Loutfy, Mona; Cox, Joseph; Andersson, Neil; de Pokomandy, Alexandra

2018-04-01

Women living with HIV in high-income settings continue to experience modifiable barriers to care. We sought to determine the features of care that facilitate access to comprehensive primary care, inclusive of HIV, comorbidity, and sexual and reproductive healthcare. Using a systematic mixed studies review design, we reviewed qualitative, mixed methods, and quantitative studies identified in Ovid MEDLINE, EMBASE, and CINAHL databases (January 2000 to August 2017). Eligibility criteria included women living with HIV; high-income countries; primary care; and healthcare accessibility. We performed a thematic synthesis using NVivo. After screening 3466 records, we retained 44 articles and identified 13 themes. Drawing on a social-ecological framework on engagement in HIV care, we situated the themes across three levels of the healthcare system: care providers, clinical care environments, and social and institutional factors. At the care provider level, features enhancing access to comprehensive primary care included positive patient-provider relationships and availability of peer support, case managers, and/or nurse navigators. Within clinical care environments, facilitators to care were appointment reminder systems, nonidentifying clinic signs, women and family spaces, transportation services, and coordination of care to meet women's HIV, comorbidity, and sexual and reproductive healthcare needs. Finally, social and institutional factors included healthcare insurance, patient and physician education, and dispelling HIV-related stigma. This review highlights several features of care that are particularly relevant to the care-seeking experience of women living with HIV. Improving their health through comprehensive care requires a variety of strategies at the provider, clinic, and greater social and institutional levels.

Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family

PubMed Central

de Aquino, Sibele-Nascimento; Paranaíba, Lívia-Maris-R.; Gomes, Andreia; dos-Santos-Neto, Pedro; Coletta, Ricardo-D.; Cardoso, Aline-Francoise; Frota, Ana-Cláudia; Martelli-Júnior, Hercílio

2016-01-01

Background The aim of this study was to describe the pattern of inheritance and the clinical features in a large family with Waardenburg syndrome type I (WS1), detailing the dental abnormalities and screening for PAX3 mutations. Material and Methods To characterize the pattern of inheritance and clinical features, 29 family members were evaluated by dermatologic, ophthalmologic, otorhinolaryngologic and orofacial examination. Molecular analysis of the PAX3 gene was performed. Results The pedigree of the family,including the last four generations, was constructed and revealed non-consanguineous marriages. Out of 29 descendants, 16 family members showed features of WS1, with 9 members showing two major criteria indicative of WS1. Five patients showed white forelock and iris hypopigmentation, and four showed dystopia canthorum and iris hypopigmentation. Two patients had hearing loss. Dental abnormalities were identified in three family members, including dental agenesis, conical teeth and taurodontism. Sequencing analysis failed to identify mutations in the PAX3 gene. Conclusions These results confirm that WS1 was transmitted in this family in an autosomal dominant pattern with variable expressivity and high penetrance. The presence of dental manifestations, especially tooth agenesis and conical teeth which resulted in considerable aesthetic impact on affected individuals was a major clinical feature. Clinical relevance: This article reveals the presence of well-defined dental changes associated with WS1 and tries to establish a possible association between these two entities showing a new spectrum of WS1. Key words:Waardenburg syndrome, hearing loss, oral manifestations, mutation. PMID:27031059

Intentional attention switching in dichotic listening: exploring the efficiency of nonspatial and spatial selection.

PubMed

Lawo, Vera; Fels, Janina; Oberem, Josefa; Koch, Iring

2014-10-01

Using an auditory variant of task switching, we examined the ability to intentionally switch attention in a dichotic-listening task. In our study, participants responded selectively to one of two simultaneously presented auditory number words (spoken by a female and a male, one for each ear) by categorizing its numerical magnitude. The mapping of gender (female vs. male) and ear (left vs. right) was unpredictable. The to-be-attended feature for gender or ear, respectively, was indicated by a visual selection cue prior to auditory stimulus onset. In Experiment 1, explicitly cued switches of the relevant feature dimension (e.g., from gender to ear) and switches of the relevant feature within a dimension (e.g., from male to female) occurred in an unpredictable manner. We found large performance costs when the relevant feature switched, but switches of the relevant feature dimension incurred only small additional costs. The feature-switch costs were larger in ear-relevant than in gender-relevant trials. In Experiment 2, we replicated these findings using a simplified design (i.e., only within-dimension switches with blocked dimensions). In Experiment 3, we examined preparation effects by manipulating the cueing interval and found a preparation benefit only when ear was cued. Together, our data suggest that the large part of attentional switch costs arises from reconfiguration at the level of relevant auditory features (e.g., left vs. right) rather than feature dimensions (ear vs. gender). Additionally, our findings suggest that ear-based target selection benefits more from preparation time (i.e., time to direct attention to one ear) than gender-based target selection.

Precision Oncology Medicine: The Clinical Relevance of Patient-Specific Biomarkers Used to Optimize Cancer Treatment.

PubMed

Schmidt, Keith T; Chau, Cindy H; Price, Douglas K; Figg, William D

2016-12-01

Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor biomarkers (eg, HER2, EGFR), directing treatment for patients whose tumors exhibit a mutation susceptible to an FDA-approved targeted therapy (eg, trastuzumab, erlotinib). Clinically relevant germline mutations in drug-metabolizing enzymes and transporters (eg, TPMT, DPYD) have been shown to impact drug response, providing a rationale for individualized dosing to optimize treatment. The use of multigene expression-based assays to analyze an array of prognostic biomarkers has been shown to help direct treatment decisions, especially in breast cancer (eg, Oncotype DX). More recently, the use of next-generation sequencing to detect many potential "actionable" cancer molecular alterations is further shifting the 1 gene-1 drug paradigm toward a more comprehensive, multigene approach. Currently, many clinical trials (eg, NCI-MATCH, NCI-MPACT) are assessing novel diagnostic tools with a combination of different targeted therapeutics while also examining tumor biomarkers that were previously unexplored in a variety of cancer histologies. Results from ongoing trials such as the NCI-MATCH will help determine the clinical utility and future development of the precision-medicine approach. © 2016, The American College of Clinical Pharmacology.

Quantitative assessment of cancer cell morphology and motility using telecentric digital holographic microscopy and machine learning.

PubMed

Lam, Van K; Nguyen, Thanh C; Chung, Byung M; Nehmetallah, George; Raub, Christopher B

2018-03-01

The noninvasive, fast acquisition of quantitative phase maps using digital holographic microscopy (DHM) allows tracking of rapid cellular motility on transparent substrates. On two-dimensional surfaces in vitro, MDA-MB-231 cancer cells assume several morphologies related to the mode of migration and substrate stiffness, relevant to mechanisms of cancer invasiveness in vivo. The quantitative phase information from DHM may accurately classify adhesive cancer cell subpopulations with clinical relevance. To test this, cells from the invasive breast cancer MDA-MB-231 cell line were cultured on glass, tissue-culture treated polystyrene, and collagen hydrogels, and imaged with DHM followed by epifluorescence microscopy after staining F-actin and nuclei. Trends in cell phase parameters were tracked on the different substrates, during cell division, and during matrix adhesion, relating them to F-actin features. Support vector machine learning algorithms were trained and tested using parameters from holographic phase reconstructions and cell geometric features from conventional phase images, and used to distinguish between elongated and rounded cell morphologies. DHM was able to distinguish between elongated and rounded morphologies of MDA-MB-231 cells with 94% accuracy, compared to 83% accuracy using cell geometric features from conventional brightfield microscopy. This finding indicates the potential of DHM to detect and monitor cancer cell morphologies relevant to cell cycle phase status, substrate adhesion, and motility. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Similarity estimation for reference image retrieval in mammograms using convolutional neural network

NASA Astrophysics Data System (ADS)

Muramatsu, Chisako; Higuchi, Shunichi; Morita, Takako; Oiwa, Mikinao; Fujita, Hiroshi

2018-02-01

Periodic breast cancer screening with mammography is considered effective in decreasing breast cancer mortality. For screening programs to be successful, an intelligent image analytic system may support radiologists' efficient image interpretation. In our previous studies, we have investigated image retrieval schemes for diagnostic references of breast lesions on mammograms and ultrasound images. Using a machine learning method, reliable similarity measures that agree with radiologists' similarity were determined and relevant images could be retrieved. However, our previous method includes a feature extraction step, in which hand crafted features were determined based on manual outlines of the masses. Obtaining the manual outlines of masses is not practical in clinical practice and such data would be operator-dependent. In this study, we investigated a similarity estimation scheme using a convolutional neural network (CNN) to skip such procedure and to determine data-driven similarity scores. By using CNN as feature extractor, in which extracted features were employed in determination of similarity measures with a conventional 3-layered neural network, the determined similarity measures were correlated well with the subjective ratings and the precision of retrieving diagnostically relevant images was comparable with that of the conventional method using handcrafted features. By using CNN for determination of similarity measure directly, the result was also comparable. By optimizing the network parameters, results may be further improved. The proposed method has a potential usefulness in determination of similarity measure without precise lesion outlines for retrieval of similar mass images on mammograms.

Religion, Spirituality, and HIV Clinical Outcomes: A Systematic Review of the Literature.

PubMed

Doolittle, B R; Justice, A C; Fiellin, D A

2018-06-01

This systematic review evaluates the association between religion, spirituality and clinical outcomes in HIV-infected individuals. A systematic literature review was conducted for all English language articles published between 1980 and 2016 in relevant databases. Six hundred fourteen studies were evaluated. 15 met inclusion criteria. Ten (67%) studies reported a positive association between religion or spirituality and a clinical HIV outcome. Two (13%) studies failed to detect such an association; and two (13%) demonstrated a negative association. One study (7%) identified features of religiosity and spirituality that had both negative and positive associations with HIV clinical outcomes. Recognizing the religious or spiritual commitments of patients may serve as an important component of patient care. Further longitudinal studies and interventions might be required to further clarify the potential impact of religion and spirituality on HIV clinical outcomes.

Deep-Learning Convolutional Neural Networks Accurately Classify Genetic Mutations in Gliomas.

PubMed

Chang, P; Grinband, J; Weinberg, B D; Bardis, M; Khy, M; Cadena, G; Su, M-Y; Cha, S; Filippi, C G; Bota, D; Baldi, P; Poisson, L M; Jain, R; Chow, D

2018-05-10

The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation. MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify isocitrate dehydrogenase 1 ( IDH1 ) mutation status, 1p/19q codeletion, and O6-methylguanine-DNA methyltransferase ( MGMT ) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification. Classification had high accuracy: IDH1 mutation status, 94%; 1p/19q codeletion, 92%; and MGMT promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features. Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training. © 2018 by American Journal of Neuroradiology.

Imaging findings in Idiopathic lobular granulomattous mastitis, case report and review of literature.

PubMed

Boarki, K; Labib, M

2010-01-01

Idiopathic lobular granulomatous mastititis is a rare inflammatory disease of the breast. Since the clinical manifestations simulate those of mammary malignancy, it is often misdiagnosed. We report a case in a 25 yrs old Egyptian woman who had presented with complaint of a painful mass in her right breast of 3 months duration. Clinical and radiological examinations were indeterminate of its nature and the diagnosis was established by histopathogical, microbiological and serological tests. Review of relevant literature mention the features of Idiopathic lobular granulomatous mastititis, which impose significant challenge on clinical, radiological and even histopathological diagnosis. These correlate well with our case scenario also. Complete resection of the lesions and/or administration of steroids are usually the recommended treatment, however about 38% patients may experience recurrence. Hence proper post treatment follow up is mandatory. Awareness among the clinicians, radiologists and pathologists about this disease entity is required and multi disciplinary approach is imperative to establish the diagnosis. We hope to convey these facts through this article with the review of relevant literature.

Characteristics of the sequence effect in Parkinson's disease.

PubMed

Kang, Suk Yun; Wasaka, Toshiaki; Shamim, Ejaz A; Auh, Sungyoung; Ueki, Yoshino; Lopez, Grisel J; Kida, Tetsuo; Jin, Seung-Hyun; Dang, Nguyet; Hallett, Mark

2010-10-15

The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer-based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo-controlled, four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.

Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities.

PubMed

Schulz, Alexander; Grafe, Peter; Hagel, Christian; Bäumer, Philipp; Morrison, Helen; Mautner, Victor-Felix; Farschtschi, Said

2018-01-01

The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum. However, the clinical relevance and respective underlying pathogenesis, varies greatly among the different NF types. In this review, we summarize and interpret the latest basic research findings, as well as clinical observations, in respect of Neurofibromatosis-associated neuropathies. Copyright © 2017 Elsevier Inc. All rights reserved.

Validation of the diagnosis of autism in general practitioner records

PubMed Central

Fombonne, Eric; Heavey, Lisa; Smeeth, Liam; Rodrigues, Laura C; Cook, Claire; Smith, Peter G; Meng, Linyan; Hall, Andrew J

2004-01-01

Background We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. Methods Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. Results For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa = .73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from .56 to 1.0). Conclusions This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high. PMID:15113435

A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial

PubMed Central

Willeboordse, Maartje; van de Kant, Kim D. G.; Tan, Frans E. S.; Mulkens, Sandra; Schellings, Julia; Crijns, Yvonne; van der Ploeg, Liesbeth; van Schayck, Constant P.; Dompeling, Edward

2016-01-01

Background There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. Methods An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. Results After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Conclusions & clinical relevance Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. Trial Registration ClinicalTrials.gov NCT00998413 PMID:27294869

Noonan syndrome

PubMed Central

Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

2014-01-01

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

Clinical analysis of genome next-generation sequencing data using the Omicia platform

PubMed Central

Coonrod, Emily M; Margraf, Rebecca L; Russell, Archie; Voelkerding, Karl V; Reese, Martin G

2013-01-01

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance. PMID:23895124

The relevance of "non-criteria" clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Antibodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features.

PubMed

Abreu, Mirhelen M; Danowski, Adriana; Wahl, Denis G; Amigo, Mary-Carmen; Tektonidou, Maria; Pacheco, Marcelo S; Fleming, Norma; Domingues, Vinicius; Sciascia, Savino; Lyra, Julia O; Petri, Michelle; Khamashta, Munther; Levy, Roger A

2015-05-01

The purpose of this task force was to critically analyze nine non-criteria manifestations of APS to support their inclusion as APS classification criteria. The Task Force Members selected the non-criteria clinical manifestations according to their clinical relevance, that is, the patient-important outcome from clinician perspective. They included superficial vein thrombosis, thrombocytopenia, renal microangiopathy, heart valve disease, livedo reticularis, migraine, chorea, seizures and myelitis, which were reviewed by this International Task Force collaboration, in addition to the seronegative APS (SN-APS). GRADE system was used to evaluate the quality of evidence of medical literature of each selected item. This critical appraisal exercise aimed to support the debate regarding the clinical picture of APS. We found that the overall GRADE analysis was very low for migraine and seizures, low for superficial venous thrombosis, thrombocytopenia, chorea, longitudinal myelitis and the so-called seronegative APS and moderate for APS nephropathy, heart valve lesions and livedo reticularis. The next step can be a critical redefinition of an APS gold standard, for instance derived from the APS ACTION registry that will include not only current APS patients but also those with antiphospholipid antibodies not meeting current classification criteria. Copyright © 2015 Elsevier B.V. All rights reserved.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Distinguishing prostate cancer from benign confounders via a cascaded classifier on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Litjens, G. J. S.; Elliott, R.; Shih, N.; Feldman, M.; Barentsz, J. O.; Hulsbergen-van de Kaa, C. A.; Kovacs, I.; Huisman, H. J.; Madabhushi, A.

2014-03-01

Learning how to separate benign confounders from prostate cancer is important because the imaging characteristics of these confounders are poorly understood. Furthermore, the typical representations of the MRI parameters might not be enough to allow discrimination. The diagnostic uncertainty this causes leads to a lower diagnostic accuracy. In this paper a new cascaded classifier is introduced to separate prostate cancer and benign confounders on MRI in conjunction with specific computer-extracted features to distinguish each of the benign classes (benign prostatic hyperplasia (BPH), inflammation, atrophy or prostatic intra-epithelial neoplasia (PIN). In this study we tried to (1) calculate different mathematical representations of the MRI parameters which more clearly express subtle differences between different classes, (2) learn which of the MRI image features will allow to distinguish specific benign confounders from prostate cancer, and (2) find the combination of computer-extracted MRI features to best discriminate cancer from the confounding classes using a cascaded classifier. One of the most important requirements for identifying MRI signatures for adenocarcinoma, BPH, atrophy, inflammation, and PIN is accurate mapping of the location and spatial extent of the confounder and cancer categories from ex vivo histopathology to MRI. Towards this end we employed an annotated prostatectomy data set of 31 patients, all of whom underwent a multi-parametric 3 Tesla MRI prior to radical prostatectomy. The prostatectomy slides were carefully co-registered to the corresponding MRI slices using an elastic registration technique. We extracted texture features from the T2-weighted imaging, pharmacokinetic features from the dynamic contrast enhanced imaging and diffusion features from the diffusion-weighted imaging for each of the confounder classes and prostate cancer. These features were selected because they form the mainstay of clinical diagnosis. Relevant features for each of the classes were selected using maximum relevance minimum redundancy feature selection, allowing us to perform classifier independent feature selection. The selected features were then incorporated in a cascading classifier, which can focus on easier sub-tasks at each stage, leaving the more difficult classification tasks for later stages. Results show that distinct features are relevant for each of the benign classes, for example the fraction of extra-vascular, extra-cellular space in a voxel is a clear discriminator for inflammation. Furthermore, the cascaded classifier outperforms both multi-class and one-shot classifiers in overall accuracy for discriminating confounders from cancer: 0.76 versus 0.71 and 0.62.

Kernel-Based Relevance Analysis with Enhanced Interpretability for Detection of Brain Activity Patterns

PubMed Central

Alvarez-Meza, Andres M.; Orozco-Gutierrez, Alvaro; Castellanos-Dominguez, German

2017-01-01

We introduce Enhanced Kernel-based Relevance Analysis (EKRA) that aims to support the automatic identification of brain activity patterns using electroencephalographic recordings. EKRA is a data-driven strategy that incorporates two kernel functions to take advantage of the available joint information, associating neural responses to a given stimulus condition. Regarding this, a Centered Kernel Alignment functional is adjusted to learning the linear projection that best discriminates the input feature set, optimizing the required free parameters automatically. Our approach is carried out in two scenarios: (i) feature selection by computing a relevance vector from extracted neural features to facilitating the physiological interpretation of a given brain activity task, and (ii) enhanced feature selection to perform an additional transformation of relevant features aiming to improve the overall identification accuracy. Accordingly, we provide an alternative feature relevance analysis strategy that allows improving the system performance while favoring the data interpretability. For the validation purpose, EKRA is tested in two well-known tasks of brain activity: motor imagery discrimination and epileptic seizure detection. The obtained results show that the EKRA approach estimates a relevant representation space extracted from the provided supervised information, emphasizing the salient input features. As a result, our proposal outperforms the state-of-the-art methods regarding brain activity discrimination accuracy with the benefit of enhanced physiological interpretation about the task at hand. PMID:29056897

Epileptic spasms are a feature of DEPDC5 mTORopathy

PubMed Central

Carvill, Gemma L.; Crompton, Douglas E.; Regan, Brigid M.; McMahon, Jacinta M.; Saykally, Julia; Zemel, Matthew; Schneider, Amy L.; Dibbens, Leanne; Howell, Katherine B.; Mandelstam, Simone; Leventer, Richard J.; Harvey, A. Simon; Mullen, Saul A.; Berkovic, Samuel F.; Sullivan, Joseph; Scheffer, Ingrid E.

2015-01-01

Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. Conclusions: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies. PMID:27066554

Imaging of autoimmune encephalitis--Relevance for clinical practice and hippocampal function.

PubMed

Heine, J; Prüss, H; Bartsch, T; Ploner, C J; Paul, F; Finke, C

2015-11-19

The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Typical clinical presentations include cognitive deficits, psychiatric symptoms, movement disorders and seizures and the majority of patients respond well to immunotherapy. Pathophysiological mechanisms and clinical features are increasingly recognized and indicate hippocampal dysfunction in most of these syndromes. Here, we review the neuroimaging characteristics of autoimmune encephalitides, including N-methyl-d-aspartate (NMDA) receptor, leucine-rich glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) encephalitis as well as more recently discovered and less frequent forms such as dipeptidyl-peptidase-like protein 6 (DPPX) or glycine receptor encephalitis. We summarize findings of routine magnetic resonance imaging (MRI) investigations as well as (18)F-fluoro-2-deoxy-d-glucose (FDG)-positron emission tomography (PET) and single photon emission tomography (SPECT) imaging and relate these observations to clinical features and disease outcome. We furthermore review results of advanced imaging analyses such as diffusion tensor imaging, volumetric analyses and resting-state functional MRI. Finally, we discuss contributions of these neuroimaging observations to the understanding of the pathophysiology of autoimmune encephalitides. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Peri-implant and periodontal tissues: a review of differences and similarities.

PubMed

Dhir, Sangeeta; Mahesh, Lanka; Kurtzman, Gregori M; Vandana, K L

2013-01-01

The health and vitality of an osseointegrated implant depends on the surrounding supporting tissues, which not only anchor the implant to the bone but also have the important function of providing a protective seal. The aim of this article is to provide a basic understanding of differences and similarities between the periodontal and peri-implant tissues at the histologic, clinical, and immunologic levels; it is essential to know these differences and similarities during the clinical handling of these similar-looking tissues. The comparative features are of clinical relevance because it is critical to understand the behavior of the soft tissue found around the tooth and implant. This knowledge is vital from the preliminary stage of treatment planning through prosthetic rehabilitation.

Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au; Tripcony, Lee; Keller, Jacqui

2012-01-01

Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis.more » Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.« less

ON BECOMING ABLE TO PLAY: INDIVIDUAL CHILD PSYCHOANALYTIC PSYCHODRAMA AND THE DEVELOPMENT OF SYMBOLIZATION.

PubMed

Quagelli, Luca; Solano, Paola

2017-10-01

In this paper, the authors analyze the relevance and transformative potential of individual psychoanalytic psychodrama in the treatment of children with severe impairments in symbolization. Central features of this modality, including promoting the representation of early traumatic experiences, are presented and discussed. Specific features include double-envelope containment of the co-therapists' group and play leader, consequent diffraction of the transference-determining portrayal, gradual integration, and initial figuration of coexisting split-off fragments. Drawing on in-depth clinical material, the authors show how psychodrama tempers the potentially traumatic effects of the encounter with the object, allowing these patients to access the transitional area of play. © 2017 The Psychoanalytic Quarterly, Inc.

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS® v2.0) identify histologic and molecular correlates of the key clinical features of disease

PubMed Central

Martin, Lisa J.; Franciosi, James P.; Collins, Margaret H.; Abonia, J. Pablo; Lee, James J.; Hommel, Kevin A.; Varni, James W.; Grotjan, J. Tommie; Eby, Michael; He, Hua; Marsolo, Keith; Putnam, Philip E.; Garza, Jose M.; Kaul, Ajay; Wen, Ting; Rothenberg, Marc E.

2015-01-01

Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS® v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastrointestinal reflux disease (GERD), nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine if clinical features of EoE, measured through the PEESS® v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated, pediatric patients with EoE (aged 2–18 years) and examined parent proxy–reported symptoms using the PEESS® v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biologic features were analyzed using Wilcoxon Rank Sum and Spearman correlation. Results The PEESS® v2.0 domains correlated to specific parent-reported symptoms: dysphagia (p = 0.0012), GERD (p = 0.0001), and nausea/vomiting (p < 0.0001). Pain correlated with multiple symptoms (p < 0.0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (p ≤ 0.0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = .37; p = 0.02). Eosinophil levels were more associated with pain (r = 0.27; p=0.06) than for dysphagia (r = 0.24; p = 0.13). The dysphagia domain correlated the most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have 1) established a validated, parent proxy–report measure for pediatric EoE — the PEESS® v2.0; 2) verified that parent-proxy effectively captures symptoms; 3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; 4) established that symptoms correlate EPX staining; and 5) observed association between mast cells and dysphagia. PMID:26051952

Ectodermal Dysplasia: A Clinical Overview for the Dental Practitioner.

PubMed

Halai, Tina; Stevens, Claire

2015-10-01

The term ectodermal dysplasia (ED) is used to describe a group of rare congenital disorders characterized by abnormalities of two or more ectodermal structures such as the skin, hair, nails, teeth and sweat glands. This paper will give an overview of the aetiology of ED and describe the manifestations and dental management of this condition. In particular, the important role of the dental practitioner in the identification and management of patients with ED will be highlighted. CPD/Clinical Relevance: Dental practitioners should be aware of the oral features of ectodermal dysplasia and be able to make timely referrals and provide appropriate continuing care for these patients.

Novel fiber optic immunosensor instrument

NASA Astrophysics Data System (ADS)

Wang, Zhiyu; Huang, Wenling; Tang, Lei; Zhou, Bo; Li, Yugi; He, Jun

1996-09-01

It has developed and performed a novel fiberoptic immunosensor instrument with operating wavelength 400 - 760 nm and repeatability cv equals 0.27%. The instrument has many excellent features such as simplified operation, faster testing time, higher sensitivity and economic cost. It has completely eliminated recovery period which traditional immunosensor owned due to use separative sensor structure. It can widely apply to test for bacteria, virus, hormone, parasite and cancer protein in clinical examination. The instrument has operated in laboratory and relevant medicine units and successfully tested monoclonal rat-anti-human of 413 cases in clinic and prepared with existing ELISA method, the coincidence probability reached 94 to 100%.

A PREP Panel, Practice-Based, Evaluation of the Handling of the Kerr Demi-Ultra Light Curing Unit.

PubMed

Burke, F J Trevor; Crisp, Russell J

2015-09-01

This paper describes the handling evaluation (by a group of practice-based researchers, the PREP Panel) of a recently introduced Light Curing Unit (LCU), the Kerr Demi-Ultra, which possesses a number of novel features such as its ultracapacitor power source, and the Light Emitting Diodes (LEDs) which provide the light output being placed close to the tip of the light guide. CPD/CLINICAL RELEVANCE: Testing of new devices and materials with respect to their handling is of importance, given that an easy to handle device should produce better clinical results than one which is difficult to use.

Countertransference in Child and Adolescent Psychiatry-A Forgotten Concept?

PubMed Central

Rasic, Daniel

2010-01-01

Objectives: The purpose of this paper is to review the evolution of the concept of countertransference, its clinical utility and unique features in the child and adolescent psychiatry setting. Methods: This article employs a selective literature review of papers relevant to countertransference in general and in child and adolescent psychiatry. Results: Reviewed papers indicate that countertransference is a ubiquitous phenomenon in child and adolescent psychiatric practice and that it can have important clinical implications. Conclusions: Recognition and management of countertransference is a crucial skill in child and adolescent psychiatry. Recommendations are made regarding its incorporation in residency training and psychiatric practice. PMID:21037914

Validity of the MCMI Drug Abuse Scale varies as a function of drug choice, race, and axis II subtypes.

PubMed

Calsyn, D A; Saxon, A J; Daisy, F

1991-06-01

The validity of the Drug Abuse Scale (T) from the Million Clinical Multiaxial Inventory (MCMI) was studied by administering the MCMI to 110 male veterans seeking treatment for opioid or cocaine dependence. Only 26 and 23% of the sample obtained base rate (BR) scores above the clinical relevant cutoffs of 84 and 74, respectively. Covariables associated with elevated scores on the T Scale were Black race, presence of narcissistic/antisocial personality features, and more severe psychopathology in general. The authors urge caution in using the Drug Abuse Scale for the purpose of identifying drug abusers.

The LAILAPS search engine: a feature model for relevance ranking in life science databases.

PubMed

Lange, Matthias; Spies, Karl; Colmsee, Christian; Flemming, Steffen; Klapperstück, Matthias; Scholz, Uwe

2010-03-25

Efficient and effective information retrieval in life sciences is one of the most pressing challenge in bioinformatics. The incredible growth of life science databases to a vast network of interconnected information systems is to the same extent a big challenge and a great chance for life science research. The knowledge found in the Web, in particular in life-science databases, are a valuable major resource. In order to bring it to the scientist desktop, it is essential to have well performing search engines. Thereby, not the response time nor the number of results is important. The most crucial factor for millions of query results is the relevance ranking. In this paper, we present a feature model for relevance ranking in life science databases and its implementation in the LAILAPS search engine. Motivated by the observation of user behavior during their inspection of search engine result, we condensed a set of 9 relevance discriminating features. These features are intuitively used by scientists, who briefly screen database entries for potential relevance. The features are both sufficient to estimate the potential relevance, and efficiently quantifiable. The derivation of a relevance prediction function that computes the relevance from this features constitutes a regression problem. To solve this problem, we used artificial neural networks that have been trained with a reference set of relevant database entries for 19 protein queries. Supporting a flexible text index and a simple data import format, this concepts are implemented in the LAILAPS search engine. It can easily be used both as search engine for comprehensive integrated life science databases and for small in-house project databases. LAILAPS is publicly available for SWISSPROT data at http://lailaps.ipk-gatersleben.de.

The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. The Catalán Group for the Study of RS3PE.

PubMed

Olivé, A; del Blanco, J; Pons, M; Vaquero, M; Tena, X

1997-02-01

To describe the clinical and laboratory features and outcome of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE). A retrospective multicenter study of patients with RS3PE fulfilling the following criteria: (1) bilateral pitting edema of both hands, (2) sudden onset of polyarthritis, (3) age > 50 years, (4) seronegative for rheumatoid factor (RF). 27 patients with RS3PE were included, mean age 71.7 years (58-92), 18 men (66.6%) and 9 women (33.3%). Relevant history was noted in 2 patients with polymyalgia rheumatica. Main clinical features were polyarthritis and edema of both hands. Polyarthritis involved metacarpophalangeal joints in 22 patients (81.5%), proximal interphalangeal joints in 19 (70.4%), wrists in 15 (55.5%), shoulders in 13 (48%), elbows in 3 (11.1%), knees in 9 (33.3%), and ankles in 7 (25.9%). All patients were RF negative. Antinuclear antibodies were positive at low titer in 8 patients. Erosions were present in one patient. Two patients developed T lymphoma and one myelodysplastic syndrome. RS3PE is a heterogeneous syndrome the clinical history, presence of erosions, and evolution to hematological diseases in our patients suggest that RS3PE may not be a distinct clinical entity.

Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.

PubMed

Vergouwen, Mervyn D I; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J E; Wijdicks, Eelco F; Muizelaar, J Paul; Mendelow, A David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G; Macdonald, R Loch; Diringer, Michael N; Broderick, Joseph P; Dreier, Jens P; Roos, Yvo B W E M

2010-10-01

In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2) functional outcome. Secondary outcome measure should be clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration. Vasospasm on angiography or transcranial Doppler can also be used as an outcome measure to investigate proof of concept but should be interpreted in conjunction with DCI or functional outcome. The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.

Demands on attention and the role of response priming in visual discrimination of feature conjunctions.

PubMed

Fournier, Lisa R; Herbert, Rhonda J; Farris, Carrie

2004-10-01

This study examined how response mapping of features within single- and multiple-feature targets affects decision-based processing and attentional capacity demands. Observers judged the presence or absence of 1 or 2 target features within an object either presented alone or with distractors. Judging the presence of 2 features relative to the less discriminable of these features alone was faster (conjunction benefits) when the task-relevant features differed in discriminability and were consistently mapped to responses. Conjunction benefits were attributed to asynchronous decision priming across attended, task-relevant dimensions. A failure to find conjunction benefits for disjunctive conjunctions was attributed to increased memory demands and variable feature-response mapping for 2- versus single-feature targets. Further, attentional demands were similar between single- and 2-feature targets when response mapping, memory demands, and discriminability of the task-relevant features were equated between targets. Implications of the findings for recent attention models are discussed. (c) 2004 APA, all rights reserved

Disposable inkjet-printed electrochemical platform for detection of clinically relevant HER-2 breast cancer biomarker.

PubMed

Carvajal, Susanita; Fera, Samantha N; Jones, Abby L; Baldo, Thaisa A; Mosa, Islam M; Rusling, James F; Krause, Colleen E

2018-05-01

Rapidly fabricated, disposable sensor platforms hold tremendous promise for point-of-care detection. Here, we present an inexpensive (< $0.25) fully inkjet printed electrochemical sensor with integrated counter, reference, and working electrodes that is easily scalable for commercial fabrication. The electrochemical sensor platform featured an inkjet printed gold working 8-electrode array (WEA) and counter electrode (CE), along with an inkjet -printed silver electrode that was chlorinated with bleach to produce a Ag/AgCl quasi-reference electrode (RE). As proof of concept, the electrochemical sensor was successfully applied for detection of clinically relevant breast cancer biomarker Human Epidermal Growth Factor Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified surface on the WEA and placed into a microfluidic device. A full sandwich immunoassay was constructed following a simultaneous injection of target protein, biotinylated antibody, and polymerized horseradish peroxide labels into the microfluidic device housing the WEA. With an ultra fast assay time, of only 15mins a clinically relevant limit of detection of 12pgmL -1 was achieved. Excellent reproducibility and sensitivity were observed through recovery assays preformed in human serum with recoveries ranging from 76% to 103%. These easily fabricated and scalable electrochemical sensor platforms can be readily adapted for multiplex detection following this rapid assay protocol for cancer diagnostics. Copyright © 2018 Elsevier B.V. All rights reserved.

Which Features Make Illustrations in Multimedia Learning Interesting?

ERIC Educational Resources Information Center

Magner, Ulrike Irmgard Elisabeth; Glogger, Inga; Renkl, Alexander

2016-01-01

How can illustrations motivate learners in multimedia learning? Which features make illustrations interesting? Beside the theoretical relevance of addressing these questions, these issues are practically relevant when instructional designers are to decide which features of illustrations can trigger situational interest irrespective of individual…

A preclinical Talbot-Lau prototype for x-ray dark-field imaging of human-sized objects.

PubMed

Hauke, C; Bartl, P; Leghissa, M; Ritschl, L; Sutter, S M; Weber, T; Zeidler, J; Freudenberger, J; Mertelmeier, T; Radicke, M; Michel, T; Anton, G; Meinel, F G; Baehr, A; Auweter, S; Bondesson, D; Gaass, T; Dinkel, J; Reiser, M; Hellbach, K

2018-06-01

Talbot-Lau x-ray interferometry provides information about the scattering and refractive properties of an object - in addition to the object's attenuation features. Until recently, this method was ineligible for imaging human-sized objects as it is challenging to adapt Talbot-Lau interferometers (TLIs) to the relevant x-ray energy ranges. In this work, we present a preclinical Talbot-Lau prototype capable of imaging human-sized objects with proper image quality at clinically acceptable dose levels. The TLI is designed to match a setup of clinical relevance as closely as possible. The system provides a scan range of 120 × 30 cm 2 by using a scanning beam geometry. Its ultimate load is 100 kg. High aspect ratios and fine grid periods of the gratings ensure a reasonable setup length and clinically relevant image quality. The system is installed in a university hospital and is, therefore, exposed to the external influences of a clinical environment. To demonstrate the system's capabilities, a full-body scan of a euthanized pig was performed. In addition, freshly excised porcine lungs with an extrinsically provoked pneumothorax were mounted into a human thorax phantom and examined with the prototype. Both examination sequences resulted in clinically relevant image quality - even in the case of a skin entrance air kerma of only 0.3 mGy which is in the range of human thoracic imaging. The presented case of a pneumothorax and a reader study showed that the prototype's dark-field images provide added value for pulmonary diagnosis. We demonstrated that a dedicated design of a Talbot-Lau interferometer can be applied to medical imaging by constructing a preclinical Talbot-Lau prototype. We experienced that the system is feasible for imaging human-sized objects and the phase-stepping approach is suitable for clinical practice. Hence, we conclude that Talbot-Lau x-ray imaging has potential for clinical use and enhances the diagnostic power of medical x-ray imaging. © 2018 American Association of Physicists in Medicine.

Time to connect: bringing social context into addiction neuroscience

PubMed Central

Heilig, Markus; Epstein, David H.; Nader, Michael A.; Shaham, Yavin

2017-01-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant. PMID:27277868

Time to connect: bringing social context into addiction neuroscience.

PubMed

Heilig, Markus; Epstein, David H; Nader, Michael A; Shaham, Yavin

2016-09-01

Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.

Writing Case Reports: Contributing to Practice and Research.

PubMed

Bavdekar, Sandeep B; Save, Sushma

2015-04-01

Case reports describe a patient with unusual or unexpected features. They represent the oldest type of medical publication. They are about generating a new hypothesis and not about proving a hypothesis. Hence, despite being considered as the lowest level of evidence; they continue to be relevant for clinical practice, research and medical education. This article intends to provide guidance regarding writing a case report to those wishing to make a foray in scientific writing through reporting an interesting case.

Contingent attentional capture across multiple feature dimensions in a temporal search task.

PubMed

Ito, Motohiro; Kawahara, Jun I

2016-01-01

The present study examined whether attention can be flexibly controlled to monitor two different feature dimensions (shape and color) in a temporal search task. Specifically, we investigated the occurrence of contingent attentional capture (i.e., interference from task-relevant distractors) and resulting set reconfiguration (i.e., enhancement of single task-relevant set). If observers can restrict searches to a specific value for each relevant feature dimension independently, the capture and reconfiguration effect should only occur when the single relevant distractor in each dimension appears. Participants identified a target letter surrounded by a non-green square or a non-square green frame. The results revealed contingent attentional capture, as target identification accuracy was lower when the distractor contained a target-defining feature than when it contained a nontarget feature. Resulting set reconfiguration was also obtained in that accuracy was superior when the current target's feature (e.g., shape) corresponded to the defining feature of the present distractor (shape) than when the current target's feature did not match the distractor's feature (color). This enhancement was not due to perceptual priming. The present study demonstrated that the principles of contingent attentional capture and resulting set reconfiguration held even when multiple target feature dimensions were monitored. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying the relevant features of the National Digital Cadastral Database (NDCDB) for spatial analysis by using the Delphi Technique

NASA Astrophysics Data System (ADS)

Halim, N. Z. A.; Sulaiman, S. A.; Talib, K.; Ng, E. G.

2018-02-01

This paper explains the process carried out in identifying the relevant features of the National Digital Cadastral Database (NDCDB) for spatial analysis. The research was initially a part of a larger research exercise to identify the significance of NDCDB from the legal, technical, role and land-based analysis perspectives. The research methodology of applying the Delphi technique is substantially discussed in this paper. A heterogeneous panel of 14 experts was created to determine the importance of NDCDB from the technical relevance standpoint. Three statements describing the relevant features of NDCDB for spatial analysis were established after three rounds of consensus building. It highlighted the NDCDB’s characteristics such as its spatial accuracy, functions, and criteria as a facilitating tool for spatial analysis. By recognising the relevant features of NDCDB for spatial analysis in this study, practical application of NDCDB for various analysis and purpose can be widely implemented.

The anatomy of decision support during inpatient care provider order entry (CPOE): Empirical observations from a decade of CPOE experience at Vanderbilt

PubMed Central

Miller, Randolph A.; Waitman, Lemuel R.; Chen, Sutin; Rosenbloom, S. Trent

2006-01-01

The authors describe a pragmatic approach to the introduction of clinical decision support at the point of care, based on a decade of experience in developing and evolving Vanderbilt’s inpatient “WizOrder” care provider order entry (CPOE) system. The inpatient care setting provides a unique opportunity to interject CPOE-based decision support features that restructure clinical workflows, deliver focused relevant educational materials, and influence how care is delivered to patients. From their empirical observations, the authors have developed a generic model for decision support within inpatient CPOE systems. They believe that the model’s utility extends beyond Vanderbilt, because it is based on characteristics of end-user workflows and on decision support considerations that are common to a variety of inpatient settings and CPOE systems. The specific approach to implementing a given clinical decision support feature within a CPOE system should involve evaluation along three axes: what type of intervention to create (for which the authors describe 4 general categories); when to introduce the intervention into the user’s workflow (for which the authors present 7 categories), and how disruptive, during use of the system, the intervention might be to end-users’ workflows (for which the authors describe 6 categories). Framing decision support in this manner may help both developers and clinical end-users plan future alterations to their systems when needs for new decision support features arise. PMID:16290243

How to Improve Time to Diagnosis in Acute Heart Failure - Clinical Signs and Chest X-ray.

PubMed

Allen, Christopher J; Guha, Kaushik; Sharma, Rakesh

2015-10-01

Acute heart failure (AHF) is a leading cause of hospitalisation in developed nations with stubbornly poor outcomes in both the short and long term. Furthermore, alongside an ageing population the incidence continues to increase. Contemporary practice guidelines accordingly emphasise the importance of early recognition of heart failure in the acute setting to facilitate the timely instigation of key investigations, appropriate management and access to specialist care; all of which improve outcome. However, the diagnosis of AHF is often challenging, with no gold standard diagnostic test and presenting clinical features that may be non-specific, particularly in the elderly where they may be atypical, or masked by co-morbidity. This short review explores the main clinical signs and radiographic changes in patients with AHF relevant to clinical practice in accordance with the best available evidence.

STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.

PubMed

Subbiah, Vivek; McMahon, Caitlin; Patel, Shreyaskumar; Zinner, Ralph; Silva, Elvio G; Elvin, Julia A; Subbiah, Ishwaria M; Ohaji, Chimela; Ganeshan, Dhakshina Moorthy; Anand, Deepa; Levenback, Charles F; Berry, Jenny; Brennan, Tim; Chmielecki, Juliann; Chalmers, Zachary R; Mayfield, John; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Ali, Siraj M

2015-06-11

Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

Dynamic Integration of Task-Relevant Visual Features in Posterior Parietal Cortex

PubMed Central

Freedman, David J.

2014-01-01

Summary The primate visual system consists of multiple hierarchically organized cortical areas, each specialized for processing distinct aspects of the visual scene. For example, color and form are encoded in ventral pathway areas such as V4 and inferior temporal cortex, while motion is preferentially processed in dorsal pathway areas such as the middle temporal area. Such representations often need to be integrated perceptually to solve tasks which depend on multiple features. We tested the hypothesis that the lateral intraparietal area (LIP) integrates disparate task-relevant visual features by recording from LIP neurons in monkeys trained to identify target stimuli composed of conjunctions of color and motion features. We show that LIP neurons exhibit integrative representations of both color and motion features when they are task relevant, and task-dependent shifts of both direction and color tuning. This suggests that LIP plays a role in flexibly integrating task-relevant sensory signals. PMID:25199703

Identifying Bottom-Up and Top-Down Components of Attentional Weight by Experimental Analysis and Computational Modeling

ERIC Educational Resources Information Center

Nordfang, Maria; Dyrholm, Mads; Bundesen, Claus

2013-01-01

The attentional weight of a visual object depends on the contrast of the features of the object to its local surroundings (feature contrast) and the relevance of the features to one's goals (feature relevance). We investigated the dependency in partial report experiments with briefly presented stimuli but unspeeded responses. The task was to…

Using wireless handheld computers to seek information at the point of care: an evaluation by clinicians.

