[Clinical features of patients with Becker muscular dystrophy and deletions of the rod domain of dystrophin gene].

PubMed

Wang, Yanyun; Zhu, Yuling; Yang, Juan; Li, Yaqin; Sun, Jiangwen; Zhan, Yixin; Zhang, Cheng

2018-02-10

OBJECTIVE To explore the clinical features of patients carrying deletions of the rod domain of the dystrophin gene. METHODS Clinical data of 12 Chinese patients with Becker muscular dystrophy (BMD) and such deletions was reviewed. RESULTS Most patients complained of muscle weakness of lower limbs. Two patients had muscle cramps, one had increased creatine kinase (CK) level, and one had dilated cardiomyopathy. CONCLUSION Compared with DMD, the clinical features of BMD are much more variable, particularly for those carrying deletions of the rod domain of the dystrophin gene. Muscular weakness may not be the sole complaint of BMD. The diagnosis of BMD cannot be excluded by moderately elevated CK. For male patients with dilated cardiomyopathy, the possibility of BMD should be considered.

Features of asthma which provide meaningful insights for understanding the disease heterogeneity.

PubMed

Deliu, M; Yavuz, T S; Sperrin, M; Belgrave, D; Sahiner, U M; Sackesen, C; Kalayci, O; Custovic, A

2018-01-01

Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Randomized clinical trials in implant therapy: relationships among methodological, statistical, clinical, paratextual features and number of citations.

PubMed

Nieri, Michele; Clauser, Carlo; Franceschi, Debora; Pagliaro, Umberto; Saletta, Daniele; Pini-Prato, Giovanpaolo

2007-08-01

The aim of the present study was to investigate the relationships among reported methodological, statistical, clinical and paratextual variables of randomized clinical trials (RCTs) in implant therapy, and their influence on subsequent research. The material consisted of the RCTs in implant therapy published through the end of the year 2000. Methodological, statistical, clinical and paratextual features of the articles were assessed and recorded. The perceived clinical relevance was subjectively evaluated by an experienced clinician on anonymous abstracts. The impact on research was measured by the number of citations found in the Science Citation Index. A new statistical technique (Structural learning of Bayesian Networks) was used to assess the relationships among the considered variables. Descriptive statistics revealed that the reported methodology and statistics of RCTs in implant therapy were defective. Follow-up of the studies was generally short. The perceived clinical relevance appeared to be associated with the objectives of the studies and with the number of published images in the original articles. The impact on research was related to the nationality of the involved institutions and to the number of published images. RCTs in implant therapy (until 2000) show important methodological and statistical flaws and may not be appropriate for guiding clinicians in their practice. The methodological and statistical quality of the studies did not appear to affect their impact on practice and research. Bayesian Networks suggest new and unexpected relationships among the methodological, statistical, clinical and paratextual features of RCTs.

Psychogenic Tremor: A Video Guide to Its Distinguishing Features

PubMed Central

Thenganatt, Mary Ann; Jankovic, Joseph

2014-01-01

Background Psychogenic tremor is the most common psychogenic movement disorder. It has characteristic clinical features that can help distinguish it from other tremor disorders. There is no diagnostic gold standard and the diagnosis is based primarily on clinical history and examination. Despite proposed diagnostic criteria, the diagnosis of psychogenic tremor can be challenging. While there are numerous studies evaluating psychogenic tremor in the literature, there are no publications that provide a video/visual guide that demonstrate the clinical characteristics of psychogenic tremor. Educating clinicians about psychogenic tremor will hopefully lead to earlier diagnosis and treatment. Methods We selected videos from the database at the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine that illustrate classic findings supporting the diagnosis of psychogenic tremor. Results We include 10 clinical vignettes with accompanying videos that highlight characteristic clinical signs of psychogenic tremor including distractibility, variability, entrainability, suggestibility, and coherence. Discussion Psychogenic tremor should be considered in the differential diagnosis of patients presenting with tremor, particularly if it is of abrupt onset, intermittent, variable and not congruous with organic tremor. The diagnosis of psychogenic tremor, however, should not be simply based on exclusion of organic tremor, such as essential, parkinsonian, or cerebellar tremor, but on positive criteria demonstrating characteristic features. Early recognition and management are critical for good long-term outcome. PMID:25243097

Poland syndrome with bilateral features: case description with review of the literature.