PubMed

Hauser, Susan E; Demner-Fushman, Dina; Jacobs, Joshua L; Humphrey, Susanne M; Ford, Glenn; Thoma, George R

2007-01-01

To evaluate: (1) the effectiveness of wireless handheld computers for online information retrieval in clinical settings; (2) the role of MEDLINE in answering clinical questions raised at the point of care. A prospective single-cohort study: accompanying medical teams on teaching rounds, five internal medicine residents used and evaluated MD on Tap, an application for handheld computers, to seek answers in real time to clinical questions arising at the point of care. All transactions were stored by an intermediate server. Evaluators recorded clinical scenarios and questions, identified MEDLINE citations that answered the questions, and submitted daily and summative reports of their experience. A senior medical librarian corroborated the relevance of the selected citation to each scenario and question. Evaluators answered 68% of 363 background and foreground clinical questions during rounding sessions using a variety of MD on Tap features in an average session length of less than four minutes. The evaluator, the number and quality of query terms, the total number of citations found for a query, and the use of auto-spellcheck significantly contributed to the probability of query success. Handheld computers with Internet access are useful tools for healthcare providers to access MEDLINE in real time. MEDLINE citations can answer specific clinical questions when several medical terms are used to form a query. The MD on Tap application is an effective interface to MEDLINE in clinical settings, allowing clinicians to quickly find relevant citations.

Using Wireless Handheld Computers to Seek Information at the Point of Care: An Evaluation by Clinicians

PubMed Central

Hauser, Susan E.; Demner-Fushman, Dina; Jacobs, Joshua L.; Humphrey, Susanne M.; Ford, Glenn; Thoma, George R.

2007-01-01

Objective To evaluate: (1) the effectiveness of wireless handheld computers for online information retrieval in clinical settings; (2) the role of MEDLINE® in answering clinical questions raised at the point of care. Design A prospective single-cohort study: accompanying medical teams on teaching rounds, five internal medicine residents used and evaluated MD on Tap, an application for handheld computers, to seek answers in real time to clinical questions arising at the point of care. Measurements All transactions were stored by an intermediate server. Evaluators recorded clinical scenarios and questions, identified MEDLINE citations that answered the questions, and submitted daily and summative reports of their experience. A senior medical librarian corroborated the relevance of the selected citation to each scenario and question. Results Evaluators answered 68% of 363 background and foreground clinical questions during rounding sessions using a variety of MD on Tap features in an average session length of less than four minutes. The evaluator, the number and quality of query terms, the total number of citations found for a query, and the use of auto-spellcheck significantly contributed to the probability of query success. Conclusion Handheld computers with Internet access are useful tools for healthcare providers to access MEDLINE in real time. MEDLINE citations can answer specific clinical questions when several medical terms are used to form a query. The MD on Tap application is an effective interface to MEDLINE in clinical settings, allowing clinicians to quickly find relevant citations. PMID:17712085

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Predicting couple therapy outcomes based on speech acoustic features

PubMed Central

Nasir, Md; Baucom, Brian Robert; Narayanan, Shrikanth

2017-01-01

Automated assessment and prediction of marital outcome in couples therapy is a challenging task but promises to be a potentially useful tool for clinical psychologists. Computational approaches for inferring therapy outcomes using observable behavioral information obtained from conversations between spouses offer objective means for understanding relationship dynamics. In this work, we explore whether the acoustics of the spoken interactions of clinically distressed spouses provide information towards assessment of therapy outcomes. The therapy outcome prediction task in this work includes detecting whether there was a relationship improvement or not (posed as a binary classification) as well as discerning varying levels of improvement or decline in the relationship status (posed as a multiclass recognition task). We use each interlocutor’s acoustic speech signal characteristics such as vocal intonation and intensity, both independently and in relation to one another, as cues for predicting the therapy outcome. We also compare prediction performance with one obtained via standardized behavioral codes characterizing the relationship dynamics provided by human experts as features for automated classification. Our experiments, using data from a longitudinal clinical study of couples in distressed relations, showed that predictions of relationship outcomes obtained directly from vocal acoustics are comparable or superior to those obtained using human-rated behavioral codes as prediction features. In addition, combining direct signal-derived features with manually coded behavioral features improved the prediction performance in most cases, indicating the complementarity of relevant information captured by humans and machine algorithms. Additionally, considering the vocal properties of the interlocutors in relation to one another, rather than in isolation, showed to be important for improving the automatic prediction. This finding supports the notion that behavioral outcome, like many other behavioral aspects, is closely related to the dynamics and mutual influence of the interlocutors during their interaction and their resulting behavioral patterns. PMID:28934302

Feature-selective Attention in Frontoparietal Cortex: Multivoxel Codes Adjust to Prioritize Task-relevant Information.

PubMed

Jackson, Jade; Rich, Anina N; Williams, Mark A; Woolgar, Alexandra

2017-02-01

Human cognition is characterized by astounding flexibility, enabling us to select appropriate information according to the objectives of our current task. A circuit of frontal and parietal brain regions, often referred to as the frontoparietal attention network or multiple-demand (MD) regions, are believed to play a fundamental role in this flexibility. There is evidence that these regions dynamically adjust their responses to selectively process information that is currently relevant for behavior, as proposed by the "adaptive coding hypothesis" [Duncan, J. An adaptive coding model of neural function in prefrontal cortex. Nature Reviews Neuroscience, 2, 820-829, 2001]. Could this provide a neural mechanism for feature-selective attention, the process by which we preferentially process one feature of a stimulus over another? We used multivariate pattern analysis of fMRI data during a perceptually challenging categorization task to investigate whether the representation of visual object features in the MD regions flexibly adjusts according to task relevance. Participants were trained to categorize visually similar novel objects along two orthogonal stimulus dimensions (length/orientation) and performed short alternating blocks in which only one of these dimensions was relevant. We found that multivoxel patterns of activation in the MD regions encoded the task-relevant distinctions more strongly than the task-irrelevant distinctions: The MD regions discriminated between stimuli of different lengths when length was relevant and between the same objects according to orientation when orientation was relevant. The data suggest a flexible neural system that adjusts its representation of visual objects to preferentially encode stimulus features that are currently relevant for behavior, providing a neural mechanism for feature-selective attention.

Orthodontics is temporomandibular disorder-neutral.

PubMed

Manfredini, Daniele; Stellini, Edoardo; Gracco, Antonio; Lombardo, Luca; Nardini, Luca Guarda; Siciliani, Giuseppe

2016-07-01

To assess if subjects with a clinical diagnosis of temporomandibular disorders (TMDs) have a similar prevalence of orthodontic history as a population of TMD-free individuals and to assess if those subjects who have a history of ideal orthodontics have fewer symptoms than those with a history of nonideal orthodontics. Two groups of age- and sex-matched individuals belonging to either a study ("TMD") or a control group were recruited. Subjects who underwent orthodontic treatment were classified as having a history of ideal or nonideal orthodontics based on the current presence of normal values in five reference occlusal features. The correlation with a history of orthodontic treatment was not clinically significant for any of the TMD diagnoses (ie, muscle pain, joint pain, disc displacement, arthrosis), with Phi (Φ) coefficient values within the -0.120 to 0.058 range. Within the subset of patients with a history of orthodontics, the correlation of ideal or nonideal orthodontic treatment with TMD diagnoses was, in general, not clinically relevant or was weakly relevant. Findings confirmed the substantial absence of clinically significant effects of orthodontics as far as TMD is concerned. The very low correlation values of a negative or positive history of ideal or nonideal orthodontics with the different TMD diagnoses suggest that orthodontic treatment could not have a true role for TMD.

Detection of clinically relevant copy number alterations in oral cancer progression using multiplexed droplet digital PCR.

PubMed

Hughesman, Curtis B; Lu, X J David; Liu, Kelly Y P; Zhu, Yuqi; Towle, Rebecca M; Haynes, Charles; Poh, Catherine F

2017-09-19

Copy number alterations (CNAs), a common genomic event during carcinogenesis, are known to affect a large fraction of the genome. Common recurrent gains or losses of specific chromosomal regions occur at frequencies that they may be considered distinctive features of tumoral cells. Here we introduce a novel multiplexed droplet digital PCR (ddPCR) assay capable of detecting recurrent CNAs that drive tumorigenesis of oral squamous cell carcinoma. Applied to DNA extracted from oral cell lines and clinical samples of various disease stages, we found good agreement between CNAs detected by our ddPCR assay with those previously reported using comparative genomic hybridization or single nucleotide polymorphism arrays. Furthermore, we demonstrate that the ability to target specific locations of the genome permits detection of clinically relevant oncogenic events such as small, submicroscopic homozygous deletions. Additional capabilities of the multiplexed ddPCR assay include the ability to infer ploidy level, quantify the change in copy number of target loci with high-level gains, and simultaneously assess the status and viral load for high-risk human papillomavirus types 16 and 18. This novel multiplexed ddPCR assay therefore may have clinical value in differentiating between benign oral lesions from those that are at risk of progressing to oral cancer.

Mutation databases for inherited renal disease: are they complete, accurate, clinically relevant, and freely available?

PubMed

Savige, Judy; Dagher, Hayat; Povey, Sue

2014-07-01

This study examined whether gene-specific DNA variant databases for inherited diseases of the kidney fulfilled the Human Variome Project recommendations of being complete, accurate, clinically relevant and freely available. A recent review identified 60 inherited renal diseases caused by mutations in 132 genes. The disease name, MIM number, gene name, together with "mutation" or "database," were used to identify web-based databases. Fifty-nine diseases (98%) due to mutations in 128 genes had a variant database. Altogether there were 349 databases (a median of 3 per gene, range 0-6), but no gene had two databases with the same number of variants, and 165 (50%) databases included fewer than 10 variants. About half the databases (180, 54%) had been updated in the previous year. Few (77, 23%) were curated by "experts" but these included nine of the 11 with the most variants. Even fewer databases (41, 12%) included clinical features apart from the name of the associated disease. Most (223, 67%) could be accessed without charge, including those for 50 genes (40%) with the maximum number of variants. Future efforts should focus on encouraging experts to collaborate on a single database for each gene affected in inherited renal disease, including both unpublished variants, and clinical phenotypes. © 2014 WILEY PERIODICALS, INC.

Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

PubMed Central

Irani, Sarosh R; Gelfand, Jeffrey M; Al-Diwani, Adam; Vincent, Angela

2014-01-01

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined. PMID:24930434

Unravelling the myotonic dystrophy type 1 clinical spectrum: A systematic registry-based study with implications for disease classification.

PubMed

De Antonio, M; Dogan, C; Hamroun, D; Mati, M; Zerrouki, S; Eymard, B; Katsahian, S; Bassez, G

2016-10-01

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Translational research in addiction: toward a framework for the development of novel therapeutics.

PubMed

Paterson, Neil E

2011-06-15

The development of novel substance use disorder (SUD) therapeutics is insufficient to meet the medical needs of a growing SUD patient population. The identification of translatable SUD models and tests is a crucial step in establishing a framework for SUD therapeutic development programs. The present review begins by identifying the clinical features of SUDs and highlights the narrow regulatory end-point required for approval of a novel SUD therapeutic. A conceptual overview of dependence is provided, followed by identification of potential intervention targets in the addiction cycle. The main components of the addiction cycle provide the framework for a discussion of preclinical models and their clinical analogs, all of which are focused on isolated behavioral end-points thought to be relevant to the persistence of compulsive drug use. Thus, the greatest obstacle to successful development is the gap between the multiplicity of preclinical and early clinical end-points and the regulatory end-point of sustained abstinence. This review proposes two pathways to bridging this gap: further development and validation of the preclinical extended access self-administration model; inclusion of secondary end-points comprising all of the measures highlighted in the present discussion in Phase 3 trials. Further, completion of the postdictive validation of analogous preclinical and clinical assays is of high priority. Ultimately, demonstration of the relevance and validity of a variety of end-points to the ultimate goal of abstinence will allow researchers to identify truly relevant therapeutic mechanisms and intervention targets, and establish a framework for SUD therapeutic development that allows optimal decision-making and resource allocation. 2011 Elsevier Inc. All rights reserved.

Immunomediated Pan-cancer Regulation Networks are Dominant Fingerprints After Treatment of Cell Lines with Demethylation.

PubMed

El Baroudi, Mariama; Cinti, Caterina; Capobianco, Enrico

2016-01-01

Pan-cancer studies are particularly relevant not only for addressing the complexity of the inherently observed heterogeneity but also for identifying clinically relevant features that may be common to the cancer types. Immune system regulations usually reveal synergistic modulation with other cancer mechanisms and in combination provide insights on possible advances in cancer immunotherapies. Network inference is a powerful approach to decipher pan-cancer systems dynamics. The methodology proposed in this study elucidates the impacts of epigenetic treatment on the drivers of complex pan-cancer regulation circuits involving cell lines of five cancer types. These patterns were observed from differential gene expression measurements following demethylation with 5-azacytidine. Networks were built to establish associations of phenotypes at molecular level with cancer hallmarks through both transcriptional and post-transcriptional regulation mechanisms. The most prominent feature that emerges from our integrative network maps, linking pathway landscapes to disease and drug-target associations, refers primarily to a mosaic of immune-system crosslinked influences. Therefore, characteristics initially evidenced in single cancer maps become motifs well summarized by network cores and fingerprints.

Conformational features of cepacian: the exopolysaccharide produced by clinical strains of Burkholderia cepacia.

PubMed

Nogueira, Carlos E Sampaio; Ruggiero, Jose R; Sist, Paola; Cescutti, Paola; Urbani, Ranieri; Rizzo, Roberto

2005-04-11

Conformational energy calculations and molecular dynamics investigations, both in water and in dimethyl sulfoxide, were carried out on the exopolysaccharide cepacian produced by the majority of the clinical strains of Burkholderia cepacia, an opportunistic pathogen causing serious lung infection in patients affected by cystic fibrosis, The investigation was aimed at defining the structural and conformational features, which might be relevant for clarification of the structure-function relationships of the polymer. The molecular dynamics calculations were carried out by Ramachandran-type energy plots of the disaccharides that constitute the polymer repeating unit. The dynamics of an oligomer composed of three repeating units were investigated in water and in Me2SO, a non-aggregating solvent. Analysis of the time persistence of hydrogen bonds showed the presence of a large number of favourable interactions in water, which were less evident in Me2SO. The calculations on the cepacian chain indicated that polymer conformational features in water were affected by the lateral chains, but were also largely dictated by the presence of solvent. Moreover, the large number of intra-chain hydrogen bonds in water disappeared in Me2SO solution, increasing the average dimension of the polymer chains.

Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

PubMed

Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

2011-12-01

Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. Copyright © 2011 Elsevier Ltd. All rights reserved.

Varying irrelevant phonetic features hinders learning of the feature being trained.

PubMed

Antoniou, Mark; Wong, Patrick C M

2016-01-01

Learning to distinguish nonnative words that differ in a critical phonetic feature can be difficult. Speech training studies typically employ methods that explicitly direct the learner's attention to the relevant nonnative feature to be learned. However, studies on vision have demonstrated that perceptual learning may occur implicitly, by exposing learners to stimulus features, even if they are irrelevant to the task, and it has recently been suggested that this task-irrelevant perceptual learning framework also applies to speech. In this study, subjects took part in a seven-day training regimen to learn to distinguish one of two nonnative features, namely, voice onset time or lexical tone, using explicit training methods consistent with most speech training studies. Critically, half of the subjects were exposed to stimuli that varied not only in the relevant feature, but in the irrelevant feature as well. The results showed that subjects who were trained with stimuli that varied in the relevant feature and held the irrelevant feature constant achieved the best learning outcomes. Varying both features hindered learning and generalization to new stimuli.

Clarifying Interpersonal Heterogeneity in Borderline Personality Disorder Using Latent Mixture Modeling

PubMed Central

Wright, Aidan G.C.; Hallquist, Michael N.; Morse, Jennifer Q.; Scott, Lori N.; Stepp, Stephanie D.; Nolf, Kimberly A.; Pilkonis, Paul A.

2013-01-01

Significant interpersonal impairment is a cardinal feature of borderline personality disorder (BPD). However, past research has demonstrated that the interpersonal profile associated with BPD varies across samples, evidence for considerable interpersonal heterogeneity. The current study used Inventory of Interpersonal Problems – Circumplex (IIP-C; Alden, Wiggins, & Pincus, 1990) scale scores to investigate interpersonal inhibitions and excesses in a large sample (N = 255) selected for significant borderline pathology. Results indicated that BPD symptom counts were unrelated to the primary dimensions of the IIP-C, but were related to generalized interpersonal distress. A latent class analysis clarified this finding by revealing six homogeneous interpersonal classes with prototypical profiles associated with Intrusive, Vindictive, Avoidant, Nonassertive, and moderate and severe Exploitable interpersonal problems. These classes differed in clinically relevant features (e.g., antisocial behaviors, self-injury, past suicide attempts). Findings are discussed in terms of the incremental clinical utility of the interpersonal circumplex model and the implications for developmental and nosological models of BPD. PMID:23514179

Integrating Query of Relational and Textual Data in Clinical Databases: A Case Study

PubMed Central

Fisk, John M.; Mutalik, Pradeep; Levin, Forrest W.; Erdos, Joseph; Taylor, Caroline; Nadkarni, Prakash

2003-01-01

Objectives: The authors designed and implemented a clinical data mart composed of an integrated information retrieval (IR) and relational database management system (RDBMS). Design: Using commodity software, which supports interactive, attribute-centric text and relational searches, the mart houses 2.8 million documents that span a five-year period and supports basic IR features such as Boolean searches, stemming, and proximity and fuzzy searching. Measurements: Results are relevance-ranked using either “total documents per patient” or “report type weighting.” Results: Non-curated medical text has a significant degree of malformation with respect to spelling and punctuation, which creates difficulties for text indexing and searching. Presently, the IR facilities of RDBMS packages lack the features necessary to handle such malformed text adequately. Conclusion: A robust IR+RDBMS system can be developed, but it requires integrating RDBMSs with third-party IR software. RDBMS vendors need to make their IR offerings more accessible to non-programmers. PMID:12509355

[Depression and epilepsy : Two clinical pictures with common causes?].

PubMed

Borgmann, M; Holtkamp, M; Adli, M; Behr, J

2016-07-01

Epilepsy and depressive disorders show a high rate of comorbidity. Thus, neurobiological similarities and a bidirectional relationship in terms of pathogenesis have been suggested. The aim of this article is to present the common neurobiological features of both disorders, to characterize the bidirectional relationship and to provide an overview of therapeutic consequences. A review of the current literature and evaluation of studies on the topics of depression and epilepsy are presented. Epilepsy and depression share common neurobiological features. In epileptic patients depression should be diagnosed early and reliably as the successful treatment has a great influence on the prognosis, quality of life and suicide risk in these individuals. In therapeutic doses, antidepressive medication with noradrenergic and specific serotonergic antidepressants (NaSSA) or selective serotonin reuptake inhibitors (SSRI) imparts no clinically relevant epileptogenic potential; however, it increases the quality of life and could have anticonvulsant effects in patients with epilepsy. Clomipramine, bupropion and maprotiline, however, should not be administered to patients with epilepsy as they are known to lower the seizure threshold.

Dental occlusion and temporomandibular disorders.

PubMed

Stone, J Caitlin; Hannah, Andrew; Nagar, Nathan

2017-10-27

Data sourcesMedline, Scopus and Google Scholar.Study selectionTwo reviewers selected studies independently. English language clinical studies assessing the association between temporomandibular disorders (TMD) and features of dental occlusion were considered.Data extraction and synthesisStudy quality was assessed based on the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was presented.ResultsIn all 25 studies (17 case-control, eight comparative) were included. Overall there was a high variability between occlusal features and TMD diagnosis. Findings were consistent with a lack of clinically relevant association between TMD and dental occlusion. Only two studies were associated with TMD in the majority (≥50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses.ConclusionsThe findings support the absence of a disease-specific association, there is no ground to hypothesise a major role for dental occlusion in the pathophysiology of TMDs. Dental clinicians are thus encouraged to move forward and abandon the old-fashioned gnathological paradig.

Clustering Suicide Attempters: Impulsive-Ambivalent, Well-Planned, or Frequent.

PubMed

Lopez-Castroman, Jorge; Nogue, Erika; Guillaume, Sebastien; Picot, Marie Christine; Courtet, Philippe

2016-06-01

Attempts to predict suicidal behavior within high-risk populations have so far shown insufficient accuracy. Although several psychosocial and clinical features have been consistently associated with suicide attempts, investigations of latent structure in well-characterized populations of suicide attempters are lacking. We analyzed a sample of 1,009 hospitalized suicide attempters that were recruited between 1999 and 2012. Eleven clinically relevant items related to the characteristics of suicidal behavior were submitted to a Hierarchical Ascendant Classification. Phenotypic profiles were compared between the resulting clusters. A decisional tree was constructed to facilitate the differentiation of individuals classified within the first 2 clusters. Most individuals were included in a cluster characterized by less lethal means and planning ("impulse-ambivalent"). A second cluster featured more carefully planned attempts ("well-planned"), more alcohol or drug use before the attempt, and more precautions to avoid interruptions. Finally, a small, third cluster included individuals reporting more attempts ("frequent"), more often serious or violent attempts, and an earlier age at first attempt. Differences across clusters by demographic and clinical characteristics were also found, particularly with the third cluster whose participants had experienced high levels of childhood abuse. Cluster analysis consistently supported 3 distinct clusters of individuals with specific features in their suicidal behaviors and phenotypic profiles that could help clinicians to better focus prevention strategies. © Copyright 2016 Physicians Postgraduate Press, Inc.

Decision Support Tools for Clinical Diagnosis of Disease in Cows with Suspected Bovine Spongiform Encephalopathy

PubMed Central

Saegerman, C.; Speybroeck, N.; Roels, S.; Vanopdenbosch, E.; Thiry, E.; Berkvens, D.

2004-01-01

Reporting of clinically suspected cattle is currently the most common method for detecting cases of bovine spongiform encephalopathy (BSE). Improvement of clinical diagnosis and decision-making remains crucial. A comparison of clinical patterns, consisting of 25 signs, was made between all 30 BSE cases, confirmed in Belgium before October 2002, and 272 suspected cases that were subsequently determined to be histologically, immunohistochemically, and scrapie-associated-fiber negative. Seasonality in reporting suspected cases was observed, with more cases being reported during wintertime when animals were kept indoors. The median duration of illness was 30 days. The 10 most relevant signs of BSE were kicking in the milking parlor, hypersensitivity to touch and/or sound, head shyness, panic-stricken response, reluctance to enter in the milking parlor, abnormal ear movement or carriage, increased alertness behavior, reduced milk yield, teeth grinding, and temperament change. Ataxia did not appear to be a specific sign of BSE. A classification and regression tree was constructed by using the following four features: age of the animal, year of birth, number of relevant BSE signs noted, and number of clinical signs, typical for listeriosis, noted. The model had a sensitivity of 100% and a specificity of 85%. This approach allows the use of an interactive decision-support tool, based entirely on odds ratios, a statistic independent of disease prevalence. PMID:14715749

Clostridium Difficile Infection Due to Pneumonia Treatment: Mortality Risk Models.

PubMed

Chmielewska, M; Zycinska, K; Lenartowicz, B; Hadzik-Błaszczyk, M; Cieplak, M; Kur, Z; Wardyn, K A

2017-01-01

One of the most common gastrointestinal infection after the antibiotic treatment of community or nosocomial pneumonia is caused by the anaerobic spore Clostridium difficile (C. difficile). The aim of this study was to retrospectively assess mortality due to C. difficile infection (CDI) in patients treated for pneumonia. We identified 94 cases of post-pneumonia CDI out of the 217 patients with CDI. The mortality issue was addressed by creating a mortality risk models using logistic regression and multivariate fractional polynomial analysis. The patients' demographics, clinical features, and laboratory results were taken into consideration. To estimate the influence of the preceding respiratory infection, a pneumonia severity scale was included in the analysis. The analysis showed two statistically significant and clinically relevant mortality models. The model with the highest prognostic strength entailed age, leukocyte count, serum creatinine and urea concentration, hematocrit, coexisting neoplasia or chronic obstructive pulmonary disease. In conclusion, we report on two prognostic models, based on clinically relevant factors, which can be of help in predicting mortality risk in C. difficile infection, secondary to the antibiotic treatment of pneumonia. These models could be useful in preventive tailoring of individual therapy.

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance.

PubMed

Fernández-Vega, Iván; Santos-Juanes, Jorge; Camacho-Urkaray, Emma; Lorente-Gea, Laura; García, Beatriz; Gutiérrez-Corres, Francisco Borja; Quirós, Luis M; Guerra-Merino, Isabel; Aguirre, José Javier

2018-02-12

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Side effects of stabilization occlusal splints: a report of three cases and literature review.

PubMed

Magdaleno, Fernando; Ginestal, Eduardo

2010-04-01

Stabilization splints are frequently used for the treatment of temporomandibular disorders (TMD) and bruxism, despite the fact that little is known about their mechanism of action or the precise conditions under which they can be recommended. Moreover, information about their possible adverse effects, which in the majority of cases include occlusal modifications of little clinical relevance, is scarce. On occasions, these splints can provoke severe occlusal alterations and other complications, which are rarely alluded to in the literature. Here presented in this paper are three case reports in which part-time stabilization splints led to irreversible occlusal alterations and a discussion of the relevant clinical implications. Such splints are reported to negatively affect the condyle-disk relation in patients who exhibit disk displacement with reduction and to modify breathing features in patients with obstructive sleep apnea, although further studies are required to unequivocally demonstrate these findings. Finally, the splint seems to modify peripheral information at the level of the Central Nervous System, leading to modifications in corporal postural tone. The clinical repercussions of such alterations are currently poorly understood. It is our hope that future research will throw fresh light on these important topics.

[Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy].

PubMed

Liu, X H; Ding, W W; Han, L; Liu, X R; Xiao, Y Y; Yang, J; Mo, Y

2017-10-02

Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion: Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

PubMed

Peterson, Lisa K; Willis, Rohan; Harris, E Nigel; Branch, Ware D; Tebo, Anne E

2016-01-01

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-β2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts. © 2016 Elsevier Inc. All rights reserved.

Optimization of breast mass classification using sequential forward floating selection (SFFS) and a support vector machine (SVM) model

PubMed Central

Tan, Maxine; Pu, Jiantao; Zheng, Bin

2014-01-01

Purpose: Improving radiologists’ performance in classification between malignant and benign breast lesions is important to increase cancer detection sensitivity and reduce false-positive recalls. For this purpose, developing computer-aided diagnosis (CAD) schemes has been attracting research interest in recent years. In this study, we investigated a new feature selection method for the task of breast mass classification. Methods: We initially computed 181 image features based on mass shape, spiculation, contrast, presence of fat or calcifications, texture, isodensity, and other morphological features. From this large image feature pool, we used a sequential forward floating selection (SFFS)-based feature selection method to select relevant features, and analyzed their performance using a support vector machine (SVM) model trained for the classification task. On a database of 600 benign and 600 malignant mass regions of interest (ROIs), we performed the study using a ten-fold cross-validation method. Feature selection and optimization of the SVM parameters were conducted on the training subsets only. Results: The area under the receiver operating characteristic curve (AUC) = 0.805±0.012 was obtained for the classification task. The results also showed that the most frequently-selected features by the SFFS-based algorithm in 10-fold iterations were those related to mass shape, isodensity and presence of fat, which are consistent with the image features frequently used by radiologists in the clinical environment for mass classification. The study also indicated that accurately computing mass spiculation features from the projection mammograms was difficult, and failed to perform well for the mass classification task due to tissue overlap within the benign mass regions. Conclusions: In conclusion, this comprehensive feature analysis study provided new and valuable information for optimizing computerized mass classification schemes that may have potential to be useful as a “second reader” in future clinical practice. PMID:24664267

Models of clinical reasoning with a focus on general practice: A critical review.

PubMed

Yazdani, Shahram; Hosseinzadeh, Mohammad; Hosseini, Fakhrolsadat

2017-10-01

Diagnosis lies at the heart of general practice. Every day general practitioners (GPs) visit patients with a wide variety of complaints and concerns, with often minor but sometimes serious symptoms. General practice has many features which differentiate it from specialty care setting, but during the last four decades little attention was paid to clinical reasoning in general practice. Therefore, we aimed to critically review the clinical reasoning models with a focus on the clinical reasoning in general practice or clinical reasoning of general practitioners to find out to what extent the existing models explain the clinical reasoning specially in primary care and also identity the gaps of the model for use in primary care settings. A systematic search to find models of clinical reasoning were performed. To have more precision, we excluded the studies that focused on neurobiological aspects of reasoning, reasoning in disciplines other than medicine decision making or decision analysis on treatment or management plan. All the articles and documents were first scanned to see whether they include important relevant contents or any models. The selected studies which described a model of clinical reasoning in general practitioners or with a focus on general practice were then reviewed and appraisal or critics of other authors on these models were included. The reviewed documents on the model were synthesized. Six models of clinical reasoning were identified including hypothetic-deductive model, pattern recognition, a dual process diagnostic reasoning model, pathway for clinical reasoning, an integrative model of clinical reasoning, and model of diagnostic reasoning strategies in primary care. Only one model had specifically focused on general practitioners reasoning. A Model of clinical reasoning that included specific features of general practice to better help the general practitioners with the difficulties of clinical reasoning in this setting is needed.

Freezing of Gait Detection in Parkinson's Disease: A Subject-Independent Detector Using Anomaly Scores.

PubMed

Pham, Thuy T; Moore, Steven T; Lewis, Simon John Geoffrey; Nguyen, Diep N; Dutkiewicz, Eryk; Fuglevand, Andrew J; McEwan, Alistair L; Leong, Philip H W

2017-11-01

Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).Freezing of gait (FoG) is common in Parkinsonian gait and strongly relates to falls. Current clinical FoG assessments are patients' self-report diaries and experts' manual video analysis. Both are subjective and yield moderate reliability. Existing detection algorithms have been predominantly designed in subject-dependent settings. In this paper, we aim to develop an automated FoG detector for subject independent. After extracting highly relevant features, we apply anomaly detection techniques to detect FoG events. Specifically, feature selection is performed using correlation and clusterability metrics. From a list of 244 feature candidates, 36 candidates were selected using saliency and robustness criteria. We develop an anomaly score detector with adaptive thresholding to identify FoG events. Then, using accuracy metrics, we reduce the feature list to seven candidates. Our novel multichannel freezing index was the most selective across all window sizes, achieving sensitivity (specificity) of (). On the other hand, freezing index from the vertical axis was the best choice for a single input, achieving sensitivity (specificity) of () for ankle and () for back sensors. Our subject-independent method is not only significantly more accurate than those previously reported, but also uses a much smaller window (e.g., versus ) and/or lower tolerance (e.g., versus ).

Validity of the construct of post-traumatic stress disorder in a low-income country: interview study of women in Gujarat, India.

PubMed

Mehta, Khyati; Vankar, Ganpat; Patel, Vikram

2005-12-01

The validity of the clinical construct of post-traumatic stress disorder (PTSD) has been questioned in non-Western cultures. This report describes in-depth interviews exploring the experiences of women who were traumatised by the communal riots in Ahmedabad, India, in March 2002. Three specific narratives are presented which describe experiences that closely resemble re-experiencing, avoidance and hyperarousal. Thus, symptoms described as characteristic features of PTSD in biomedical classifications are clearly expressed by the women in our study, and are attributed by them to trauma and grief. We conclude that PTSD may be a relevant clinical construct in the Indian context.

Health information systems.

PubMed

Hovenga, Evelyn J S; Grain, Heather

2013-01-01

Health information provides the foundation for all decision making in healthcare whether clinical at the bed side, or at a national government level. This information is generally collected as part of systems which support administrative or clinical workflow and practice. This chapter describes the many and varied features of systems such as electronic health records (EHRs), how they fit with health information systems and how they collectively manage information flow. Systems engineering methods and tools are described together with their use to suit the health industry. This focuses on the need for suitable system architectures and semantic interoperability. These concepts and their relevance to the health industry are explained. The relationship and requirements for appropriate data governance in these systems is also considered.

[Pheochromocytoma and paraganglioma in childhood: a report of 2 cases report].

PubMed

Mosquera Gorostidi, A; Justo Ranera, A; Zakirian Denis, S E; González Temprano, N; Sagaseta de Ilúrdoz Uranga, M; Molina Garicano, J

2015-01-01

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors in children and most of them are sporadic. However, they represent the most common endocrine tumor in childhood, and hereditary tumor syndromes are most relevant in these age. Advances in genetic, biochemistry and imaging techniques have revised the management of these tumors; thus A biochemical study should be always initiated once the clinical diagnosis is suspected, followed by imaging and molecular studies, particularly in the context of known familial disease. The diagnostic and therapeutic features are reviewed after the presentation of two clinical cases, where the second one is a patient with type 1 Neurofibromatosis. Copyright © 2014. Published by Elsevier Espana.

Selection-for-action in visual search.

PubMed

Hannus, Aave; Cornelissen, Frans W; Lindemann, Oliver; Bekkering, Harold

2005-01-01

Grasping an object rather than pointing to it enhances processing of its orientation but not its color. Apparently, visual discrimination is selectively enhanced for a behaviorally relevant feature. In two experiments we investigated the limitations and targets of this bias. Specifically, in Experiment 1 we were interested to find out whether the effect is capacity demanding, therefore we manipulated the set-size of the display. The results indicated a clear cognitive processing capacity requirement, i.e. the magnitude of the effect decreased for a larger set size. Consequently, in Experiment 2, we investigated if the enhancement effect occurs only at the level of behaviorally relevant feature or at a level common to different features. Therefore we manipulated the discriminability of the behaviorally neutral feature (color). Again, results showed that this manipulation influenced the action enhancement of the behaviorally relevant feature. Particularly, the effect of the color manipulation on the action enhancement suggests that the action effect is more likely to bias the competition between different visual features rather than to enhance the processing of the relevant feature. We offer a theoretical account that integrates the action-intention effect within the biased competition model of visual selective attention.

Clinical features for diagnosis of pneumonia in children younger than 5 years: a systematic review and meta-analysis.

PubMed

Rambaud-Althaus, Clotilde; Althaus, Fabrice; Genton, Blaise; D'Acremont, Valérie

2015-04-01

Pneumonia is the biggest cause of deaths in young children in developing countries, but early diagnosis and intervention can effectively reduce mortality. We aimed to assess the diagnostic value of clinical signs and symptoms to identify radiological pneumonia in children younger than 5 years and to review the accuracy of WHO criteria for diagnosis of clinical pneumonia. We searched Medline (PubMed), Embase (Ovid), the Cochrane Database of Systematic Reviews, and reference lists of relevant studies, without date restrictions, to identify articles assessing clinical predictors of radiological pneumonia in children. Selection was based on: design (diagnostic accuracy studies), target disease (pneumonia), participants (children aged <5 years), setting (ambulatory or hospital care), index test (clinical features), and reference standard (chest radiography). Quality assessment was based on the 2011 Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. For each index test, we calculated sensitivity and specificity and, when the tests were assessed in four or more studies, calculated pooled estimates with use of bivariate model and hierarchical summary receiver operation characteristics plots for meta-analysis. We included 18 articles in our analysis. WHO-approved signs age-related fast breathing (six studies; pooled sensitivity 0·62, 95% CI 0·26-0·89; specificity 0·59, 0·29-0·84) and lower chest wall indrawing (four studies; 0·48, 0·16-0·82; 0·72, 0·47-0·89) showed poor diagnostic performance in the meta-analysis. Features with the highest pooled positive likelihood ratios were respiratory rate higher than 50 breaths per min (1·90, 1·45-2·48), grunting (1·78, 1·10-2·88), chest indrawing (1·76, 0·86-3·58), and nasal flaring (1·75, 1·20-2·56). Features with the lowest pooled negative likelihood ratio were cough (0·30, 0·09-0·96), history of fever (0·53, 0·41-0·69), and respiratory rate higher than 40 breaths per min (0·43, 0·23-0·83). Not one clinical feature was sufficient to diagnose pneumonia definitively. Combination of clinical features in a decision tree might improve diagnostic performance, but the addition of new point-of-care tests for diagnosis of bacterial pneumonia would help to attain an acceptable level of accuracy. Swiss National Science Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

PubMed Central

Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

2012-01-01

An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration–TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network. PMID:22366791

[The influence of phychological features and learning styles on the academic performance of medical students].

PubMed

Bitran, Marcela; Lafuente, Montserrat; Zúñiga, Denisse; Viviani, Paola; Mena, Beltrán

2004-09-01

The degree of difficulty we experience while learning different concepts and skills depends, among other things, on our psychological features and learning style. This may be particularly true for medical students, whose formation involves the acquisition of multiple cognitive, affective and psychomotor skills. To assess whether the psychological features and learning styles of medical students are associated with their academic performance. The psychological preferences and learning styles of 66 students of the 2001-graduating cohort were determined with the Myers Briggs Type Inventory (MBTI) and the Kolb Learning Style Inventory (LSI), respectively. The academic performance was assessed by the Calificación Médica Nacional (CMN), Chile and by the marks obtained during the Basic (1st to 3rd), Preclinical (4th and 5th) and Clinical (6th and 7th) years of undergraduate training. The psychological features, together with the sex of students were found to be associated with the performance in the Preclinical and Clinical years, and to the CMN. In men, the interest and ability to communicate with people and the concern for harmony, and in women the tendency to function in a systematic and orderly way are the features associated to high academic performance. No associations were found between learning styles and academic performance. The finding that the psychological preferences of medical students are relevent to their academic performance opens a new perspective to analyze the medical education and to design programs aimed at improving learning.

Characterization of the major histopathological components of thyroid nodules using sonographic textural features for clinical diagnosis and management.

PubMed

Chen, Shao-Jer; Yu, Sung-Nien; Tzeng, Jeh-En; Chen, Yen-Ting; Chang, Ku-Yaw; Cheng, Kuo-Sheng; Hsiao, Fu-Tsung; Wei, Chang-Kuo

2009-02-01

In this study, the characteristic sonographic textural feature that represents the major histopathologic components of the thyroid nodules was objectively quantified to facilitate clinical diagnosis and management. A total of 157 regions-of-interest thyroid ultrasound image was recruited in the study. The sonographic system used was the GE LOGIQ 700), (General Electric Healthcare, Chalfant St. Giles, UK). The parameters affecting image acquisition were kept in the same condition for all lesions. Commonly used texture analysis methods were applied to characterize thyroid ultrasound images. Image features were classified according to the corresponding pathologic findings. To estimate their relevance and performance to classification, ReliefF was used as a feature selector. Among the various textural features, the sum average value derived from co-occurrence matrix can well reflect echogenicity and can effectively differentiate between follicles and fibrosis base thyroid nodules. Fibrosis shows lowest echogenicity and lowest difference sum average value. Enlarged follicles show highest echogenicity and difference sum average values. Papillary cancer or follicular tumors show the difference sum average values and echogenicity between. The rule of thumb for the echogenicity is that the more follicles are mixed in, the higher the echo of the follicular tumor and papillary cancer will be and vice versa for fibrosis mixed. Areas with intermediate and lower echo should address the possibility of follicular or papillary neoplasm mixed with either follicles or fibrosis. These areas provide more cellular information for ultrasound guided aspiration

Demographic and clinical features of patients with fibromyalgia syndrome of different settings: a gender comparison.

PubMed

Häuser, Winfried; Kühn-Becker, Hedi; von Wilmoswky, Hubertus; Settan, Margit; Brähler, Elmar; Petzke, Frank

2011-04-01

Well-established gender differences in the clinical picture of fibromyalgia syndrome (FMS) have been suggested. However, studies on gender differences in demographic and clinical features of FMS have contradictory results. Their significance is limited by the small number of patients included and selection bias of single settings. The purpose of this study was to compare demographic characteristics (age, family status) and clinical variables (duration of chronic pain and FMS diagnosis, tender point count, number of pain sites, and somatic and depressive symptoms) of male and female patients in different settings (general population, FMS self-help organization, and different clinical settings). FMS was diagnosed according to survey criteria in the general population and in the self-help organization setting and by 1990 criteria of the American College of Rheumatology in the clinical settings. Tender point examination was performed according to the manual tender point survey protocol in clinical settings. Somatic and depressive symptoms were assessed by validated questionnaires. A total of 1023 patients (885 female, 138 male) were included in the analysis. Compared with male participants, female participants reported a longer duration of chronic widespread pain (P = 0.009) and time since FMS diagnosis (P = 0.05), and they had a higher tender point count (P = 0.04). There were no gender differences in age, family status, number of pain sites, or somatic and depressive symptoms. We found no relevant gender differences in the clinical picture of FMS. The assumption of well-established gender differences in the clinical picture of FMS could not be supported. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation.

PubMed

Preller, Katrin H; Herdener, Marcus; Pokorny, Thomas; Planzer, Amanda; Kraehenmann, Rainer; Stämpfli, Philipp; Liechti, Matthias E; Seifritz, Erich; Vollenweider, Franz X

2017-02-06

A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT 2A R antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT 2A R subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lateral epicondylitis and beyond: imaging of lateral elbow pain with clinical-radiologic correlation.

PubMed

Kotnis, Nikhil A; Chiavaras, Mary M; Harish, Srinivasan

2012-04-01

The diagnosis of lateral epicondylitis is often straightforward and can be made on the basis of clinical findings. However, radiological assessment is valuable where the clinical picture is less clear or where symptoms are refractory to treatment. Demographics, aspects of clinical history, or certain physical signs may suggest an alternate diagnosis. Knowledge of the typical clinical presentation and imaging findings of lateral epicondylitis, in addition to other potential causes of lateral elbow pain, is necessary. These include entrapment of the posterior interosseous and lateral antebrachial cutaneous nerves, posterolateral rotatory instability, posterolateral plica syndrome, Panner's disease, osteochondritis dissecans of the capitellum, radiocapitellar overload syndrome, occult fractures and chondral-osseous impaction injuries, and radiocapitellar arthritis. Knowledge of these potential masquerades of lateral epicondylitis and their characteristic clinical and imaging features is essential for accurate diagnosis. The goal of this review is to provide an approach to the imaging of lateral elbow pain, discussing the relevant anatomy, various causes, and discriminating factors, which will allow for an accurate diagnosis.

Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state.

PubMed

Adiputra, Yohanes; Chen, Shao-Liang

2015-05-20

The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition, features, clinical applications, and pitfalls of measurement of FFR. We searched database for primary studies published in English. The database of National Library of Medicine (NLM), MEDLINE, and PubMed up to July 2014 was used to conduct a search using the keyword term "FFR". The articles about the definition, features, clinical application, and pitfalls of measurement of FFR were identified, retrieved, and reviewed. Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. FFR is a valuable tool to determine the functional significance of coronary stenosis. It combines physiological and anatomical information, and can be followed immediately by percutaneous coronary intervention (PCI) if necessary. The technique of FFR measurement can be performed easily, rapidly, and safely in the catheterization laboratory. By systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be made an even more effective and better treatment than it is currently. The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory.