PubMed

Baban, Anwar; Torre, Michele; Bianca, Sebastiano; Buluggiu, Anna; Rossello, Mario Igor; Calevo, Maria Grazia; Valle, Maura; Ravazzolo, Roberto; Jasonni, Vincenzo; Lerone, Margherita

2009-07-01

Poland syndrome (PS) has been described as unilateral pectoral muscle deficiency variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia/aplasia of the pectoralis muscle and upper limb defects in association with variable thoracic muscles, chest wall deformities and lower limb defects have been infrequently reported in the literature. We report on a 3(1/2)-year-old girl with clinical features consisting in bilateral asymmetric pectoral muscle defects (complete agenesis on the left side and agenesis of the sternocostal head on the right side), nipple hypoplasia, left rib defect, and right hand symbrachydactyly. In this study, we reviewed the bilateral features present in our patient and those described in the literature. Hypotheses explaining bilateral features in PS are reviewed.

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.

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

PubMed Central

Goldstein, Lori J.; Gray, Robert; Badve, Sunil; Childs, Barrett H.; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L.; Ravdin, Peter M.; Davidson, Nancy E.; Sledge, George W.; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Sparano, Joseph A.

2008-01-01

Purpose Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments. PMID:18678838

Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

PubMed

Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

2008-09-01

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation.

PubMed

Minoia, Francesca; Bertamino, Marta; Picco, Paolo; Severino, Mariasavina; Rossi, Andrea; Fiorillo, Chiara; Minetti, Carlo; Nesti, Claudia; Santorelli, Filippo Maria; Di Rocco, Maja

2017-01-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.

Data management by using R: big data clinical research series.

PubMed

Zhang, Zhongheng

2015-11-01

Electronic medical record (EMR) system has been widely used in clinical practice. Instead of traditional record system by hand writing and recording, the EMR makes big data clinical research feasible. The most important feature of big data research is its real-world setting. Furthermore, big data research can provide all aspects of information related to healthcare. However, big data research requires some skills on data management, which however, is always lacking in the curriculum of medical education. This greatly hinders doctors from testing their clinical hypothesis by using EMR. To make ends meet, a series of articles introducing data management techniques are put forward to guide clinicians to big data clinical research. The present educational article firstly introduces some basic knowledge on R language, followed by some data management skills on creating new variables, recoding variables and renaming variables. These are very basic skills and may be used in every project of big data research.

Integrated Cox's model for predicting survival time of glioblastoma multiforme.

PubMed

Ai, Zhibing; Li, Longti; Fu, Rui; Lu, Jing-Min; He, Jing-Dong; Li, Sen

2017-04-01

Glioblastoma multiforme is the most common primary brain tumor and is highly lethal. This study aims to figure out signatures for predicting the survival time of patients with glioblastoma multiforme. Clinical information, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism array data of patients with glioblastoma multiforme were retrieved from The Cancer Genome Atlas. Patients were separated into two groups by using 1 year as a cutoff, and a logistic regression model was used to figure out any variables that can predict whether the patient was able to live longer than 1 year. Furthermore, Cox's model was used to find out features that were correlated with the survival time. Finally, a Cox model integrated the significant clinical variables, messenger RNA expression, microRNA expression, and single-nucleotide polymorphism was built. Although the classification method failed, signatures of clinical features, messenger RNA expression levels, and microRNA expression levels were figured out by using Cox's model. However, no single-nucleotide polymorphisms related to prognosis were found. The selected clinical features were age at initial diagnosis, Karnofsky score, and race, all of which had been suggested to correlate with survival time. Both of the two significant microRNAs, microRNA-221 and microRNA-222, were targeted to p27 Kip1 protein, which implied the important role of p27 Kip1 on the prognosis of glioblastoma multiforme patients. Our results suggested that survival modeling was more suitable than classification to figure out prognostic biomarkers for patients with glioblastoma multiforme. An integrated model containing clinical features, messenger RNA levels, and microRNA expression levels was built, which has the potential to be used in clinics and thus to improve the survival status of glioblastoma multiforme patients.

Evaluation of clinical and histopathologic prognostic factors for survival in canine osteosarcoma of the extracranial flat and irregular bones.

PubMed

Kruse, M A; Holmes, E S; Balko, J A; Fernandez, S; Brown, D C; Goldschmidt, M H

2013-07-01

Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

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.

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.

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.

[Malabsorption is a leading clinical sign of small bowel disease].

PubMed

Parfenov, A I; Krums, L M

The paper presents a variety of clinical manifestations of malabsorption syndrome (MAS) in celiac disease, collagenous sprue, Whipple's disease, Crohn's disease, intestinal lymphangiectasia, amyloidosis, common variable immune deficiency, and treatment of short bowel syndrome. It shows the specific features of the pathophysiology, diagnosis, and treatment of MAS in small bowel diseases.

Discrimination between Alzheimer's Disease and Late Onset Bipolar Disorder Using Multivariate Analysis.

PubMed

Besga, Ariadna; Gonzalez, Itxaso; Echeburua, Enrique; Savio, Alexandre; Ayerdi, Borja; Chyzhyk, Darya; Madrigal, Jose L M; Leza, Juan C; Graña, Manuel; Gonzalez-Pinto, Ana Maria

2015-01-01

Late onset bipolar disorder (LOBD) is often difficult to distinguish from degenerative dementias, such as Alzheimer disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence in the elder population is not negligible and it is increasing. Both pathologies share pathophysiological neuroinflammation features. Improvements in differential diagnosis of LOBD and AD will help to select the best personalized treatment. The aim of this study is to assess the relative significance of clinical observations, neuropsychological tests, and specific blood plasma biomarkers (inflammatory and neurotrophic), separately and combined, in the differential diagnosis of LOBD versus AD. It was carried out evaluating the accuracy achieved by classification-based computer-aided diagnosis (CAD) systems based on these variables. A sample of healthy controls (HC) (n = 26), AD patients (n = 37), and LOBD patients (n = 32) was recruited at the Alava University Hospital. Clinical observations, neuropsychological tests, and plasma biomarkers were measured at recruitment time. We applied multivariate machine learning classification methods to discriminate subjects from HC, AD, and LOBD populations in the study. We analyzed, for each classification contrast, feature sets combining clinical observations, neuropsychological measures, and biological markers, including inflammation biomarkers. Furthermore, we analyzed reduced feature sets containing variables with significative differences determined by a Welch's t-test. Furthermore, a battery of classifier architectures were applied, encompassing linear and non-linear Support Vector Machines (SVM), Random Forests (RF), Classification and regression trees (CART), and their performance was evaluated in a leave-one-out (LOO) cross-validation scheme. Post hoc analysis of Gini index in CART classifiers provided a measure of each variable importance. Welch's t-test found one biomarker (Malondialdehyde) with significative differences (p < 0.001) in LOBD vs. AD contrast. Classification results with the best features are as follows: discrimination of HC vs. AD patients reaches accuracy 97.21% and AUC 98.17%. Discrimination of LOBD vs. AD patients reaches accuracy 90.26% and AUC 89.57%. Discrimination of HC vs LOBD patients achieves accuracy 95.76% and AUC 88.46%. It is feasible to build CAD systems for differential diagnosis of LOBD and AD on the basis of a reduced set of clinical variables. Clinical observations provide the greatest discrimination. Neuropsychological tests are improved by the addition of biomarkers, and both contribute significantly to improve the overall predictive performance.

Host-dependent variables: The missing link to personalized medicine.

PubMed

Demlova, Regina; Zdrazilova-Dubska, Lenka; Sterba, Jaroslav; Stanta, Giorgio; Valik, Dalibor

2018-04-26

Individualized medicine has the potential to tailor anticancer therapy with the best response and highest safety margin to provide better patient care. However, modern targeted therapies are still being tested through clinical trials comparing preselected patient cohorts and assessed upon behaviour of group averages. Clinically manifesting malignant disease requires identification of host- and tumour-dependent variables such as biological characteristics of the tumour and its microenvironment including immune response features, and overall capacity of the host to receive, tolerate and efficiently utilize treatment. Contemporary medical oncology including clinical trial design need to refocus from assessing group averages to individuality taking into consideration time dependent host-associated characteristics and reinventing outliers to be appreciated as naturally occurring variables collectively determining the ultimate outcome of malignant disease. Copyright © 2018. Published by Elsevier Ltd.