Feature relevance assessment for the semantic interpretation of 3D point cloud data

NASA Astrophysics Data System (ADS)

Weinmann, M.; Jutzi, B.; Mallet, C.

2013-10-01

The automatic analysis of large 3D point clouds represents a crucial task in photogrammetry, remote sensing and computer vision. In this paper, we propose a new methodology for the semantic interpretation of such point clouds which involves feature relevance assessment in order to reduce both processing time and memory consumption. Given a standard benchmark dataset with 1.3 million 3D points, we first extract a set of 21 geometric 3D and 2D features. Subsequently, we apply a classifier-independent ranking procedure which involves a general relevance metric in order to derive compact and robust subsets of versatile features which are generally applicable for a large variety of subsequent tasks. This metric is based on 7 different feature selection strategies and thus addresses different intrinsic properties of the given data. For the example of semantically interpreting 3D point cloud data, we demonstrate the great potential of smaller subsets consisting of only the most relevant features with 4 different state-of-the-art classifiers. The results reveal that, instead of including as many features as possible in order to compensate for lack of knowledge, a crucial task such as scene interpretation can be carried out with only few versatile features and even improved accuracy.

Classification of childhood asthma phenotypes and long-term clinical responses to inhaled anti-inflammatory medications.

PubMed

Howrylak, Judie A; Fuhlbrigge, Anne L; Strunk, Robert C; Zeiger, Robert S; Weiss, Scott T; Raby, Benjamin A

2014-05-01

Although recent studies have identified the presence of phenotypic clusters in asthmatic patients, the clinical significance and temporal stability of these clusters have not been explored. Our aim was to examine the clinical relevance and temporal stability of phenotypic clusters in children with asthma. We applied spectral clustering to clinical data from 1041 children with asthma participating in the Childhood Asthma Management Program. Posttreatment randomization follow-up data collected over 48 months were used to determine the effect of these clusters on pulmonary function and treatment response to inhaled anti-inflammatory medication. We found 5 reproducible patient clusters that could be differentiated on the basis of 3 groups of features: atopic burden, degree of airway obstruction, and history of exacerbation. Cluster grouping predicted long-term asthma control, as measured by the need for oral prednisone (P < .0001) or additional controller medications (P = .001), as well as longitudinal differences in pulmonary function (P < .0001). We also found that the 2 clusters with the highest rates of exacerbation had different responses to inhaled corticosteroids when compared with the other clusters. One cluster demonstrated a positive response to both budesonide (P = .02) and nedocromil (P = .01) compared with placebo, whereas the other cluster demonstrated minimal responses to both budesonide (P = .12) and nedocromil (P = .56) compared with placebo. Phenotypic clustering can be used to identify longitudinally consistent and clinically relevant patient subgroups, with implications for targeted therapeutic strategies and clinical trials design.

MO-A-BRB-01: TG191: Clinical Use of Luminescent Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kry, S.

This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3)more » To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.« less

MO-A-BRB-00: TG191: Clinical Use of Luminescent Dosimeters

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

This presentation will highlight the upcoming TG-191 report: Clinical Use of Luminescent Dosimeters. Luminescent dosimetry based on TLD and OSLD is a practical, accurate, and precise technique for point dosimetry in medical physics applications. The charges of Task Group 191 were to detail the methodologies for practical and optimal luminescent dosimetry in a clinical setting. This includes (1) To review the variety of TLD/OSL materials available, including features and limitations of each. (2) To outline the optimal steps to achieve accurate and precise dosimetry with luminescent detectors and to evaluate the uncertainty induced when less rigorous procedures are used. (3)more » To develop consensus guidelines on the optimal use of luminescent dosimeters for clinical practice. (4) To develop guidelines for special medically relevant uses of TLDs/OSLs (e.g., mixed field i.e. photon/neutron dosimetry, particle beam dosimetry, skin dosimetry). While this report provides general guidelines for arbitrary TLD and OSLD processes, the report, and therefore this presentation, provide specific guidance for TLD-100 (LiF:Ti,Mg) and nanoDot (Al2O3:C) dosimeters because of their prevalence in clinical practice. Learning Objectives: Understand the available dosimetry systems, and basic theory of their operation Understand the range of dose determination methodologies and the uncertainties associated with them Become familiar with special considerations for TLD/OSLD relevant for special clinical situations Learn recommended commissioning and QA procedures for these dosimetry systems.« less

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

PubMed Central

Ciceri, Pietro; Müller, Susanne; O’Mahony, Alison; Fedorov, Oleg; Filippakopoulos, Panagis; Hunt, Jeremy P.; Lasater, Elisabeth A.; Pallares, Gabriel; Picaud, Sarah; Wells, Christopher; Martin, Sarah; Wodicka, Lisa M.; Shah, Neil P.; Treiber, Daniel K.; Knapp, Stefan

2014-01-01

Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination therapies, which can pose significant clinical development challenges. Epigenetic reader domains of the bromodomain family have recently emerged as novel targets for cancer therapy. Here we report that several clinical kinase inhibitors also inhibit bromodomains with therapeutically relevant potencies and are best classified as dual kinase/bromodomain inhibitors. Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, is particularly noteworthy as these combinations of activities on independent oncogenic pathways exemplify a novel strategy for rational single agent polypharmacological targeting. Furthermore, structure-activity relationships and co-crystal structures identify design features that enable a general platform for the rational design of dual kinase/bromodomain inhibitors. PMID:24584101

Implementing human factors in clinical practice

PubMed Central

Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

2015-01-01

Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. Results The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. Conclusions In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. PMID:24631959

Dissociative Disorders: Between Neurosis and Psychosis

PubMed Central

Devillé, C.; Moeglin, C.; Sentissi, O.

2014-01-01

Dissociative disorders are a set of disorders defined by a disturbance affecting functions that are normally integrated with a prevalence of 2.4 percent in industrialised countries. These disorders are often poorly diagnosed or misdiagnosed because of sharing common clinical features with psychotic disorders, but requiring a very different trajectory of care. Repeated clinical situations in a crisis centre in Geneva provided us with a critical overview of current evidence of knowledge in clinical and etiopathological field about dissociative disorders. Because of their multiple expressions and the overlap with psychotic disorders, we focused on the clinical aspects using three different situations to better understand their specificity and to extend our thinking to the relevance of terms “neurosis” and “psychosis.” Finally, we hope that this work might help physicians and psychiatrists to become more aware of this complex set of disorders while making a diagnosis. PMID:25405051

MalaCards: an integrated compendium for diseases and their annotation

PubMed Central

Rappaport, Noa; Nativ, Noam; Stelzer, Gil; Twik, Michal; Guan-Golan, Yaron; Iny Stein, Tsippi; Bahir, Iris; Belinky, Frida; Morrey, C. Paul; Safran, Marilyn; Lancet, Doron

2013-01-01

Comprehensive disease classification, integration and annotation are crucial for biomedical discovery. At present, disease compilation is incomplete, heterogeneous and often lacking systematic inquiry mechanisms. We introduce MalaCards, an integrated database of human maladies and their annotations, modeled on the architecture and strategy of the GeneCards database of human genes. MalaCards mines and merges 44 data sources to generate a computerized card for each of 16 919 human diseases. Each MalaCard contains disease-specific prioritized annotations, as well as inter-disease connections, empowered by the GeneCards relational database, its searches and GeneDecks set analyses. First, we generate a disease list from 15 ranked sources, using disease-name unification heuristics. Next, we use four schemes to populate MalaCards sections: (i) directly interrogating disease resources, to establish integrated disease names, synonyms, summaries, drugs/therapeutics, clinical features, genetic tests and anatomical context; (ii) searching GeneCards for related publications, and for associated genes with corresponding relevance scores; (iii) analyzing disease-associated gene sets in GeneDecks to yield affiliated pathways, phenotypes, compounds and GO terms, sorted by a composite relevance score and presented with GeneCards links; and (iv) searching within MalaCards itself, e.g. for additional related diseases and anatomical context. The latter forms the basis for the construction of a disease network, based on shared MalaCards annotations, embodying associations based on etiology, clinical features and clinical conditions. This broadly disposed network has a power-law degree distribution, suggesting that this might be an inherent property of such networks. Work in progress includes hierarchical malady classification, ontological mapping and disease set analyses, striving to make MalaCards an even more effective tool for biomedical research. Database URL: http://www.malacards.org/ PMID:23584832

Initial development of a computer-aided diagnosis tool for solitary pulmonary nodules

NASA Astrophysics Data System (ADS)

Catarious, David M., Jr.; Baydush, Alan H.; Floyd, Carey E., Jr.

2001-07-01

This paper describes the development of a computer-aided diagnosis (CAD) tool for solitary pulmonary nodules. This CAD tool is built upon physically meaningful features that were selected because of their relevance to shape and texture. These features included a modified version of the Hotelling statistic (HS), a channelized HS, three measures of fractal properties, two measures of spicularity, and three manually measured shape features. These features were measured from a difficult database consisting of 237 regions of interest (ROIs) extracted from digitized chest radiographs. The center of each 256x256 pixel ROI contained a suspicious lesion which was sent to follow-up by a radiologist and whose nature was later clinically determined. Linear discriminant analysis (LDA) was used to search the feature space via sequential forward search using percentage correct as the performance metric. An optimized feature subset, selected for the highest accuracy, was then fed into a three layer artificial neural network (ANN). The ANN's performance was assessed by receiver operating characteristic (ROC) analysis. A leave-one-out testing/training methodology was employed for the ROC analysis. The performance of this system is competitive with that of three radiologists on the same database.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

PubMed

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), and alterations in PIK3CA , NF1 , CDKN2A , or CDKN2C were identified in 7% of samples. Responses to treatment with the kinase inhibitors sunitinib, everolimus, and pazopanib are presented in conjunction with tumor genomics. © AlphaMed Press 2017.

Fall risks assessment among community dwelling elderly using wearable wireless sensors

NASA Astrophysics Data System (ADS)

Lockhart, Thurmon E.; Soangra, Rahul; Frames, Chris

2014-06-01

Postural stability characteristics are considered to be important in maintaining functional independence free of falls and healthy life style especially for the growing elderly population. This study focuses on developing tools of clinical value in fall prevention: 1) Implementation of sensors that are minimally obtrusive and reliably record movement data. 2) Unobtrusively gather data from wearable sensors from four community centers 3) developed and implemented linear and non-linear signal analysis algorithms to extract clinically relevant information using wearable technology. In all a total of 100 community dwelling elderly individuals (66 non-fallers and 34 fallers) participated in the experiment. All participants were asked to stand-still in eyes open (EO) and eyes closed (EC) condition on forceplate with one wireless inertial sensor affixed at sternum level. Participants' history of falls had been recorded for last 2 years, with emphasis on frequency and characteristics of falls. Any participant with at least one fall in the prior year were classified as faller and the others as non-faller. The results indicated several key factors/features of postural characteristics relevant to balance control and stability during quite stance and, showed good predictive capability of fall risks among older adults. Wearable technology allowed us to gather data where it matters the most to answer fall related questions, i.e. the community setting environments. This study opens new prospects of clinical testing using postural variables with a wearable sensor that may be relevant for assessing fall risks at home and patient environment in near future.

Adding ultrasound to clinical examination reduced frequency of enthesitis in primary care psoriasis patients with musculoskeletal complaints.

PubMed

van der Ven, Myrthe; Karreman, Maren C; Weel, Angelique E A M; Tchetverikov, Ilja; Vis, Marijn; Nijsten, Tamar E C; Hazes, Johanna M W; Luime, Jolanda J

2016-01-01

Part of the psoriasis patients with musculoskeletal complaints will have inflammation of the entheses. Entheseal inflammation is difficult to assess by clinical examination only. Therefore, we aimed to determine the frequency of clinically relevant ultrasound inflammation at the most commonly assessed entheses (MASEI; Madrid Sonographic Enthesis Index) in primary care psoriasis patients with one or more tender entheses. Adult primary care psoriasis patients with musculoskeletal complaints (tender enthesis or arthritis at physical examination) had an ultrasound examination of seven entheses according to the MASEI. Clinically relevant ultrasound inflammation was defined as active inflammation on ultrasound in combination with at least one clinical feature at the same enthesis. Active ultrasound inflammation contained positive power Doppler signal or in case of the plantar aponeurosis increased thickness. Structural changes entailed calcifications, enthesophytes, increased thickness, hypoechogeneicity indicating irregular fibre structure and erosions. Clinically, an enthesis was scored positive by a tender enthesis at clinical examination, reported pain in the history or self-reported pain in the questionnaires. Of 542 primary care psoriasis patient, 111 patients had tender entheses and/or arthritis. These patients were both clinically and ultrasonographically evaluated. Active ultrasound inflammation accompanied with pain or tenderness at the enthesis was found in 36% of the patients (n=40). Most common were inflammation at the knee (n=11) and at the plantar aponeurosis (n=10). Structural changes were observed in 95% of the psoriasis patients independent of their clinical manifestation. We found concurrent presence of ultrasound inflammatory changes and clinical symptoms in 36% of the primary care psoriasis patients who had tenderness at one or more entheseal sites.

Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade.

PubMed

Vasconcelos, Mailton; Stein, Dirson João; de Almeida, Rosa Maria M

2015-01-01

Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

A unified framework for image retrieval using keyword and visual features.

PubMed

Jing, Feng; Li, Mingling; Zhang, Hong-Jiang; Zhang, Bo

2005-07-01

In this paper, a unified image retrieval framework based on both keyword annotations and visual features is proposed. In this framework, a set of statistical models are built based on visual features of a small set of manually labeled images to represent semantic concepts and used to propagate keywords to other unlabeled images. These models are updated periodically when more images implicitly labeled by users become available through relevance feedback. In this sense, the keyword models serve the function of accumulation and memorization of knowledge learned from user-provided relevance feedback. Furthermore, two sets of effective and efficient similarity measures and relevance feedback schemes are proposed for query by keyword scenario and query by image example scenario, respectively. Keyword models are combined with visual features in these schemes. In particular, a new, entropy-based active learning strategy is introduced to improve the efficiency of relevance feedback for query by keyword. Furthermore, a new algorithm is proposed to estimate the keyword features of the search concept for query by image example. It is shown to be more appropriate than two existing relevance feedback algorithms. Experimental results demonstrate the effectiveness of the proposed framework.

A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling.

PubMed

Leger, Stefan; Zwanenburg, Alex; Pilz, Karoline; Lohaus, Fabian; Linge, Annett; Zöphel, Klaus; Kotzerke, Jörg; Schreiber, Andreas; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Troost, Esther G C; Löck, Steffen; Richter, Christian

2017-10-16

Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g. C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

Multiplexed Electrochemical Immunosensors for Clinical Biomarkers

PubMed Central

Yáñez-Sedeño, Paloma; Campuzano, Susana; Pingarrón, José M.

2017-01-01

Management and prognosis of disease requires the accurate determination of specific biomarkers indicative of normal or disease-related biological processes or responses to therapy. Moreover since multiple determinations of biomarkers have demonstrated to provide more accurate information than individual determinations to assist the clinician in prognosis and diagnosis, the detection of several clinical biomarkers by using the same analytical device hold enormous potential for early detection and personalized therapy and will simplify the diagnosis providing more information in less time. In this field, electrochemical immunosensors have demonstrated to offer interesting alternatives against conventional strategies due to their simplicity, fast response, low cost, high sensitivity and compatibility with multiplexed determination, microfabrication technology and decentralized determinations, features which made them very attractive for integration in point-of-care (POC) devices. Therefore, in this review, the relevance and current challenges of multiplexed determination of clinical biomarkers are briefly introduced, and an overview of the electrochemical immunosensing platforms developed so far for this purpose is given in order to demonstrate the great potential of these methodologies. After highlighting the main features of the selected examples, the unsolved challenges and future directions in this field are also briefly discussed. PMID:28448466

A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing.

PubMed

Colombi, Marina; Dordoni, Chiara; Cinquina, Valeria; Venturini, Marina; Ritelli, Marco

2018-01-01

The 2017 EDS revised nosology indicates that minimal criteria suggestive for classical Ehlers-Danlos syndrome (cEDS) are skin hyperextensibility plus atrophic scarring together with either generalized joint hypermobility (gJHM) and/or at least three minor criteria that include cutaneous features and gJHM complications. Confirmatory molecular testing is obligatory to reach a final diagnosis. Although the large majority of the patients presents with these clinical features, some do not and might remain undiagnosed or misdiagnosed. Here we describe a family with 2 affected members, a 23-year-old proposita and her 51-year-old mother, who presented subtle cutaneous signs, including a variable degree of skin hyperextensibility without extensive widened atrophic scars that apparently better fitted with the overlapping hypermobile EDS. The proposita also presented gastrointestinal symptoms secondary to aberrant mast cells mediators release, making the clinical picture even more puzzling. Both patients were diagnosed by molecular testing that revealed a COL5A1 splice mutation. This report highlights the relevance of molecular analysis in patients presenting rather mild signs of EDS, especially in familial cases, and the importance of clinical expertise to make such a diagnosis. Copyright © 2017. Published by Elsevier Masson SAS.

Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.

PubMed

Rogalski, Emily; Sridhar, Jaiashre; Rader, Benjamin; Martersteck, Adam; Chen, Kewei; Cobia, Derin; Thompson, Cynthia K; Weintraub, Sandra; Bigio, Eileen H; Mesulam, M-Marsel

2016-09-27

To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. © 2016 American Academy of Neurology.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features.

PubMed

Robakis, Daphne

2017-01-01

Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features

PubMed Central

Robakis, Daphne

2017-01-01

Background Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Methods Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. Results The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. Discussion We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder. PMID:28546883

Attention to Distinct Goal-relevant Features Differentially Guides Semantic Knowledge Retrieval.

PubMed

Hanson, Gavin K; Chrysikou, Evangelia G

2017-07-01

A critical aspect of conceptual knowledge is the selective activation of goal-relevant aspects of meaning. Although the contributions of ventrolateral prefrontal and posterior temporal areas to semantic cognition are well established, the precise role of posterior parietal cortex in semantic control remains unknown. Here, we examined whether this region modulates attention to goal-relevant features within semantic memory according to the same principles that determine the salience of task-relevant object properties during visual attention. Using multivoxel pattern analysis, we decoded attentional referents during a semantic judgment task, in which participants matched an object cue to a target according to concrete (i.e., color, shape) or abstract (i.e., function, thematic context) semantic features. The goal-relevant semantic feature participants attended to (e.g., color or shape, function or theme) could be decoded from task-associated cortical activity with above-chance accuracy, a pattern that held for both concrete and abstract semantic features. A Bayesian confusion matrix analysis further identified differential contributions to representing attentional demands toward specific object properties across lateral prefrontal, posterior temporal, and inferior parietal regions, with the dorsolateral pFC supporting distinctions between higher-order properties and the left intraparietal sulcus being the only region supporting distinctions across all semantic features. These results are the first to demonstrate that patterns of neural activity in the parietal cortex are sensitive to which features of a concept are attended to, thus supporting the contributions of posterior parietal cortex to semantic control.

Identifying marker genes in transcription profiling data using a mixture of feature relevance experts.

PubMed

Chow, M L; Moler, E J; Mian, I S

2001-03-08

Transcription profiling experiments permit the expression levels of many genes to be measured simultaneously. Given profiling data from two types of samples, genes that most distinguish the samples (marker genes) are good candidates for subsequent in-depth experimental studies and developing decision support systems for diagnosis, prognosis, and monitoring. This work proposes a mixture of feature relevance experts as a method for identifying marker genes and illustrates the idea using published data from samples labeled as acute lymphoblastic and myeloid leukemia (ALL, AML). A feature relevance expert implements an algorithm that calculates how well a gene distinguishes samples, reorders genes according to this relevance measure, and uses a supervised learning method [here, support vector machines (SVMs)] to determine the generalization performances of different nested gene subsets. The mixture of three feature relevance experts examined implement two existing and one novel feature relevance measures. For each expert, a gene subset consisting of the top 50 genes distinguished ALL from AML samples as completely as all 7,070 genes. The 125 genes at the union of the top 50s are plausible markers for a prototype decision support system. Chromosomal aberration and other data support the prediction that the three genes at the intersection of the top 50s, cystatin C, azurocidin, and adipsin, are good targets for investigating the basic biology of ALL/AML. The same data were employed to identify markers that distinguish samples based on their labels of T cell/B cell, peripheral blood/bone marrow, and male/female. Selenoprotein W may discriminate T cells from B cells. Results from analysis of transcription profiling data from tumor/nontumor colon adenocarcinoma samples support the general utility of the aforementioned approach. Theoretical issues such as choosing SVM kernels and their parameters, training and evaluating feature relevance experts, and the impact of potentially mislabeled samples on marker identification (feature selection) are discussed.

Joint Concept Correlation and Feature-Concept Relevance Learning for Multilabel Classification.

PubMed

Zhao, Xiaowei; Ma, Zhigang; Li, Zhi; Li, Zhihui

2018-02-01

In recent years, multilabel classification has attracted significant attention in multimedia annotation. However, most of the multilabel classification methods focus only on the inherent correlations existing among multiple labels and concepts and ignore the relevance between features and the target concepts. To obtain more robust multilabel classification results, we propose a new multilabel classification method aiming to capture the correlations among multiple concepts by leveraging hypergraph that is proved to be beneficial for relational learning. Moreover, we consider mining feature-concept relevance, which is often overlooked by many multilabel learning algorithms. To better show the feature-concept relevance, we impose a sparsity constraint on the proposed method. We compare the proposed method with several other multilabel classification methods and evaluate the classification performance by mean average precision on several data sets. The experimental results show that the proposed method outperforms the state-of-the-art methods.

Patient-centred care in general dental practice - a systematic review of the literature

PubMed Central

2014-01-01

Background Delivering improvements in quality is a key objective within most healthcare systems, and a view which has been widely embraced within the NHS in the United Kingdom. Within the NHS, quality is evaluated across three key dimensions: clinical effectiveness, safety and patient experience, with the latter modelled on the Picker Principles of Patient-Centred Care (PCC). Quality improvement is an important feature of the current dental contract reforms in England, with “patient experience” likely to have a central role in the evaluation of quality. An understanding and appreciation of the evidence underpinning PCC within dentistry is highly relevant if we are to use this as a measure of quality in general dental practice. Methods A systematic review of the literature was undertaken to identify the features of PCC relevant to dentistry and ascertain the current research evidence base underpinning its use as a measure of quality within general dental practice. Results Three papers were identified which met the inclusion criteria and demonstrated the use of primary research to provide an understanding of the key features of PCC within dentistry. None of the papers identified were based in general dental practice and none of the three studies sought the views of patients. Some distinct differences were noted between the key features of PCC reported within the dental literature and those developed within the NHS Patient Experience Framework. Conclusions This systematic review reveals a lack of understanding of PCC within dentistry, and in particular general dental practice. There is currently a poor evidence base to support the use of the current patient reported outcome measures as indicators of patient-centredness. Further research is necessary to understand the important features of PCC in dentistry and patients’ views should be central to this research. PMID:24902842

The clinical potential of Enhanced-ice-COLD-PCR.

PubMed

Tost, Jörg

2016-01-01

Enhanced-ice-COLD-PCR (E-ice-COLD-PCR) is a novel assay format that allows for the efficient enrichment and sensitive detection of all mutations in a region of interest using a chemically modified blocking oligonucleotide, which impedes the amplification of wild-type sequences. The assay is compatible with DNA extracted from tissue and cell-free circulating DNA. The main features of E-ice-COLD-PCR are the simplicity of the setup and the optimization of the assay, the use of standard laboratory equipment and the very short time to results (~4 h including DNA extraction, enrichment and sequence-based identification of mutations). E-ice-COLD-PCR is therefore a highly promising technology for a number of basic research as well as clinical applications including detection of clinically relevant mutated subclones and monitoring of treatment response or disease recurrence.

[Usher syndrome: clinical features, diagnostic options, and therapeutic prospects].

PubMed

Seeliger, M W; Fischer, M D; Pfister, M

2009-06-01

Usher syndrome denotes a clinically and genetically heterogeneous combination of retinitis pigmentosa and sensorineural deafness. The division into subtypes I, II, and III is based on the degree of hearing loss: Type I is characterized by deafness from birth together with ataxia and retarded motor development, type II by a stationary deafness of a moderate degree, and type III by a progressive deafness with adult onset. In Germany, Usher syndrome currently bears particular relevance because in January 2009 a new compulsory screening of auditory function in newborn infants was introduced. Consequently, it can be expected that a higher number of patients with Usher syndrome will be identified in early childhood and referred to ophthalmologists. The focus of this work is to introduce the typical clinical picture of Usher syndrome, summarize diagnostic options, and give an overview of therapeutic strategies.

Profilin sensitization detected in the office by skin prick test: a study of prevalence and clinical relevance of profilin as a plant food allergen.

PubMed

Asero, R; Monsalve, R; Barber, D

2008-06-01

Profilin, a pan-allergen present in all eukaryotic cells, is one of the main causes of cross-sensitization between pollen and plant-derived foods, but its clinical relevance as a food allergen is still debated. To investigate the prevalence of profilin sensitization in a pollen-allergic population and its clinical relevance as a food allergen. Two hundred consecutive patients with pollen allergy underwent skin prick tests (SPT) with purified natural date palm profilin (Pho d 2; 50 microg/mL; Alk Abello, Madrid, Spain). Those reporting adverse reactions to foods (confirmed by SPT with either commercial food extracts or fresh foods) underwent SPT with an apple extract containing uniquely Mal d 1 (2 microg/mL; ALK-Abello), and with a commercial peach extract containing uniquely lipid transfer protein (LTP 30 microg/mL; ALK-Abello). Sixty patients (30%) showed skin reactivity to date palm profilin, Pho d 2. All were sensitized to grass pollen, and most of them reacted to birch, mugwort, ragweed and plantain pollen as well. SPT with pellitory and cypress scored negative in a high proportion of profilin reactors [26/60 (43%) and 33/60 (55%), respectively]. More than one half (34/60 [57%]) of profilin reactors had food allergy; 21 of these were monosensitized to profilin, 11 were sensitized to both profilin and Bet v 1 homologous protein, one to both profilin and LTP, and one to all the three allergens. The large majority of profilin-allergic patients reported oral allergy syndrome as the only food-induced symptom and were able to tolerate the offending foods if they were cooked or otherwise processed. Twenty-eight of 34 reported reactivity to two or more plant-derived foods. Rosaceae, tree nuts, melon and watermelon, tomato, pineapple, citrus fruits and banana were the more frequently offending foods. Profilin should be considered a clinically relevant food allergen. Allergy to melon, watermelon, tomato, banana, pineapple and orange may be considered as a marker of profilin hypersensitivity. This study underlines the clinical importance of being able to diagnose hypersensitivity to single food allergenic proteins by SPT, particularly when the relevant food allergen sources contain several allergens that show different chemical/physical features and, hence, completely different risk profiles.

Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumors in patients

PubMed Central

Grisanzio, Chiara; Seeley, Apryle; Chang, Michelle; Collins, Michael; Di Napoli, Arianna; Cheng, Su-Chun; Percy, Andrew; Beroukhim, Rameen; Signoretti, Sabina

2013-01-01

Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumor tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphologic, phenotypic, and genetic characteristics of the kidney tumor tissues before and after implantation. Twenty kidney tumors were transplanted into mice. Successful tumor growth was detected in 19 cases (95%). The histopathologic and immunophenotypic features of the xenografts and those of the original tumors largely overlapped in all the cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumors and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6 of 10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing, and for deeper understanding of kidney carcinogenesis. PMID:21710693

Modeling the Evolution of Beliefs Using an Attentional Focus Mechanism

PubMed Central

Marković, Dimitrije; Gläscher, Jan; Bossaerts, Peter; O’Doherty, John; Kiebel, Stefan J.

2015-01-01

For making decisions in everyday life we often have first to infer the set of environmental features that are relevant for the current task. Here we investigated the computational mechanisms underlying the evolution of beliefs about the relevance of environmental features in a dynamical and noisy environment. For this purpose we designed a probabilistic Wisconsin card sorting task (WCST) with belief solicitation, in which subjects were presented with stimuli composed of multiple visual features. At each moment in time a particular feature was relevant for obtaining reward, and participants had to infer which feature was relevant and report their beliefs accordingly. To test the hypothesis that attentional focus modulates the belief update process, we derived and fitted several probabilistic and non-probabilistic behavioral models, which either incorporate a dynamical model of attentional focus, in the form of a hierarchical winner-take-all neuronal network, or a diffusive model, without attention-like features. We used Bayesian model selection to identify the most likely generative model of subjects’ behavior and found that attention-like features in the behavioral model are essential for explaining subjects’ responses. Furthermore, we demonstrate a method for integrating both connectionist and Bayesian models of decision making within a single framework that allowed us to infer hidden belief processes of human subjects. PMID:26495984

Insight in pediatric obsessive-compulsive disorder: associations with clinical presentation.

PubMed

Storch, Eric A; Milsom, Vanessa A; Merlo, Lisa J; Larson, Michael; Geffken, Gary R; Jacob, Marni L; Murphy, Tanya K; Goodman, Wayne K

2008-08-15

Insight has emerged as a significant treatment outcome predictor in adult obsessive-compulsive disorder (OCD), with some suggesting that OCD with poor insight represents a distinct clinical subtype. Despite its clinical relevance, limited data exist on insight in pediatric OCD patients. The present study investigated the relation between poor insight and clinical characteristics among children and adolescents with OCD (N=78, ages 6-20 years). Forty-five percent of the sample (n=35) was considered to have low levels of insight into their symptoms, as determined by clinician rating on item 11 of the Children's Yale-Brown Obsessive-Compulsive Scale. Pearson product-moment correlations showed a significant, inverse relation between insight and OCD severity. Relative to the high insight group, parents of patients with low insight reported higher levels of OCD-related impairment and family accommodation. These findings suggest that OCD with poor insight may represent a distinct clinical feature that may require more intensive and multimodal treatment approaches.

A bootstrap based Neyman-Pearson test for identifying variable importance.

PubMed

Ditzler, Gregory; Polikar, Robi; Rosen, Gail

2015-04-01

Selection of most informative features that leads to a small loss on future data are arguably one of the most important steps in classification, data analysis and model selection. Several feature selection (FS) algorithms are available; however, due to noise present in any data set, FS algorithms are typically accompanied by an appropriate cross-validation scheme. In this brief, we propose a statistical hypothesis test derived from the Neyman-Pearson lemma for determining if a feature is statistically relevant. The proposed approach can be applied as a wrapper to any FS algorithm, regardless of the FS criteria used by that algorithm, to determine whether a feature belongs in the relevant set. Perhaps more importantly, this procedure efficiently determines the number of relevant features given an initial starting point. We provide freely available software implementations of the proposed methodology.

Mammogram classification scheme using 2D-discrete wavelet and local binary pattern for detection of breast cancer

NASA Astrophysics Data System (ADS)

Adi Putra, Januar

2018-04-01

In this paper, we propose a new mammogram classification scheme to classify the breast tissues as normal or abnormal. Feature matrix is generated using Local Binary Pattern to all the detailed coefficients from 2D-DWT of the region of interest (ROI) of a mammogram. Feature selection is done by selecting the relevant features that affect the classification. Feature selection is used to reduce the dimensionality of data and features that are not relevant, in this paper the F-test and Ttest will be performed to the results of the feature extraction dataset to reduce and select the relevant feature. The best features are used in a Neural Network classifier for classification. In this research we use MIAS and DDSM database. In addition to the suggested scheme, the competent schemes are also simulated for comparative analysis. It is observed that the proposed scheme has a better say with respect to accuracy, specificity and sensitivity. Based on experiments, the performance of the proposed scheme can produce high accuracy that is 92.71%, while the lowest accuracy obtained is 77.08%.

Selecting relevant 3D image features of margin sharpness and texture for lung nodule retrieval.

PubMed

Ferreira, José Raniery; de Azevedo-Marques, Paulo Mazzoncini; Oliveira, Marcelo Costa

2017-03-01

Lung cancer is the leading cause of cancer-related deaths in the world. Its diagnosis is a challenge task to specialists due to several aspects on the classification of lung nodules. Therefore, it is important to integrate content-based image retrieval methods on the lung nodule classification process, since they are capable of retrieving similar cases from databases that were previously diagnosed. However, this mechanism depends on extracting relevant image features in order to obtain high efficiency. The goal of this paper is to perform the selection of 3D image features of margin sharpness and texture that can be relevant on the retrieval of similar cancerous and benign lung nodules. A total of 48 3D image attributes were extracted from the nodule volume. Border sharpness features were extracted from perpendicular lines drawn over the lesion boundary. Second-order texture features were extracted from a cooccurrence matrix. Relevant features were selected by a correlation-based method and a statistical significance analysis. Retrieval performance was assessed according to the nodule's potential malignancy on the 10 most similar cases and by the parameters of precision and recall. Statistical significant features reduced retrieval performance. Correlation-based method selected 2 margin sharpness attributes and 6 texture attributes and obtained higher precision compared to all 48 extracted features on similar nodule retrieval. Feature space dimensionality reduction of 83 % obtained higher retrieval performance and presented to be a computationaly low cost method of retrieving similar nodules for the diagnosis of lung cancer.

Renal oncocytoma with invasive histopathologic features -  case report.

PubMed

Kolníková, G; Marinová, P; Gál, V; Mečiarová, I; Mišanko, V; Rampalová, J; Jáni, P; Orthová, S; Ondriaš, F; Caňo, M

2014-01-01

Renal oncocytoma is an uncommon tumor, classified as a benign renal neoplasm in the World Health Organisation classification of renal tumours. Despite it there were described several reports with invasive histopathologic features. We describe a case of renal oncocytoma with bizzare cells and invasion of renal sinus fat tissue. We performed immunohistochemical analysis of the case and a review of relevant literature. In order to set up the right dia-gnosis the perfect co- operation of clinicians and pathologists is necessary. In our opinion, in accordance with other authors, the renal oncocytomas should be considered as having a very low rather than no malignant potential, in spite of clinically benign behavior, supplementing a hypothesis, whether renal oncocytomas may be considered as a precancerous lesion of chromophobe carcinoma.

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force

PubMed Central

Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G; Dols, Annemiek; Al Jurdi, Rayan K; Forester, Brent P; Kessing, Lars Vedel; Beyer, John; Manes, Facundo; Rej, Soham; Rosa, Adriane R; Schouws, Sigfried NTM; Tsai, Shang-Ying; Young, Robert C; Shulman, Kenneth I

2015-01-01

Objectives In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). Methods This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. Results The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data has brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Conclusions Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. PMID:26384588

The effects of repeated nitroglycerin administrations in rats; modeling migraine-related endpoints and chronification.

PubMed

Harris, Hannah M; Carpenter, Jessica M; Black, Jonathan R; Smitherman, Todd A; Sufka, Kenneth J

2017-06-01

Rodent models typically use a single nitroglycerin injection to induce migraine, yet migraine in clinical populations presents as recurrent episodes. Further, these models quantify behavioral endpoints that do not align with the clinical features of episodic migraine or migraine chronification and therefore may limit translational relevance. Rats received 5 nitroglycerin (10mg/kg/2ml), propylene glycol/ethanol vehicle, or saline injections every third day over 15days. Behavioral endpoints were assessed 110min post nitroglycerin administration and included time spent light/dark chambers for photophobia as well as activity, facial pain expressions, and tactile allodynia. Animals administered nitroglycerin displayed photophobia, decreased activity, and increased facial pain expression. Similar alterations in photophobia and activity were seen in the vehicle treated animals, but these tended to diminish by the 4th or 5th injection. The presentation of spontaneous tactile allodynia was observed in the nitroglycerin group by the 5th episode. Most NTG migraine models entail a single NTG administration and quantification of evoked allodynia. This paradigm employs recurring NTG episodes and clinically-relevant measures of photophobia, hypoactivity and facial grimace endpoints as well as introduces a novel arena apparatus to quantify spontaneous allodynia. This repeated NTG procedure and endpoint measures aligns with the frequency and clinical presentation of episodic migraine and its chronification, respectively. Further, propylene glycol ethanol vehicle contributes to migraine endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

eGARD: Extracting associations between genomic anomalies and drug responses from text

PubMed Central

Rao, Shruti; McGarvey, Peter; Wu, Cathy; Madhavan, Subha; Vijay-Shanker, K.

2017-01-01

Tumor molecular profiling plays an integral role in identifying genomic anomalies which may help in personalizing cancer treatments, improving patient outcomes and minimizing risks associated with different therapies. However, critical information regarding the evidence of clinical utility of such anomalies is largely buried in biomedical literature. It is becoming prohibitive for biocurators, clinical researchers and oncologists to keep up with the rapidly growing volume and breadth of information, especially those that describe therapeutic implications of biomarkers and therefore relevant for treatment selection. In an effort to improve and speed up the process of manually reviewing and extracting relevant information from literature, we have developed a natural language processing (NLP)-based text mining (TM) system called eGARD (extracting Genomic Anomalies association with Response to Drugs). This system relies on the syntactic nature of sentences coupled with various textual features to extract relations between genomic anomalies and drug response from MEDLINE abstracts. Our system achieved high precision, recall and F-measure of up to 0.95, 0.86 and 0.90, respectively, on annotated evaluation datasets created in-house and obtained externally from PharmGKB. Additionally, the system extracted information that helps determine the confidence level of extraction to support prioritization of curation. Such a system will enable clinical researchers to explore the use of published markers to stratify patients upfront for ‘best-fit’ therapies and readily generate hypotheses for new clinical trials. PMID:29261751

Clinical relevance in anesthesia journals.

PubMed

Lauritsen, Jakob; Møller, Ann M

2006-04-01

The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles. In the last few years, more attention has been paid to evidence-based medicine in anesthesia. Several articles on the subject have focused on the need to base clinical decisions on sound research employing both methodological rigor and clinically relevant outcomes. The number of systematic reviews in anesthesia literature is increasing as well as the focus on diminishing the number of surrogate outcomes. It has been shown that the impact factor is not a valid measure of establishing the level of clinical relevance to a journal. This review presents definitions of clinically relevant anesthesia articles. A clinically relevant article employs both methodological rigor and a clinically relevant outcome. The terms methodological rigor and clinical outcomes are fully discussed in the review as well as problems with journal impact factors.

Attention improves encoding of task-relevant features in the human visual cortex

PubMed Central

Jehee, Janneke F.M.; Brady, Devin K.; Tong, Frank

2011-01-01

When spatial attention is directed towards a particular stimulus, increased activity is commonly observed in corresponding locations of the visual cortex. Does this attentional increase in activity indicate improved processing of all features contained within the attended stimulus, or might spatial attention selectively enhance the features relevant to the observer’s task? We used fMRI decoding methods to measure the strength of orientation-selective activity patterns in the human visual cortex while subjects performed either an orientation or contrast discrimination task, involving one of two laterally presented gratings. Greater overall BOLD activation with spatial attention was observed in areas V1-V4 for both tasks. However, multivariate pattern analysis revealed that orientation-selective responses were enhanced by attention only when orientation was the task-relevant feature, and not when the grating’s contrast had to be attended. In a second experiment, observers discriminated the orientation or color of a specific lateral grating. Here, orientation-selective responses were enhanced in both tasks but color-selective responses were enhanced only when color was task-relevant. In both experiments, task-specific enhancement of feature-selective activity was not confined to the attended stimulus location, but instead spread to other locations in the visual field, suggesting the concurrent involvement of a global feature-based attentional mechanism. These results suggest that attention can be remarkably selective in its ability to enhance particular task-relevant features, and further reveal that increases in overall BOLD amplitude are not necessarily accompanied by improved processing of stimulus information. PMID:21632942

Attention improves encoding of task-relevant features in the human visual cortex.

PubMed

Jehee, Janneke F M; Brady, Devin K; Tong, Frank

2011-06-01

When spatial attention is directed toward a particular stimulus, increased activity is commonly observed in corresponding locations of the visual cortex. Does this attentional increase in activity indicate improved processing of all features contained within the attended stimulus, or might spatial attention selectively enhance the features relevant to the observer's task? We used fMRI decoding methods to measure the strength of orientation-selective activity patterns in the human visual cortex while subjects performed either an orientation or contrast discrimination task, involving one of two laterally presented gratings. Greater overall BOLD activation with spatial attention was observed in visual cortical areas V1-V4 for both tasks. However, multivariate pattern analysis revealed that orientation-selective responses were enhanced by attention only when orientation was the task-relevant feature and not when the contrast of the grating had to be attended. In a second experiment, observers discriminated the orientation or color of a specific lateral grating. Here, orientation-selective responses were enhanced in both tasks, but color-selective responses were enhanced only when color was task relevant. In both experiments, task-specific enhancement of feature-selective activity was not confined to the attended stimulus location but instead spread to other locations in the visual field, suggesting the concurrent involvement of a global feature-based attentional mechanism. These results suggest that attention can be remarkably selective in its ability to enhance particular task-relevant features and further reveal that increases in overall BOLD amplitude are not necessarily accompanied by improved processing of stimulus information.

Relevance of and New Developments in Serology for Toxoplasmosis.

PubMed

Dard, Céline; Fricker-Hidalgo, Hélène; Brenier-Pinchart, Marie-Pierre; Pelloux, Hervé

2016-06-01

Toxoplasmosis is a widespread parasitic disease caused by the intracellular parasite Toxoplasma gondii with a wide spectrum of clinical outcomes. The biological diagnosis of toxoplasmosis is often difficult and of paramount importance because clinical features are not sufficient to discriminate between toxoplasmosis and other illnesses. Serological tests are the most widely used biological tools for the diagnosis of toxoplasmosis worldwide. This review focuses on the crucial role of serology in providing answers to the most important questions related to the epidemiology and diagnosis of toxoplasmosis in human pathology. Notwithstanding their undeniable importance, serological tools need to be continuously improved and the interpretation of the ensuing results remains complex in many circumstances. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scleroderma renal crisis in a case of mixed connective tissue disease.

PubMed

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

Spatial modeling and classification of corneal shape.

PubMed

Marsolo, Keith; Twa, Michael; Bullimore, Mark A; Parthasarathy, Srinivasan

2007-03-01

One of the most promising applications of data mining is in biomedical data used in patient diagnosis. Any method of data analysis intended to support the clinical decision-making process should meet several criteria: it should capture clinically relevant features, be computationally feasible, and provide easily interpretable results. In an initial study, we examined the feasibility of using Zernike polynomials to represent biomedical instrument data in conjunction with a decision tree classifier to distinguish between the diseased and non-diseased eyes. Here, we provide a comprehensive follow-up to that work, examining a second representation, pseudo-Zernike polynomials, to determine whether they provide any increase in classification accuracy. We compare the fidelity of both methods using residual root-mean-square (rms) error and evaluate accuracy using several classifiers: neural networks, C4.5 decision trees, Voting Feature Intervals, and Naïve Bayes. We also examine the effect of several meta-learning strategies: boosting, bagging, and Random Forests (RFs). We present results comparing accuracy as it relates to dataset and transformation resolution over a larger, more challenging, multi-class dataset. They show that classification accuracy is similar for both data transformations, but differs by classifier. We find that the Zernike polynomials provide better feature representation than the pseudo-Zernikes and that the decision trees yield the best balance of classification accuracy and interpretability.

Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson's disease.

PubMed

Iakovakis, Dimitrios; Hadjidimitriou, Stelios; Charisis, Vasileios; Bostantzopoulou, Sevasti; Katsarou, Zoe; Hadjileontiadis, Leontios J

2018-05-16

Parkinson's disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients' quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject's status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.

Diarylpyrimidine-dihydrobenzyloxopyrimidine hybrids: new, wide-spectrum anti-HIV-1 agents active at (sub)-nanomolar level.

PubMed

Rotili, Dante; Tarantino, Domenico; Artico, Marino; Nawrozkij, Maxim B; Gonzalez-Ortega, Emmanuel; Clotet, Bonaventura; Samuele, Alberta; Esté, José A; Maga, Giovanni; Mai, Antonello

2011-04-28

Here, we describe a novel small series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine peculiar structural features of diarylpyrimidines (DAPYs) and dihydro-alkoxy-benzyl-oxopyrimidines (DABOs). These DAPY-DABO hybrids (1-4) showed a characteristic SAR profile and a nanomolar anti-HIV-1 activity at both enzymatic and cellular level. In particular, the two compounds 4d and 2d, with a (sub)nanomolar activity against wild-type and clinically relevant HIV-1 mutant strains, were selected as lead compounds for next optimization studies.

Autism: Oxytocin, serotonin, and social reward.

PubMed

Dölen, Gül

2015-01-01

Over 70 years since the first description of the disease, disrupted social behavior remains a core clinical feature of autistic spectrum disorder. The complex etiology of the disorder portends the need for a better understanding of the brain mechanisms that enable social behaviors, particularly those that are relevant to autism which is characterized by a failure to develop peer relationships, difficulty with emotional reciprocity and imitative play, and disrupted language and communication skills. Toward this end, the current review will examine recent progress that has been made toward understanding the neural mechanisms underlying consociate social attachments.

Cerebrotendinous xanthomatosis.

PubMed

van Hellenberg Hubar, J L; Joosten, E M; Wevers, R A

1992-01-01

Cerebrotendinous xanthomatosis (CTX) is a familial sterol storage disease based on an inborn error of metabolism involving bile acid synthesis. Predominant clinical features are a chronic progressive neurological syndrome, mental deterioration, bilateral cataract and xanthomas. The presence of xanthomas usually leads to the diagnosis, and the reverse is probably also true: without xanthomas the diagnosis will often not be made. CTX may therefore be less rare than commonly thought, and the incidence of xanthomas in CTX may be overestimated. Four cases without xanthomas among the presenting symptoms are described, and the relevance of xanthomas in CTX is discussed.

Roel Verhaak, Ph.D., Presents the Somatic Genomic Landscape of Glioblastoma - TCGA

Cancer.gov

Diffuse lower grade gliomas (LGGs) are infiltrative neoplasms of the central nervous system that include astrocytoma, oligodendroglioma and oligo-astrocytoma histologies of grades II and III. Roel G.W. Verhaak, Ph.D., presents a comprehensive analysis of 293 LGGs using multiple advanced genomic, transcriptomic and proteomic platforms from The Cancer Genome Atlas to provide a deeper understanding of the molecular features of this group of neoplasms, to classify them in a clinically-relevant manner, and to provide a public resource that identifies potential targets for emerging therapies.

Automatic detection of diabetic retinopathy features in ultra-wide field retinal images

NASA Astrophysics Data System (ADS)

Levenkova, Anastasia; Sowmya, Arcot; Kalloniatis, Michael; Ly, Angelica; Ho, Arthur

2017-03-01

Diabetic retinopathy (DR) is a major cause of irreversible vision loss. DR screening relies on retinal clinical signs (features). Opportunities for computer-aided DR feature detection have emerged with the development of Ultra-WideField (UWF) digital scanning laser technology. UWF imaging covers 82% greater retinal area (200°), against 45° in conventional cameras3 , allowing more clinically relevant retinopathy to be detected4 . UWF images also provide a high resolution of 3078 x 2702 pixels. Currently DR screening uses 7 overlapping conventional fundus images, and the UWF images provide similar results1,4. However, in 40% of cases, more retinopathy was found outside the 7-field ETDRS) fields by UWF and in 10% of cases, retinopathy was reclassified as more severe4 . This is because UWF imaging allows examination of both the central retina and more peripheral regions, with the latter implicated in DR6 . We have developed an algorithm for automatic recognition of DR features, including bright (cotton wool spots and exudates) and dark lesions (microaneurysms and blot, dot and flame haemorrhages) in UWF images. The algorithm extracts features from grayscale (green "red-free" laser light) and colour-composite UWF images, including intensity, Histogram-of-Gradient and Local binary patterns. Pixel-based classification is performed with three different classifiers. The main contribution is the automatic detection of DR features in the peripheral retina. The method is evaluated by leave-one-out cross-validation on 25 UWF retinal images with 167 bright lesions, and 61 other images with 1089 dark lesions. The SVM classifier performs best with AUC of 94.4% / 95.31% for bright / dark lesions.

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions

PubMed Central

Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro

2017-01-01

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions. PMID:28700720

Too upset to think: the interplay of borderline personality features, negative emotions, and social problem solving in the laboratory.

PubMed

Dixon-Gordon, Katherine L; Chapman, Alexander L; Lovasz, Nathalie; Walters, Kris

2011-10-01

Borderline personality disorder (BPD) is associated with poor social problem solving and problems with emotion regulation. In this study, the social problem-solving performance of undergraduates with high (n = 26), mid (n = 32), or low (n = 29) levels of BPD features was assessed with the Social Problem-Solving Inventory-Revised and using the means-ends problem-solving procedure before and after a social rejection stressor. The high-BP group, but not the low-BP group, showed a significant reduction in relevant solutions to social problems and more inappropriate solutions following the negative emotion induction. Increases in self-reported negative emotions during the emotion induction mediated the relationship between BP features and reductions in social problem-solving performance. In addition, the high-BP group demonstrated trait deficits in social problem solving on the Social Problem-Solving Inventory-Revised. These findings suggest that future research must examine social problem solving under differing emotional conditions, and that clinical interventions to improve social problem solving among persons with BP features should focus on responses to emotional contexts.

Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions.

PubMed

Rodríguez, Alejandro; Tembl, José; Mesa-Gresa, Patricia; Muñoz, Miguel Ángel; Montoya, Pedro; Rey, Beatriz

2017-01-01

The aim of this study is to characterize in resting-state conditions the cerebral blood flow velocity (CBFV) signals of fibromyalgia patients. The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors. The characterization features were used in a lineal model to discriminate between fibromyalgia patients and healthy controls, providing a high accuracy. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions.

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries.

PubMed

Noor, Siti Salwa Md; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-11-16

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability.

Borderline Personality Disorder and Self-Conscious Affect: Too Much Shame But Not Enough Guilt?

PubMed Central

Peters, Jessica R.; Geiger, Paul J.

2016-01-01

Shame has emerged as a particularly relevant emotion to the maintenance and exacerbation of borderline personality disorder (BPD) features; however, little attention has been paid to the potentially differing effects of other forms of self-conscious affect. While guilt has been demonstrated to have adaptive functions in the social psychology literature, it has not been previously explored whether a lack of socially adaptive guilt might also contribute to BPD-related dysfunction. The present study examined the relationship between BPD features and self-conscious emotions in a sample of undergraduate students (n=839). Increased shame and decreased guilt independently accounted for significant variance in the association between BPD features and anger, hostility, and externalization of blame. Only increased shame significantly mediated the association between BPD features and anger rumination, and only decreased guilt significantly mediated the relationship between BPD features and aggression. These findings suggest BPD and its associated problems with anger and externalizing may be characterized not only by high levels of shame, but also by lower levels of guilt. Clinical implications include the need to differentiate between self-conscious emotions and teach adaptive responses to warranted guilt. PMID:26866901

Borderline personality disorder and self-conscious affect: Too much shame but not enough guilt?

PubMed

Peters, Jessica R; Geiger, Paul J

2016-07-01

Shame has emerged as a particularly relevant emotion to the maintenance and exacerbation of borderline personality disorder (BPD) features; however, little attention has been paid to the potentially differing effects of other forms of self-conscious affect. While guilt has been demonstrated to have adaptive functions in the social psychology literature, it has not been previously explored whether a lack of socially adaptive guilt might also contribute to BPD-related dysfunction. The present study examined the relationship between BPD features and self-conscious emotions in a sample of undergraduate students (n = 839). Increased shame and decreased guilt independently accounted for significant variance in the association between BPD features and anger, hostility, and externalization of blame. Only increased shame significantly mediated the association between BPD features and anger rumination, and only decreased guilt significantly mediated the relationship between BPD features and aggression. These findings suggest BPD and its associated problems with anger and externalizing may be characterized not only by high levels of shame, but also by lower levels of guilt. Clinical implications include the need to differentiate between self-conscious emotions and teach adaptive responses to warranted guilt. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Inconsistency as a diagnostic tool in a society of intelligent agents.

PubMed

McShane, Marjorie; Beale, Stephen; Nirenburg, Sergei; Jarrell, Bruce; Fantry, George

2012-07-01

To use the detection of clinically relevant inconsistencies to support the reasoning capabilities of intelligent agents acting as physicians and tutors in the realm of clinical medicine. We are developing a cognitive architecture, OntoAgent, that supports the creation and deployment of intelligent agents capable of simulating human-like abilities. The agents, which have a simulated mind and, if applicable, a simulated body, are intended to operate as members of multi-agent teams featuring both artificial and human agents. The agent architecture and its underlying knowledge resources and processors are being developed in a sufficiently generic way to support a variety of applications. We show how several types of inconsistency can be detected and leveraged by intelligent agents in the setting of clinical medicine. The types of inconsistencies discussed include: test results not supporting the doctor's hypothesis; the results of a treatment trial not supporting a clinical diagnosis; and information reported by the patient not being consistent with observations. We show the opportunities afforded by detecting each inconsistency, such as rethinking a hypothesis, reevaluating evidence, and motivating or teaching a patient. Inconsistency is not always the absence of the goal of consistency; rather, it can be a valuable trigger for further exploration in the realm of clinical medicine. The OntoAgent cognitive architecture, along with its extensive suite of knowledge resources an processors, is sufficient to support sophisticated agent functioning such as detecting clinically relevant inconsistencies and using them to benefit patient-centered medical training and practice. Copyright © 2012 Elsevier B.V. All rights reserved.

Reliability, Validity and Treatment Sensitivity of the Schizophrenia Cognition Rating Scale

PubMed Central

Keefe, Richard S.E.; Davis, Vicki G.; Spagnola, Nathan B.; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas L.; Narasimhan, Meera; Harvey, Philip D.

2014-01-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r= −0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient self-report is the sole information source. PMID:25028065

Reliability, validity and treatment sensitivity of the Schizophrenia Cognition Rating Scale.

PubMed

Keefe, Richard S E; Davis, Vicki G; Spagnola, Nathan B; Hilt, Dana; Dgetluck, Nancy; Ruse, Stacy; Patterson, Thomas D; Narasimhan, Meera; Harvey, Philip D

2015-02-01

Cognitive functioning can be assessed with performance-based assessments such as neuropsychological tests and with interview-based assessments. Both assessment methods have the potential to assess whether treatments for schizophrenia improve clinically relevant aspects of cognitive impairment. However, little is known about the reliability, validity and treatment responsiveness of interview-based measures, especially in the context of clinical trials. Data from two studies were utilized to assess these features of the Schizophrenia Cognition Rating Scale (SCoRS). One of the studies was a validation study involving 79 patients with schizophrenia assessed at 3 academic research centers in the US. The other study was a 32-site clinical trial conducted in the US and Europe comparing the effects of encenicline, an alpha-7 nicotine agonist, to placebo in 319 patients with schizophrenia. The SCoRS interviewer ratings demonstrated excellent test-retest reliability in several different circumstances, including those that did not involve treatment (ICC> 0.90), and during treatment (ICC>0.80). SCoRS interviewer ratings were related to cognitive performance as measured by the MCCB (r=-0.35), and demonstrated significant sensitivity to treatment with encenicline compared to placebo (P<.001). These data suggest that the SCoRS has potential as a clinically relevant measure in clinical trials aiming to improve cognition in schizophrenia, and may be useful for clinical practice. The weaknesses of the SCoRS include its reliance on informant information, which is not available for some patients, and reduced validity when patient's self-report is the sole information source. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Targeting targeted agents: open issues for clinical trial design.

PubMed

Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

2009-05-22

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

Treating impaired cognition in schizophrenia: the case for combining cognitive-enhancing drugs with cognitive remediation.

PubMed

Michalopoulou, Panayiota G; Lewis, Shôn W; Wykes, Til; Jaeger, Judith; Kapur, Shitij

2013-08-01

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Publications in anesthesia journals: quality and clinical relevance.

PubMed

Lauritsen, Jakob; Moller, Ann M

2004-11-01

Clinicians performing evidence-based anesthesia rely on anesthesia journals for clinically relevant information. The objective of this study was to analyze the proportion of clinically relevant articles in five high impact anesthesia journals. We evaluated all articles published in Anesthesiology, Anesthesia & Analgesia, British Journal of Anesthesia, Anesthesia, and Acta Anaesthesiologica Scandinavica from January to June, 2000. Articles were assessed and classified according to type, outcome, and design; 1379 articles consisting of 5468 pages were evaluated and categorized. The most common types of article were animal and laboratory research (31.2%) and randomized clinical trial (20.4%). A clinically relevant article was defined as an article that used a statistically valid method and had a clinically relevant end-point. Altogether 18.6% of the pages had as their subject matter clinically relevant trials. We compared the Journal Impact Factor (a measure of the number of citations per article in a journal) and the proportion of clinically relevant pages and found that they were inversely proportional to each other.

Modelling fragile X syndrome in the laboratory setting: A behavioral perspective.

PubMed

Melancia, Francesca; Trezza, Viviana

2018-04-25

Fragile X syndrome is the most common form of inherited mental retardation and the most frequent monogenic cause of syndromic autism spectrum disorders. The syndrome is caused by the loss of the Fragile X Mental Retardation Protein (FMRP), a key RNA-binding protein involved in synaptic plasticity and neuronal morphology. Patients show intellectual disability, social deficits, repetitive behaviors and impairments in social communication. The aim of this review is to outline the importance of behavioral phenotyping of animal models of FXS from a developmental perspective, by showing how the behavioral characteristics of FXS at the clinical level can be translated into effective, developmentally-specific and clinically meaningful behavioral readouts in the laboratory setting. After introducing the behavioral features, diagnostic criteria and off-label pharmacotherapy of FXS, we outline how FXS-relevant behavioral features can be modelled in laboratory animals in the course of development: we review the progress to date, discuss how behavioral phenotyping in animal models of FXS is essential to identify potential treatments, and discuss caveats and future directions in this research field. Copyright © 2018. Published by Elsevier B.V.

Is filtering difficulty the basis of attentional deficits in schizophrenia?

PubMed

Ravizza, Susan M; Robertson, Lynn C; Carter, Cameron S; Nordahl, Thomas E; Salo, Ruth E

2007-06-30

The distractibility that schizophrenia patients display may be the result of a deficiency in filtering out irrelevant information. The aim of the current study was to assess whether patients with schizophrenia exhibit greater difficulty when task-irrelevant features change compared to healthy participants. Thirteen medicated outpatients with a diagnosis of schizophrenia and thirteen age- and parental education-matched controls performed a target selection task in which the task-relevant letter or the task-irrelevant features of color, and/or location repeated or switched. Participants were required to respond by pressing the appropriate key associated with the target letter. These patients with schizophrenia were slower when the task-relevant target letter switched than when it repeated. In contrast, schizophrenia patients performed similarly to controls when task-irrelevant information changed. Thus, we found no evidence that patients with schizophrenia were impaired in inhibiting irrelevant perceptual features. In contrast, changes in task-relevant features were problematic for patients relative to control participants. These results suggest that medicated outpatients who are mild to moderately symptomatic do not exhibit global impairments of feature processing. Instead, impairments are restricted to situations when task-relevant features vary. The current findings also suggest that when a course of action is not implied by an irrelevant feature, outpatients' behavior is not modulated by extraneous visual information any more than in healthy controls.

Subacute sclerosing panencephalitis presenting as acute cerebellar ataxia and brain stem hyperintensities.

PubMed

Saini, Arushi Gahlot; Sankhyan, Naveen; Padmanabh, Hansashree; Sahu, Jitendra Kumar; Vyas, Sameer; Singhi, Pratibha

2016-05-01

Subacute sclerosing panencephalitis is a devastating neurodegenerative disease with a characteristic clinical course. Atypical presentations may be seen in 10% of the cases. To describe the atypical clinical and radiological features of SSPE in a child form endemic country. A 5-year-old boy presented with acute-onset cerebellar ataxia without associated encephalopathy, focal motor deficits, seizures or cognitive decline. He had varicella-like illness with vesicular, itchy truncal rash erupting one month prior to the onset of these symptoms. He underwent detailed neurological assessment, relevant laboratory and radiological investigations. Neuroimaging revealed peculiar brain stem lesions involving the pons and cerebellum suggestive of demyelination. With a presumptive diagnosis of clinically isolated syndrome of demyelination, he was administered pulse methylprednisolone (30 mg/kg/day for 5 days). Four weeks later he developed myoclonic jerks. Electroencephalogram showed characteristic periodic complexes time-locked with myoclonus. CSF and serum anti-measles antibody titres were elevated (1:625). Our report highlights that subacute sclerosing panencephalitis can present atypically as isolated acute cerebellar ataxia and peculiar involvement of longitudinal and sparing of transverse pontine fibres. The predominant brainstem abnormalities in the clinical setting may mimick acute demyelinating syndrome. Hence, it is important to recognize these features of subacute sclerosing panencephalitis in children, especially in the endemic countries. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The clinical features of the overlap between COPD and asthma

PubMed Central

2011-01-01

Background The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma. Methods We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study. Results 119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness. Conclusion Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history. Trial registration ClinicalTrials.gov: NCT00608764 PMID:21951550

Clinical Relevance of Coronary Fractional Flow Reserve: Art-of-state

PubMed Central

Adiputra, Yohanes; Chen, Shao-Liang

2015-01-01

Objective: The objective was to delineate the current knowledge of fractional flow reserve (FFR) in terms of definition, features, clinical applications, and pitfalls of measurement of FFR. Data Sources: We searched database for primary studies published in English. The database of National Library of Medicine (NLM), MEDLINE, and PubMed up to July 2014 was used to conduct a search using the keyword term “FFR”. Study Selection: The articles about the definition, features, clinical application, and pitfalls of measurement of FFR were identified, retrieved, and reviewed. Results: Coronary pressure-derived FFR rapidly assesses the hemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterization laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes. Conclusions: FFR is a valuable tool to determine the functional significance of coronary stenosis. It combines physiological and anatomical information, and can be followed immediately by percutaneous coronary intervention (PCI) if necessary. The technique of FFR measurement can be performed easily, rapidly, and safely in the catheterization laboratory. By systematic use of FFR in dubious stenosis and multi-vessel disease, PCI can be made an even more effective and better treatment than it is currently. The current clinical evidence for FFR should encourage cardiologists to use this tool in the catheterization laboratory. PMID:25963364

Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds.

PubMed

Smith, E E; Angstadt, S; Monteiro, N; Zhang, W; Khademhosseini, A; Yelick, P C

2018-06-01

Tooth loss is a significant health issue currently affecting millions of people worldwide. Artificial dental implants, the current gold standard tooth replacement therapy, do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Here we propose bioengineered tooth buds as a superior alternative tooth replacement therapy. We describe improved methods to create highly cellularized bioengineered tooth bud constructs that formed hallmark features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells, and mineralized dental tissue formation. These constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats. To our knowledge, this is the first report describing the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development. We propose future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.

EEG-based emotion recognition in music listening.

PubMed

Lin, Yuan-Pin; Wang, Chi-Hong; Jung, Tzyy-Ping; Wu, Tien-Lin; Jeng, Shyh-Kang; Duann, Jeng-Ren; Chen, Jyh-Horng

2010-07-01

Ongoing brain activity can be recorded as electroencephalograph (EEG) to discover the links between emotional states and brain activity. This study applied machine-learning algorithms to categorize EEG dynamics according to subject self-reported emotional states during music listening. A framework was proposed to optimize EEG-based emotion recognition by systematically 1) seeking emotion-specific EEG features and 2) exploring the efficacy of the classifiers. Support vector machine was employed to classify four emotional states (joy, anger, sadness, and pleasure) and obtained an averaged classification accuracy of 82.29% +/- 3.06% across 26 subjects. Further, this study identified 30 subject-independent features that were most relevant to emotional processing across subjects and explored the feasibility of using fewer electrodes to characterize the EEG dynamics during music listening. The identified features were primarily derived from electrodes placed near the frontal and the parietal lobes, consistent with many of the findings in the literature. This study might lead to a practical system for noninvasive assessment of the emotional states in practical or clinical applications.

Speech-feature discrimination in children with Asperger syndrome as determined with the multi-feature mismatch negativity paradigm.

PubMed

Kujala, T; Kuuluvainen, S; Saalasti, S; Jansson-Verkasalo, E; von Wendt, L; Lepistö, T

2010-09-01

Asperger syndrome, belonging to the autistic spectrum of disorders, involves deficits in social interaction and prosodic use of language but normal development of formal language abilities. Auditory processing involves both hyper- and hypoactive reactivity to acoustic changes. Responses composed of mismatch negativity (MMN) and obligatory components were recorded for five types of deviations in syllables (vowel, vowel duration, consonant, syllable frequency, syllable intensity) with the multi-feature paradigm from 8-12-year old children with Asperger syndrome. Children with Asperger syndrome had larger MMNs for intensity and smaller MMNs for frequency changes than typically developing children, whereas no MMN group differences were found for the other deviant stimuli. Furthermore, children with Asperger syndrome performed more poorly than controls in Comprehension of Instructions subtest of a language test battery. Cortical speech-sound discrimination is aberrant in children with Asperger syndrome. This is evident both as hypersensitive and depressed neural reactions to speech-sound changes, and is associated with features (frequency, intensity) which are relevant for prosodic processing. The multi-feature MMN paradigm, which includes variation and thereby resembles natural speech hearing circumstances, suggests abnormal pattern of speech discrimination in Asperger syndrome, including both hypo- and hypersensitive responses for speech features. 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000-2010.

PubMed

Sulis, G; El Hamad, I; Fabiani, M; Rusconi, S; Maggiolo, F; Guaraldi, G; Bozzi, G; Bernardini, C; Lichtner, M; Stentarelli, C; Carenzi, L; Francisci, D; Saracino, A; Castelli, F

2014-10-01

Migrants account for approximately 8.7% of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8%; adjusted odds ratio [(AOR) = 1.55, 95% confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95% CI 0.97-2.04), though of borderline significance. Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.

Hymenoptera venom allergy in outdoor workers: Occupational exposure, clinical features and effects of allergen immunotherapy.

PubMed

Toletone, Alessandra; Voltolini, Susanna; Passalacqua, Giovanni; Dini, Guglielmo; Bignardi, Donatella; Minale, Paola; Massa, Emanuela; Signori, Alessio; Troise, Costantino; Durando, Paolo

2017-02-01

To describe (i) the clinical characteristics of workers, exposed to hymenoptera stings, with an ascertained diagnosis of Hymenoptera Venom Allergy (HVA), (ii) the specific role of occupational exposure, (iii) the effect of Venom Immunotherapy (VIT) in reducing the severity of allergic episodes in workers exposed to repeated stings of hymenoptera, and (iv) the management of the occupational consequences caused by allergic reactions due to hymenoptera stings. Between 2000 and 2013 an observational study, including patients referred to the regional reference hospital of Liguria, Italy, with an ascertained diagnosis of HVA and treated with VIT, was performed. A structured questionnaire was administered to all patients to investigate the occupational features of allergic reactions. These were graded according to standard systems in patients at the first episode, and after re-stings, during VIT. One-hundred and 8four out of the 202 patients referred had a complete data set. In 32 (17.4%) patients, the allergic reaction occurred during work activities performed outdoor. Of these, 31.2% previously stung by hymenoptera at work, and receiving VIT, were re-stung during occupational activity. The grades of reaction developed under VIT treatment resulted clinically less severe than of those occurred at the first sting (p-value = 0.031). Our findings confirmed the clinical relevance of HVA, and described its occupational features in outdoor workers with sensitization, stressing the importance of an early identification and proper management of the professional categories recognized at high risk of hymenoptera stings. The Occupational Physician should be supported by other specialists to recommend appropriate diagnostic procedures and the prescription of VIT, which resulted an effective treatment for the prevention of episodes of severe reactions in workers with a proven HVA.

Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography.

PubMed

Ouyang, Yanling; Pleyer, Uwe; Shao, Qing; Keane, Pearse A; Stübiger, Nicole; Joussen, Antonia M; Sadda, Srinivas R; Heussen, Florian M

2014-01-01

To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Evaluation of Cystoid Change Phenotypes in Ocular Toxoplasmosis Using Optical Coherence Tomography

PubMed Central

Shao, Qing; Keane, Pearse A.; Stübiger, Nicole; Joussen, Antonia M.; Sadda, Srinivas R.; Heussen, Florian M.

2014-01-01

Purpose To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Methods Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Results Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. Conclusions In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise “normal” looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis. PMID:24505261

An overview of PET/MR, focused on clinical applications.

PubMed

Catalano, Onofrio Antonio; Masch, William Roger; Catana, Ciprian; Mahmood, Umar; Sahani, Dushyant Vasudeo; Gee, Michael Stanley; Menezes, Leon; Soricelli, Andrea; Salvatore, Marco; Gervais, Debra; Rosen, Bruce Robert

2017-02-01

Hybrid PET/MR scanners are innovative imaging devices that simultaneously or sequentially acquire and fuse anatomical and functional data from magnetic resonance (MR) with metabolic information from positron emission tomography (PET) (Delso et al. in J Nucl Med 52:1914-1922, 2011; Zaidi et al. in Phys Med Biol 56:3091-3106, 2011). Hybrid PET/MR scanners have the potential to greatly impact not only on medical research but also, and more importantly, on patient management. Although their clinical applications are still under investigation, the increased worldwide availability of PET/MR scanners, and the growing published literature are important determinants in their rising utilization for primarily clinical applications. In this manuscript, we provide a summary of the physical features of PET/MR, including its limitations, which are most relevant to clinical PET/MR implementation and to interpretation. Thereafter, we discuss the most important current and emergent clinical applications of such hybrid technology in the abdomen and pelvis, both in the field of oncologic and non-oncologic imaging, and we provide, when possible, a comparison with clinically consolidated imaging techniques, like for example PET/CT.

Imaging Diagnosis of Splanchnic Venous Thrombosis

PubMed Central

Rajesh, S.; Mukund, Amar

2015-01-01

Splanchnic vein thrombosis (SVT) is a broad term that includes Budd-Chiari syndrome and occlusion of veins that constitute the portal venous system. Due to the common risk factors involved in the pathogenesis of these clinically distinct disorders, concurrent involvement of two different regions is quite common. In acute and subacute SVT, the symptoms may overlap with a variety of other abdominal emergencies while in chronic SVT, the extent of portal hypertension and its attendant complications determine the clinical course. As a result, clinical diagnosis is often difficult and is frequently reliant on imaging. Tremendous improvements in vascular imaging in recent years have ensured that this once rare entity is being increasingly detected. Treatment of acute SVT requires immediate anticoagulation. Transcatheter thrombolysis or transjugular intrahepatic portosystemic shunt is used in the event of clinical deterioration. In cases with peritonitis, immediate laparotomy and bowel resection may be required for irreversible bowel ischemia. In chronic SVT, the underlying cause should be identified and treated. The imaging manifestations of the clinical syndromes resulting from SVT are comprehensively discussed here along with a brief review of the relevant clinical features and therapeutic approach. PMID:26600801

About the composition of self-relevance: Conjunctions not features are bound to the self.

PubMed

Schäfer, Sarah; Frings, Christian; Wentura, Dirk

2016-06-01

Sui and colleagues (Journal of Experimental Psychology: Human Perception and Performance, 38, 1105-1117, 2012) introduced a matching paradigm to investigate prioritized processing of instructed self-relevance. They arbitrarily assigned simple geometric shapes to the participant and two other persons. Subsequently, the task was to judge whether label-shape pairings matched or not. The authors found a remarkable self-prioritization effect, that is, for matching self-related trials verification was very fast and accurate in comparison to the non-matching conditions. We analyzed whether single features or feature conjunctions are tagged to the self. In particular, we assigned colored shapes to the labels and included partial-matching trials (i.e., trials in which only one feature matched the label, whereas the other feature did not match the label). If single features are tagged to the self, partial matches would result in interference, whereas they should elicit the same data pattern as non-matching trials if only feature conjunctions are tagged to the self. Our data suggest the latter; only feature conjunctions are tagged to the self and are processed in a prioritized manner. This result emphasizes the functionality of self-relevance as a selection mechanism.

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation and Retrieval.

PubMed

Lee, Chia-Ju; Devine, Beth; Tarczy-Hornoch, Peter

2017-01-01

Pharmacogenomics holds promise as a critical component of precision medicine. Yet, the use of pharmacogenomics in routine clinical care is minimal, partly due to the lack of efficient and effective use of existing evidence. This paper describes the design, development, implementation and evaluation of a knowledge-based system that fulfills three critical features: a) providing clinically relevant evidence, b) applying an evidence-based approach, and c) using semantically computable formalism, to facilitate efficient evidence assessment to support timely decisions on adoption of pharmacogenomics in clinical care. To illustrate functionality, the system was piloted in the context of clopidogrel and warfarin pharmacogenomics. In contrast to existing pharmacogenomics knowledge bases, the developed system is the first to exploit the expressivity and reasoning power of logic-based representation formalism to enable unambiguous expression and automatic retrieval of pharmacogenomics evidence to support systematic review with meta-analysis.

Personality, Schizophrenia, and Violence: A Longitudinal Study.

PubMed

Candini, Valentina; Ghisi, Marta; Bottesi, Gioia; Ferrari, Clarissa; Bulgari, Viola; Iozzino, Laura; Boero, Maria Elena; De Francesco, Alessandra; Maggi, Paolo; Segalini, Beatrice; Zuccalli, Vanessa; Giobbio, Gian Marco; Rossi, Giuseppe; de Girolamo, Giovanni

2017-07-31

The aims of this study were (a) to investigate the presence of clinically significant personality traits and personality disorders (PD) in patients living in residential facilities, with or without a history of violence (69 and 46, respectively); and (b) to investigate any associations between clinically significant personality traits and PDs, aggression, impulsivity, hostility, and violent behavior during a 1-year follow-up. The most frequent primary diagnoses were schizophrenia (58.3%) and PD (20.9%). Those with a history of violence demonstrated more antisocial and alcohol dependence features and lower depressive PD symptoms than the control group. Hostility levels, antisocial symptoms, and drug dependence, as well as a Structured Clinical Interview for DSM-IV Axis II diagnosis of PD, predicted aggressive and violent behavior during follow-up. The study confirms the relevance of assessing PDs both to evaluate the risk of violent behavior and to plan appropriate preventive and treatment intervention.

[Basic symptoms in schizophrenia, their clinical study and relevance in research].

PubMed

Miret, Salvador; Fatjó-Vilas, Mar; Peralta, Víctor; Fañanás, Lourdes

2016-01-01

Basic symptoms consist of subtle sub-clinical disturbances subjectively experienced by schizophrenia patients. These are mainly related to drive, affect, thinking and language, perception, memory, motor action, central vegetative functions, control of cognitive processes, and stress tolerance. Initially described by Huber, from a phenomenological approach, basic symptoms are part of the earliest features of schizophrenia, and they can evolve along the course of the disorder. Their assessment during the prodromal phase of the disease (together with ultra-high risk criteria) is one of the 2 main approaches that allow the definition of states of clinical risk for the development of psychosis. The present review provides an updated view of the concept of basic symptoms, highlighting its potential value in establishing neurobiological correlates of interest in aetiopathogenic research. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value

PubMed Central

Berlth, Felix; Bollschweiler, Elfriede; Drebber, Uta; Hoelscher, Arnulf H; Moenig, Stefan

2014-01-01

Several pathohistological classification systems exist for the diagnosis of gastric cancer. Many studies have investigated the correlation between the pathohistological characteristics in gastric cancer and patient characteristics, disease specific criteria and overall outcome. It is still controversial as to which classification system imparts the most reliable information, and therefore, the choice of system may vary in clinical routine. In addition to the most common classification systems, such as the Laurén and the World Health Organization (WHO) classifications, other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients. In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer, there is no sole classification system that is consistently used worldwide in diagnostics and research. However, several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making, which underlines the importance of a reliable classification system for gastric cancer. The latest results from gastric cancer studies indicate that it might be useful to integrate DNA- and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance. This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer. PMID:24914328

Features of hypochondriasis and illness worry in the general population in Germany.

PubMed

Martin, Alexandra; Jacobi, Frank

2006-01-01

Although hypochondriasis is considered to be of high relevance in the healthcare sector, its prevalence in the general population has been investigated in few studies. The aims of this study were to estimate prevalence rates of hypochondriasis and of subthreshold conditions and to describe their associated features such as quality of life and healthcare utilization in a representative community sample. Analyses of the present study are based on the German Health Interview and Examination Survey-Mental Health Supplement (N = 4181, representative for the German population from 18-65 years). The assessment included interviews for somatic conditions and mental disorders and self-report ratings on health-related quality of life, healthcare utilization, disability days, and physical activity. Only three cases (0.05%) were identified as meeting full criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis. The prevalence rate of the less restrictively defined form of hypochondriasis, ("subthreshold hypochondriasis") was 0.58% and an additional 2.12% reported having had illness worries for at least 6 months but did not meet further hypochondriasis criteria. The two subthreshold diagnostic groups provided strong evidence of difference from the nonhypochondriac controls: comorbidity with psychiatric and medical disorders and healthcare utilization were higher, and quality of life was markedly reduced. The results provide additional support to not only consider "full" DSM-IV hypochondriasis, which is a very rare disorder in the general population, but also to include less restrictive hypochondriac conditions--associated with a clinically relevant degree of psychological and physical impairment--into clinical and scientific considerations.

Paranasal sinus mucoceles: our clinical experiments

PubMed Central

Topdag, Murat; Iseri, Mete; Sari, Fatih; Erdogan, Selvet; Keskin, I Gurkan

2015-01-01

Objectives: We present the clinical and radiological features, treatment protocols, and medium-long-term results of our patients following surgery for paranasal sinus mucocele, along with a review of the relevant literature. Materials and methods: A total of 18 patients (11 women and 7 men) who underwent surgery for paranasal sinus mucocele at Kocaeli University Faculty of Medicine, Department of Otolaryngology, between 2006 and 2013 were examined retrospectively. The mean patient age was 41 (range 4-73). Demographic and radiological features, symptoms, treatment protocols, and postoperative outcomes were recorded. Results: The most frequently affected sinus was the maxillary sinus (n=9, 50%) followed by the frontal sinus (n=6, 33%) and sphenoidal sinus (n=3, 16%). The main symptom was headache. Endoscopic marsupialization of the mucocele was applied in all 18 patients, while frontal sinus exploration with the osteoplastic flap procedure was performed in one patient and the Caldwell-Luc operation was performed in another patient. The Caldwell-Luc procedure was subsequently required in one patient (6%) and endoscopic revision surgery was required in another patient (6%). Conclusion: Sinus mucocele that enlarges, eroding the surrounding bone tissue, and induces various clinical symptoms due to the impression of the expansile mass, is treated surgically, and must be planned carefully to prevent serious complications. PMID:26770462

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility

PubMed Central

Haghighi, Amirreza; Haghighi, Alireza; Setoodeh, Aria; Saleh-Gohari, Nasrollah; Astuti, Dewi; Barrett, Timothy G

2013-01-01

Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families. The clinical diagnosis of WFS was confirmed by the existence of diabetes mellitus and optic atrophy in the affected patients, who in addition had severe neurodegenerative complications. Sequencing of WFS1 was undertaken in one affected member from each family. Targeted mutations were tested in all members of relevant families. Patients had most of the reported features of WFS. Two affected males in the first family had fathered unaffected children. We identified two homozygous mutations previously reported with apparently milder phenotypes: family 1: c.631G>A (p.Asp211Asn) in exon 5, and family 2: c.1456C>T (p.Gln486*) in exon 8. Heterozygous carriers were unaffected. This is the first report of male Wolfram patients who have successfully fathered children. Surprisingly, they also had almost all the complications associated with WFS. Our report has implications for genetic counseling and family planning advice for other affected families. PMID:22781099

Rapid Whole-Genome Sequencing for Genetic Disease Diagnosis in Neonatal Intensive Care Units

PubMed Central

Saunders, Carol Jean; Miller, Neil Andrew; Soden, Sarah Elizabeth; Dinwiddie, Darrell Lee; Noll, Aaron; Alnadi, Noor Abu; Andraws, Nevene; Patterson, Melanie LeAnn; Krivohlavek, Lisa Ann; Fellis, Joel; Humphray, Sean; Saffrey, Peter; Kingsbury, Zoya; Weir, Jacqueline Claire; Betley, Jason; Grocock, Russell James; Margulies, Elliott Harrison; Farrow, Emily Gwendolyn; Artman, Michael; Safina, Nicole Pauline; Petrikin, Joshua Erin; Hall, Kevin Peter; Kingsmore, Stephen Francis

2014-01-01

Monogenic diseases are frequent causes of neonatal morbidity and mortality, and disease presentations are often undifferentiated at birth. More than 3500 monogenic diseases have been characterized, but clinical testing is available for only some of them and many feature clinical and genetic heterogeneity. Hence, an immense unmet need exists for improved molecular diagnosis in infants. Because disease progression is extremely rapid, albeit heterogeneous, in newborns, molecular diagnoses must occur quickly to be relevant for clinical decision-making. We describe 50-hour differential diagnosis of genetic disorders by whole-genome sequencing (WGS) that features automated bioinformatic analysis and is intended to be a prototype for use in neonatal intensive care units. Retrospective 50-hour WGS identified known molecular diagnoses in two children. Prospective WGS disclosed potential molecular diagnosis of a severe GJB2-related skin disease in one neonate; BRAT1-related lethal neonatal rigidity and multifocal seizure syndrome in another infant; identified BCL9L as a novel, recessive visceral heterotaxy gene (HTX6) in a pedigree; and ruled out known candidate genes in one infant. Sequencing of parents or affected siblings expedited the identification of disease genes in prospective cases. Thus, rapid WGS can potentially broaden and foreshorten differential diagnosis, resulting in fewer empirical treatments and faster progression to genetic and prognostic counseling. PMID:23035047

Identifying clinical features in primary care electronic health record studies: methods for codelist development.

PubMed

Watson, Jessica; Nicholson, Brian D; Hamilton, Willie; Price, Sarah

2017-11-22

Analysis of routinely collected electronic health record (EHR) data from primary care is reliant on the creation of codelists to define clinical features of interest. To improve scientific rigour, transparency and replicability, we describe and demonstrate a standardised reproducible methodology for clinical codelist development. We describe a three-stage process for developing clinical codelists. First, the clear definition a priori of the clinical feature of interest using reliable clinical resources. Second, development of a list of potential codes using statistical software to comprehensively search all available codes. Third, a modified Delphi process to reach consensus between primary care practitioners on the most relevant codes, including the generation of an 'uncertainty' variable to allow sensitivity analysis. These methods are illustrated by developing a codelist for shortness of breath in a primary care EHR sample, including modifiable syntax for commonly used statistical software. The codelist was used to estimate the frequency of shortness of breath in a cohort of 28 216 patients aged over 18 years who received an incident diagnosis of lung cancer between 1 January 2000 and 30 November 2016 in the Clinical Practice Research Datalink (CPRD). Of 78 candidate codes, 29 were excluded as inappropriate. Complete agreement was reached for 44 (90%) of the remaining codes, with partial disagreement over 5 (10%). 13 091 episodes of shortness of breath were identified in the cohort of 28 216 patients. Sensitivity analysis demonstrates that codes with the greatest uncertainty tend to be rarely used in clinical practice. Although initially time consuming, using a rigorous and reproducible method for codelist generation 'future-proofs' findings and an auditable, modifiable syntax for codelist generation enables sharing and replication of EHR studies. Published codelists should be badged by quality and report the methods of codelist generation including: definitions and justifications associated with each codelist; the syntax or search method; the number of candidate codes identified; and the categorisation of codes after Delphi review. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Models of clinical reasoning with a focus on general practice: A critical review

PubMed Central

YAZDANI, SHAHRAM; HOSSEINZADEH, MOHAMMAD; HOSSEINI, FAKHROLSADAT

2017-01-01

Introduction: Diagnosis lies at the heart of general practice. Every day general practitioners (GPs) visit patients with a wide variety of complaints and concerns, with often minor but sometimes serious symptoms. General practice has many features which differentiate it from specialty care setting, but during the last four decades little attention was paid to clinical reasoning in general practice. Therefore, we aimed to critically review the clinical reasoning models with a focus on the clinical reasoning in general practice or clinical reasoning of general practitioners to find out to what extent the existing models explain the clinical reasoning specially in primary care and also identity the gaps of the model for use in primary care settings. Methods: A systematic search to find models of clinical reasoning were performed. To have more precision, we excluded the studies that focused on neurobiological aspects of reasoning, reasoning in disciplines other than medicine decision making or decision analysis on treatment or management plan. All the articles and documents were first scanned to see whether they include important relevant contents or any models. The selected studies which described a model of clinical reasoning in general practitioners or with a focus on general practice were then reviewed and appraisal or critics of other authors on these models were included. The reviewed documents on the model were synthesized. Results: Six models of clinical reasoning were identified including hypothetic-deductive model, pattern recognition, a dual process diagnostic reasoning model, pathway for clinical reasoning, an integrative model of clinical reasoning, and model of diagnostic reasoning strategies in primary care. Only one model had specifically focused on general practitioners reasoning. Conclusion: A Model of clinical reasoning that included specific features of general practice to better help the general practitioners with the difficulties of clinical reasoning in this setting is needed. PMID:28979912

Proposed morphologic classification of prostate cancer with neuroendocrine differentiation.

PubMed

Epstein, Jonathan I; Amin, Mahul B; Beltran, Himisha; Lotan, Tamara L; Mosquera, Juan-Miguel; Reuter, Victor E; Robinson, Brian D; Troncoso, Patricia; Rubin, Mark A

2014-06-01

On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.

Prevalence and clinical characteristics of adult-onset atopic dermatitis with positive skin prick testing to mites.

PubMed

Kulthanan, Kanokvalai; Chularojanamontri, Leena; Manapajon, Araya; Nuchkull, Piyavadee

2011-12-01

The clinical role of house dust mite (HDM) in atopic dermatitis (AD) is still controversial. The aim of the study is to assess the prevalence, clinical relevance and characteristics of adult-onset AD patients with positive skin prick tests (SPT) to mites. The case record forms of adult-onset AD patients who underwent SPT at the Skin Allergy Clinic, Siriraj Hospital were reviewed. Forty-one of 62 patients (66.1%) had positive SPT to mites. The frequency of intrinsic AD among adult-onset AD was 4.8% (3/62). SPT to HDM tended to be positive in patients who had personal or family history of atopy, positive SPT to several specific antigens or who presented with elevated serum IgE, chelitis, recurrent conjunctivitis and perifollicular accentuation, respectively. CONCLUSION The prevalence of adult-onset AD patients with mite sensitivity was high. There were some notable features that tended to be present in mite sensitive adult-onset AD patients.

Implementing human factors in clinical practice.

PubMed

Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

2015-05-01

To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical relevance of liquid chromatography tandem mass spectrometry as an analytical method in microdose clinical studies.

PubMed

Yamane, Naoe; Tozuka, Zenzaburo; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

2011-08-01

To investigate the potency of LC-MS/MS by means of sensitivity and the applicability for cassette dosing in microdose clinical trials. Thirty one top-selling 31 drugs were spiked to human plasma, extracted, and analyzed by LC-MS/MS. The lower limits of quantification for each drug varied from 0.08 to 50 pg/mL, and were lower than one eighth of the assumed maximum plasma concentration at microdose in all drugs except for losartan, indicating the high performance in acquisition of full pharmacokinetic profiles at microdose. We also succeeded in simultaneous analysis of multiple compounds, assuming a situation of cassette dosing in which multiple drug candidates would be administrated simultaneously. Together with the features of LC-MS/MS, such as immediate verification, the utilization of non-radiolabeled drugs and no special facilities, we suppose that LC-MS/MS analysis would be widely applicable in conducting microdose clinical studies.

Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

PubMed

Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring

2018-02-01

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

Immunological network signatures of cancer progression and survival

PubMed Central

2011-01-01

Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides. PMID:21453479

Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis.

PubMed

Smith, M E; Eller, N L; McFarland, H F; Racke, M K; Raine, C S

1999-10-01

A prominent feature of the clinical spectrum of multiple sclerosis (MS) is its high incidence of onset in the third decade of life and the relative rarity of clinical manifestations during childhood and adolescence, features suggestive of age-related restriction of clinical expression. Experimental allergic encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune demyelination with many similarities to MS, has a uniform rapid onset and a high incidence of clinical and pathological disease in adult (mature) animals. Like MS, EAE is most commonly seen and studied in female adults. In this study, age-related resistance to clinical EAE has been examined with the adoptive transfer model of EAE in SJL mice that received myelin basic protein-sensitized cells from animals 10 days (sucklings) to 12 weeks (young adults) of age. A variable delay before expression of clinical EAE was observed between the different age groups. The preclinical period was longest in the younger (<14 days of age) animals, and shortest in animals 6 to 8 weeks old at time of transfer. Young animals initially resistant to EAE eventually expressed well-developed clinical signs by 6 to 7 weeks of age. This was followed by a remitting, relapsing clinical course. For each age at time of sensitization, increased susceptibility of females compared to males was observed. Examination of the CNS of younger animal groups during the preclinical period showed lesions of acute EAE. Older age groups developed onset of signs coincident with acute CNS lesions. This age-related resistance to clinical EAE in developing mice is reminiscent of an age-related characteristic of MS previously difficult to study in vivo. The associated subclinical CNS pathology and age-related immune functions found in young animals may be relevant to the increasing clinical expression of MS with maturation, and may allow study of factors associated with the known occasional poor correlation of CNS inflammation and demyelination and clinical changes in this disease.

Feature saliency and feedback information interactively impact visual category learning

PubMed Central

Hammer, Rubi; Sloutsky, Vladimir; Grill-Spector, Kalanit

2015-01-01

Visual category learning (VCL) involves detecting which features are most relevant for categorization. VCL relies on attentional learning, which enables effectively redirecting attention to object’s features most relevant for categorization, while ‘filtering out’ irrelevant features. When features relevant for categorization are not salient, VCL relies also on perceptual learning, which enables becoming more sensitive to subtle yet important differences between objects. Little is known about how attentional learning and perceptual learning interact when VCL relies on both processes at the same time. Here we tested this interaction. Participants performed VCL tasks in which they learned to categorize novel stimuli by detecting the feature dimension relevant for categorization. Tasks varied both in feature saliency (low-saliency tasks that required perceptual learning vs. high-saliency tasks), and in feedback information (tasks with mid-information, moderately ambiguous feedback that increased attentional load, vs. tasks with high-information non-ambiguous feedback). We found that mid-information and high-information feedback were similarly effective for VCL in high-saliency tasks. This suggests that an increased attentional load, associated with the processing of moderately ambiguous feedback, has little effect on VCL when features are salient. In low-saliency tasks, VCL relied on slower perceptual learning; but when the feedback was highly informative participants were able to ultimately attain the same performance as during the high-saliency VCL tasks. However, VCL was significantly compromised in the low-saliency mid-information feedback task. We suggest that such low-saliency mid-information learning scenarios are characterized by a ‘cognitive loop paradox’ where two interdependent learning processes have to take place simultaneously. PMID:25745404

Embodying compassion: a virtual reality paradigm for overcoming excessive self-criticism.

PubMed

Falconer, Caroline J; Slater, Mel; Rovira, Aitor; King, John A; Gilbert, Paul; Antley, Angus; Brewin, Chris R

2014-01-01

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions.

Embodying Compassion: A Virtual Reality Paradigm for Overcoming Excessive Self-Criticism

PubMed Central

Falconer, Caroline J.; Slater, Mel; Rovira, Aitor; King, John A.; Gilbert, Paul; Antley, Angus; Brewin, Chris R.

2014-01-01

Virtual reality has been successfully used to study and treat psychological disorders such as phobias and posttraumatic stress disorder but has rarely been applied to clinically-relevant emotions other than fear and anxiety. Self-criticism is a ubiquitous feature of psychopathology and can be treated by increasing levels of self-compassion. We exploited the known effects of identification with a virtual body to arrange for healthy female volunteers high in self-criticism to experience self-compassion from an embodied first-person perspective within immersive virtual reality. Whereas observation and practice of compassionate responses reduced self-criticism, the additional experience of embodiment also increased self-compassion and feelings of being safe. The results suggest potential new uses for immersive virtual reality in a range of clinical conditions. PMID:25389766

Facial anatomy.

PubMed

Marur, Tania; Tuna, Yakup; Demirci, Selman

2014-01-01

Dermatologic problems of the face affect both function and aesthetics, which are based on complex anatomical features. Treating dermatologic problems while preserving the aesthetics and functions of the face requires knowledge of normal anatomy. When performing successfully invasive procedures of the face, it is essential to understand its underlying topographic anatomy. This chapter presents the anatomy of the facial musculature and neurovascular structures in a systematic way with some clinically important aspects. We describe the attachments of the mimetic and masticatory muscles and emphasize their functions and nerve supply. We highlight clinically relevant facial topographic anatomy by explaining the course and location of the sensory and motor nerves of the face and facial vasculature with their relations. Additionally, this chapter reviews the recent nomenclature of the branching pattern of the facial artery. © 2013 Elsevier Inc. All rights reserved.

Crossed fused renal ectopia in a Persian cat

PubMed Central

Seo, Sang-Hyuk; Lee, Hyun-A; Suh, Sang-Il; Choi, Ran; Park, In-Chul; Hyun, Changbaig

2017-01-01

Case summary This report describes a rare case of crossed fused renal ectopia (CFRE) in a cat. A mature intact male Persian cat presented with bloody nasal discharge and ascites. Diagnostic studies revealed an ectopic left kidney fused with an orthotopic right kidney and a concurrent feline infectious peritonitis (FIP) infection. The FIP was responsible for clinical signs in this cat, while clinical signs associated with CFRE were not obvious. Despite receiving intensive treatment, the cat died. A post-mortem examination was not performed because the owners declined approval. Relevance and novel information To the best of our knowledge, this is the first report of L-shaped CFRE in a cat. In addition, this report describes the CT features of L-shaped CFRE in a cat. PMID:28491454

Incidental findings in multislice computed tomography prior to transcatheter aortic valve implantation: frequency, clinical relevance and outcome.

PubMed

Trenkwalder, Teresa; Lahmann, Anna Lena; Nowicka, Magdalena; Pellegrini, Costanza; Rheude, Tobias; Mayr, N Patrick; Voss, Stephanie; Bleiziffer, Sabine; Lange, Rüdiger; Joner, Michael; Kasel, Albert M; Kastrati, Adnan; Schunkert, Heribert; Husser, Oliver; Hadamitzky, Martin; Hengstenberg, Christian

2018-02-21

Multislice computed tomography (MSCT) has emerged as the mainstay in patients planned for transcatheter aortic valve implantation (TAVI). Incidental findings (IF) in MSCT are common. However, the exact incidence, clinical relevance and further consequences of IF are unclear and it is controversial whether IF adversely affect patients' outcome. We analyzed MSCT data of 1050 patients screened for TAVI between January 2011 and December 2014. Median follow-up of patients was 20 months. In total, 3194 IF were identified, which were classified into clinically non-relevant IF (2872, 90%) and clinically relevant IF (322, 10%). In 25% of patients (258/1050) at least one clinically relevant IF was present. Age (80 ± 7 vs. 80 ± 7 years; p = 0.198) and EuroSCORE II (3.6% [2.1-5.7] vs. 3.6% [2.1-5.9]; p = 0.874) was similar between patients with and without a clinically relevant IF. TAVI was performed less frequently in patients with a clinically relevant IF (76% vs. 85%; p < 0.001), with more patients receiving surgical aortic valve replacement in that group (14% vs. 11%; p = 0.042), possibly due to the high rate of incidental aneurysms of the ascending aorta (n = 48). If TAVI was performed mortality did not differ (30-days: 4% vs. 3%; p = 0.339, 1-year: 11% vs. 14%; p = 0.226) between patients with and without a clinically relevant IF. Our study is the largest study to analyze prevalence, clinical relevance and therapeutic consequences of IF during screening for TAVI. IF in pre-procedural MSCT are common and clinically relevant in one-quarter of patients. However, these findings had no impact on overall mortality.

Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both alzheimer's disease and non-tauopathic frontotemporal lobar degeneration.

PubMed

Brenowitz, Willa D; Monsell, Sarah E; Schmitt, Frederick A; Kukull, Walter A; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively "pure" HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials.

Hippocampal sclerosis of aging is a key Alzheimer's disease mimic: clinical-pathologic correlations and comparisons with both Alzheimer's disease and non-tauopathic frontotemporal lobar degeneration

PubMed Central

Brenowitz, Willa D.; Monsell, Sarah E.; Schmitt, Frederick A.; Kukull, Walter A.; Nelson, Peter T.

2013-01-01

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (N=9,817 participants), the neuropathologic diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (N=1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (N=210). Reporting of HS pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively “pure” HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2 -5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials. PMID:24270205

Rare cancers: a sea of opportunity.

PubMed

Boyd, Niki; Dancey, Janet E; Gilks, C Blake; Huntsman, David G

2016-02-01

Rare cancers, as a collective, account for around a quarter of all cancer diagnoses and deaths. Historically, they have been divided into two groups: cancers defined by their unusual histogenesis (cell of origin or differentiation state)--including chordomas or adult granulosa cell tumours--and histologically defined subtypes of common cancers. Most tumour types in the first group are still clinically and biologically relevant, and have been disproportionately important as sources of insight into cancer biology. By contrast, most of those in the second group have been shown to have neither defining molecular features nor clinical utility. Omics-based analyses have splintered common cancers into a myriad of molecularly, rather than histologically, defined subsets of common cancers, many of which have immediate clinical relevance. Now, almost all rare cancers are either histomolecular entities, which often have pathognomonic mutations, or molecularly defined subsets of more common cancers. The presence of specific genetic variants provides rationale for the testing of targeted drugs in rare cancers. However, in addition to molecular alterations, it is crucial to consider the contributions of both mutation and cell context in the development, biology, and behaviour of these cancers. Patients with rare cancers are disadvantaged because of the challenge of leading clinical trials in this setting due to poor accrual. However, the number of patients with rare cancers will only increase as more molecular subsets of common cancers are identified, necessitating a shift in the focus of clinical trials and research into these cancer types, which, by epidemiological definitions, will become rare tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

Problematic internet use in gamblers: impact on clinical and cognitive measures.

PubMed

Chamberlain, Samuel R; Redden, Sarah A; Leppink, Eric; Grant, Jon E

2017-12-01

Gambling is a commonplace phenomenon, existing along a continuum from occasional gambling to functionally impairing gambling disorder. The internet may act as a conduit for some gambling behaviors. The impact of problematic internet use on clinical and cognitive features relevant to gambling has received little research attention. A total of 206 adults aged 18-30 years who gamble at least five times per year were recruited from the general community and undertook detailed clinical and cognitive assessments. Problematic internet use was defined using a total score of 5 or more on Young's Diagnostic Questionnaire (YDQ). Linear regression was employed to evaluate the relative contribution of addictive-related, impulsive-related, and compulsive-related measures in predicting YDQ total scores in gamblers. Gamblers with problematic internet use (18% of the sample) reported lower quality of life, lower self-esteem, elevated rates of intermittent explosive disorder, gambling disorder symptoms, attention deficit hyperactivity disorder (ADHD) symptoms, antisocial personality disorder, and posttraumatic stress disorder (PTSD), as well as relative deficits in decision making and spatial working memory. In linear regression, the extent of problematic internet use was most significantly associated with increased gambling disorder symptoms and increased ADHD symptoms. Problematic internet use in gamblers is associated with worse quality of life, more problem/pathological gambling symptoms, more psychiatric morbidities, and select cognitive impairment. Refinement of the definition of problematic internet use and exploration of its clinical and cognitive associations are likely to be highly relevant to the treatment of problematic gambling.

Prediction of lysine glutarylation sites by maximum relevance minimum redundancy feature selection.

PubMed

Ju, Zhe; He, Jian-Jun

2018-06-01

Lysine glutarylation is new type of protein acylation modification in both prokaryotes and eukaryotes. To better understand the molecular mechanism of glutarylation, it is important to identify glutarylated substrates and their corresponding glutarylation sites accurately. In this study, a novel bioinformatics tool named GlutPred is developed to predict glutarylation sites by using multiple feature extraction and maximum relevance minimum redundancy feature selection. On the one hand, amino acid factors, binary encoding, and the composition of k-spaced amino acid pairs features are incorporated to encode glutarylation sites. And the maximum relevance minimum redundancy method and the incremental feature selection algorithm are adopted to remove the redundant features. On the other hand, a biased support vector machine algorithm is used to handle the imbalanced problem in glutarylation sites training dataset. As illustrated by 10-fold cross-validation, the performance of GlutPred achieves a satisfactory performance with a Sensitivity of 64.80%, a Specificity of 76.60%, an Accuracy of 74.90% and a Matthew's correlation coefficient of 0.3194. Feature analysis shows that some k-spaced amino acid pair features play the most important roles in the prediction of glutarylation sites. The conclusions derived from this study might provide some clues for understanding the molecular mechanisms of glutarylation. Copyright © 2018 Elsevier Inc. All rights reserved.

Integrating the glioblastoma microenvironment into engineered experimental models

PubMed Central

Xiao, Weikun; Sohrabi, Alireza; Seidlits, Stephanie K

2017-01-01

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed. PMID:28883992

National athletic trainers' association position statement: skin diseases.

PubMed

Zinder, Steven M; Basler, Rodney S W; Foley, Jack; Scarlata, Chris; Vasily, David B

2010-01-01

To present recommendations for the prevention, education, and management of skin infections in athletes. Trauma, environmental factors, and infectious agents act together to continually attack the integrity of the skin. Close quarters combined with general poor hygiene practices make athletes particularly vulnerable to contracting skin diseases. An understanding of basic prophylactic measures, clinical features, and swift management of common skin diseases is essential for certified athletic trainers to aid in preventing the spread of infectious agents. These guidelines are intended to provide relevant information on skin infections and to give specific recommendations for certified athletic trainers and others participating in athletic health care.

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma*#

PubMed Central

Dai, Jin; Chen, Shen-jie; Yang, Bing-sheng; Lü, Shu-min; Zhu, Min; Xu, Yi-fei; Chen, Jie; Cai, Hong-wen; Mao, Wei

2017-01-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed. PMID:28471119

Recurrence of non-cardiogenic pulmonary edema and sustained hypotension shock in cystic pheochromocytoma.

PubMed

Dai, Jin; Chen, Shen-Jie; Yang, Bing-Sheng; Lü, Shu-Min; Zhu, Min; Xu, Yi-Fei; Chen, Jie; Cai, Hong-Wen; Mao, Wei

2017-05-01

Pheochromocytoma is a rare neuroendocrine tumor which derives from chromaffin cells of the adrenal gland or relevant to sympathetic nerves and ganglia. The clinical features of pheochromocytoma are various. Paroxysmal episodes of serious hypertension, headache, palpitation, and diaphoresis are the typical manifestations (Bravo, 2004). Hypotension shock, pulmonary edema, and acute coronary syndrome induced by pheochromocytoma are uncommon (Malindretos et al., 2008; Batisse-Lignier et al., 2015). In this study, we present a rare case of cystic pheochromocytoma causing recurrent hypotension shock, non-cardiogenic pulmonary edema, and acute coronary syndrome, and the possible mechanisms are discussed.

Acanthamoeba polyphaga mimivirus and other giant viruses: an open field to outstanding discoveries

PubMed Central

2014-01-01

In 2003, Acanthamoeba polyphaga mimivirus (APMV) was first described and began to impact researchers around the world, due to its structural and genetic complexity. This virus founded the family Mimiviridae. In recent years, several new giant viruses have been isolated from different environments and specimens. Giant virus research is in its initial phase and information that may arise in the coming years may change current conceptions of life, diversity and evolution. Thus, this review aims to condense the studies conducted so far about the features and peculiarities of APMV, from its discovery to its clinical relevance. PMID:24976356

γ-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer’s Disease

PubMed Central

Serneels, Lutgarde; Van Biervliet, Jérôme; Craessaerts, Katleen; Dejaegere, Tim; Horré, Katrien; Van Houtvin, Tine; Esselmann, Hermann; Paul, Sabine; Schäfer, Martin K.; Berezovska, Oksana; Hyman, Bradley T.; Sprangers, Ben; Sciot, Raf; Moons, Lieve; Jucker, Mathias; Yang, Zhixiang; May, Patrick C.; Karran, Eric; Wiltfang, Jens; D’Hooge, Rudi; De Strooper, Bart

2009-01-01

The γ-secretase complex plays a role in Alzheimer’s disease (AD) and cancer progression. The development of clinical useful inhibitors, however, is complicated by the role of the γ-secretase complex in regulated intramembrane proteolysis of Notch and other essential proteins. Different γ-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues. Here we show that these complexes have heterogeneous biochemical and physiological properties. Specific inactivation of the Aph1B γ-secretase in a murine Alzheimer’s disease model led to improvements of Alzheimer’s disease-relevant phenotypic features without any Notch-related side effects. The Aph1B complex contributes to total γ-secretase activity in the human brain, thus specific targeting of Aph1B-containing γ-secretase complexes may be helpful in generating less toxic therapies for Alzheimer’s disease. PMID:19299585

Visualizing Article Similarities via Sparsified Article Network and Map Projection for Systematic Reviews.

PubMed

Ji, Xiaonan; Machiraju, Raghu; Ritter, Alan; Yen, Po-Yin

2017-01-01

Systematic Reviews (SRs) of biomedical literature summarize evidence from high-quality studies to inform clinical decisions, but are time and labor intensive due to the large number of article collections. Article similarities established from textual features have been shown to assist in the identification of relevant articles, thus facilitating the article screening process efficiently. In this study, we visualized article similarities to extend its utilization in practical settings for SR researchers, aiming to promote human comprehension of article distributions and hidden patterns. To prompt an effective visualization in an interpretable, intuitive, and scalable way, we implemented a graph-based network visualization with three network sparsification approaches and a distance-based map projection via dimensionality reduction. We evaluated and compared three network sparsification approaches and the visualization types (article network vs. article map). We demonstrated the effectiveness in revealing article distribution and exhibiting clustering patterns of relevant articles with practical meanings for SRs.

Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features

PubMed Central

Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T.

2016-01-01

Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be useful for monitoring disease progression over time or evaluating therapeutic interventions. PMID:27445790

Inertial sensors to quantify the pivot shift test in the treatment of anterior cruciate ligament injury

PubMed Central

ZAFFAGNINI, STEFANO; LOPOMO, NICOLA; SIGNORELLI, CECILIA; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; BONANZINGA, TOMMASO; GRASSI, ALBERTO; RAGGI, FEDERICO; VISANI, ANDREA; MARCACCI, MAURILIO

2014-01-01

The main purpose of this article was to describe in detail, from the perspective of the clinical end user, a previously presented non-invasive methodology, applied in the treatment of anterior cruciate ligament injury, in which inertial sensors are used to quantify the pivot shift test. The outcomes obtained and relative considerations were compared with findings emerging from a review of the relevant updated literature. The detailed description here provided covers the system, the parameters identified and the testing procedure; it also includes the technical specifications of the hardware, the features introduced in the updated version of the software and the application of the system in clinical practice. The comparison of the technical considerations and clinical results with the updated literature confirmed the system’s optimal ergonomics, good reproducibility and clinical reliability. The novel approach here analyzed has been shown to overcome the weaknesses of other available devices and systems. Therefore, since it can be considered a new paradigm in the quantification of pivot shift test, we can recommend its routine use in clinical practice. PMID:25606555

Ethical issues with informed consent from potential living kidney donors.

PubMed

Petrini, C

2010-05-01

Living organ donation and participation in clinical research trials have several features in common from an ethical perspective. The primary similarity is risk justification: the risk of harm to living organ donors and clinical research participants is justified by a resulting benefit to one or more other individuals. Some authors hold that organ donation and clinical trial participation are full-fledged duties. Such an implicit likening of the two leads to several considerations regarding informed consent in each situation. Informed consent raises ethical concerns in every medical context, and some of those concerns, such as competence, understanding, autonomy, and free or voluntary choice, are uniquely relevant to living organ donation and clinical trial participation. Most countries regulate informed consent procedures for living organ donation in great detail, and although informed consent procedures for clinical trial participation are somewhat less detailed, their rules are subject to review by ethics committees. It would be constructive for research participation informed consent procedures and living organ donation informed consent procedures to learn from one another. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Strengths and Weaknesses of Pre-Clinical Models for Human Melanoma Treatment: Dawn of Dogs’ Revolution for Immunotherapy

PubMed Central

Barutello, Giuseppina; Rolih, Valeria; Arigoni, Maddalena; Tarone, Lidia; Conti, Laura

2018-01-01

Despite several therapeutic advances, malignant melanoma still remains a fatal disease for which novel and long-term curative treatments are needed. The successful development of innovative therapies strongly depends on the availability of appropriate pre-clinical models. For this purpose, several mouse models holding the promise to provide insight into molecular biology and clinical behavior of melanoma have been generated. The most relevant ones and their contribution for the advancement of therapeutic approaches for the treatment of human melanoma patients will be here summarized. However, as models, mice do not recapitulate all the features of human melanoma, thus their strengths and weaknesses need to be carefully identified and considered for the translation of the results into the human clinics. In this panorama, the concept of comparative oncology acquires a priceless value. The revolutionary importance of spontaneous canine melanoma as a translational model for the pre-clinical investigation of melanoma progression and treatment will be here discussed, with a special consideration to the development of innovative immunotherapeutic approaches. PMID:29534457

Predictive Suppression of Cortical Excitability and Its Deficit in Schizophrenia

PubMed Central

Schroeder, Charles E.; Leitman, David I.

2013-01-01

Recent neuroscience advances suggest that when interacting with our environment, along with previous experience, we use contextual cues and regularities to form predictions that guide our perceptions and actions. The goal of such active “predictive sensing” is to selectively enhance the processing and representation of behaviorally relevant information in an efficient manner. Since a hallmark of schizophrenia is impaired information selection, we tested whether this deficiency stems from dysfunctional predictive sensing by measuring the degree to which neuronal activity predicts relevant events. In healthy subjects, we established that these mechanisms are engaged in an effort-dependent manner and that, based on a correspondence between human scalp and intracranial nonhuman primate recordings, their main role is a predictive suppression of excitability in task-irrelevant regions. In contrast, schizophrenia patients displayed a reduced alignment of neuronal activity to attended stimuli, which correlated with their behavioral performance deficits and clinical symptoms. These results support the relevance of predictive sensing for normal and aberrant brain function, and highlight the importance of neuronal mechanisms that mold internal ongoing neuronal activity to model key features of the external environment. PMID:23843536

The clinical toxicology of γ-hydroxybutyrate, γ-butyrolactone and 1,4-butanediol.

PubMed

Schep, Leo J; Knudsen, Kai; Slaughter, Robin J; Vale, J Allister; Mégarbane, Bruno

2012-07-01

Gamma-hydroxybutyrate (GHB) and its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD), are drugs of abuse which act primarily as central nervous system (CNS) depressants. In recent years, the rising recreational use of these drugs has led to an increasing burden upon health care providers. Understanding their toxicity is therefore essential for the successful management of intoxicated patients. We review the epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to GHB and its analogs and discuss the features and management of GHB withdrawal. OVID MEDLINE and ISI Web of Science databases were searched using the terms "GHB," "gamma-hydroxybutyrate," "gamma-hydroxybutyric acid," "4-hydroxybutanoic acid," "sodium oxybate," "gamma-butyrolactone," "GBL," "1,4-butanediol," and "1,4-BD" alone and in combination with the keywords "pharmacokinetics," "kinetics," "poisoning," "poison," "toxicity," "ingestion," "adverse effects," "overdose," and "intoxication." In addition, bibliographies of identified articles were screened for additional relevant studies including nonindexed reports. Non-peer-reviewed sources were also included: books, relevant newspaper reports, and applicable Internet resources. These searches produced 2059 nonduplicate citations of which 219 were considered relevant. There is limited information regarding statistical trends on world-wide use of GHB and its analogs. European data suggests that the use of GHB is generally low; however, there is some evidence of higher use among some sub-populations, settings, and geographical areas. In the United States of America, poison control center data have shown that enquiries regarding GHB have decreased between 2002 and 2010 suggesting a decline in use over this timeframe. GHB is an endogenous neurotransmitter synthesized from glutamate with a high affinity for GHB-receptors, present on both on pre- and postsynaptic neurons, thereby inhibiting GABA release. In overdose, GHB acts both directly as a partial GABA(b) receptor agonist and indirectly through its metabolism to form GABA. GHB is rapidly absorbed by the oral route with peak blood concentrations typically occurring within 1 hour. It has a relatively small volume of distribution and is rapidly distributed across the blood-brain barrier. GHB is metabolized primarily in the liver and is eliminated rapidly with a reported 20-60 minute half-life. The majority of a dose is eliminated completely within 4-8 hours. The related chemicals, 1,4-butanediol and gamma butyrolactone, are metabolized endogenously to GHB. CLINICAL FEATURES OF POISONING: GHB produces CNS and respiratory depression of relatively short duration. Other commonly reported features include gastrointestinal upset, bradycardia, myoclonus, and hypothermia. Fatalities have been reported. MANAGEMENT OF POISONING: Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Airway protection, intubation, and/or assisted ventilation may be indicated for severe respiratory depression. Gastrointestinal decontamination is unlikely to be beneficial. Pharmacological intervention is rarely required for bradycardia; however, atropine administration may occasionally be warranted. WITHDRAWAL SYNDROME: Abstinence after chronic use may result in a withdrawal syndrome, which may persist for days in severe cases. Features include auditory and visual hallucinations, tremors, tachycardia, hypertension, sweating, anxiety, agitation, paranoia, insomnia, disorientation, confusion, and aggression/combativeness. Benzodiazepine administration appears to be the treatment of choice, with barbiturates, baclofen, or propofol as second line management options. GHB poisoning can cause potentially life-threatening CNS and respiratory depression, requiring appropriate, symptom-directed supportive care to ensure complete recovery. Withdrawal from GHB may continue for up to 21 days and can be life-threatening, though treatment with benzodiazepines is usually effective.

Clinical, endoscopic and manometric features of the primary motor disorders of the esophagus.

PubMed

Martinez, Júlio César; Lima, Gustavo Rosa de Almeida; Silva, Diego Henrique; Duarte, Alexandre Ferreira; Novo, Neil Ferreira; da Silva, Ernesto Carlos; Pinto, Pérsio Campos Correia; Maia, Alexandre Moreira

2015-01-01

Significant incidence, diagnostic difficulties, clinical relevance and therapeutic efficacy associated with the small number of publications on the primary esophageal motor disorders, motivated the present study. To determine the manometric prevalence of these disorders and correlate them to the endoscopic and clinical findings. A retrospective study of 2614 patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric examinations diagnosed with primary esophageal motor disorder, were sought-clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic (hiatal hernia, erosive esophagitis, food waste) that motivated the performance of manometry. Were found 49 cases of achalasia, 73 diffuse spasm, 89 nutcracker esophagus, 82 ineffective esophageal motility, and six lower esophageal sphincter hypertension. In relation to the correlations, it was observed that in 119 patients clinical conditions were associated with dysphagia, found in achalasia more than in other conditions; in relationship between endoscopic findings and clinical conditions there was no statistical significance between data. The clinical and endoscopic findings have little value in the characterization of the primary motor disorders of the esophagus, showing even more the need for manometry, particularly in the preoperative period of gastroesophageal reflux disease.

Acute myeloid leukaemia with myelodysplastic features in children: a report of Japanese Paediatric Leukaemia/Lymphoma Study Group.

PubMed

Kinoshita, Akitoshi; Miyachi, Hayato; Matsushita, Hiromichi; Yabe, Miharu; Taki, Tomohiko; Watanabe, Tomoyuki; Saito, Akiko M; Tomizawa, Daisuke; Taga, Takashi; Takahashi, Hiroyuki; Matsuo, Hidemasa; Kodama, Kumi; Ohki, Kentaro; Hayashi, Yasuhide; Tawa, Akio; Horibe, Keizo; Adachi, Souichi

2014-10-01

The clinical characteristics and prognostic relevance of acute myeloid leukaemia (AML) with myelodysplastic features remains to be clarified in children. We prospectively examined 443 newly diagnosed patients in a multicentre clinical trial for paediatric de novo AML, and found 'AML with myelodysplasia-related changes' (AML-MRC) according to the 2008 World Health Organization classification in 93 (21·0%), in whom 59 were diagnosed from myelodysplasia-related cytogenetics alone, 28 from multilineage dysplasia alone and six from a combination of both. Compared with 111 patients with 'AML, not otherwise specified' (AML-NOS), patients with 'AML-MRC' presented at a younger age, with a lower white blood cell count, higher incidence of 20-30% bone marrow blasts, unfavourable cytogenetics and a lower frequency of Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD), NPM1 and CEBPA mutations. Complete remission rate and 3-year probability of event-free survival were significantly worse in 'AML-MRC' patients (67·7 vs. 85·6%, P < 0·01, 37·1% vs. 53·8%, P = 0·02, respectively), but 3-year overall survival and relapse-free survival were comparable with 'AML-NOS' patients. By multivariate analysis, FLT3-ITD was solely associated with worse overall survival. These results support the distinctive features of the category 'AML-MRC' even in children. © 2014 John Wiley & Sons Ltd.

FTIR microspectroscopic characterization of Spitz nevi

NASA Astrophysics Data System (ADS)

Giorgini, Elisabetta; Tosi, Giorgio; Conti, Carla; Staibano, Stefania; Ilardi, Gennaro; Sabbatini, Simona

2015-04-01

In the last 10 years, few efforts have been carried out to apply vibrational spectroscopy in the study of dermal pathologies in order to characterize the most relevant spectral markers for distinguishing benign from cancerous lesions. Spitz nevi are a special group of benign melanocytic lesions, characterized by spindled and/or epithelioid nevomelanocytes, with peculiar clinical, dermoscopic and histopathological features. The "atypical forms" of Spitz nevi are among the commonest problems of differential diagnosis with the so-called "spitzoid melanomas". The clinical and histological criteria for discriminating these two entities are very subtle and often still quite subjective, and, in a significant percentage of cases, can lead to diagnostic pitfalls and inadequate therapies. Therefore, it is noteworthy to outline that the diagnosis of melanocytic lesions still represents a challenging problem and a continue matter of discussion. We exploited FTIR microspectroscopy to study the different kinds of spitzoid melanocytes, in order to define the most relevant spectral markers of each specimen and to achieve objective information on "borderline" histologically atypical lesions. In particular, the spectroscopic investigation was carried out on melanocytes deriving from normal skin (as a normal control), malignant melanoma and Spitz nevi. The presence of the characteristic bands of melanin was investigated, too.

Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State*♦

PubMed Central

Fourati, Zaineb; Ruza, Reinis Reinholds; Laverty, Duncan; Drège, Emmanuelle; Delarue-Cochin, Sandrine; Joseph, Delphine; Koehl, Patrice; Smart, Trevor; Delarue, Marc

2017-01-01

Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in clinical practice, the prototypic binding site for this class of drugs within pLGICs is yet to be described. In this study, we present the first X-ray structures of barbiturates bound to GLIC, a cationic prokaryotic pLGIC with excellent structural homology to other relevant channels sensitive to general anesthetics and, as shown here, to barbiturates, at clinically relevant concentrations. Several derivatives of barbiturates containing anomalous scatterers were synthesized, and these derivatives helped us unambiguously identify a unique barbiturate binding site within the central ion channel pore in a closed conformation. In addition, docking calculations around the observed binding site for all three states of the receptor, including a model of the desensitized state, showed that barbiturates preferentially stabilize the closed state. The identification of this pore binding site sheds light on the mechanism of barbiturate inhibition of cationic pLGICs and allows the rationalization of several structural and functional features previously observed for barbiturates. PMID:27986812

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force.

PubMed

Sajatovic, Martha; Strejilevich, Sergio A; Gildengers, Ariel G; Dols, Annemiek; Al Jurdi, Rayan K; Forester, Brent P; Kessing, Lars Vedel; Beyer, John; Manes, Facundo; Rej, Soham; Rosa, Adriane R; Schouws, Sigfried Ntm; Tsai, Shang-Ying; Young, Robert C; Shulman, Kenneth I

2015-11-01

In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

WCE video segmentation using textons

NASA Astrophysics Data System (ADS)

Gallo, Giovanni; Granata, Eliana

2010-03-01

Wireless Capsule Endoscopy (WCE) integrates wireless transmission with image and video technology. It has been used to examine the small intestine non invasively. Medical specialists look for signicative events in the WCE video by direct visual inspection manually labelling, in tiring and up to one hour long sessions, clinical relevant frames. This limits the WCE usage. To automatically discriminate digestive organs such as esophagus, stomach, small intestine and colon is of great advantage. In this paper we propose to use textons for the automatic discrimination of abrupt changes within a video. In particular, we consider, as features, for each frame hue, saturation, value, high-frequency energy content and the responses to a bank of Gabor filters. The experiments have been conducted on ten video segments extracted from WCE videos, in which the signicative events have been previously labelled by experts. Results have shown that the proposed method may eliminate up to 70% of the frames from further investigations. The direct analysis of the doctors may hence be concentrated only on eventful frames. A graphical tool showing sudden changes in the textons frequencies for each frame is also proposed as a visual aid to find clinically relevant segments of the video.

Neural evidence reveals the rapid effects of reward history on selective attention.

PubMed

MacLean, Mary H; Giesbrecht, Barry

2015-05-05

Selective attention is often framed as being primarily driven by two factors: task-relevance and physical salience. However, factors like selection and reward history, which are neither currently task-relevant nor physically salient, can reliably and persistently influence visual selective attention. The current study investigated the nature of the persistent effects of irrelevant, physically non-salient, reward-associated features. These features affected one of the earliest reliable neural indicators of visual selective attention in humans, the P1 event-related potential, measured one week after the reward associations were learned. However, the effects of reward history were moderated by current task demands. The modulation of visually evoked activity supports the hypothesis that reward history influences the innate salience of reward associated features, such that even when no longer relevant, nor physically salient, these features have a rapid, persistent, and robust effect on early visual selective attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiple mechanisms in the perception of face gender: Effect of sex-irrelevant features.

PubMed

Komori, Masashi; Kawamura, Satoru; Ishihara, Shigekazu

2011-06-01

Effects of sex-relevant and sex-irrelevant facial features on the evaluation of facial gender were investigated. Participants rated masculinity of 48 male facial photographs and femininity of 48 female facial photographs. Eighty feature points were measured on each of the facial photographs. Using a generalized Procrustes analysis, facial shapes were converted into multidimensional vectors, with the average face as a starting point. Each vector was decomposed into a sex-relevant subvector and a sex-irrelevant subvector which were, respectively, parallel and orthogonal to the main male-female axis. Principal components analysis (PCA) was performed on the sex-irrelevant subvectors. One principal component was negatively correlated with both perceived masculinity and femininity, and another was correlated only with femininity, though both components were orthogonal to the male-female dimension (and thus by definition sex-irrelevant). These results indicate that evaluation of facial gender depends on sex-irrelevant as well as sex-relevant facial features.

An Optimization-Based Method for Feature Ranking in Nonlinear Regression Problems.

PubMed

Bravi, Luca; Piccialli, Veronica; Sciandrone, Marco

2017-04-01

In this paper, we consider the feature ranking problem, where, given a set of training instances, the task is to associate a score with the features in order to assess their relevance. Feature ranking is a very important tool for decision support systems, and may be used as an auxiliary step of feature selection to reduce the high dimensionality of real-world data. We focus on regression problems by assuming that the process underlying the generated data can be approximated by a continuous function (for instance, a feedforward neural network). We formally state the notion of relevance of a feature by introducing a minimum zero-norm inversion problem of a neural network, which is a nonsmooth, constrained optimization problem. We employ a concave approximation of the zero-norm function, and we define a smooth, global optimization problem to be solved in order to assess the relevance of the features. We present the new feature ranking method based on the solution of instances of the global optimization problem depending on the available training data. Computational experiments on both artificial and real data sets are performed, and point out that the proposed feature ranking method is a valid alternative to existing methods in terms of effectiveness. The obtained results also show that the method is costly in terms of CPU time, and this may be a limitation in the solution of large-dimensional problems.

Machine learning-based analysis of MR radiomics can help to improve the diagnostic performance of PI-RADS v2 in clinically relevant prostate cancer.

PubMed

Wang, Jing; Wu, Chen-Jiang; Bao, Mei-Ling; Zhang, Jing; Wang, Xiao-Ning; Zhang, Yu-Dong

2017-10-01

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923-0.976]) than PI-RADS (Az: 0.878 [0.834-0.914], p < 0.001). The Az between them was insignificant for PCa versus PZ (0.972 [0.945-0.988] vs. 0.940 [0.905-0.965], p = 0.097). When radiomics was added, performance of PI-RADS was significantly improved for PCa versus PZ (Az: 0.983 [0.960-0.995]) and PCa versus TZ (Az: 0.968 [0.940-0.985]). Machine learning analysis of MR radiomics can help improve the performance of PI-RADS in clinically relevant PCa. • Machine-based analysis of MR radiomics outperformed in TZ cancer against PI-RADS. • Adding MR radiomics significantly improved the performance of PI-RADS. • DKI-derived Dapp and Kapp were two strong markers for the diagnosis of PCa.

Understanding user intents in online health forums.

PubMed

Zhang, Thomas; Cho, Jason H D; Zhai, Chengxiang

2015-07-01

Online health forums provide a convenient way for patients to obtain medical information and connect with physicians and peers outside of clinical settings. However, large quantities of unstructured and diversified content generated on these forums make it difficult for users to digest and extract useful information. Understanding user intents would enable forums to find and recommend relevant information to users by filtering out threads that do not match particular intents. In this paper, we derive a taxonomy of intents to capture user information needs in online health forums and propose novel pattern-based features for use with a multiclass support vector machine (SVM) classifier to classify original thread posts according to their underlying intents. Since no dataset existed for this task, we employ three annotators to manually label a dataset of 1192 HealthBoards posts spanning four forum topics. Experimental results show that a SVM using pattern-based features is highly capable of identifying user intents in forum posts, reaching a maximum precision of 75%, and that a SVM-based hierarchical classifier using both pattern and word features outperforms its SVM counterpart that uses only word features. Furthermore, comparable classification performance can be achieved by training and testing on posts from different forum topics.

Hyperspectral Image Enhancement and Mixture Deep-Learning Classification of Corneal Epithelium Injuries

PubMed Central

Md Noor, Siti Salwa; Michael, Kaleena; Marshall, Stephen; Ren, Jinchang

2017-01-01

In our preliminary study, the reflectance signatures obtained from hyperspectral imaging (HSI) of normal and abnormal corneal epithelium tissues of porcine show similar morphology with subtle differences. Here we present image enhancement algorithms that can be used to improve the interpretability of data into clinically relevant information to facilitate diagnostics. A total of 25 corneal epithelium images without the application of eye staining were used. Three image feature extraction approaches were applied for image classification: (i) image feature classification from histogram using a support vector machine with a Gaussian radial basis function (SVM-GRBF); (ii) physical image feature classification using deep-learning Convolutional Neural Networks (CNNs) only; and (iii) the combined classification of CNNs and SVM-Linear. The performance results indicate that our chosen image features from the histogram and length-scale parameter were able to classify with up to 100% accuracy; particularly, at CNNs and CNNs-SVM, by employing 80% of the data sample for training and 20% for testing. Thus, in the assessment of corneal epithelium injuries, HSI has high potential as a method that could surpass current technologies regarding speed, objectivity, and reliability. PMID:29144388

How is depression experienced around the world? A systematic review of qualitative literature

PubMed Central

Haroz, E.E.; Ritchey, M.; Bass, J.K.; Kohrt, B.A.; Augustinavicius, J.; Michalopoulos, L.; Burkey, M.D.; Bolton, P.

2017-01-01

To date global research on depression has used assessment tools based on research and clinical experience drawn from Western populations (i.e., in North American, European and Australian). There may be features of depression in non-Western populations which are not captured in current diagnostic criteria or measurement tools, as well as criteria for depression that are not relevant in other regions. We investigated this possibility through a systematic review of qualitative studies of depression worldwide. Nine online databases were searched for records that used qualitative methods to study depression. Initial searches were conducted between August 2012 and December 2012; an updated search was repeated in June of 2015 to include relevant literature published between December 30, 2012 and May 30, 2015. No date limits were set for inclusion of articles. A total of 16,130 records were identified and 138 met full inclusion criteria. Included studies were published between 1976 and 2015. These 138 studies represented data on 170 different study populations (some reported on multiple samples) and 77 different nationalities/ethnicities. Variation in results by geographical region, gender, and study context were examined to determine the consistency of descriptions across populations. Fisher’s exact tests were used to compare frequencies of features across region, gender and context. Seven of the 15 features with the highest relative frequency form part of the DSM-5 diagnosis of Major Depressive Disorder (MDD). However, many of the other features with relatively high frequencies across the studies are associated features in the DSM, but are not prioritized as diagnostic criteria and therefore not included in standard instruments. The DSM-5 diagnostic criteria of problems with concentration and psychomotor agitation or slowing were infrequently mentioned. This research suggests that the DSM model and standard instruments currently based on the DSM may not adequately reflect the experience of depression at the worldwide or regional levels. PMID:28069271

How is depression experienced around the world? A systematic review of qualitative literature.