Clinical phenotype of ASD-associated DYRK1A haploinsufficiency.

PubMed

Earl, Rachel K; Turner, Tychele N; Mefford, Heather C; Hudac, Caitlin M; Gerdts, Jennifer; Eichler, Evan E; Bernier, Raphael A

2017-01-01

DYRK1A is a gene recurrently disrupted in 0.1-0.5% of the ASD population. A growing number of case reports with DYRK1A haploinsufficiency exhibit common phenotypic features including microcephaly, intellectual disability, speech delay, and facial dysmorphisms. Phenotypic information from previously published DYRK1A cases ( n  = 51) and participants in an ongoing study at the University of Washington (UW, n  = 10) were compiled. Frequencies of recurrent phenotypic features in this population were compared to features observed in a large sample with idiopathic ASD from the Simons Simplex Collection ( n  = 1981). UW DYRK1A cases were further characterized quantitatively and compared to a randomly subsampled set of idiopathic ASD cases matched on age and gender ( n  = 10) and to cases with an ASD-associated disruptive mutation to CHD8 ( n  = 12). Contribution of familial genetic background to clinical heterogeneity was assessed by comparing head circumference, IQ, and ASD-related symptoms of UW DYRK1A cases to their unaffected parents. DYRK1A haploinsufficiency results in a common phenotypic profile including intellectual disability, speech and motor difficulties, microcephaly, feeding difficulties, and vision abnormalities. Eighty-nine percent of DYRK1A cases ascertained for ASD presented with a constellation of five or more of these symptoms. When compared quantitatively, DYRK1A cases presented with significantly lower IQ and adaptive functioning compared to idiopathic cases and significantly smaller head size compared to both idiopathic and CHD8 cases. Phenotypic variability in parental head circumference, IQ, and ASD-related symptoms corresponded to observed variability in affected child phenotype. Results confirm a core clinical phenotype for DYRK1A disruptions, with a combination of features that is distinct from idiopathic ASD. Cases with DYRK1A mutations are also distinguishable from disruptive mutations to CHD8 by head size. Measurable, quantitative characterization of DYRK1A haploinsufficiency illuminates clinical variability, which may be, in part, due to familial genetic background.

Single neuropsychological test scores associated with rate of cognitive decline in early Alzheimer disease.

PubMed

Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro

2014-01-01

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.

Sarcoidosis diagnostic score (SDS): a systematic evaluation to enhance the diagnosis of sarcoidosis.

PubMed

Bickett, Alexandra N; Lower, Elyse E; Baughman, Robert P

2018-05-17

The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of possible sarcoidosis patients. Biopsy confirmed sarcoidosis patients seen during a seven-month time period at the University of Cincinnati Sarcoidosis clinic were prospectively identified. Non-sarcoidosis patients seen at the same clinic were used as controls. Using a modified WASOG organ assessment instrument, we scored all patients for presence of biopsy, one or more highly probable symptom, and one or more at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy). The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 biopsy confirmed sarcoidosis, 150 controls) to establish cut-off values for SDS biopsy and SDS clinical and a validation cohort of 380 patients (103 biopsy confirmed sarcoidosis patients and 277 controls). The best cutoff value for SDS biopsy was > 6 (sensitivity =99.3%; specificity=100%). For the total the 980 patients, an SDS clinical > 3 had a sensitivity of 94.2%, specificity of 88.8%, and a likelihood ratio of 7.9. An SDS clinical score > 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multi-organ involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis. Copyright © 2018. Published by Elsevier Inc.