PubMed

Haroz, E E; Ritchey, M; Bass, J K; Kohrt, B A; Augustinavicius, J; Michalopoulos, L; Burkey, M D; Bolton, P

2017-06-01

To date global research on depression has used assessment tools based on research and clinical experience drawn from Western populations (i.e., in North American, European and Australian). There may be features of depression in non-Western populations which are not captured in current diagnostic criteria or measurement tools, as well as criteria for depression that are not relevant in other regions. We investigated this possibility through a systematic review of qualitative studies of depression worldwide. Nine online databases were searched for records that used qualitative methods to study depression. Initial searches were conducted between August 2012 and December 2012; an updated search was repeated in June of 2015 to include relevant literature published between December 30, 2012 and May 30, 2015. No date limits were set for inclusion of articles. A total of 16,130 records were identified and 138 met full inclusion criteria. Included studies were published between 1976 and 2015. These 138 studies represented data on 170 different study populations (some reported on multiple samples) and 77 different nationalities/ethnicities. Variation in results by geographical region, gender, and study context were examined to determine the consistency of descriptions across populations. Fisher's exact tests were used to compare frequencies of features across region, gender and context. Seven of the 15 features with the highest relative frequency form part of the DSM-5 diagnosis of Major Depressive Disorder (MDD). However, many of the other features with relatively high frequencies across the studies are associated features in the DSM, but are not prioritized as diagnostic criteria and therefore not included in standard instruments. The DSM-5 diagnostic criteria of problems with concentration and psychomotor agitation or slowing were infrequently mentioned. This research suggests that the DSM model and standard instruments currently based on the DSM may not adequately reflect the experience of depression at the worldwide or regional levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fully automated motion correction in first-pass myocardial perfusion MR image sequences.

PubMed

Milles, Julien; van der Geest, Rob J; Jerosch-Herold, Michael; Reiber, Johan H C; Lelieveldt, Boudewijn P F

2008-11-01

This paper presents a novel method for registration of cardiac perfusion magnetic resonance imaging (MRI). The presented method is capable of automatically registering perfusion data, using independent component analysis (ICA) to extract physiologically relevant features together with their time-intensity behavior. A time-varying reference image mimicking intensity changes in the data of interest is computed based on the results of that ICA. This reference image is used in a two-pass registration framework. Qualitative and quantitative validation of the method is carried out using 46 clinical quality, short-axis, perfusion MR datasets comprising 100 images each. Despite varying image quality and motion patterns in the evaluation set, validation of the method showed a reduction of the average right ventricle (LV) motion from 1.26+/-0.87 to 0.64+/-0.46 pixels. Time-intensity curves are also improved after registration with an average error reduced from 2.65+/-7.89% to 0.87+/-3.88% between registered data and manual gold standard. Comparison of clinically relevant parameters computed using registered data and the manual gold standard show a good agreement. Additional tests with a simulated free-breathing protocol showed robustness against considerable deviations from a standard breathing protocol. We conclude that this fully automatic ICA-based method shows an accuracy, a robustness and a computation speed adequate for use in a clinical environment.

Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

PubMed

Hanchard, Neil A; Umana, Luis A; D'Alessandro, Lisa; Azamian, Mahshid; Poopola, Mojisola; Morris, Shaine A; Fernbach, Susan; Lalani, Seema R; Towbin, Jeffrey A; Zender, Gloria A; Fitzgerald-Butt, Sara; Garg, Vidu; Bowman, Jessica; Zapata, Gladys; Hernandez, Patricia; Arrington, Cammon B; Furthner, Dieter; Prakash, Siddharth K; Bowles, Neil E; McBride, Kim L; Belmont, John W

2017-08-01

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals. © 2017 Wiley Periodicals, Inc.

Diagnosis, follow-up and treatment of cystic fibrosis-related liver disease.

PubMed

van de Peppel, Ivo P; Bertolini, Anna; Jonker, Johan W; Bodewes, Frank A J A; Verkade, Henkjan J

2017-11-01

To provide an insight and overview of the challenges in the diagnosis, follow-up and treatment of cystic fibrosis-related liver disease (CFLD). The variable pathophysiology of CFLD complicates its diagnosis and treatment. A 'gold standard' for CFLD diagnosis is lacking. Over the past years, new techniques to diagnose features of CFLD, such as transient elastography, have been investigated. Although most of these tests confirm cystic fibrosis-related liver involvement (CFLI), they are, however, not suitable to distinguish various phenotypical presentations or predict progression to clinically relevant cirrhosis or portal hypertension. A combined initiative from the European and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has been started, aimed to obtain consensus on CFLD criteria and definitions. Currently, only ursodeoxycholic acid is used in CFLD treatment, although it has not been convincingly demonstrated to change the natural course of the disease. Drugs that directly target cystic fibrosis transmembrane conductance regulator protein dysfunction show promising results; however, more long-term follow-up and validation studies are needed. CFLD is an umbrella term referring to a wide variety of liver manifestations with variable clinical needs and consequences. CFLD with portal hypertension is the most severe form of CFLD due to its significant implications on morbidity and mortality. The clinical relevance of other CFLI is uncertain. Consensus on CFLD definitions is essential to validate new diagnostic tools and therapeutic outcome measures.

Pregnancy-Related Anxiety: Evidence of Distinct Clinical Significance from a Prospective Longitudinal Study

PubMed Central

Blackmore, Emma Robertson; Gustafsson, Hanna; Gilchrist, Michelle; Wyman, Claire; O’Connor, Thomas G

2016-01-01

Background Pregnancy-related anxiety (PrA) has attracted considerable research attention, but questions remain about its distinctiveness from conventional constructs and measures. In a high psychosocial risk, ethnically diverse sample, we examine the degree to which PrA is distinct from continuous and diagnostic measures of anxiety and worry in terms of longitudinal course, associations with psychosocial and perinatal risk, and prediction of postnatal mood disturbance. Methods 345 women oversampled for prenatal anxiety and depression were selected from an urban obstetrics clinic serving a predominantly low-income, ethnically diverse population. PrA was assessed at 20 and 32 weeks gestation; anxiety and depression symptoms were assessed from questionnaire and from clinical interview at 20 and 32 weeks gestation and again at 2 and 6 months postnatally. Data relevant to psychosocial and obstetric risks were ascertained from interview, medical exam, and chart review. Results Two distinct factors of PrA were identified, indexing specific concerns about the child’s health and about the birth; these two PrA factors showed distinct longitudinal patterns in the prenatal period, and modest associations with general measures of anxiety and depression from questionnaire and clinical interview. PrA was also distinguished from conventional symptom measures in its associated features and prediction of birth weight and postnatal mood. Limitations The sample was at high psychosocial risk and ethnically diverse; findings may not generalize to other samples. Conclusions PrA can be distinguished from general measures of anxiety in pregnancy in terms of longitudinal course, associated features, and prediction to postnatal mood disturbance, and may warrant specific clinical attention. PMID:26999549

Measurement of food-related approach-avoidance biases: Larger biases when food stimuli are task relevant.

PubMed

Lender, Anja; Meule, Adrian; Rinck, Mike; Brockmeyer, Timo; Blechert, Jens

2018-06-01

Strong implicit responses to food have evolved to avoid energy depletion but contribute to overeating in today's affluent environments. The Approach-Avoidance Task (AAT) supposedly assesses implicit biases in response to food stimuli: Participants push pictures on a monitor "away" or pull them "near" with a joystick that controls a corresponding image zoom. One version of the task couples movement direction with image content-independent features, for example, pulling blue-framed images and pushing green-framed images regardless of content ('irrelevant feature version'). However, participants might selectively attend to this feature and ignore image content and, thus, such a task setup might underestimate existing biases. The present study tested this attention account by comparing two irrelevant feature versions of the task with either a more peripheral (image frame color: green vs. blue) or central (small circle vs. cross overlaid over the image content) image feature as response instruction to a 'relevant feature version', in which participants responded to the image content, thus making it impossible to ignore that content. Images of chocolate-containing foods and of objects were used, and several trait and state measures were acquired to validate the obtained biases. Results revealed a robust approach bias towards food only in the relevant feature condition. Interestingly, a positive correlation with state chocolate craving during the task was found when all three conditions were combined, indicative of criterion validity of all three versions. However, no correlations were found with trait chocolate craving. Results provide a strong case for the relevant feature version of the AAT for bias measurement. They also point to several methodological avenues for future research around selective attention in the irrelevant versions and task validity regarding trait vs. state variables. Copyright © 2018 Elsevier Ltd. All rights reserved.

Planning to avoid trouble in the operating room: experts' formulation of the preoperative plan.

PubMed

Zilbert, Nathan R; St-Martin, Laurent; Regehr, Glenn; Gallinger, Steven; Moulton, Carol-Anne

2015-01-01

The purpose of this study was to capture the preoperative plans of expert hepato-pancreato-biliary (HPB) surgeons with the goal of finding consistent aspects of the preoperative planning process. HPB surgeons were asked to think aloud when reviewing 4 preoperative computed tomography scans of patients with distal pancreatic tumors. The imaging features they identified and the planned actions they proposed were tabulated. Surgeons viewed the tabulated list of imaging features for each case and rated the relevance of each feature for their subsequent preoperative plan. Average rater intraclass correlation coefficients were calculated for each type of data collected (imaging features detected, planned actions reported, and relevance of each feature) to establish whether the surgeons were consistent with one another in their responses. Average rater intraclass correlation coefficient values greater than 0.7 were considered indicative of consistency. Division of General Surgery, University of Toronto. HPB surgeons affiliated with the University of Toronto. A total of 11 HPB surgeons thought aloud when reviewing 4 computed tomography scans. Surgeons were consistent in the imaging features they detected but inconsistent in the planned actions they reported. Of the HPB surgeons, 8 completed the assessment of feature relevance. For 3 of the 4 cases, the surgeons were consistent in rating the relevance of specific imaging features on their preoperative plans. These results suggest that HPB surgeons are consistent in some aspects of the preoperative planning process but not others. The findings further our understanding of the preoperative planning process and will guide future research on the best ways to incorporate the teaching and evaluation of preoperative planning into surgical training. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Case-controlled clinical and histopathological study of conjunctivochalasis.

PubMed

Francis, I C; Chan, D G; Kim, P; Wilcsek, G; Filipic, M; Yong, J; Coroneo, M T

2005-03-01

Conjunctivochalasis, a secondary cause of the watery eye, is frequently seen in the older age group as an elevation of the bulbar conjunctiva lying along the lateral or central lower lid margin. A prospective, interventional, case-controlled clinical and histopathological study was conducted. The relevant features of 18 patients (29 eyes) who had their conjunctivochalasis resected as part of the surgical management of their watery eye syndrome were examined. In the control group, tissue was obtained from an age matched series of 24 normal subjects undergoing routine cataract surgery. 24 controls (24 specimens) and 18 patients (29 specimens) had conjunctival strip biopsies, taken from the usual lid margin level bulbar conjunctiva in line with the inferior limbus (controls), and the clinically apparent conjunctivochalasis (patients). These were submitted for histological study. 23 of 24 control sections demonstrated normal conjunctival variation. Four of 29 patient specimens demonstrated a chronic non-granulomatous conjunctivitis, while three eyes of the patient group (two patients) demonstrated features of elastosis. Of the four patients who had the inflammatory infiltrates, three had functional nasolacrimal duct obstructions (FNLDOs) and one had a primary acquired nasolacrimal duct obstruction (PANDO). Of the two patients who had elastosis, one had an FNLDO and the other had normal lacrimal drainage and was Jones 1 positive. Six of 18 patients--that is, seven of 29 specimens of conjunctivochalasis demonstrated signs of elastosis or of chronic non-granulomatous inflammation. Clinically, patients had a spectrum of aetiologies of their watery eye syndrome.

Concise Review: The Periosteum: Tapping into a Reservoir of Clinically Useful Progenitor Cells

PubMed Central

Chang, Hana

2012-01-01

Elucidation of the periosteum and its regenerative potential has become a hot topic in orthopedics. Yet few review articles address the unique features of periosteum-derived cells, particularly in light of translational therapies and engineering solutions inspired by the periosteum's remarkable regenerative capacity. This review strives to define periosteum-derived cells in light of cumulative research in the field; in addition, it addresses clinical translation of current insights, hurdles to advancement, and open questions in the field. First, we examine the periosteal niche and its inhabitant cells and the key characteristics of these cells in the context of mesenchymal stem cells and their relevance for clinical translation. We compare periosteum-derived cells with those derived from the marrow niche in in vivo studies, addressing commonalities as well as features unique to periosteum cells that make them potentially ideal candidates for clinical application. Thereafter, we review the differentiation and tissue-building properties of periosteum cells in vitro, evaluating their efficacy in comparison with marrow-derived cells. Finally, we address a new concept of banking periosteum and periosteum-derived cells as a novel alternative to currently available autogenic umbilical blood and perinatal tissue sources of stem cells for today's population of aging adults who were “born too early” to bank their own perinatal tissues. Elucidating similarities and differences inherent to multipotent cells from distinct tissue niches and their differentiation and tissue regeneration capacities will facilitate the use of such cells and their translation to regenerative medicine. PMID:23197852

Bronchial anthracofibrosis: an emerging pulmonary disease due to biomass fuel exposure.

PubMed

Gupta, A; Shah, A

2011-05-01

1) To document current knowledge of bronchial anthracofibrosis (BAF), an emerging pulmonary disease recognised just over a decade ago; 2) to highlight the demographic profile, and clinical, radiological and bronchoscopic features peculiar to BAF; and 3) to discuss the postulated causes and clinical conditions associated with BAF, emphasising the need to characterise and recognise it as a distinct clinical disorder. An extensive search of the literature was performed in Medline/PubMed and other databases with key terms 'anthracosis', 'biomass fuels', 'bronchial anthracofibrosis' and 'pulmonary tuberculosis'. The bibliographies of papers identified were searched for further relevant articles. A total of 17 studies and six case series/reports describing 1320 patients with bronchoscopically confirmed BAF were documented. BAF was predominantly observed in elderly housewives in rural areas with prolonged exposure to biomass fuel, and was associated with respiratory diseases such as tuberculosis (TB), chronic obstructive pulmonary disease, pneumonia and malignancy. Exposure to biomass fuel smoke emerged as the main causative factor, but the possibility of an occupational lung disorder was also raised. Characteristic clinical, thorax computed tomography and bronchoscopic features of BAF were identified and its differentiation from endobronchial TB and bronchogenic carcinoma was described. As a pulmonary disease, BAF is yet to be highlighted in both developing and industrialised countries. BAF is currently diagnosed only on bronchoscopy, whereas a suitable non-invasive diagnostic modality would enable rapid diagnosis and increased recognition. Approaches for patients with BAF need to be developed and the serious hazards of biomass fuel use should be emphasised.

Vertigo in childhood: proposal for a diagnostic algorithm based upon clinical experience.

PubMed

Casani, A P; Dallan, I; Navari, E; Sellari Franceschini, S; Cerchiai, N

2015-06-01

The aim of this paper is to analyse, after clinical experience with a series of patients with established diagnoses and review of the literature, all relevant anamnestic features in order to build a simple diagnostic algorithm for vertigo in childhood. This study is a retrospective chart review. A series of 37 children underwent complete clinical and instrumental vestibular examination. Only neurological disorders or genetic diseases represented exclusion criteria. All diagnoses were reviewed after applying the most recent diagnostic guidelines. In our experience, the most common aetiology for dizziness is vestibular migraine (38%), followed by acute labyrinthitis/neuritis (16%) and somatoform vertigo (16%). Benign paroxysmal vertigo was diagnosed in 4 patients (11%) and paroxysmal torticollis was diagnosed in a 1-year-old child. In 8% (3 patients) of cases, the dizziness had a post-traumatic origin: 1 canalolithiasis of the posterior semicircular canal and 2 labyrinthine concussions, respectively. Menière's disease was diagnosed in 2 cases. A bilateral vestibular failure of unknown origin caused chronic dizziness in 1 patient. In conclusion, this algorithm could represent a good tool for guiding clinical suspicion to correct diagnostic assessment in dizzy children where no neurological findings are detectable. The algorithm has just a few simple steps, based mainly on two aspects to be investigated early: temporal features of vertigo and presence of hearing impairment. A different algorithm has been proposed for cases in which a traumatic origin is suspected.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities.

PubMed

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities

NASA Astrophysics Data System (ADS)

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

Bipolar postpartum depression: An update and recommendations.

PubMed

Sharma, Verinder; Doobay, Minakshi; Baczynski, Christine

2017-09-01

Over the past few years there has been a surge of interest in the study of bipolar postpartum depression (PPD); however, questions remain about its prevalence, screening, clinical features, and treatment. Three electronic databases, MEDLINE/PubMed (1966-2016), PsycINFO (1806-2016), and the Cochrane Database of Systematic Reviews, were searched using a combination of the keywords bipolar, depression, postpartum, peripartum, prevalence, screening, diagnosis, treatment, drugs, and psychotherapy. The reference lists of articles identified were also searched. All relevant articles published in English were included. Depending on the population studied, 21.4-54% of women with PPD have a diagnosis of bipolar disorder (BD). Characteristic clinical features include younger age at illness onset, first onset of depression after childbirth, onset immediately after delivery, atypical depressive symptoms, psychotic features, mixed features, and history of BD in first-degree family members. Treatment should be guided by symptom acuity, safety concerns, the patient's response to past treatments, drug tolerability, and breastfeeding preference. In the absence of controlled treatment data, preference should be given to drugs normally indicated for bipolar depression including lithium, quetiapine and lamotrigine. Although antidepressants have been studied in combination with mood stabilizers in bipolar depression, these drugs should be avoided due to likelihood of elevated risk of induction of manic symptoms in the postpartum period. In the postpartum period, bipolar PPD is common, can be differentiated from unipolar PPD, and needs to be identified promptly in order to expedite appropriate treatment. Future studies on pharmacotherapy and psychotherapy should focus on the acute and preventative treatment of bipolar PPD. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrating multiple immunogenetic data sources for feature extraction and mining somatic hypermutation patterns: the case of "towards analysis" in chronic lymphocytic leukaemia.

PubMed

Kavakiotis, Ioannis; Xochelli, Aliki; Agathangelidis, Andreas; Tsoumakas, Grigorios; Maglaveras, Nicos; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Vlahavas, Ioannis; Chouvarda, Ioanna

2016-06-06

Somatic Hypermutation (SHM) refers to the introduction of mutations within rearranged V(D)J genes, a process that increases the diversity of Immunoglobulins (IGs). The analysis of SHM has offered critical insight into the physiology and pathology of B cells, leading to strong prognostication markers for clinical outcome in chronic lymphocytic leukaemia (CLL), the most frequent adult B-cell malignancy. In this paper we present a methodology for integrating multiple immunogenetic and clinocobiological data sources in order to extract features and create high quality datasets for SHM analysis in IG receptors of CLL patients. This dataset is used as the basis for a higher level integration procedure, inspired form social choice theory. This is applied in the Towards Analysis, our attempt to investigate the potential ontogenetic transformation of genes belonging to specific stereotyped CLL subsets towards other genes or gene families, through SHM. The data integration process, followed by feature extraction, resulted in the generation of a dataset containing information about mutations occurring through SHM. The Towards analysis performed on the integrated dataset applying voting techniques, revealed the distinct behaviour of subset #201 compared to other subsets, as regards SHM related movements among gene clans, both in allele-conserved and non-conserved gene areas. With respect to movement between genes, a high percentage movement towards pseudo genes was found in all CLL subsets. This data integration and feature extraction process can set the basis for exploratory analysis or a fully automated computational data mining approach on many as yet unanswered, clinically relevant biological questions.

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

PubMed

Germain, M A; Hatton, A; Williams, S; Matthews, J B; Stone, M H; Fisher, J; Ingham, E

2003-02-01

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions.

PubMed

Bonneville, Fabrice; Savatovsky, Julien; Chiras, Jacques

2007-10-01

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions in the cerebellopontine angle (CPA). However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion's site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Part 1 describes the different enhancing extra-axial CPA masses primarily arising from the cerebellopontine cistern and its contents, including vestibular and non-vestibular schwannomas, meningioma, metastasis, aneurysm, tuberculosis and other miscellaneous meningeal lesions.

Nanoparticulate delivery systems for antiviral drugs.

PubMed

Lembo, David; Cavalli, Roberta

2010-01-01

Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

[Current Knee Arthroplasty Designs and Kinematics: Differences in Radii, Conformity and Pivoting].

PubMed

Calliess, Tilman; Savov, Peter; Ettinger, Max; Karkosch, Roman

2018-06-14

Today, there is an almost endless variety of knee prosthesis models on the market from which the surgeon can choose. Although the designs appear closer and closer to one another, the industry makes a great effort to emphasise different features as beneficial and a stand-alone. It is increasingly difficult to keep an overview and to assess the clinical relevance of the diverse features. There is a clear lack of independent comparative studies and evidence is low. Nevertheless, different design philosophies require special surgical techniques, so that the surgeon must be familiar with the peculiarity of his/her prosthesis. Also, a differentiated indication for different designs appears to be an interesting concept. The aim of this essay is to give a brief overview of the major design concepts of current unconstrained knee prosthesis designs and their differences regarding biomechanics and kinematics. Georg Thieme Verlag KG Stuttgart · New York.

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Classification of patients with low back-related leg pain: a systematic review.

PubMed

Stynes, Siobhán; Konstantinou, Kika; Dunn, Kate M

2016-05-23

The identification of clinically relevant subgroups of low back pain (LBP) is considered the number one LBP research priority in primary care. One subgroup of LBP patients are those with back related leg pain. Leg pain frequently accompanies LBP and is associated with increased levels of disability and higher health costs than simple low back pain. Distinguishing between different types of low back-related leg pain (LBLP) is important for clinical management and research applications, but there is currently no clear agreement on how to define and identify LBLP due to nerve root involvement. The aim of this systematic review was to identify, describe and appraise papers that classify or subgroup populations with LBLP, and summarise how leg pain due to nerve root involvement is described and diagnosed in the various systems. The search strategy involved nine electronic databases including Medline and Embase, reference lists of eligible studies and relevant reviews. Selected papers were appraised independently by two reviewers using a standardised scoring tool. Of 13,358 initial potential eligible citations, 50 relevant papers were identified that reported on 22 classification systems. Papers were grouped according to purpose and criteria of the classification systems. Five themes emerged: (i) clinical features (ii) pathoanatomy (iii) treatment-based approach (iv) screening tools and prediction rules and (v) pain mechanisms. Three of the twenty two systems focused specifically on LBLP populations. Systems that scored highest following quality appraisal were ones where authors generally included statistical methods to develop their classifications, and supporting work had been published on the systems' validity, reliability and generalisability. There was lack of consistency in how LBLP due to nerve root involvement was described and diagnosed within the systems. Numerous classification systems exist that include patients with leg pain, a minority of them focus specifically on distinguishing between different presentations of leg pain. Further work is needed to identify clinically meaningful subgroups of LBLP patients, ideally based on large primary care cohort populations and using recommended methods for classification system development.

[Isolation of Aspergillus tritici from internal environment (Chile): Ecological and clinical scope].

PubMed

Vieille Oyarzo, Peggy; Cruz Choappa, Rodrigo; Piontelli Laforet, Eduardo

2018-03-29

Indoor environments provide important protective habitats for humans, who live or work in them most of the time. Many of these environments lack ventilation, which affects the composition of microbial communities, especially that of the fungal community. The aim of this study is to report the isolation of Aspergillus section Candidi from indoor environments of the School of Medicine at Universidad de Valparaiso, Chile, and identification through morpho-physiological and molecular approaches. Their ecological and clinical features were highlighted. An environmental non-volumetric sampling was performed on PDA medium; 2 petri dishes were exposed in 10 different places to select the Aspergillus samples. Subcultures were performed on agar Czapek with yeast extract (CYA), malt extract agar (MEA) and creatin sacarose agar (CREA) media only for the morpho-physiological and later the molecular identification of white spore species. Of the 20 samples analyzed, one Aspergillus belonging to Candidi section was isolated. Based on its morphology and molecular features, it was classified as Aspergillustritici Mehrotra & Basu. Its ecology and medical relevance are reviewed and discussed. Copyright © 2017 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

PubMed Central

Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

PubMed

Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

2009-01-01

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

An Indian child with Kindler syndrome resulting from a new homozygous nonsense mutation (C468X) in the KIND1 gene.

PubMed

Sethuraman, G; Fassihi, H; Ashton, G H S; Bansal, A; Kabra, M; Sharma, V K; McGrath, J A

2005-05-01

Kindler syndrome is an inherited skin condition that presents with blistering followed by photosensitivity and a progressive poikiloderma. The disorder results from mutations in the KIND1 gene, encoding the protein kindlin-1, a recently characterized 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We report the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous nonsense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and chronic sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counselling in this family and in assessing carrier status in unaffected family members.

Good cognitive performances in a child with Prader-Willi syndrome.

PubMed

Nugnes, Rosa; Zito, Eugenio; Mozzillo, Enza; Camarca, Maria Erminia; Riccio, Maria Pia; Terrone, Gaetano; Melis, Daniela; Bravaccio, Carmela; Franzese, Adriana

2013-11-15

We report the case of a child affected by Prader-Willi syndrome (PWS) with good cognitive performances and without relevant behavioral abnormalities.The diagnosis of PWS, suspected on the basis of clinical features and past history, was confirmed by DNA methylation analysis. Additional genetic testing revealed a maternal uniparental disomy. Intellectual profile was analyzed by WISC-III and Raven's Progressive Matrices CPM, while the behavior was evaluated by K-SADS-PL and Child Behavior Checklist/4-18 to the parents.WISC-III test showed a Total Intelligence Quotient (T-IQ = 79) at the border level for age. The Verbal Intelligence Quotient (V-IQ) showed a lower score than the Performance Intelligence Quotient (P-IQ) (78 and 85, respectively). Raven's Matrices CPM showed an intelligence level at 75-90° percentile for age. Concerning behavioral evaluation, a difficulty in impulse control was observed, with persistent but controllable search for food, without a clear psychopathological meaning. Also according to K-SADS-PL no areas of psychopathological dimensions were detected. In conclusion, in presence of consisting clinical features of PWS and high diagnostic suspicion, the diagnosis of PWS should be considered even in presence of a borderline IQ and in absence of psychopathological abnormalities.

A conceptual framework for evaluating data suitability for observational studies.

PubMed

Shang, Ning; Weng, Chunhua; Hripcsak, George

2017-09-08

To contribute a conceptual framework for evaluating data suitability to satisfy the research needs of observational studies. Suitability considerations were derived from a systematic literature review on researchers' common data needs in observational studies and a scoping review on frequent clinical database design considerations, and were harmonized to construct a suitability conceptual framework using a bottom-up approach. The relationships among the suitability categories are explored from the perspective of 4 facets of data: intrinsic, contextual, representational, and accessible. A web-based national survey of domain experts was conducted to validate the framework. Data suitability for observational studies hinges on the following key categories: Explicitness of Policy and Data Governance, Relevance, Availability of Descriptive Metadata and Provenance Documentation, Usability, and Quality. We describe 16 measures and 33 sub-measures. The survey uncovered the relevance of all categories, with a 5-point Likert importance score of 3.9 ± 1.0 for Explicitness of Policy and Data Governance, 4.1 ± 1.0 for Relevance, 3.9 ± 0.9 for Availability of Descriptive Metadata and Provenance Documentation, 4.2 ± 1.0 for Usability, and 4.0 ± 0.9 for Quality. The suitability framework evaluates a clinical data source's fitness for research use. Its construction reflects both researchers' points of view and data custodians' design features. The feedback from domain experts rated Usability, Relevance, and Quality categories as the most important considerations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

PubMed

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

A survey on features of allergic rhinitis in children.

PubMed

Zicari, A M; Indinnimeo, L; De Castro, G; Incorvaia, C; Frati, F; Dell'Albani, I; Puccinelli, P; Scolari, M; Duse, M

2013-05-01

A number of epidemiologic studies evaluated the prevalence of allergic rhinitis (AR), but few data are available on its different clinical presentations. We addressed this survey to assess the features of AR in children and adolescents. Thirty-five centers in Italy included 2623 pediatric patients with rhinitis, of whom 2319 suffered from AR, while 304 had other kinds of rhinitis. For each patient a standardized questionnaire was filled in, including ARIA classification, the duration of symptoms, the allergen identified as clinically relevant, the co-morbidities, the kind of treatment, the response to treatment, the satisfaction with the treatment, and the feasibility of allergen immunotherapy (AIT). Of the 2319 patients, 597 (25.7%) had mild intermittent, 701 (30.2%) mild persistent, 174 (7.5%) moderate-severe intermittent, and 773 (33.3%) moderate-severe persistent AR. The allergens most relevant were grass pollen and dust mites. The most frequently used drugs were oral antihistamines (83.1%) and topical corticosteroids (63.5%). The response to treatment was judged as excellent in 13.5%, good in 45.1%, fair in 30.8%, poor in 10%, and very bad in 0.6% of cases. The satisfaction with treatment was judged as very satisfactory in 15.2%, satisfactory in 61.8%, unsatisfactory in 22.4%, and very unsatisfactory in 0.5% of cases. AIT was considered indicated in 53.1% of patients with mild intermittent, 79.2% of moderate-severe intermittent, 72.6% of mild persistent, and 82.7% of moderate-severe persistent AR. The limitation of this study is that the population was not unselected and this prevents epidemiological significance. These results offer confirmation of the adequacy of ARIA guidelines in classifying patients with AR and of the association of severe phenotype with lack of success of drug treatment.

An experimental model of allergic asthma in cats sensitized to house dust mite or bermuda grass allergen.

PubMed

Norris Reinero, Carol R; Decile, Kendra C; Berghaus, Roy D; Williams, Kurt J; Leutenegger, Christian M; Walby, William F; Schelegle, Edward S; Hyde, Dallas M; Gershwin, Laurel J

2004-10-01

Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimpe, T; Marchessoux, C; Rostang, J

Purpose: Use of color images in medical imaging has increased significantly the last few years. As of today there is no agreed standard on how color information needs to be visualized on medical color displays, resulting into large variability of color appearance and it making consistency and quality assurance a challenge. This paper presents a proposal for an extension of DICOM GSDF towards color. Methods: Visualization needs for several color modalities (multimodality imaging, nuclear medicine, digital pathology, quantitative imaging applications…) have been studied. On this basis a proposal was made for desired color behavior of color medical display systems andmore » its behavior and effect on color medical images was analyzed. Results: Several medical color modalities could benefit from perceptually linear color visualization for similar reasons as why GSDF was put in place for greyscale medical images. An extension of the GSDF (Greyscale Standard Display Function) to color is proposed: CSDF (color standard display function). CSDF is based on deltaE2000 and offers a perceptually linear color behavior. CSDF uses GSDF as its neutral grey behavior. A comparison between sRGB/GSDF and CSDF confirms that CSDF significantly improves perceptual color linearity. Furthermore, results also indicate that because of the improved perceptual linearity, CSDF has the potential to increase perceived contrast of clinically relevant color features. Conclusion: There is a need for an extension of GSDF towards color visualization in order to guarantee consistency and quality. A first proposal (CSDF) for such extension has been made. Behavior of a CSDF calibrated display has been characterized and compared with sRGB/GSDF behavior. First results indicate that CSDF could have a positive influence on perceived contrast of clinically relevant color features and could offer benefits for quantitative imaging applications. Authors are employees of Barco Healthcare.« less

Optimizing biologically targeted clinical trials for neurofibromatosis

PubMed Central

Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J

2014-01-01

Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

Ambiguity Within Nursing Practice: An Evolutionary Concept Analysis.

PubMed

McMahon, Michelle A; Dluhy, Nancy M

2017-02-01

To analyze the concept of ambiguity in a nursing context. Ambiguity is inherent within nursing practice. As health care becomes increasingly complex, nurses must continue to successfully deal with greater amounts of clinical ambiguity. Although ambiguity is discussed in nursing, minimal concept refinement exists to capture the contextual intricacies from a nursing lens. Nurse perception of an ambiguous clinical event, in combination with nurse tolerance level for ambiguity, can impact nurse response. Yet, little is known about what constitutes ambiguity within nursing practice (AWNP). Rodgers evolutionary method was used to explore AWNP, with emphasis on nurse thinking during ambiguous clinical situations. Literature searches across multiple databases yielded 38 articles for analysis. Attributes of AWNP include (a) variations in cues/available information, (b) multiple interpretations, (c) novel/nonroutine presentations, and (d) unpredictable. Antecedents include (a) a context-specific, clinical situation with ambiguous features needing evaluation and (b) an individual to sense a knowledge gap or perceive ambiguity. Consequences include ranges of (a) emotional, (b) behavioral, and (c) cognitive clinician responses. Preliminary findings support AWNP as a distinct concept in which ambiguity perceived by the nurse likely affects judgment, decision making, and clinical interventions. AWNP is a clinically relevant concept requiring continued development.

Remembering Complex Objects in Visual Working Memory: Do Capacity Limits Restrict Objects or Features?

PubMed Central

Hardman, Kyle; Cowan, Nelson

2014-01-01

Visual working memory stores stimuli from our environment as representations that can be accessed by high-level control processes. This study addresses a longstanding debate in the literature about whether storage limits in visual working memory include a limit to the complexity of discrete items. We examined the issue with a number of change-detection experiments that used complex stimuli which possessed multiple features per stimulus item. We manipulated the number of relevant features of the stimulus objects in order to vary feature load. In all of our experiments, we found that increased feature load led to a reduction in change-detection accuracy. However, we found that feature load alone could not account for the results, but that a consideration of the number of relevant objects was also required. This study supports capacity limits for both feature and object storage in visual working memory. PMID:25089739

Feature-based attentional modulations in the absence of direct visual stimulation.

PubMed

Serences, John T; Boynton, Geoffrey M

2007-07-19

When faced with a crowded visual scene, observers must selectively attend to behaviorally relevant objects to avoid sensory overload. Often this selection process is guided by prior knowledge of a target-defining feature (e.g., the color red when looking for an apple), which enhances the firing rate of visual neurons that are selective for the attended feature. Here, we used functional magnetic resonance imaging and a pattern classification algorithm to predict the attentional state of human observers as they monitored a visual feature (one of two directions of motion). We find that feature-specific attention effects spread across the visual field-even to regions of the scene that do not contain a stimulus. This spread of feature-based attention to empty regions of space may facilitate the perception of behaviorally relevant stimuli by increasing sensitivity to attended features at all locations in the visual field.

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Researchers’ and Clinicians’ Perceptions of Recruiting Participants to Clinical Research: A Thematic Meta-Synthesis

PubMed Central

Newington, Lisa; Metcalfe, Alison

2014-01-01

Background Recruiting the desired number of research participants is frequently problematic with resulting financial and clinical implications. The views of individuals responsible for participant recruitment have not been previously reviewed. This systematic review and thematic meta-synthesis explores researchers’ and clinicians’ experiences and perceptions of recruiting participants to clinical research, with the aim of informing improved recruitment systems and strategies. Methods Studies published between January 1995 and May 2013 were identified from: Ovid MEDLINE, Ovid EMBASE, Ovid PSYCHINFO, ASSIA, British Nursing Index, Scopus, Web of Science, CINAHL and PubMed. Included studies were original peer reviewed research, with qualitative methodologies and an aim of exploring the views of clinicians and/or researchers on recruitment to clinical research. Studies discussing the recruitment of patients unable to give informed consent were excluded. The findings sections of the relevant studies were free coded to identify key concepts which were grouped into hierarchical themes. The quality of the identified studies was assessed and the relative contribution of each paper was checked to ensure individual studies did not dominate in any theme. Results Eighteen relevant papers were identified which examined the views of researchers and clinicians in 10 clinical specialties. Five main themes emerged: building a research community, securing resources, the nature of research, professional identities and recruitment strategies. The views of researchers and clinicians were similar, although the role of ‘researcher’ was inconsistently defined. Conclusions The general experience of recruiting participants to clinical research was one of competition and compromise. Competition arose over funding, staffing and participants, and between clinical and research responsibilities. Compromise was needed to create study designs that were acceptable to patients, clinicians and researchers. Forging relationships between clinical and research teams featured extensively, however the involvement of patients and the public within the research community was rarely discussed. PMID:24734142

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Defining delirium for the International Classification of Diseases, 11th Revision.

PubMed

Meagher, David J; Maclullich, Alasdair M J; Laurila, Jouko V

2008-09-01

The development of ICD-11 provides an opportunity to update the description of delirium according to emerging data that have added to our understanding of this complex neuropsychiatric syndrome. Synthetic article based on published work considered by the authors to be relevant to the definition of delirium. The current DSM-IV definition of delirium is preferred to the ICD-10 because of its greater inclusivity. Evidence does not support major changes in the principal components of present definitions but a number of key issues for the updated definition were identified. These include better account of non-cognitive features, more guidance for rating contextual diagnostic items, clearer definition regarding the interface with dementia, and accounting for illness severity, clinical subtypes and course. Development of the ICD definition of delirium can allow for more targeted research and clinical effort.

Battery-free, wireless sensors for full-body pressure and temperature mapping

PubMed Central

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R.; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A.

2018-01-01

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. PMID:29618561

Application of Immunohistochemistry and Molecular Diagnostics to Clinically Relevant Problems in Endometrial Cancer Bojana Djordjevic, Shannon Westin, Russell R. Broaddus

PubMed Central

Djordjevic, Bojana; Westin, Shannon; Broaddus, Russell R.

2012-01-01

Synopsis A number of different clinical scenarios are presented in which lab-based analyses beyond the usual diagnosis based on light microscopic examination of H&E stained slides – immunohistochemistry and PCR-based assays such as sequencing, mutation testing, microsatellite instability analysis, and determination of MLH1 methylation - are most helpful for guiding diagnosis and treatment of endometrial cancer. The central goal of this information is to provide a practical guide of key current and emerging issues in diagnostic endometrial cancer pathology that require the use of ancillary laboratory techniques, such as immunohistochemistry and molecular testing. The authors present the common diagnostic problems in endometrial carcinoma pathology, types of endometrial carcinoma, description of tissue testing and markers, pathological features, and targeted therapy. PMID:23687522

Electroencephalogram Signal Classification for Automated Epileptic Seizure Detection Using Genetic Algorithm

PubMed Central

Nanthini, B. Suguna; Santhi, B.

2017-01-01

Background: Epilepsy causes when the repeated seizure occurs in the brain. Electroencephalogram (EEG) test provides valuable information about the brain functions and can be useful to detect brain disorder, especially for epilepsy. In this study, application for an automated seizure detection model has been introduced successfully. Materials and Methods: The EEG signals are decomposed into sub-bands by discrete wavelet transform using db2 (daubechies) wavelet. The eight statistical features, the four gray level co-occurrence matrix and Renyi entropy estimation with four different degrees of order, are extracted from the raw EEG and its sub-bands. Genetic algorithm (GA) is used to select eight relevant features from the 16 dimension features. The model has been trained and tested using support vector machine (SVM) classifier successfully for EEG signals. The performance of the SVM classifier is evaluated for two different databases. Results: The study has been experimented through two different analyses and achieved satisfactory performance for automated seizure detection using relevant features as the input to the SVM classifier. Conclusion: Relevant features using GA give better accuracy performance for seizure detection. PMID:28781480

Protein Interactome of Muscle Invasive Bladder Cancer

PubMed Central

Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

2015-01-01

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

Divergent sensory phenotypes in nonspecific arm pain: comparisons with cervical radiculopathy.

PubMed

Moloney, Niamh; Hall, Toby; Doody, Catherine

2015-02-01

To investigate whether distinct sensory phenotypes were identifiable in individuals with nonspecific arm pain (NSAP) and whether these differed from those in people with cervical radiculopathy. A secondary question considered whether the frequency of features of neuropathic pain, kinesiophobia, high pain ratings, hyperalgesia, and allodynia differed according to subgroups of sensory phenotypes. Cross-sectional study. Higher education institution. Forty office workers with NSAP, 17 people with cervical radiculopathy, and 40 age- and sex-matched healthy controls (N=97). Not applicable. Participants were assessed using quantitative sensory testing (QST) comprising thermal and vibration detection thresholds and thermal and pressure pain thresholds; clinical examination; and relevant questionnaires. Sensory phenotypes were identified for each individual in the patient groups using z-score transformation of the QST data. Individuals with NSAP and cervical radiculopathy present with a spectrum of sensory abnormalities; a dominant sensory phenotype was not identifiable in individuals with NSAP. No distinct pattern between clinical features and questionnaire results across sensory phenotypes was identified in either group. When considering sensory phenotypes, neither individuals with NSAP nor individuals with cervical radiculopathy should be considered homogeneous. Therefore, people with either condition may warrant different intervention approaches according to their individual sensory phenotype. Issues relating to the clinical identification of sensory hypersensitivity and the validity of QST are highlighted. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The development of a core syllabus for the teaching of head and neck anatomy to medical students.

PubMed

Tubbs, R Shane; Sorenson, Edward P; Sharma, Amit; Benninger, Brion; Norton, Neil; Loukas, Marios; Moxham, Bernard J

2014-04-01

The study of human anatomy has traditionally served as a fundamental component in the basic science education of medical students, yet there exists a remarkable lack of firm guidance on essential features that must be included in a gross anatomy course, which would constitute a "Core Syllabus" of absolutely mandatory structures and related clinical pathologies. While universal agreement on the details of a core syllabus is elusive, there is a general consensus that a core syllabus aims to identify the minimum level of knowledge expected of recently qualified medical graduates in order to carry out clinical procedures safely and effectively, while avoiding overloading students with unnecessary facts that have less immediate application to their future careers as clinicians. This paper aims to identify consensus standards of essential features of Head and Neck anatomy via a Delphi Panel consisting of anatomists and clinicians who evaluated syllabus content structures (greater than 1,000) as "essential", "important", "acceptable", or "not required." The goal is to provide guidance for program/course directors who intend to provide the optimal balance between establishing a comprehensive list of clinically relevant essential structures and an overwhelming litany, which would otherwise overburden trainees in their initial years of medical school with superficial rote learning, which potentially dilutes the key and enduring fundamental lessons that prepare students for training in any medical field. Copyright © 2014 Wiley Periodicals, Inc.

Pancreatic fistula risk for pancreatoduodenectomy: an international survey of surgeon perception.

PubMed

McMillan, Matthew T; Malleo, Giuseppe; Bassi, Claudio; Sprys, Michael H; Ecker, Brett L; Drebin, Jeffrey A; Vollmer, Charles M

2017-06-01

Clinically relevant postoperative pancreatic fistula (CR-POPF) is a morbid complication following pancreatoduodenectomy (PD). It is unclear how pancreatic surgeons perceive risk for this complication, and the implications thereof. A web-based survey was distributed to members of 22 international GI surgical societies. CR-POPF risk factors were categorized as follows: (i) patient factors, (ii) pancreatic gland characteristics, (iii) intraoperative variables, (iv) perioperative mitigation techniques, or (v) institutional features. Surveys were completed by 897 surgeons worldwide. The most commonly cited contributors to CR-POPF risk were gland characteristics (90.7%), while patient and intraoperative factors were selected 71.2 and 69.3% of the time, respectively. Conversely, institutional features (31.7%) and perioperative mitigation techniques (21.3%) were rarely recognized. Eighty percent of surgeons use drain amylase concentration to guide drain removal decision-making; however, only 45.2% of surgeon remove drains early based upon drain amylase values. When evaluating clinical scenarios, surgeons were able to identify both negligible and high risk scenarios but struggled to differentiate between low and moderate CR-POPF risk. This international study analyzed how surgeons discern CR-POPF risk for PD. There was considerable variability in surgeons' perceptions of risk, which may have an adverse effect on the clinical use of risk adjustment measures. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

In chronic spontaneous urticaria, high numbers of dermal endothelial cells, but not mast cells, are linked to recurrent angio-oedema.

PubMed

Terhorst, D; Koti, I; Krause, K; Metz, M; Maurer, M

2018-03-01

Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder characterized by recurrent weals, angio-oedema or both. Recent studies have shown that the number of endothelial cells is increased in the skin of patients with CSU, but the underlying mechanisms and clinical implications of this are unclear. To evaluate whether mast cell (MC) or endothelial cell (EC) numbers correlate with CSU and whether they are relevant for disease duration, disease activity or the presence of clinical features. We determined the numbers of CD31+ ECs and MCs in nonlesional skin of 30 patients with CSU using quantitative histomorphometry, and assessed their correlation with each other and with clinical features such as disease duration, disease activity and occurrence of angio-oedema. The numbers of MCs and ECs were high in the nonlesional skin of patients with CSU, but did not correlate with each other. Neither MC number nor EC number correlated with disease duration or disease activity. Interestingly, patients with high numbers of cutaneous CD31+ ECs had higher rates of recurrent angio-oedema and vice versa. Based on these findings, we speculate that vascular remodelling and MC hyperplasia in patients with CSU occurs independently and via different mechanisms. Targeting of the mechanisms that drive neoangiogenesis in CSU may result in novel therapeutic strategies for the management of patients with angio-oedema. © 2017 British Association of Dermatologists.

Using machine learning to predict radiation pneumonitis in patients with stage I non-small cell lung cancer treated with stereotactic body radiation therapy

NASA Astrophysics Data System (ADS)

Valdes, Gilmer; Solberg, Timothy D.; Heskel, Marina; Ungar, Lyle; Simone, Charles B., II

2016-08-01

To develop a patient-specific ‘big data’ clinical decision tool to predict pneumonitis in stage I non-small cell lung cancer (NSCLC) patients after stereotactic body radiation therapy (SBRT). 61 features were recorded for 201 consecutive patients with stage I NSCLC treated with SBRT, in whom 8 (4.0%) developed radiation pneumonitis. Pneumonitis thresholds were found for each feature individually using decision stumps. The performance of three different algorithms (Decision Trees, Random Forests, RUSBoost) was evaluated. Learning curves were developed and the training error analyzed and compared to the testing error in order to evaluate the factors needed to obtain a cross-validated error smaller than 0.1. These included the addition of new features, increasing the complexity of the algorithm and enlarging the sample size and number of events. In the univariate analysis, the most important feature selected was the diffusion capacity of the lung for carbon monoxide (DLCO adj%). On multivariate analysis, the three most important features selected were the dose to 15 cc of the heart, dose to 4 cc of the trachea or bronchus, and race. Higher accuracy could be achieved if the RUSBoost algorithm was used with regularization. To predict radiation pneumonitis within an error smaller than 10%, we estimate that a sample size of 800 patients is required. Clinically relevant thresholds that put patients at risk of developing radiation pneumonitis were determined in a cohort of 201 stage I NSCLC patients treated with SBRT. The consistency of these thresholds can provide radiation oncologists with an estimate of their reliability and may inform treatment planning and patient counseling. The accuracy of the classification is limited by the number of patients in the study and not by the features gathered or the complexity of the algorithm.

The cost of selective attention in category learning: Developmental differences between adults and infants

PubMed Central

Best, Catherine A.; Yim, Hyungwook; Sloutsky, Vladimir M.

2013-01-01

Selective attention plays an important role in category learning. However, immaturities of top-down attentional control during infancy coupled with successful category learning suggest that early category learning is achieved without attending selectively. Research presented here examines this possibility by focusing on category learning in infants (6–8 months old) and adults. Participants were trained on a novel visual category. Halfway through the experiment, unbeknownst to participants, the to-be-learned category switched to another category, where previously relevant features became irrelevant and previously irrelevant features became relevant. If participants attend selectively to the relevant features of the first category, they should incur a cost of selective attention immediately after the unknown category switch. Results revealed that adults demonstrated a cost, as evidenced by a decrease in accuracy and response time on test trials as well as a decrease in visual attention to newly relevant features. In contrast, infants did not demonstrate a similar cost of selective attention as adults despite evidence of learning both to-be-learned categories. Findings are discussed as supporting multiple systems of category learning and as suggesting that learning mechanisms engaged by adults may be different from those engaged by infants. PMID:23773914

21 CFR 1271.75 - How do I screen a donor?

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Risk factors for, and clinical evidence of, relevant communicable disease agents and diseases... risk factors for and clinical evidence of relevant cell-associated communicable disease agents and... having either of the following: (1) A risk factor for or clinical evidence of any of the relevant...

Web-based international studies in limited populations of pediatric leukemia.

PubMed

Valsecchi, Maria Grazia; Silvestri, Daniela; Covezzoli, Anna; De Lorenzo, Paola

2008-02-01

Recent progress in cancer research leads to the characterization of small subgroups of patients by genetic/biological features. Clinical studies in this setting are frequently promoted by international networks of independent researchers and are limited by practical and methodological constraints, not least the regulations recently issued by national and international institutions (EU Directive 2001/20/EC). We reviewed various methods in the design of international multicenter studies, with focus on randomized clinical trials. This paper reports our experience in planning and conducting international studies in childhood leukemia. We applied a decentralized study conduct based on a two-level structure, comprising a national and an international coordinating level. For the more recent trials this structure was implemented as a web-based system. This approach accommodates major legal requirements (e.g., safety reporting) and ensures Good Clinical Practice principles by implementing risk-oriented monitoring procedures. Setting up international non-commercial trials is increasingly complicated. Still, they are strongly needed for answering relevant questions in limited populations. (c) 2007 Wiley-Liss, Inc.

Development and evaluation of an electronic health record configuration and customization laboratory course for clinical informatics students.

PubMed

Mohan, Vishnu; Hersh, William R

2013-01-01

There is a need for informatics educational programs to develop laboratory courses that facilitate hands-on access to an EHR, and allow students to learn and evaluate functionality and configuration options. This is particularly relevant given the diversity of backgrounds of informatics students. We implemented an EHR laboratory course that allowed students to explore an EHR in both inpatient and outpatient clinical environments. The course focused on specific elements of the EHR including order set development, customization, clinical decision support, ancillary services, and billing and coding functionality. Students were surveyed at the end of the course for their satisfaction with the learning experience. We detailed challenges as well as lessons learned after analyzing student evaluations of this course. Features that promote the successful offering of an online EHR course, include (1) using more than one EHR to allow students to compare functionalities, (2) ensuring appropriate course calibration, (3) countering issues specific to EHR usability, and (4) fostering a fertile environment for rich online conversations are discussed.

Mobile phone interference with medical equipment and its clinical relevance: a systematic review.

PubMed

Lawrentschuk, Nathan; Bolton, Damien M

2004-08-02

To conduct a systematic review of studies on clinically relevant digital mobile phone electromagnetic interference with medical equipment. MEDLINE and SUMSEARCH were searched for the period 1966-2004. The Cochrane Library and Database of Abstracts of Reviews of Effects were also searched for systematic reviews. Studies were eligible if published in a peer-reviewed journal in English, and if they included testing of digital mobile phones for clinically relevant interference with medical equipment used to monitor or treat patients, but not implantable medical devices. As there was considerable heterogeneity in medical equipment studied and the conduct of testing, results were summarised rather than subjected to meta-analysis. Clinically relevant electromagnetic interference (EMI) secondary to mobile phones potentially endangering patients occurred in 45 of 479 devices tested at 900 MHz and 14 of 457 devices tested at 1800 MHz. However, in the largest studies, the prevalence of clinically relevant EMI was low. Most clinically relevant EMI occurred when mobile phones were used within 1 m of medical equipment. Although testing was not standardised between studies and equipment tested was not identical, it is of concern that at least 4% of devices tested in any study were susceptible to clinically relevant EMI. All studies recommend some type of restriction of mobile phone use in hospitals, with use greater than 1 m from equipment and restrictions in clinical areas being the most common.

Prediction of citation counts for clinical articles at two years using data available within three weeks of publication: retrospective cohort study

PubMed Central

2008-01-01

Objective To determine if citation counts at two years could be predicted for clinical articles that pass basic criteria for critical appraisal using data within three weeks of publication from external sources and an online article rating service. Design Retrospective cohort study. Setting Online rating service, Canada. Participants 1274 articles from 105 journals published from January to June 2005, randomly divided into a 60:40 split to provide derivation and validation datasets. Main outcome measures 20 article and journal features, including ratings of clinical relevance and newsworthiness, routinely collected by the McMaster online rating of evidence system, compared with citation counts at two years. Results The derivation analysis showed that the regression equation accounted for 60% of the variation (R2=0.60, 95% confidence interval 0.538 to 0.629). This model applied to the validation dataset gave a similar prediction (R2=0.56, 0.476 to 0.596, shrinkage 0.04; shrinkage measures how well the derived equation matches data from the validation dataset). Cited articles in the top half and top third were predicted with 83% and 61% sensitivity and 72% and 82% specificity. Higher citations were predicted by indexing in numerous databases; number of authors; abstraction in synoptic journals; clinical relevance scores; number of cited references; and original, multicentred, and therapy articles from journals with a greater proportion of articles abstracted. Conclusion Citation counts can be reliably predicted at two years using data within three weeks of publication. PMID:18292132

[From querulous neurosis to querulous delusion: the psychopathological aspects of persistent dysfunctional complaining].

PubMed

Tewarie, P R M; van der Zwaard, R

2016-01-01

The clinical concept of querulous behaviour is used only sporadically in modern psychiatry, although the concept seems to be just as clinical relevant as it was many years ago. The extension of the right to complain has played a role in the acceptance of querulous behaviour. Judicial bodies and other government organisations are being kept busier than ever because people who feel they have been denied justice became entangled in interminable litigation. Gradually, querulous behaviour causes the initial sense of injustice to disappear and querulous patients are damaged economically, socially and personally and experience suffering and function less efficiently. To describe the history, clinical features, differential diagnosis, possible psychodynamic hypotheses and possible ways of treating querulous behaviour.
We studied the literature using PubMed, PsychInfo, Google and Google Scholar. There seems to be a spectrum with fluent transitions from normal complaining behaviour, querulous behaviour which is based on a paranoid, narcissistic or obsessive-compulsive personality structure, to severe pathologies like a delusional disorder. There is little evidence that pharmacotherapy or psychotherapy is effective. Nevertheless, there are opportunities for administering psychiatric treatment in order to alleviate the loss and suffering for the patients and their next-of-kin. Querulous behaviour is an old clinical concept that still has relevance today for the individual patient, complaints officers and society in general. Our current diagnostic systems provide sufficient opportunities for diagnosing patients correctly. Patients may be best served by judicial mediation at an early stage, combined with psychiatric treatment aimed at controlling emotions and restricting harmful behaviour.

Electron microscopic changes of detrusor in benign enlargement of prostate and its clinical correlation.

PubMed

Yadav, Sher Singh; Bhattar, Rohit; Sharma, Lokesh; Banga, Gautam; Sadasukhi, Trilok Chandra

2017-01-01

To study the ultra structural changes in bladder musculature in cases of BPE and their clinical relevance. In this descriptive longitudinal, controlled, observational study patients were enrolled into three groups, group 1, group 2A and group 2B. Control group (group-1) consisted of age matched normal male patients, who underwent surveillance or diagnostic cystoscopy for microscopic hematuria or irritative symptoms. Case group (group-2) comprised of patients with BPE, undergoing TURP. Case group (group-2) was further classified into: Category 2A (patients not on catheter) and cat-egory 2B (patients on catheter). All relevant clinical parameters like IPSS, prostate size, Qmax, PVR were recorded. Cystoscopy and bladder biopsy were performed in all patients. Various ultrastructural parameters like myocytes, fascicular pattern, interstitial tissue, nerve hypertrophy and cell junction pattern were analyzed under electron microscope and they were clinically correlated using appropriate statistical tests. Control group had significant difference as compared to case group in terms of baseline parameters like IPSS, flow rate and prostate size, both preoperatively and postoperatively, except for PVR, which was seen only preoperatively. There was statistically significant difference in ultrastructural patterns between case and control group in all five electron microscopic patterns. However, no significant difference was found between the subcategories of case groups. BPE is responsible for ultra structural changes in detrusor muscle and these changes remain persistent even after TURP. Nerve hypertrophy, which was not thoroughly discussed in previous studies, is also one of the salient feature of this study. Copyright® by the International Brazilian Journal of Urology.

Cascade detection for the extraction of localized sequence features; specificity results for HIV-1 protease and structure-function results for the Schellman loop.

PubMed

Newell, Nicholas E

2011-12-15

The extraction of the set of features most relevant to function from classified biological sequence sets is still a challenging problem. A central issue is the determination of expected counts for higher order features so that artifact features may be screened. Cascade detection (CD), a new algorithm for the extraction of localized features from sequence sets, is introduced. CD is a natural extension of the proportional modeling techniques used in contingency table analysis into the domain of feature detection. The algorithm is successfully tested on synthetic data and then applied to feature detection problems from two different domains to demonstrate its broad utility. An analysis of HIV-1 protease specificity reveals patterns of strong first-order features that group hydrophobic residues by side chain geometry and exhibit substantial symmetry about the cleavage site. Higher order results suggest that favorable cooperativity is weak by comparison and broadly distributed, but indicate possible synergies between negative charge and hydrophobicity in the substrate. Structure-function results for the Schellman loop, a helix-capping motif in proteins, contain strong first-order features and also show statistically significant cooperativities that provide new insights into the design of the motif. These include a new 'hydrophobic staple' and multiple amphipathic and electrostatic pair features. CD should prove useful not only for sequence analysis, but also for the detection of multifactor synergies in cross-classified data from clinical studies or other sources. Windows XP/7 application and data files available at: https://sites.google.com/site/cascadedetect/home. nacnewell@comcast.net Supplementary information is available at Bioinformatics online.

Patient-specific analysis of post-operative aortic hemodynamics: a focus on thoracic endovascular repair (TEVAR)

NASA Astrophysics Data System (ADS)

Auricchio, F.; Conti, M.; Lefieux, A.; Morganti, S.; Reali, A.; Sardanelli, F.; Secchi, F.; Trimarchi, S.; Veneziani, A.

2014-10-01

The purpose of this study is to quantitatively evaluate the impact of endovascular repair on aortic hemodynamics. The study addresses the assessment of post-operative hemodynamic conditions of a real clinical case through patient-specific analysis, combining accurate medical image analysis and advanced computational fluid-dynamics (CFD). Although the main clinical concern was firstly directed to the endoluminal protrusion of the prosthesis, the CFD simulations have demonstrated that there are two other important areas where the local hemodynamics is impaired and a disturbed blood flow is present: the first one is the ostium of the subclavian artery, which is partially closed by the graft; the second one is the stenosis of the distal thoracic aorta. Besides the clinical relevance of these specific findings, this study highlights how CFD analyses allow to observe important flow effects resulting from the specific features of patient vessel geometries. Consequently, our results demonstrate the potential impact of computational biomechanics not only on the basic knowledge of physiopathology, but also on the clinical practice, thanks to a quantitative extraction of knowledge made possible by merging medical data and mathematical models.

Computational models of the pulmonary circulation: Insights and the move towards clinically directed studies

PubMed Central

Tawhai, Merryn H.; Clark, Alys R.; Burrowes, Kelly S.

2011-01-01

Biophysically-based computational models provide a tool for integrating and explaining experimental data, observations, and hypotheses. Computational models of the pulmonary circulation have evolved from minimal and efficient constructs that have been used to study individual mechanisms that contribute to lung perfusion, to sophisticated multi-scale and -physics structure-based models that predict integrated structure-function relationships within a heterogeneous organ. This review considers the utility of computational models in providing new insights into the function of the pulmonary circulation, and their application in clinically motivated studies. We review mathematical and computational models of the pulmonary circulation based on their application; we begin with models that seek to answer questions in basic science and physiology and progress to models that aim to have clinical application. In looking forward, we discuss the relative merits and clinical relevance of computational models: what important features are still lacking; and how these models may ultimately be applied to further increasing our understanding of the mechanisms occurring in disease of the pulmonary circulation. PMID:22034608

A cognitive perspective on medical expertise: theory and implication.

PubMed

Schmidt, H G; Norman, G R; Boshuizen, H P

1990-10-01

A new theory of the development of expertise in medicine is outlined. Contrary to existing views, this theory assumes that expertise is not so much a matter of superior reasoning skills or in-depth knowledge of pathophysiological states as it is based on cognitive structures that describe the features of prototypical or even actual patients. These cognitive structures, referred to as "illness scripts," contain relatively little knowledge about pathophysiological causes of symptoms and complaints but a wealth of clinically relevant information about disease, its consequences, and the context under which illness develops. By contrast, intermediate-level students without clinical experience typically use pathophysiological, causal models of disease when solving problems. The authors review evidence supporting the theory and discuss its implications for the understanding of five phenomena extensively documented in the clinical-reasoning literature: (1) content specificity in diagnostic performance; (2) typical differences in data-gathering techniques between medical students and physicians; (3) difficulties involved in setting standards; (4) a decline in performance on certain measures of clinical reasoning with increasing expertise; and (5) a paradoxical association between errors and longer response times in visual diagnosis.

Clinical relevance of contextual factors as triggers of placebo and nocebo effects in musculoskeletal pain.

PubMed

Rossettini, Giacomo; Carlino, Elisa; Testa, Marco

2018-01-22

Placebo and nocebo effects are embodied psycho-neurobiological responses capable of modulating pain and producing changes at different neurobiological, body at perceptual and cognitive levels. These modifications are triggered by different contextual factors (CFs) presented in the therapeutic encounter between patient and healthcare providers, such as healing rituals and signs. The CFs directly impact on the quality of the therapeutic outcome: a positive context, that is a context characterized by the presence of positive CFs, can reduce pain by producing placebo effects, while a negative context, characterized by the presence of negative CFs, can aggravate pain by creating nocebo effects. Despite the increasing interest about this topic; the detailed study of CFs as triggers of placebo and nocebo effects is still lacked in the management of musculoskeletal pain.Increasing evidence suggest a relevant role of CFs in musculoskeletal pain management. CFs are a complex sets of internal, external or relational elements encompassing: patient's expectation, history, baseline characteristics; clinician's behavior, belief, verbal suggestions and therapeutic touch; positive therapeutic encounter, patient-centered approach and social learning; overt therapy, posology of intervention, modality of treatment administration; marketing features of treatment and health care setting. Different explanatory models such as classical conditioning and expectancy can explain how CFs trigger placebo and nocebo effects. CFs act through specific neural networks and neurotransmitters that were described as mediators of placebo and nocebo effects.Available findings suggest a relevant clinical role and impact of CFs. They should be integrated in the clinical reasoning to increase the number of treatment solutions, boosts their efficacy and improve the quality of the decision-making. From a clinical perspective, the mindful manipulation of CFs represents a useful opportunity to enrich a well-established therapy in therapeutic setting within the ethical border. From a translational perspective, there is a strong need of research studies on CFs close to routine and real-world clinical practice in order to underline the uncertainty of therapy action and help clinicians to implement knowledge in daily practice.

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.

PubMed

Goldstein, Lee E; McKee, Ann C; Stanton, Patric K

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath.

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy

PubMed Central

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath. PMID:25478023

Reward- and attention-related biasing of sensory selection in visual cortex.

PubMed

Buschschulte, Antje; Boehler, Carsten N; Strumpf, Hendrik; Stoppel, Christian; Heinze, Hans-Jochen; Schoenfeld, Mircea A; Hopf, Jens-Max

2014-05-01

Attention to task-relevant features leads to a biasing of sensory selection in extrastriate cortex. Features signaling reward seem to produce a similar bias, but how modulatory effects due to reward and attention relate to each other is largely unexplored. To address this issue, it is critical to separate top-down settings defining reward relevance from those defining attention. To this end, we used a visual search paradigm in which the target's definition (attention to color) was dissociated from reward relevance by delivering monetary reward on search frames where a certain task-irrelevant color was combined with the target-defining color to form the target object. We assessed the state of neural biasing for the attended and reward-relevant color by analyzing the neuromagnetic brain response to asynchronously presented irrelevant distractor probes drawn in the target-defining color, the reward-relevant color, and a completely irrelevant color as a reference. We observed that for the prospect of moderate rewards, the target-defining color but not the reward-relevant color produced a selective enhancement of the neuromagnetic response between 180 and 280 msec in ventral extrastriate visual cortex. Increasing reward prospect caused a delayed attenuation (220-250 msec) of the response to reward probes, which followed a prior (160-180 msec) response enhancement in dorsal ACC. Notably, shorter latency responses in dorsal ACC were associated with stronger attenuation in extrastriate visual cortex. Finally, an analysis of the brain response to the search frames revealed that the presence of the reward-relevant color in search distractors elicited an enhanced response that was abolished after increasing reward size. The present data together indicate that when top-down definitions of reward relevance and attention are separated, the behavioral significance of reward-associated features is still rapidly coded in higher-level cortex areas, thereby commanding effective top-down inhibitory control to counter a selection bias for those features in extrastriate visual cortex.

Teachers' Source Evaluation Self-Efficacy Predicts Their Use of Relevant Source Features When Evaluating the Trustworthiness of Web Sources on Special Education

ERIC Educational Resources Information Center

Andreassen, Rune; Bråten, Ivar

2013-01-01

Building on prior research and theory concerning source evaluation and the role of self-efficacy in the context of online learning, this study investigated the relationship between teachers' beliefs about their capability to evaluate the trustworthiness of sources and their reliance on relevant source features when judging the trustworthiness…

Scaly scalp associated with crusted scabies: case series.

PubMed

Anbar, T S; El-Domyati, M B; Mansour, H A; Ahmad, H M

2007-07-13

The diagnosis of crusted scabies is becoming more relevant due to the increase in number of immunocompromised patients. To date, more than 200 cases have been reported in the literature. However, crusted scabies seems to be under-diagnosed because of its unusual presentations. In this case series we present history, clinical manifestations, KOH smear, and histopathological findings of a series of four patients with crusted scabies. Scaly scalp was a prominent feature of the disease in all cases. Examination of and treatment of the scalp of patients with suspected crusted scabies should not be neglected. A KOH smear from the scalp offers a simple and reliable technique for diagnosis.

Cryopyrin-associated periodic syndrome.

PubMed

Posch, Christian; Kaulfersch, Wilhelm; Rappersberger, Klemens

2014-01-01

Cryopyrin-associated periodic syndromes (CAPS) are characterized by apparently unprovoked attacks of fever, rashes, and musculoskeletal and sensorineural inflammation accompanied by high acute-phase reactants. Excessive interleukin-1 (IL-1) signaling appears to be a constant feature in the pathomechanism of the disease, driven by a gain-of-function mutation in the NLRP3 gene. Herein, we present the case of a 9-month-old boy with recurrent nonpruritic rashes and episodes of fever. The difficulties of early diagnosis due to initially mild clinical symptoms and the dramatic response to anti-IL-1 therapy after diagnosis emphasize the practical relevance of considering CAPS as a differential diagnosis in these patients. © 2012 Wiley Periodicals, Inc.

National Athletic Trainers' Association Position Statement: Skin Diseases

PubMed Central

Zinder, Steven M.; Basler, Rodney S. W.; Foley, Jack; Scarlata, Chris; Vasily, David B.

2010-01-01

Abstract Objective: To present recommendations for the prevention, education, and management of skin infections in athletes. Background: Trauma, environmental factors, and infectious agents act together to continually attack the integrity of the skin. Close quarters combined with general poor hygiene practices make athletes particularly vulnerable to contracting skin diseases. An understanding of basic prophylactic measures, clinical features, and swift management of common skin diseases is essential for certified athletic trainers to aid in preventing the spread of infectious agents. Recommendations: These guidelines are intended to provide relevant information on skin infections and to give specific recommendations for certified athletic trainers and others participating in athletic health care. PMID:20617918

Evidence-based medicine: liposuction.

PubMed

Matarasso, Alan; Levine, Steven M

2013-12-01

After reading this article, the participant should be able to: 1. Perform preoperative assessment and patient selection for liposuction surgeries. 2. Explain the differences among the various types of anesthesia and wetting solutions used in liposuction. 3. Identify the available literature about skin-tightening procedures. 4. Convey to patients the complication profile for various modalities of liposuction. 5. Recall important ASPS consensus guidelines when discussing liposuction. The article was prepared to feature recent evidence-based publications pertaining to liposuction. The authors placed special emphasis on the most clinically relevant data. In addition, they highlighted current data regarding liposuction-related fields, including autologous fat transfer and minimally invasive skin tightening.

The exploration of meditation in the neuroscience of attention and consciousness.

PubMed

Raffone, Antonino; Srinivasan, Narayanan

2010-02-01

Many recent behavioral and neuroscientific studies have revealed the importance of investigating meditation states and traits to achieve an increased understanding of cognitive and affective neuroplasticity, attention and self-awareness, as well as for their increasingly recognized clinical relevance. The investigation of states and traits related to meditation has especially pronounced implications for the neuroscience of attention, consciousness, self-awareness, empathy and theory of mind. In this article we present the main features of meditation-based mental training and characterize the current scientific approach to meditation states and traits with special reference to attention and consciousness, in light of the articles contributed to this issue.

Clinical anatomy of the elbow and shoulder.

PubMed

Villaseñor-Ovies, Pablo; Vargas, Angélica; Chiapas-Gasca, Karla; Canoso, Juan J; Hernández-Díaz, Cristina; Saavedra, Miguel Ángel; Navarro-Zarza, José Eduardo; Kalish, Robert A

The elbow patients herein discussed feature common soft tissue conditions such as tennis elbow, golfers' elbow and olecranon bursitis. Relevant anatomical structures for these conditions can easily be identified and demonstrated by cross examination by instructors and participants. Patients usually present rotator cuff tendinopathy, frozen shoulder, axillary neuropathy and suprascapular neuropathy. The structures involved in tendinopathy and frozen shoulder can be easily identified and demonstrated under normal conditions. The axillary and the suprascapular nerves have surface landmarks but cannot be palpated. In neuropathy however, physical findings in both neuropathies are pathognomonic and will be discussed. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Co-occurrence of chancroid and gonorrhea.

PubMed

Nawaf, Al-Mutairi; Joshi, Arun; Tayeh, Mohammad

2006-01-01

Gonorrhea and chancroid are common sexually transmitted infections in many parts of the world. Still, co-occurrence of these two conditions is uncommonly reported. We present here a patient who presented with painful genital ulcers and urethral discharge simultaneously acquired from a single exposure, which turned out to be chancroid and gonorrhea, respectively. Both conditions responded well to a single intramuscular dose of ceftriaxone 250 mg. This report describes the uncommon occurrence of gonorrhea and chancroid in a patient. Clinical features, relevant investigations, treatment options of these two sexually transmitted infections, and possible implications in view of the human immunodeficiency virus (HIV) pandemic are briefly discussed.

Herpes simplex encephalitis with thalamic, brainstem and cerebellar involvement.

PubMed

Garg, Meenal; Kulkarni, Shilpa; Udwadia Hegde, Anaita

2018-04-01

Herpes simplex virus encephalitis is a common and treatable cause of acute encephalitis in all age groups. Certain radiological features such as temporal parenchymal involvement facilitate the diagnosis. The use of herpes simplex virus polymerase chain reaction has expanded the clinical and imaging spectrum. We report the case of a young patient who presented with a movement disorder and predominant involvement of thalami, brainstem and cerebellum on magnetic resonance imaging, and was diagnosed with herpes simplex virus encephalitis. Differentiation from Japanese encephalitis may be difficult in these patients, especially in endemic areas, and may necessitate the use of relevant investigations in all patients.

EHDViz: clinical dashboard development using open-source technologies

PubMed Central

Badgeley, Marcus A; Shameer, Khader; Glicksberg, Benjamin S; Tomlinson, Max S; Levin, Matthew A; McCormick, Patrick J; Kasarskis, Andrew; Reich, David L; Dudley, Joel T

2016-01-01

Objective To design, develop and prototype clinical dashboards to integrate high-frequency health and wellness data streams using interactive and real-time data visualisation and analytics modalities. Materials and methods We developed a clinical dashboard development framework called electronic healthcare data visualization (EHDViz) toolkit for generating web-based, real-time clinical dashboards for visualising heterogeneous biomedical, healthcare and wellness data. The EHDViz is an extensible toolkit that uses R packages for data management, normalisation and producing high-quality visualisations over the web using R/Shiny web server architecture. We have developed use cases to illustrate utility of EHDViz in different scenarios of clinical and wellness setting as a visualisation aid for improving healthcare delivery. Results Using EHDViz, we prototyped clinical dashboards to demonstrate the contextual versatility of EHDViz toolkit. An outpatient cohort was used to visualise population health management tasks (n=14 221), and an inpatient cohort was used to visualise real-time acuity risk in a clinical unit (n=445), and a quantified-self example using wellness data from a fitness activity monitor worn by a single individual was also discussed (n-of-1). The back-end system retrieves relevant data from data source, populates the main panel of the application and integrates user-defined data features in real-time and renders output using modern web browsers. The visualisation elements can be customised using health features, disease names, procedure names or medical codes to populate the visualisations. The source code of EHDViz and various prototypes developed using EHDViz are available in the public domain at http://ehdviz.dudleylab.org. Conclusions Collaborative data visualisations, wellness trend predictions, risk estimation, proactive acuity status monitoring and knowledge of complex disease indicators are essential components of implementing data-driven precision medicine. As an open-source visualisation framework capable of integrating health assessment, EHDViz aims to be a valuable toolkit for rapid design, development and implementation of scalable clinical data visualisation dashboards. PMID:27013597

Amygdala and auditory cortex exhibit distinct sensitivity to relevant acoustic features of auditory emotions.

PubMed

Pannese, Alessia; Grandjean, Didier; Frühholz, Sascha

2016-12-01

Discriminating between auditory signals of different affective value is critical to successful social interaction. It is commonly held that acoustic decoding of such signals occurs in the auditory system, whereas affective decoding occurs in the amygdala. However, given that the amygdala receives direct subcortical projections that bypass the auditory cortex, it is possible that some acoustic decoding occurs in the amygdala as well, when the acoustic features are relevant for affective discrimination. We tested this hypothesis by combining functional neuroimaging with the neurophysiological phenomena of repetition suppression (RS) and repetition enhancement (RE) in human listeners. Our results show that both amygdala and auditory cortex responded differentially to physical voice features, suggesting that the amygdala and auditory cortex decode the affective quality of the voice not only by processing the emotional content from previously processed acoustic features, but also by processing the acoustic features themselves, when these are relevant to the identification of the voice's affective value. Specifically, we found that the auditory cortex is sensitive to spectral high-frequency voice cues when discriminating vocal anger from vocal fear and joy, whereas the amygdala is sensitive to vocal pitch when discriminating between negative vocal emotions (i.e., anger and fear). Vocal pitch is an instantaneously recognized voice feature, which is potentially transferred to the amygdala by direct subcortical projections. These results together provide evidence that, besides the auditory cortex, the amygdala too processes acoustic information, when this is relevant to the discrimination of auditory emotions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feature-Selective Attention Adaptively Shifts Noise Correlations in Primary Auditory Cortex.

PubMed

Downer, Joshua D; Rapone, Brittany; Verhein, Jessica; O'Connor, Kevin N; Sutter, Mitchell L

2017-05-24

Sensory environments often contain an overwhelming amount of information, with both relevant and irrelevant information competing for neural resources. Feature attention mediates this competition by selecting the sensory features needed to form a coherent percept. How attention affects the activity of populations of neurons to support this process is poorly understood because population coding is typically studied through simulations in which one sensory feature is encoded without competition. Therefore, to study the effects of feature attention on population-based neural coding, investigations must be extended to include stimuli with both relevant and irrelevant features. We measured noise correlations ( r noise ) within small neural populations in primary auditory cortex while rhesus macaques performed a novel feature-selective attention task. We found that the effect of feature-selective attention on r noise depended not only on the population tuning to the attended feature, but also on the tuning to the distractor feature. To attempt to explain how these observed effects might support enhanced perceptual performance, we propose an extension of a simple and influential model in which shifts in r noise can simultaneously enhance the representation of the attended feature while suppressing the distractor. These findings present a novel mechanism by which attention modulates neural populations to support sensory processing in cluttered environments. SIGNIFICANCE STATEMENT Although feature-selective attention constitutes one of the building blocks of listening in natural environments, its neural bases remain obscure. To address this, we developed a novel auditory feature-selective attention task and measured noise correlations ( r noise ) in rhesus macaque A1 during task performance. Unlike previous studies showing that the effect of attention on r noise depends on population tuning to the attended feature, we show that the effect of attention depends on the tuning to the distractor feature as well. We suggest that these effects represent an efficient process by which sensory cortex simultaneously enhances relevant information and suppresses irrelevant information. Copyright © 2017 the authors 0270-6474/17/375378-15$15.00/0.

Feature-Selective Attention Adaptively Shifts Noise Correlations in Primary Auditory Cortex

PubMed Central

2017-01-01

Sensory environments often contain an overwhelming amount of information, with both relevant and irrelevant information competing for neural resources. Feature attention mediates this competition by selecting the sensory features needed to form a coherent percept. How attention affects the activity of populations of neurons to support this process is poorly understood because population coding is typically studied through simulations in which one sensory feature is encoded without competition. Therefore, to study the effects of feature attention on population-based neural coding, investigations must be extended to include stimuli with both relevant and irrelevant features. We measured noise correlations (rnoise) within small neural populations in primary auditory cortex while rhesus macaques performed a novel feature-selective attention task. We found that the effect of feature-selective attention on rnoise depended not only on the population tuning to the attended feature, but also on the tuning to the distractor feature. To attempt to explain how these observed effects might support enhanced perceptual performance, we propose an extension of a simple and influential model in which shifts in rnoise can simultaneously enhance the representation of the attended feature while suppressing the distractor. These findings present a novel mechanism by which attention modulates neural populations to support sensory processing in cluttered environments. SIGNIFICANCE STATEMENT Although feature-selective attention constitutes one of the building blocks of listening in natural environments, its neural bases remain obscure. To address this, we developed a novel auditory feature-selective attention task and measured noise correlations (rnoise) in rhesus macaque A1 during task performance. Unlike previous studies showing that the effect of attention on rnoise depends on population tuning to the attended feature, we show that the effect of attention depends on the tuning to the distractor feature as well. We suggest that these effects represent an efficient process by which sensory cortex simultaneously enhances relevant information and suppresses irrelevant information. PMID:28432139

Clinical relevance of findings in trials of CBT for depression.

PubMed

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

Exploring the Association Between Emotional Abuse and Childhood Borderline Personality Features: The Moderating Role of Personality Traits

PubMed Central

Gratz, Kim L.; Latzman, Robert D.; Tull, Matthew T.; Reynolds, Elizabeth K.; Lejuez, C. W.

2012-01-01

Most of the extant literature on borderline personality disorder has focused on the course, consequences, and correlates of this disorder among adults. However, little is known about childhood borderline personality (BP) features, or the factors associated with the emergence of BP pathology in childhood. A greater understanding of childhood BP features and associated risk factors has important implications for the development of primary and secondary prevention programs. The goal of the present study was to examine the interrelationships among two BP-relevant traits (affective dysfunction and impulsivity), a BP-relevant environmental stressor (emotional abuse), and BP features in a sample of 225 children aged 11 to 14 years. Results provide support for the role of both trait vulnerabilities and environmental stressors in childhood BP features. Further, findings highlight the moderating role of affective dysfunction in the relationship between emotional abuse and childhood BP features. PMID:21658531

Comparison of Different EHG Feature Selection Methods for the Detection of Preterm Labor

PubMed Central

Alamedine, D.; Khalil, M.; Marque, C.

2013-01-01

Numerous types of linear and nonlinear features have been extracted from the electrohysterogram (EHG) in order to classify labor and pregnancy contractions. As a result, the number of available features is now very large. The goal of this study is to reduce the number of features by selecting only the relevant ones which are useful for solving the classification problem. This paper presents three methods for feature subset selection that can be applied to choose the best subsets for classifying labor and pregnancy contractions: an algorithm using the Jeffrey divergence (JD) distance, a sequential forward selection (SFS) algorithm, and a binary particle swarm optimization (BPSO) algorithm. The two last methods are based on a classifier and were tested with three types of classifiers. These methods have allowed us to identify common features which are relevant for contraction classification. PMID:24454536

Uterine Fibroid Embolization for Symptomatic Fibroids: Study at a Teaching Hospital in Kenya

PubMed Central

Mutai, John Kiprop; Vinayak, Sudhir; Stones, William; Hacking, Nigel; Mariara, Charles

2015-01-01

Objective: Characterization of magnetic (MRI) features in women undergoing uterine fibroid embolization (UFE) and identification of clinical correlates in an African population. Materials and Methods: Patients with symptomatic fibroids who are selected to undergo UFE at the hospital formed the study population. The baseline MRI features, baseline symptom score, short-term imaging outcome, and mid-term symptom scores were analyzed for interval changes. Assessment of potential associations between short-term imaging features and mid-term symptom scores was also done. Results: UFE resulted in statistically significant reduction (P < 0.001) of dominant fibroid, uterine volumes, and reduction of symptom severity scores, which were 43.7%, 40.1%, and 37.8%, respectively. Also, 59% of respondents had more than 10 fibroids. The predominant location of the dominant fibroid was intramural. No statistically significant association was found between clinical and radiological outcome. Conclusion: The response of uterine fibroids to embolization in the African population is not different from the findings reported in other studies from the west. The presence of multiple and large fibroids in this study is consistent with the case mix described in other studies of African-American populations. Patient counseling should emphasize the independence of volume reduction and symptom improvement. Though volume changes are of relevance for the radiologist in understanding the evolution of the condition and identifying potential technical treatment failures, it should not be the main basis of evaluation of treatment success. PMID:25883858

Developing care pathways--lessons from the Steele Review implementation in England.

PubMed

Rooney, Eric

2014-02-01

This paper sets out to discuss the concept of care pathways, review their definition, features and implementation and using an example from the NHS dental system in England guide the development of an elder care pathway. Care pathways have developed from quality management approaches in industry and focus on a number of steps which are intended to lead to expected outcomes. The existing definition and descriptors of care pathways serve well, but miss the complex process underlying the development of pathways, their structure, implementation and evaluation. The literature identifies key features of clinical pathways and from the developing field of implementation science, the factors likely to support pathway implementation. Pathways must be generic enough to enable them to be applicable broadly, but specific enough for them to be locally relevant and population specific. The development of care pathways in the National Health Service (NHS) Dental Service in England is described and when compared with the implementation science literature exhibits features identified as positive factors for implementation. As a result a contribution to the pathway definition literature is offered. Learning from the literature and the practical experience described from England, the process for developing dental care pathways for dependent elders should begin with the creation of a high level pathway, which is cognisant of the clinical and implementation science evidence base. © 2014 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

Financial conflict-of-interest policies in clinical research: issues for clinical investigators.

PubMed

Boyd, Elizabeth A; Cho, Mildred K; Bero, Lisa A

2003-08-01

As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.

Drug development in neuropsychopharmacology.

PubMed

Fritze, Jürgen

2008-03-01

Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

Cachexia: clinical features when inflammation drives malnutrition.

PubMed

Laviano, Alessandro; Koverech, Angela; Mari, Alessia

2015-11-01

Cachexia is a clinically relevant syndrome which impacts on quality of life, morbidity and mortality of patients suffering from acute and chronic diseases. The hallmark of cachexia is muscle loss, which is triggered by disease-associated inflammatory response. Cachexia is a continuum and therefore a staging system is needed. Initially, a three-stage system (i.e. pre-cachexia, cachexia and refractory cachexia) was proposed. More recent evidence supports the use of a five-stage classification system, based on patient's BMI and severity of weight loss, to better predict clinical outcome. Also, large clinical trials in cancer patients demonstrated that cachexia emerging during chemotherapy has greater influence on survival than weight loss at baseline. Therefore, becoming widely accepted is the importance of routinely monitoring patients' nutritional status to detect early changes and diagnose cachexia in its early phases. Although cachexia is associated with the presence of anabolic resistance, it has been shown that sustained yet physiological hyperaminoacidaemia, as well as the use of specific nutrients, is able to overcome impaired protein synthesis and revert catabolism. More importantly, clinical evidence demonstrates that preservation of nutritional status during chemotherapy or improvement of body weight after weight loss is associated with longer survival in cancer patients.

Temporal characteristics of decisions in hospital encounters: a threshold for shared decision making? A qualitative study.

PubMed

Ofstad, Eirik H; Frich, Jan C; Schei, Edvin; Frankel, Richard M; Gulbrandsen, Pål

2014-11-01

To identify and characterize physicians' statements that contained evidence of clinically relevant decisions in encounters with patients in different hospital settings. Qualitative analysis of 50 videotaped encounters from wards, the emergency room (ER) and outpatient clinics in a department of internal medicine at a Norwegian university hospital. Clinical decisions could be grouped in a temporal order: decisions which had already been made, and were brought into the encounter by the physician (preformed decisions), decisions made in the present (here-and-now decisions), and decisions prescribing future actions given a certain course of events (conditional decisions). Preformed decisions were a hallmark in the ward and conditional decisions a main feature of ER encounters. Clinical decisions related to a patient-physician encounter spanned a time frame exceeding the duration of the encounter. While a distribution of decisions over time and space fosters sharing and dilution of responsibility between providers, it makes the decision making process hard to access for patients. In order to plan when and how to involve patients in decisions, physicians need increased awareness of when clinical decisions are made, who usually makes them, and who should make them. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A New Challenge to Research Ethics: Patients-Led Research (PLR) and the Role of Internet Based Social Networks.