Incidence and clinical variables associated with streptococcal throat infections: a prospective diagnostic cohort study

PubMed Central

Little, Paul; Hobbs, FD Richard; Mant, David; McNulty, Cliodna AM; Mullee, Mark

2012-01-01

Background Management of pharyngitis is commonly based on features which are thought to be associated with Lancefield group A beta-haemolytic streptococci (GABHS) but it is debatable which features best predict GABHS. Non-group A strains share major virulence factors with group A, but it is unclear how commonly they present and whether their presentation differs. Aim To assess the incidence and clinical variables associated with streptococcal infections. Design and setting Prospective diagnostic cohort study in UK primary care. Method The presence of pathogenic streptococci from throat swabs was assessed among patients aged ≥5 years presenting with acute sore throat. Results Pathogenic streptococci were found in 204/597 patients (34%, 95% CI = 31 to 38%): 33% (68/204) were non-group A streptococci, mostly C (n = 29), G (n = 18) and B (n = 17); rarely D (n = 3) and Streptococcus pneumoniae (n = 1). Patients presented with similar features whether the streptococci were group A or non-group A. The features best predicting A, C or G beta-haemolytic streptococci were patient’s assessment of severity (odds ratio [OR] for a bad sore throat 3.31, 95% CI = 1.24 to 8.83); doctors’ assessment of severity (severely inflamed tonsils OR 2.28, 95% CI = 1.39 to 3.74); absence of a bad cough (OR 2.73, 95% CI = 1.56 to 4.76), absence of a coryza (OR 1.54, 95% CI = 0.99 to 2.41); and moderately bad or worse muscle aches (OR 2.20, 95% CI = 1.41 to 3.42). Conclusion Non-group A strains commonly cause streptococcal sore throats, and present with similar symptomatic clinical features to group A streptococci. The best features to predict streptococcal sore throat presenting in primary care deserve revisiting. PMID:23211183

Incidence and clinical variables associated with streptococcal throat infections: a prospective diagnostic cohort study.

PubMed

Little, Paul; Hobbs, F D Richard; Mant, David; McNulty, Cliodna A M; Mullee, Mark

2012-11-01

Management of pharyngitis is commonly based on features which are thought to be associated with Lancefield group A beta-haemolytic streptococci (GABHS) but it is debatable which features best predict GABHS. Non-group A strains share major virulence factors with group A, but it is unclear how commonly they present and whether their presentation differs. To assess the incidence and clinical variables associated with streptococcal infections. Prospective diagnostic cohort study in UK primary care. The presence of pathogenic streptococci from throat swabs was assessed among patients aged ≥5 years presenting with acute sore throat. Pathogenic streptococci were found in 204/597 patients (34%, 95% CI = 31 to 38%): 33% (68/204) were non-group A streptococci, mostly C (n = 29), G (n = 18) and B (n = 17); rarely D (n = 3) and Streptococcus pneumoniae (n = 1). Patients presented with similar features whether the streptococci were group A or non-group A. The features best predicting A, C or G beta-haemolytic streptococci were patient's assessment of severity (odds ratio [OR] for a bad sore throat 3.31, 95% CI = 1.24 to 8.83); doctors' assessment of severity (severely inflamed tonsils OR 2.28, 95% CI = 1.39 to 3.74); absence of a bad cough (OR 2.73, 95% CI = 1.56 to 4.76), absence of a coryza (OR 1.54, 95% CI = 0.99 to 2.41); and moderately bad or worse muscle aches (OR 2.20, 95% CI = 1.41 to 3.42). Non-group A strains commonly cause streptococcal sore throats, and present with similar symptomatic clinical features to group A streptococci. The best features to predict streptococcal sore throat presenting in primary care deserve revisiting.

Comparsion analysis of data mining models applied to clinical research in traditional Chinese medicine.

PubMed

Zhao, Yufeng; Xie, Qi; He, Liyun; Liu, Baoyan; Li, Kun; Zhang, Xiang; Bai, Wenjing; Luo, Lin; Jing, Xianghong; Huo, Ruili

2014-10-01

To help researchers selecting appropriate data mining models to provide better evidence for the clinical practice of Traditional Chinese Medicine (TCM) diagnosis and therapy. Clinical issues based on data mining models were comprehensively summarized from four significant elements of the clinical studies: symptoms, symptom patterns, herbs, and efficacy. Existing problems were further generalized to determine the relevant factors of the performance of data mining models, e.g. data type, samples, parameters, variable labels. Combining these relevant factors, the TCM clinical data features were compared with regards to statistical characters and informatics properties. Data models were compared simultaneously from the view of applied conditions and suitable scopes. The main application problems were the inconsistent data type and the small samples for the used data mining models, which caused the inappropriate results, even the mistake results. These features, i.e. advantages, disadvantages, satisfied data types, tasks of data mining, and the TCM issues, were summarized and compared. By aiming at the special features of different data mining models, the clinical doctors could select the suitable data mining models to resolve the TCM problem.