PubMed

Lamas, Eugenia; Salinas, Rodrigo; Vuillaume, Dominique

2016-01-01

A characteristic feature of the development of health-related social networks is the emergence of internet-based virtual communities, composed of patients. These communities go beyond the mere interchange of information concerning their conditions, intervening in the planning and execution of clinical research, including randomised controlled trials, in collaboration with health professionals. That was the case, in 2009, when patients suffering amyotrophic lateral sclerosis, a rare and severe disease, conducted a clinical trial in USA, organising themselves through an online platform. This initiative launched a new model for the planning and conduction of clinical research: "Participants-Led Research" (PLR). The distinctive particularities of this new research paradigm represent a challenge to the traditional standards used for judging the ethical soundness of clinical investigation. That is the case, for example, of informed consent. This article aims at identifying the ethical, legal, and social issues (ELSI) posed by PLR and the relevant concepts that may help in solving them. The following issues, in particular, are analysed, that may give place to a new social contract for the ethical assessment of clinical research: consent for participating in research and personal integrity; data protection and confidentiality; benefits sharing and intellectual property.

Nanoparticles and clinically applicable cell tracking

PubMed Central

Guenoun, Jamal; van Tiel, Sandra T; Krestin, Gabriel P

2015-01-01

In vivo cell tracking has emerged as a much sought after tool for design and monitoring of cell-based treatment strategies. Various techniques are available for pre-clinical animal studies, from which much has been learned and still can be learned. However, there is also a need for clinically translatable techniques. Central to in vivo cell imaging is labelling of cells with agents that can give rise to signals in vivo, that can be detected and measured non-invasively. The current imaging technology of choice for clinical translation is MRI in combination with labelling of cells with magnetic agents. The main challenge encountered during the cell labelling procedure is to efficiently incorporate the label into the cell, such that the labelled cells can be imaged at high sensitivity for prolonged periods of time, without the labelling process affecting the functionality of the cells. In this respect, nanoparticles offer attractive features since their structure and chemical properties can be modified to facilitate cellular incorporation and because they can carry a high payload of the relevant label into cells. While these technologies have already been applied in clinical trials and have increased the understanding of cell-based therapy mechanism, many challenges are still faced. PMID:26248872

Identification of a Recurrent Microdeletion at 17q23.1q23.2 Flanked by Segmental Duplications Associated with Heart Defects and Limb Abnormalities

PubMed Central

Ballif, Blake C.; Theisen, Aaron; Rosenfeld, Jill A.; Traylor, Ryan N.; Gastier-Foster, Julie; Thrush, Devon Lamb; Astbury, Caroline; Bartholomew, Dennis; McBride, Kim L.; Pyatt, Robert E.; Shane, Kate; Smith, Wendy E.; Banks, Valerie; Gallentine, William B.; Brock, Pamela; Rudd, M. Katharine; Adam, Margaret P.; Keene, Julia A.; Phillips, John A.; Pfotenhauer, Jean P.; Gowans, Gordon C.; Stankiewicz, Pawel; Bejjani, Bassem A.; Shaffer, Lisa G.

2010-01-01

Segmental duplications, which comprise ∼5%–10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are ∼2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is ∼2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome. PMID:20206336

Molecular features of biguanides required for targeting of mitochondrial respiratory complex I and activation of AMP-kinase.

PubMed

Bridges, Hannah R; Sirviö, Ville A; Agip, Ahmed-Noor A; Hirst, Judy

2016-08-09

The biguanides are a family of drugs with diverse clinical applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil, which is widely used for the prevention of malaria, does not. The molecular structures of phenformin and proguanil are closely related and both inhibit isolated complex I. Proguanil does not inhibit respiration in cells and mitochondria because it is unable to access complex I. The molecular features that determine which biguanides accumulate in mitochondria, enabling them to inhibit complex I in vivo, are not known. Here, a family of seven biguanides are used to reveal the molecular features that determine why phenformin enters mitochondria and inhibits respiration whereas proguanil does not. All seven biguanides inhibit isolated complex I, but only four of them inhibit respiration in cells and mitochondria. Direct conjugation of a phenyl group and bis-substitution of the biguanide moiety prevent uptake into mitochondria, irrespective of the compound hydrophobicity. This high selectivity suggests that biguanide uptake into mitochondria is protein mediated, and is not by passive diffusion. Only those biguanides that enter mitochondria and inhibit complex I activate AMP kinase, strengthening links between complex I and the downstream effects of biguanide treatments. Biguanides inhibit mitochondrial complex I, but specific molecular features control the uptake of substituted biguanides into mitochondria, so only some biguanides inhibit mitochondrial respiration in vivo. Biguanides with restricted intracellular access may be used to determine physiologically relevant targets of biguanide action, and for the rational design of substituted biguanides for diverse clinical applications.

Pancreatic abnormalities detected by endoscopic ultrasound (EUS) in patients without clinical signs of pancreatic disease: any difference between standard and Rosemont classification scoring?

PubMed

Petrone, Maria Chiara; Terracciano, Fulvia; Perri, Francesco; Carrara, Silvia; Cavestro, Giulia Martina; Mariani, Alberto; Testoni, Pier Alberto; Arcidiacono, Paolo Giorgio

2014-01-01

The prevalence of nine EUS features of chronic pancreatitis (CP) according to the standard Wiersema classification has been investigated in 489 patients undergoing EUS for an indication not related to pancreatico-biliary disease. We showed that 82 subjects (16.8%) had at least one ductular or parenchymal abnormality. Among them, 18 (3.7% of study population) had ≥3 Wiersema criteria suggestive of CP. Recently, a new classification (Rosemont) of EUS findings consistent, suggestive or indeterminate for CP has been proposed. To stratify healthy subjects into different subgroups on the basis of EUS features of CP according to the Wiersema and Rosemont classifications and to evaluate the agreement in the diagnosis of CP with the two scoring systems. Weighted kappa statistics was computed to evaluate the strength of agreement between the two scoring systems. Univariate and multivariate analysis between any EUS abnormality and habits were performed. Eighty-two EUS videos were reviewed. Using the Wiersema classification, 18 subjects showed ≥3 EUS features suggestive of CP. The EUS diagnosis of CP in these 18 subjects was considered as consistent in only one patient, according to Rosemont classification. Weighted Kappa statistics was 0.34 showing that the strength of agreement was 'fair'. Alcohol use and smoking were identified as risk factors for having pancreatic abnormalities on EUS. The prevalence of EUS features consistent or suggestive of CP in healthy subjects according to the Rosemont classification is lower than that assessed by Wiersema criteria. In that regard the Rosemont classification seems to be more accurate in excluding clinically relevant CP. Overall agreement between the two classifications is fair. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Qing-Feng; Wang, Wei-Hu; Wang, Shu-Lian

Purpose: To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment. Methods and Materials: A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL. Results: Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patientsmore » with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL. Conclusions: Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL.« less

Glucocerebrosidase Mutations in Parkinson Disease.

PubMed

O'Regan, Grace; deSouza, Ruth-Mary; Balestrino, Roberta; Schapira, Anthony H

2017-01-01

Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD, other than certain features that can be identified in the specialist research setting but not in routine clinical practice. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD. The clinical similarity with idiopathic PD and the chance to identify PD at a pre-clinical stage provides a unique opportunity to research therapeutic options for early PD, before major irreversible neurodegeneration occurs. However, to date, the molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are not fully elucidated. Experimental models to define the molecular mechanisms and test therapeutic options include cell culture, transgenic mice and other in vivo models amenable to genetic manipulation, such as drosophilia. Some key pathological pathways of interest in the context of GBA mutations include alpha synuclein aggregation, lysosomal-autophagy axis changes and endoplasmic reticulum stress. Therapeutic agents that exploit these pathways are being developed and include the small molecule chaperone Ambroxol. This review aims to summarise the main features of GBA-PD and provide insights into the pathological relevance of GBA mutations on molecular pathways and the therapeutic implications for PD resulting from investigation of the role of GBA in PD.

Genotype-Phenotype Correlation of Hereditary Erythrocytosis Mutations, a single center experience.

PubMed

Oliveira, Jennifer L; Coon, Lea M; Frederick, Lori A; Hein, Molly; Swanson, Kenneth C; Savedra, Michelle E; Porter, Tavanna R; Patnaik, Mrinal M; Tefferi, Ayalew; Pardanani, Animesh; Grebe, Stefan K; Viswanatha, David S; Hoyer, James D

2018-05-23

Hereditary erythrocytosis is associated with high oxygen affinity hemoglobin variants (HOAs), 2,3-bisphosphoglycerate deficiency and abnormalities in EPOR and the oxygen-sensing pathway proteins PHD, HIF2α, and VHL. Our laboratory has 40 years of experience with hemoglobin disorder testing and we have characterized HOAs using varied protein and molecular techniques including functional assessment by p50 analysis. In addition, we have more recently commenced adding the assessment of clinically relevant regions of the VHL, BPGM, EPOR, EGLN1 (PHD2), and EPAS1 (HIF2A) genes in a more comprehensive hereditary erythrocytosis panel of tests. Review of our experience confirms a wide spectrum of alterations associated with erythrocytosis which we have correlated with phenotypic and clinical features. Through generic hemoglobinopathy testing we have identified 762 patients with 81 distinct HOA Hb variants (61 β, 20 α), including 12 that were first identified by our laboratory. Of the 1192 cases received for an evaluation specific for hereditary erythrocytosis, approximately 12% had reportable alterations: 85 pathogenic/likely pathogenic mutations and 58 variants of unknown significance. Many have not been previously reported. Correlation with clinical and phenotypic data supports an algorithmic approach to guide economical evaluation; although, testing is expanded if the suspected causes are negative or of uncertain significance. Clinical features are similar and range from asymptomatic to recurrent headaches, fatigue, restless legs, chest pain, exertional dyspnea and thrombotic episodes. Many patients were chronically phlebotomized with reported relief of symptoms. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

The relevance of non-human primate and rodent malaria models for humans

PubMed Central

2011-01-01

At the 2010 Keystone Symposium on "Malaria: new approaches to understanding Host-Parasite interactions", an extra scientific session to discuss animal models in malaria research was convened at the request of participants. This was prompted by the concern of investigators that skepticism in the malaria community about the use and relevance of animal models, particularly rodent models of severe malaria, has impacted on funding decisions and publication of research using animal models. Several speakers took the opportunity to demonstrate the similarities between findings in rodent models and human severe disease, as well as points of difference. The variety of malaria presentations in the different experimental models parallels the wide diversity of human malaria disease and, therefore, might be viewed as a strength. Many of the key features of human malaria can be replicated in a variety of nonhuman primate models, which are very under-utilized. The importance of animal models in the discovery of new anti-malarial drugs was emphasized. The major conclusions of the session were that experimental and human studies should be more closely linked so that they inform each other, and that there should be wider access to relevant clinical material. PMID:21288352

A novel algorithm for reducing false arrhythmia alarms in intensive care units.

PubMed

Srivastava, Chandan; Sharma, Sonal; Jalali, Ali

2016-08-01

Alarm fatigue in intensive care units (ICU) is one of the top healthcare issues in the US. False alarms in ICU will decrease the quality of care and staff response time over the alarms. Normally, false alarm will cause desensitization of the clinical staff which leads to warnings and misleading, if the triggered alarm is true. In this study, we have proposed a multi-model ensemble approach to reduce the false alarm rate in monitoring systems. We have used 750 patient records from PhysioNet database. At First arrhythmia based features from electrocardiogram (ECG), arterial blood pressure (ABP) and photoplethysmogram (PPG) features were extracted from the records. Next, the dataset has been separated into two subsets on the basis of available features information. The first dataset (DS1) is the combination of ECG physiological, ABP and PPG features. Their correlation coefficient and p-values criteria have been applied for relevant alarm-wise feature-set selection, and random forest classifier was used for model development and validation. The threshold based approach was used on second dataset (DS2) which is the combination of arrhythmia, ABP and PPG features. The developed ensemble model is able to achieve sensitivity 83.33-100 % (average 95.56 %) being true alarms and suppress false alarms rate 66.67-89% (average 77.25%). The predictability of classifier shows the advantage to deal with unbalanced set of information, therefore overall model performance has reached to 83.96% accuracy.

The taccalonolides: microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms.

PubMed

Risinger, April L; Jackson, Evelyn M; Polin, Lisa A; Helms, Gregory L; LeBoeuf, Desiree A; Joe, Patrick A; Hopper-Borge, Elizabeth; Ludueña, Richard F; Kruh, Gary D; Mooberry, Susan L

2008-11-01

The taccalonolides are a class of structurally and mechanistically distinct microtubule-stabilizing agents isolated from Tacca chantrieri. A crucial feature of the taxane family of microtubule stabilizers is their susceptibility to cellular resistance mechanisms including overexpression of P-glycoprotein (Pgp), multidrug resistance protein 7 (MRP7), and the betaIII isotype of tubulin. The ability of four taccalonolides, A, E, B, and N, to circumvent these multidrug resistance mechanisms was studied. Taccalonolides A, E, B, and N were effective in vitro against cell lines that overexpress Pgp and MRP7. In addition, taccalonolides A and E were highly active in vivo against a doxorubicin- and paclitaxel-resistant Pgp-expressing tumor, Mam17/ADR. An isogenic HeLa-derived cell line that expresses the betaIII isotype of tubulin was generated to evaluate the effect of betaIII-tubulin on drug sensitivity. When compared with parental HeLa cells, the betaIII-tubulin-overexpressing cell line was less sensitive to paclitaxel, docetaxel, epothilone B, and vinblastine. In striking contrast, the betaIII-tubulin-overexpressing cell line showed greater sensitivity to all four taccalonolides. These data cumulatively suggest that the taccalonolides have advantages over the taxanes in their ability to circumvent multiple drug resistance mechanisms. The ability of the taccalonolides to overcome clinically relevant mechanisms of drug resistance in vitro and in vivo confirms that the taccalonolides represent a valuable addition to the family of microtubule-stabilizing compounds with clinical potential.

Enrichment, Isolation and Molecular Characterization of EpCAM-Negative Circulating Tumor Cells.

PubMed

Lampignano, Rita; Schneck, Helen; Neumann, Martin; Fehm, Tanja; Neubauer, Hans

2017-01-01

The presence of EpCAM-positive circulating tumor cells (CTCs) in the peripheral blood is associated with poor clinical outcomes in breast, colorectal and prostate cancer, as well as the prognosis of other tumor types. In addition, recent studies have suggested that the presence of CTCs undergoing epithelial-to-mesenchymal transition and, as such, may exhibit reduced or no expression of epithelial proteins e.g. EpCAM, might be related to disease progression in metastatic breast cancer (MBC) patients. Analyzing the neoplastic nature of this EpCAM-low/negative (EpCAM-neg) subpopulation remains an open issue as the current standard detection methods for CTCs are not efficient at identifying this subpopulation of cells. The possible association of EpCAM-neg CTCs with EpCAM-positive (EpCAM-pos) CTCs and role in the clinicopathological features and prognosis of MBC patients has still to be demonstrated. Several technologies have been developed and are currently being tested for the identification and the downstream analyses of EpCAM-pos CTCs. These technologies can be adapted and implemented into workflows to isolate and investigate EpCAM-neg cells to understand their biology and clinical relevance. This chapter will endeavour to explain the rationale behind the identification and analyses of all CTC subgroups, as well as to review the current strategies employed to enrich, isolate and characterize EpCAM-negative CTCs. Finally, the latest findings in the field will briefly be discussed with regard to their clinical relevance.

The Search for Reliable Biomarkers of Disease in Multiple Chemical Sensitivity and Other Environmental Intolerances

PubMed Central

De Luca, Chiara; Raskovic, Desanka; Pacifico, Valeria; Thai, Jeffrey Chung Sheun; Korkina, Liudmila

2011-01-01

Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or “medically unexplained symptoms”. The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes. PMID:21845158

Classifying the evolutionary and ecological features of neoplasms.

PubMed

Maley, Carlo C; Aktipis, Athena; Graham, Trevor A; Sottoriva, Andrea; Boddy, Amy M; Janiszewska, Michalina; Silva, Ariosto S; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J; Anderson, Karen S; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D; Hwang, E Shelley; Polyak, Kornelia; Anderson, Alexander R A; Brown, Joel S; Greaves, Mel; Shibata, Darryl

2017-10-01

Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research.

[Phenotypic heterogeneity of chronic obstructive pulmonary disease].

PubMed

Garcia-Aymerich, Judith; Agustí, Alvar; Barberà, Joan A; Belda, José; Farrero, Eva; Ferrer, Antoni; Ferrer, Jaume; Gáldiz, Juan B; Gea, Joaquim; Gómez, Federico P; Monsó, Eduard; Morera, Josep; Roca, Josep; Sauleda, Jaume; Antó, Josep M

2009-03-01

A functional definition of chronic obstructive pulmonary disease (COPD) based on airflow limitation has largely dominated the field. However, a view has emerged that COPD involves a complex array of cellular, organic, functional, and clinical events, with a growing interest in disentangling the phenotypic heterogeneity of COPD. The present review is based on the opinion of the authors, who have extensive research experience in several aspects of COPD. The starting assumption of the review is that current knowledge on the pathophysiology and clinical features of COPD allows us to classify phenotypic information in terms of the following dimensions: respiratory symptoms and health status, acute exacerbations, lung function, structural changes, local and systemic inflammation, and systemic effects. Twenty-six phenotypic traits were identified and assigned to one of the 6 dimensions. For each dimension, a summary is provided of the best evidence on the relationships among phenotypic traits, in particular among those corresponding to different dimensions, and on the relationship between these traits and relevant events in the natural history of COPD. The information has been organized graphically into a phenotypic matrix where each cell representing a pair of phenotypic traits is linked to relevant references. The information provided has the potential to increase our understanding of the heterogeneity of COPD phenotypes and help us plan future studies on aspects that are as yet unexplored.

Post-conflict slowing after incongruent stimuli: from general to conflict-specific.

PubMed

Rey-Mermet, Alodie; Meier, Beat

2017-05-01

Encountering a cognitive conflict not only slows current performance, but it can also affect subsequent performance, in particular when the conflict is induced with bivalent stimuli (i.e., stimuli with relevant features for two different tasks) or with incongruent trials (i.e., stimuli with relevant features for two response alternatives). The post-conflict slowing following bivalent stimuli, called "bivalency effect", affects all subsequent stimuli, irrespective of whether the subsequent stimuli share relevant features with the conflict stimuli. To date, it is unknown whether the conflict induced by incongruent stimuli results in a similar post-conflict slowing. To investigate this, we performed six experiments in which participants switched between two tasks. In one task, incongruent stimuli appeared occasionally; in the other task, stimuli shared no feature with the incongruent trials. The results showed an initial performance slowing that affected all tasks after incongruent trials. On further trials, however, the slowing only affected the task sharing features with the conflict stimuli. Therefore, the post-conflict slowing following incongruent stimuli is first general and then becomes conflict-specific across trials. These findings are discussed within current task switching and cognitive control accounts.

The cost of selective attention in category learning: developmental differences between adults and infants.

PubMed

Best, Catherine A; Yim, Hyungwook; Sloutsky, Vladimir M

2013-10-01

Selective attention plays an important role in category learning. However, immaturities of top-down attentional control during infancy coupled with successful category learning suggest that early category learning is achieved without attending selectively. Research presented here examines this possibility by focusing on category learning in infants (6-8months old) and adults. Participants were trained on a novel visual category. Halfway through the experiment, unbeknownst to participants, the to-be-learned category switched to another category, where previously relevant features became irrelevant and previously irrelevant features became relevant. If participants attend selectively to the relevant features of the first category, they should incur a cost of selective attention immediately after the unknown category switch. Results revealed that adults demonstrated a cost, as evidenced by a decrease in accuracy and response time on test trials as well as a decrease in visual attention to newly relevant features. In contrast, infants did not demonstrate a similar cost of selective attention as adults despite evidence of learning both to-be-learned categories. Findings are discussed as supporting multiple systems of category learning and as suggesting that learning mechanisms engaged by adults may be different from those engaged by infants. Copyright © 2013 Elsevier Inc. All rights reserved.

Quantitative Analysis of the Cervical Texture by Ultrasound and Correlation with Gestational Age.

PubMed

Baños, Núria; Perez-Moreno, Alvaro; Migliorelli, Federico; Triginer, Laura; Cobo, Teresa; Bonet-Carne, Elisenda; Gratacos, Eduard; Palacio, Montse

2017-01-01

Quantitative texture analysis has been proposed to extract robust features from the ultrasound image to detect subtle changes in the textures of the images. The aim of this study was to evaluate the feasibility of quantitative cervical texture analysis to assess cervical tissue changes throughout pregnancy. This was a cross-sectional study including singleton pregnancies between 20.0 and 41.6 weeks of gestation from women who delivered at term. Cervical length was measured, and a selected region of interest in the cervix was delineated. A model to predict gestational age based on features extracted from cervical images was developed following three steps: data splitting, feature transformation, and regression model computation. Seven hundred images, 30 per gestational week, were included for analysis. There was a strong correlation between the gestational age at which the images were obtained and the estimated gestational age by quantitative analysis of the cervical texture (R = 0.88). This study provides evidence that quantitative analysis of cervical texture can extract features from cervical ultrasound images which correlate with gestational age. Further research is needed to evaluate its applicability as a biomarker of the risk of spontaneous preterm birth, as well as its role in cervical assessment in other clinical situations in which cervical evaluation might be relevant. © 2016 S. Karger AG, Basel.

DISCOVER-AQ

Atmospheric Science Data Center

2017-01-31

... Relevant Documents:  DISCOVER-AQ - Airborne Science Data for Atmospheric Composition DISCOVER-AQ - NASA Earth ... DISCOVER-AQ - Mission Highlight Featured Articles : Articles featuring DISCOVER-AQ data products SCAR-B ...

Remembering complex objects in visual working memory: do capacity limits restrict objects or features?

PubMed

Hardman, Kyle O; Cowan, Nelson

2015-03-01

Visual working memory stores stimuli from our environment as representations that can be accessed by high-level control processes. This study addresses a longstanding debate in the literature about whether storage limits in visual working memory include a limit to the complexity of discrete items. We examined the issue with a number of change-detection experiments that used complex stimuli that possessed multiple features per stimulus item. We manipulated the number of relevant features of the stimulus objects in order to vary feature load. In all of our experiments, we found that increased feature load led to a reduction in change-detection accuracy. However, we found that feature load alone could not account for the results but that a consideration of the number of relevant objects was also required. This study supports capacity limits for both feature and object storage in visual working memory. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

PubMed

Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhancing clinical concept extraction with distributional semantics

PubMed Central

Cohen, Trevor; Wu, Stephen; Gonzalez, Graciela

2011-01-01

Extracting concepts (such as drugs, symptoms, and diagnoses) from clinical narratives constitutes a basic enabling technology to unlock the knowledge within and support more advanced reasoning applications such as diagnosis explanation, disease progression modeling, and intelligent analysis of the effectiveness of treatment. The recent release of annotated training sets of de-identified clinical narratives has contributed to the development and refinement of concept extraction methods. However, as the annotation process is labor-intensive, training data are necessarily limited in the concepts and concept patterns covered, which impacts the performance of supervised machine learning applications trained with these data. This paper proposes an approach to minimize this limitation by combining supervised machine learning with empirical learning of semantic relatedness from the distribution of the relevant words in additional unannotated text. The approach uses a sequential discriminative classifier (Conditional Random Fields) to extract the mentions of medical problems, treatments and tests from clinical narratives. It takes advantage of all Medline abstracts indexed as being of the publication type “clinical trials” to estimate the relatedness between words in the i2b2/VA training and testing corpora. In addition to the traditional features such as dictionary matching, pattern matching and part-of-speech tags, we also used as a feature words that appear in similar contexts to the word in question (that is, words that have a similar vector representation measured with the commonly used cosine metric, where vector representations are derived using methods of distributional semantics). To the best of our knowledge, this is the first effort exploring the use of distributional semantics, the semantics derived empirically from unannotated text often using vector space models, for a sequence classification task such as concept extraction. Therefore, we first experimented with different sliding window models and found the model with parameters that led to best performance in a preliminary sequence labeling task. The evaluation of this approach, performed against the i2b2/VA concept extraction corpus, showed that incorporating features based on the distribution of words across a large unannotated corpus significantly aids concept extraction. Compared to a supervised-only approach as a baseline, the micro-averaged f-measure for exact match increased from 80.3% to 82.3% and the micro-averaged f-measure based on inexact match increased from 89.7% to 91.3%. These improvements are highly significant according to the bootstrap resampling method and also considering the performance of other systems. Thus, distributional semantic features significantly improve the performance of concept extraction from clinical narratives by taking advantage of word distribution information obtained from unannotated data. PMID:22085698

Psychological Characteristics in Acute Mild Traumatic Brain Injury: An MMPI-2 Study.

PubMed

Gass, Carlton S; Rogers, David; Kinne, Erica

2017-01-01

The psychological characteristics of acute traumatic brain injury (TBI) have received limited research focus, despite empirical evidence of their relevance for subsequent psychological adjustment and early therapeutic intervention. This study addressed a wide range of psychological features in 47 individuals who were hospitalized as a result of acute mild TBI (mTBI). Participants were screened from amongst consecutive TBI admissions for moderate to severe brain injury, and for pre-injury neurological, psychiatric, or substance abuse histories. Clinical and content scale scores on the MMPI-2 were explored in relation to patient gender, age, level of education, and extent of cognitive complaints. The results revealed diverse psychosocial problem areas across the sample, the most common of which were somatic and cognitive complaints, compromised insight, and a naively optimistic self-perception. The mediating roles of injury severity and demographic variables are discussed. Clinical implications and specific recommendations are presented.

Blood analysis by Raman spectroscopy.

PubMed

Enejder, Annika M K; Koo, Tae-Woong; Oh, Jeankun; Hunter, Martin; Sasic, Slobodan; Feld, Michael S; Horowitz, Gary L

2002-11-15

Concentrations of multiple analytes were simultaneously measured in whole blood with clinical accuracy, without sample processing, using near-infrared Raman spectroscopy. Spectra were acquired with an instrument employing nonimaging optics, designed using Monte Carlo simulations of the influence of light-scattering-absorbing blood cells on the excitation and emission of Raman light in turbid medium. Raman spectra were collected from whole blood drawn from 31 individuals. Quantitative predictions of glucose, urea, total protein, albumin, triglycerides, hematocrit, and hemoglobin were made by means of partial least-squares (PLS) analysis with clinically relevant precision (r(2) values >0.93). The similarity of the features of the PLS calibration spectra to those of the respective analyte spectra illustrates that the predictions are based on molecular information carried by the Raman light. This demonstrates the feasibility of using Raman spectroscopy for quantitative measurements of biomolecular contents in highly light-scattering and absorbing media.

Molecular diagnostics in the management of rhabdomyosarcoma.

PubMed

Arnold, Michael A; Barr, Fredric G

2017-02-01

A classification of rhabdomyosarcoma (RMS) with prognostic relevance has primarily relied on clinical features and histologic classification as either embryonal or alveolar RMS. The PAX3-FOXO1 and PAX7-FOXO1 gene fusions occur in 80% of cases with the alveolar subtype and are more predictive of outcome than histologic classification. Identifying additional molecular hallmarks that further subclassify RMS is an active area of research. Areas Covered: The authors review the current state of the PAX3-FOXO1 and PAX7-FOXO1 fusions as prognostic biomarkers. Emerging biomarkers, including mRNA expression profiling, MYOD1 mutations, RAS pathway mutations and gene fusions involving NCOA2 or VGLL2 are also reviewed. Expert commentary: Strategies for modifying RMS risk stratification based on molecular biomarkers are emerging with the potential to transform the clinical management of RMS, ultimately improving patient outcomes by tailoring therapy to predicted patient risk and identifying targets for novel therapies.

Multivariate longitudinal data analysis with mixed effects hidden Markov models.

PubMed

Raffa, Jesse D; Dubin, Joel A

2015-09-01

Multiple longitudinal responses are often collected as a means to capture relevant features of the true outcome of interest, which is often hidden and not directly measurable. We outline an approach which models these multivariate longitudinal responses as generated from a hidden disease process. We propose a class of models which uses a hidden Markov model with separate but correlated random effects between multiple longitudinal responses. This approach was motivated by a smoking cessation clinical trial, where a bivariate longitudinal response involving both a continuous and a binomial response was collected for each participant to monitor smoking behavior. A Bayesian method using Markov chain Monte Carlo is used. Comparison of separate univariate response models to the bivariate response models was undertaken. Our methods are demonstrated on the smoking cessation clinical trial dataset, and properties of our approach are examined through extensive simulation studies. © 2015, The International Biometric Society.

An exploratory survey on the views of European tissue engineers concerning the ethical issues of tissue engineering research.

PubMed

Trommelmans, Leen; Selling, Joseph; Dierickx, Kris

2009-09-01

We present the first exploratory survey about the views of tissue engineers on the ethical issues of tissue engineering (TE), conducted among participants of a large European TE consortium. We analyzed the topics for which ethical guidance is necessary and the preferred dissemination channels, which are relevant issues and goals of clinical trials with human tissue-engineered products, and which information is to be given to trial participants. The need for comprehensive, specific ethical guidance of TE is a first key finding of this survey. Second, it becomes clear that little clarity exists on some crucial issues in the setup and conduct of clinical trials in TE. Identifying the unique features of TE and their repercussions for the ethical conduct of TE research and therapy is necessary. Third, prospective trial participants are to be informed about a wide variety of issues before taking part in the trial.

Low molecular weight heparins in the prevention of deep-vein thrombosis in general surgery.

PubMed

Breddin, H K

1999-01-01

Unfractionated heparin (UFH) was the established treatment in the early 1980s for the prophylaxis of venous thromboembolic disease (VTED) in patients undergoing general surgery. This was one of the earliest indications in which low molecular weight heparins (LMWHs) were tested, and about 40 trials have revealed that these agents are at least as effective and safe as UFH with a tendency of superiority when higher dosages are used. In most trials, the fibrinogen uptake test has been used to assess the frequency of deep vein thrombosis. LMWHs exhibit a number of improved features over UFH, including ease of administration and convenient once daily dosing, facilitating outpatient management. A still open question is the ideal time and dose of the first one or two injections of a LMWH. To determine the clinical relevance of product differentiation further, clinical trials, directly comparing different LMWHs, are required.

Ferroptosis and Cell Death Analysis by Flow Cytometry.

PubMed

Chen, Daishi; Eyupoglu, Ilker Y; Savaskan, Nicolai

2017-01-01

Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia. Distinguishing cell viability and cell death is essential for experimental and clinical applications and a key component in flow cytometry experiments. Dead cells can compromise the integrity of the data by nonspecific binding of antibodies and dyes. Therefore it is essential that dead cells are robustly and reproducibly identified and characterized by means of cytometry application. Here we describe a procedure to detect and quantify cell death and its specific form ferroptosis based on standard flow cytometry techniques.

PATENTS IN GENOMICS AND HUMAN GENETICS

PubMed Central

Cook-Deegan, Robert; Heaney, Christopher

2010-01-01

Genomics and human genetics are scientifically fundamental and commercially valuable. These fields grew to prominence in an era of growth in government and nonprofit research funding, and of even greater growth of privately funded research and development in biotechnology and pharmaceuticals. Patents on DNA technologies are a central feature of this story, illustrating how patent law adapts---and sometimes fails to adapt---to emerging genomic technologies. In instrumentation and for therapeutic proteins, patents have largely played their traditional role of inducing investment in engineering and product development, including expensive postdiscovery clinical research to prove safety and efficacy. Patents on methods and DNA sequences relevant to clinical genetic testing show less evidence of benefits and more evidence of problems and impediments, largely attributable to university exclusive licensing practices. Whole-genome sequencing will confront uncertainty about infringing granted patents but jurisprudence trends away from upholding the broadest and potentially most troublesome patent claims. PMID:20590431

[Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report].

PubMed

Schmidt, L G; Schlünder, M; Reischies, F M

1988-03-01

Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day-clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment.

Treatment of ALK-rearranged non-small cell lung cancer: A review of the landscape and approach to emerging patterns of treatment resistance in the Australian context.

PubMed

Itchins, M; Chia, P L; Hayes, S A; Howell, V M; Gill, A J; Cooper, W A; John, T; Mitchell, P; Millward, M; Clarke, S J; Solomon, B; Pavlakis, N

2017-08-01

Since the identification of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) in 2005, the treatment of ALK-rearranged NSCLC (ALK+ NSCLC) has evolved at a rapid pace. This molecularly distinct subset of NSCLC has uniquely important biology, clinicopathologic features and mechanisms of drug resistance which impact on the choice of treatment for a patient with this disease. There are multiple ALK tyrosine kinase inhibitors now available in clinical practice with efficacy data continuing to emerge and guide the optimal treatment algorithm. A detailed search of medical databases and clinical trial registries was conducted to capture all relevant articles on this topic enabling an updated detailed overview of the landscape of management of ALK-rearranged NSCLC. © 2017 John Wiley & Sons Australia, Ltd.

Solution-based circuits enable rapid and multiplexed pathogen detection.

PubMed

Lam, Brian; Das, Jagotamoy; Holmes, Richard D; Live, Ludovic; Sage, Andrew; Sargent, Edward H; Kelley, Shana O

2013-01-01

Electronic readout of markers of disease provides compelling simplicity, sensitivity and specificity in the detection of small panels of biomarkers in clinical samples; however, the most important emerging tests for disease, such as infectious disease speciation and antibiotic-resistance profiling, will need to interrogate samples for many dozens of biomarkers. Electronic readout of large panels of markers has been hampered by the difficulty of addressing large arrays of electrode-based sensors on inexpensive platforms. Here we report a new concept--solution-based circuits formed on chip--that makes highly multiplexed electrochemical sensing feasible on passive chips. The solution-based circuits switch the information-carrying signal readout channels and eliminate all measurable crosstalk from adjacent, biomolecule-specific microsensors. We build chips that feature this advance and prove that they analyse unpurified samples successfully, and accurately classify pathogens at clinically relevant concentrations. We also show that signature molecules can be accurately read 2  minutes after sample introduction.

MememxGATE: Unearthing Latent Content Features for Improved Search and Relevancy Ranking Across Scientific Literature

NASA Astrophysics Data System (ADS)

Wilson, B. D.; McGibbney, L. J.; Mattmann, C. A.; Ramirez, P.; Joyce, M.; Whitehall, K. D.

2015-12-01

Quantifying scientific relevancy is of increasing importance to NASA and the research community. Scientific relevancy may be defined by mapping the impacts of a particular NASA mission, instrument, and/or retrieved variables to disciplines such as climate predictions, natural hazards detection and mitigation processes, education, and scientific discoveries. Related to relevancy, is the ability to expose data with similar attributes. This in turn depends upon the ability for us to extract latent, implicit document features from scientific data and resources and make them explicit, accessible and useable for search activities amongst others. This paper presents MemexGATE; a server side application, command line interface and computing environment for running large scale metadata extraction, general architecture text engineering, document classification and indexing tasks over document resources such as social media streams, scientific literature archives, legal documentation, etc. This work builds on existing experiences using MemexGATE (funded, developed and validated through the DARPA Memex Progrjam PI Mattmann) for extracting and leveraging latent content features from document resources within the Materials Research domain. We extend the software functionality capability to the domain of scientific literature with emphasis on the expansion of gazetteer lists, named entity rules, natural language construct labeling (e.g. synonym, antonym, hyponym, etc.) efforts to enable extraction of latent content features from data hosted by wide variety of scientific literature vendors (AGU Meeting Abstract Database, Springer, Wiley Online, Elsevier, etc.) hosting earth science literature. Such literature makes both implicit and explicit references to NASA datasets and relationships between such concepts stored across EOSDIS DAAC's hence we envisage that a significant part of this effort will also include development and understanding of relevancy signals which can ultimately be utilized for improved search and relevancy ranking across scientific literature.

Statistical interpretation of machine learning-based feature importance scores for biomarker discovery.

PubMed

Huynh-Thu, Vân Anh; Saeys, Yvan; Wehenkel, Louis; Geurts, Pierre

2012-07-01

Univariate statistical tests are widely used for biomarker discovery in bioinformatics. These procedures are simple, fast and their output is easily interpretable by biologists but they can only identify variables that provide a significant amount of information in isolation from the other variables. As biological processes are expected to involve complex interactions between variables, univariate methods thus potentially miss some informative biomarkers. Variable relevance scores provided by machine learning techniques, however, are potentially able to highlight multivariate interacting effects, but unlike the p-values returned by univariate tests, these relevance scores are usually not statistically interpretable. This lack of interpretability hampers the determination of a relevance threshold for extracting a feature subset from the rankings and also prevents the wide adoption of these methods by practicians. We evaluated several, existing and novel, procedures that extract relevant features from rankings derived from machine learning approaches. These procedures replace the relevance scores with measures that can be interpreted in a statistical way, such as p-values, false discovery rates, or family wise error rates, for which it is easier to determine a significance level. Experiments were performed on several artificial problems as well as on real microarray datasets. Although the methods differ in terms of computing times and the tradeoff, they achieve in terms of false positives and false negatives, some of them greatly help in the extraction of truly relevant biomarkers and should thus be of great practical interest for biologists and physicians. As a side conclusion, our experiments also clearly highlight that using model performance as a criterion for feature selection is often counter-productive. Python source codes of all tested methods, as well as the MATLAB scripts used for data simulation, can be found in the Supplementary Material.

Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system.

PubMed

Song, B G; Min, Y W; Lee, H; Min, B-H; Lee, J H; Rhee, P-L; Kim, J J

2018-03-01

Integrated relaxation pressure (IRP) is a key metric for diagnosing esophagogastric junction outflow obstruction (EGJOO). However, its normal value might be different according to the manufacturer of high-resolution manometry (HRM). This study aimed to investigate optimal value of IRP for diagnosing EGJOO in Sandhill HRM and to find clinicomanometric variables to segregate clinically relevant EGJOO. We analyzed 262 consecutive subjects who underwent HRM between June 2011 and December 2016 showing elevated median IRP (> 15 mm Hg) but did not satisfy criteria for achalasia. Clinically relevant subjects were defined as follows: (i) subsequent HRM met achalasia criteria during follow-up (early achalasia); (ii) Eckardt score was decreased at least two points without exceeding a score of 3 after pneumatic dilatation (variant achalasia); and (iii) significant passage disturbance on esophagogram without structural abnormality (possible achalasia). Seven subjects were clinically relevant, including two subjects with early achalasia, four subjects with variant achalasia, and one subject with possible achalasia. All clinically relevant subjects had IRP 20 mm Hg or above. Among subjects (n = 122) with IRP 20 mm Hg or more, clinically relevant group (n = 7) had significantly higher rate of dysphagia (100% vs 24.3%, P < .001) and compartmentalized pressurization (85.7% vs 21.7%, P = .001) compared to clinically non-relevant group (n = 115). Our results suggest that IRP of 20 mm Hg or higher could segregate clinically relevant subjects showing EGJOO in Sandhill HRM. Additionally, if subjects have both dysphagia and compartmentalized pressurization, careful follow-up is essential. © 2017 John Wiley & Sons Ltd.

Manifestations of Gorlin-Goltz syndrome.

PubMed

Larsen, Anne Kristine; Mikkelsen, Dorthe Bisgaard; Hertz, Jens Michael; Bygum, Anette

2014-05-01

Gorlin-Goltz syndrome is an uncommon hereditary condition caused by mutations in the PTCH1 gene causing a wide range of developmental abnormalities. Multiple basal cell carcinomas, palmoplantar pits and jaw cysts are cardinal features. Many clinicians are unfamiliar with the different manifestations and the fact that patients are especially sensitive to ionizing radiation. This was a retrospective analysis of patients with Gorlin-Goltz syndrome seen at the Department of Dermatology and Allergy Centre or at Department of Plastic Surgery, Odense University Hospital, Denmark, in the period from 1994 to 2013. A total of 17 patients from eight families fulfilled the diagnostic criteria. In all, 14 patients had basal cell carcinomas, 12 patients had jaw cysts and ten patients had calcification of the falx cerebri. Other clinical features were frontal bossing, kyphoscoliosis, rib anomalies, coalitio, cleft lip/palate, eye anomalies, milia and syndactyly. In one family, medulloblastoma and astrocytoma occurred. Traditional treatment principles of basal cell carcinomas were used including radiotherapy performed in six patients. PTCH1 mutations were identified in five families and none of these mutations had previously been described. The patient cohort illustrates classic and rare disease manifestations. It is necessary to remind clinicians that radiation therapy in Gorlin-Goltz syndrome is relatively contraindicated. Today, mutation analysis can be used for confirmation of the diagnosis and for predictive genetic testing. Patients should be offered genetic counselling and life-long surveillance. not relevant. not relevant.

Stimulus-response correspondence effect as a function of temporal overlap between relevant and irrelevant information processing.

PubMed

Wang, Dong-Yuan Debbie; Richard, F Dan; Ray, Brittany

2016-01-01

The stimulus-response correspondence (SRC) effect refers to advantages in performance when stimulus and response correspond in dimensions or features, even if the common features are irrelevant to the task. Previous research indicated that the SRC effect depends on the temporal course of stimulus information processing. The current study investigated how the temporal overlap between relevant and irrelevant stimulus processing influences the SRC effect. In this experiment, the irrelevant stimulus (a previously associated tone) preceded the relevant stimulus (a coloured rectangle). The irrelevant and relevant stimuli onset asynchrony was varied to manipulate the temporal overlap between the irrelevant and relevant stimuli processing. Results indicated that the SRC effect size varied as a quadratic function of the temporal overlap between the relevant stimulus and irrelevant stimulus. This finding extends previous experimental observations that the SRC effect size varies in an increasing or decreasing function with reaction time. The current study demonstrated a quadratic function between effect size and the temporal overlap.

Understanding psychiatric disorder by capturing ecologically relevant features of learning and decision-making.

PubMed

Scholl, Jacqueline; Klein-Flügge, Miriam

2017-09-28

Recent research in cognitive neuroscience has begun to uncover the processes underlying increasingly complex voluntary behaviours, including learning and decision-making. Partly this success has been possible by progressing from simple experimental tasks to paradigms that incorporate more ecological features. More specifically, the premise is that to understand cognitions and brain functions relevant for real life, we need to introduce some of the ecological challenges that we have evolved to solve. This often entails an increase in task complexity, which can be managed by using computational models to help parse complex behaviours into specific component mechanisms. Here we propose that using computational models with tasks that capture ecologically relevant learning and decision-making processes may provide a critical advantage for capturing the mechanisms underlying symptoms of disorders in psychiatry. As a result, it may help develop mechanistic approaches towards diagnosis and treatment. We begin this review by mapping out the basic concepts and models of learning and decision-making. We then move on to consider specific challenges that emerge in realistic environments and describe how they can be captured by tasks. These include changes of context, uncertainty, reflexive/emotional biases, cost-benefit decision-making, and balancing exploration and exploitation. Where appropriate we highlight future or current links to psychiatry. We particularly draw examples from research on clinical depression, a disorder that greatly compromises motivated behaviours in real-life, but where simpler paradigms have yielded mixed results. Finally, we highlight several paradigms that could be used to help provide new insights into the mechanisms of psychiatric disorders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

PubMed Central

2011-01-01

Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time. PMID:21816065