Model-Free Conditional Independence Feature Screening For Ultrahigh Dimensional Data.

PubMed

Wang, Luheng; Liu, Jingyuan; Li, Yong; Li, Runze

2017-03-01

Feature screening plays an important role in ultrahigh dimensional data analysis. This paper is concerned with conditional feature screening when one is interested in detecting the association between the response and ultrahigh dimensional predictors (e.g., genetic makers) given a low-dimensional exposure variable (such as clinical variables or environmental variables). To this end, we first propose a new index to measure conditional independence, and further develop a conditional screening procedure based on the newly proposed index. We systematically study the theoretical property of the proposed procedure and establish the sure screening and ranking consistency properties under some very mild conditions. The newly proposed screening procedure enjoys some appealing properties. (a) It is model-free in that its implementation does not require a specification on the model structure; (b) it is robust to heavy-tailed distributions or outliers in both directions of response and predictors; and (c) it can deal with both feature screening and the conditional screening in a unified way. We study the finite sample performance of the proposed procedure by Monte Carlo simulations and further illustrate the proposed method through two real data examples.

Otofaciocervical syndrome and metachondromatosis in a girl: Presentation of a novel association and remarks on clinical variability of branchial-arch disorders.

PubMed

Salinas-Torres, Victor M; Salinas-Torres, Rafael A

2016-06-01

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial, ear, branchial, and musculoskeletal anomalies, along with hearing loss and mild intellectual disability. Clinically, its distinction from branchiootorenal syndrome can be difficult. To date, the coexistence of OFCS and metachondromatosis has not been reported. Here, we describe a sporadic patient with both OFCS and metachondromatosis. This novel association prompts us to do some remarks on the clinical variability of branchial-arch disorders; in fact, our observations are consistent with the highly variable expressivity of OFCS and illustrate the need of a more accurate characterization of these branchial-arch disorders. In the meantime, involvement of clavicles, scapulae and shoulders remains a distinctive feature of OFCS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An examination of generalized anxiety disorder and dysthymia utilizing the Rorschach inkblot method.

PubMed

Slavin-Mulford, Jenelle; Clements, Alyssa; Hilsenroth, Mark; Charnas, Jocelyn; Zodan, Jennifer

2016-06-30

This study examined transdiagnostic features of generalized anxiety disorder (GAD) and dysthymia in an outpatient clinical sample. Fifteen patients who met DSM-IV criteria for GAD and twenty-one patients who met DSM-IV criteria for dysthymia but who did not have comorbid anxiety disorder were evaluated utilizing the Rorschach. Salient clinical variables were then compared. Results showed that patients with GAD scored significantly higher on variables related to cognitive agitation and a desire/need for external soothing. In addition, there was a trend for patients with GAD to produce higher scores on a measure of ruminative focus on negative aspects of the self. Thus, not surprisingly, GAD patients' experienced more distress than the dysthymic patients. The implications of these findings are discussed with regards to better understanding the shared and distinct features of GAD and dysthymia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Uncovering Clinical Features of De Novo Philadelphia Positive Myelodysplasia.

PubMed

Armas, Aristides; Chen, Chen; Mims, Martha; Rivero, Gustavo

2017-01-01

Myelodysplastic syndrome (MDS) is cytogenetically heterogeneous and retains variable risk for acute myeloid leukemia transformation. Though not yet fully understood, there is an association between genetic abnormalities and defects in gene expression. The functional role for infrequent cytogenetic alteration remains unclear. An uncommon chromosomic abnormality is the presence of the Philadelphia (Ph) chromosome. Here, we report a patient with Ph+ MDS treated with low dose Dasatinib who achieved hematologic response for 7 months. In addition, we also examined the English literature on all de novo Ph + MDS cases between 1996 and 2015 to gain insight into clinical features and outcome.

Uncovering Clinical Features of De Novo Philadelphia Positive Myelodysplasia

PubMed Central

Armas, Aristides; Chen, Chen; Mims, Martha

2017-01-01

Myelodysplastic syndrome (MDS) is cytogenetically heterogeneous and retains variable risk for acute myeloid leukemia transformation. Though not yet fully understood, there is an association between genetic abnormalities and defects in gene expression. The functional role for infrequent cytogenetic alteration remains unclear. An uncommon chromosomic abnormality is the presence of the Philadelphia (Ph) chromosome. Here, we report a patient with Ph+ MDS treated with low dose Dasatinib who achieved hematologic response for 7 months. In addition, we also examined the English literature on all de novo Ph + MDS cases between 1996 and 2015 to gain insight into clinical features and outcome. PMID:28321349

A de novo 11q23 deletion in a patient presenting with severe ophthalmologic findings, psychomotor retardation and facial dysmorphism.

PubMed

Şimşek-Kiper, Pelin Özlem; Bayram, Yavuz; Ütine, Gülen Eda; Alanay, Yasemin; Boduroğlu, Koray

2014-01-01

Distal 11q deletion, previously known as Jacobsen syndrome, is caused by segmental aneusomy for the distal end of the long arm of chromosome 11. Typical clinical features include facial dysmorphism, mild-to-moderate psychomotor retardation, trigonocephaly, cardiac defects, and thrombocytopenia. There is a significant variability in the range of clinical features. We report herein a five-year-old girl with severe ophthalmological findings, facial dysmorphism, and psychomotor retardation with normal platelet function, in whom a de novo 11q23 deletion was detected, suggesting that distal 11q monosomy should be kept in mind in patients presenting with dysmorphic facial features and psychomotor retardation even in the absence of hematological findings.

[Clinical features of major depressive disorders treated in secondary health care facilities in Chile].

PubMed

Salvo, Lilian; Saldivia, Sandra; Parra, Carlos; Rodríguez, Román; Cifuentes, Manuel; Acevedo, Paola; Díaz, Marcela; Ormazabal, Mitza; Guerra, Ivonne; Navarrete, Nicol; Bravo, Verónica; Castro, Andrea

2017-03-01

Depression is considered the second leading cause of disability worldwide. To describe the clinical characteristics and the evolution of major depressive disorder (MDD) in secondary care. To evaluate the association between socio-demographic and clinic variables with the first or recurrent major depressive events (MDE). Clinical features, treatment, remission and duration of MDE were evaluated during a follow up lasting 12 months in 112 participants aged 44 ± 15 years (79% women). Patients were assessed as outpatients every three months at three psychiatric care centers of Chile. Clinical interviews were carried out using DSM-IV diagnostic criteria checklists and the Hamilton Depression Scale was applied. Most patients were referred from primary care. The mean time lapse for referral to the secondary level was 10.8 months. Most patients had episodes that were recurrent, severe, with a high rate of psychosis, with suicide attempts and melancholic features and with psychiatric and medical comorbidities. Remission rate was 27.5%. In only 16 % of patients, the episode lasted six months or less. The group with recurrent episodes had different age, sex and clinical features. MDD treated at the secondary care level is severe and its symptoms are intense. The time lapse prior to referral was prolonged. Primary care management and referral of these patients should be studied more closely.

A practical approach to Sasang constitutional diagnosis using vocal features

PubMed Central

2013-01-01

Background Sasang constitutional medicine (SCM) is a type of tailored medicine that divides human beings into four Sasang constitutional (SC) types. Diagnosis of SC types is crucial to proper treatment in SCM. Voice characteristics have been used as an essential clue for diagnosing SC types. In the past, many studies tried to extract quantitative vocal features to make diagnosis models; however, these studies were flawed by limited data collected from one or a few sites, long recording time, and low accuracy. We propose a practical diagnosis model having only a few variables, which decreases model complexity. This in turn, makes our model appropriate for clinical applications. Methods A total of 2,341 participants’ voice recordings were used in making a SC classification model and to test the generalization ability of the model. Although the voice data consisted of five vowels and two repeated sentences per participant, we used only the sentence part for our study. A total of 21 features were extracted, and an advanced feature selection method—the least absolute shrinkage and selection operator (LASSO)—was applied to reduce the number of variables for classifier learning. A SC classification model was developed using multinomial logistic regression via LASSO. Results We compared the proposed classification model to the previous study, which used both sentences and five vowels from the same patient’s group. The classification accuracies for the test set were 47.9% and 40.4% for male and female, respectively. Our result showed that the proposed method was superior to the previous study in that it required shorter voice recordings, is more applicable to practical use, and had better generalization performance. Conclusions We proposed a practical SC classification method and showed that our model having fewer variables outperformed the model having many variables in the generalization test. We attempted to reduce the number of variables in two ways: 1) the initial number of candidate features was decreased by considering shorter voice recording, and 2) LASSO was introduced for reducing model complexity. The proposed method is suitable for an actual clinical environment. Moreover, we expect it to yield more stable results because of the model’s simplicity. PMID:24200041

[Discriminant analysis to predict the clinical diagnosis of primary immunodeficiencies: a preliminary report].

PubMed

Murata, Chiharu; Ramírez, Ana Belén; Ramírez, Guadalupe; Cruz, Alonso; Morales, José Luis; Lugo-Reyes, Saul Oswaldo

2015-01-01

The features in a clinical history from a patient with suspected primary immunodeficiency (PID) direct the differential diagnosis through pattern recognition. PIDs are a heterogeneous group of more than 250 congenital diseases with increased susceptibility to infection, inflammation, autoimmunity, allergy and malignancy. Linear discriminant analysis (LDA) is a multivariate supervised classification method to sort objects of study into groups by finding linear combinations of a number of variables. To identify the features that best explain membership of pediatric PID patients to a group of defect or disease. An analytic cross-sectional study was done with a pre-existing database with clinical and laboratory records from 168 patients with PID, followed at the National Institute of Pediatrics during 1991-2012, it was used to build linear discriminant models that would explain membership of each patient to the different group defects and to the most prevalent PIDs in our registry. After a preliminary run only 30 features were included (4 demographic, 10 clinical, 10 laboratory, 6 germs), with which the training models were developed through a stepwise regression algorithm. We compared the automatic feature selection with a selection made by a human expert, and then assessed the diagnostic usefulness of the resulting models (sensitivity, specificity, prediction accuracy and kappa coefficient), with 95% confidence intervals. The models incorporated 6 to 14 features to explain membership of PID patients to the five most abundant defect groups (combined, antibody, well-defined, dysregulation and phagocytosis), and to the four most prevalent PID diseases (X-linked agammaglobulinemia, chronic granulomatous disease, common variable immunodeficiency and ataxiatelangiectasia). In practically all cases of feature selection the machine outperformed the human expert. Diagnosis prediction using the equations created had a global accuracy of 83 to 94%, with sensitivity of 60 to 100%, specificity of 83 to 95% and kappa coefficient of 0.37 to 0.76. In general, the selection of features has clinical plausibility, and the practical advantage of utilizing only clinical attributes, infecting germs and routine lab results (blood cell counts and serum immunoglobulins). The performance of the model as a diagnostic tool was acceptable. The study's main limitations are a limited sample size and a lack of cross validation. This is only the first step in the construction of a machine learning system, with a wider approach that includes a larger database and different methodologies, to assist the clinical diagnosis of primary immunodeficiencies.

Clinical features of body dysmorphic disorder in adolescents and adults

PubMed Central

Phillips, Katharine A.; Didie, Elizabeth R.; Menard, William; Pagano, Maria E.; Fay, Christina; Weisberg, Risa B.

2006-01-01

Body dysmorphic disorder (BDD) usually begins during adolescence, but its clinical features have received little investigation in this age group. Two hundred individuals with BDD (36 adolescents; 164 adults) completed interviewer-administered and self-report measures. Adolescents were preoccupied with numerous aspects of their appearance, most often their skin, hair, and stomach. Among the adolescents, 94.3% reported moderate, severe, or extreme distress due to BDD, 80.6% had a history of suicidal ideation, and 44.4% had attempted suicide. Adolescents experienced high rates and levels of impairment in school, work, and other aspects of psychosocial functioning. Adolescents and adults were comparable on most variables, although adolescents had significantly more delusional BDD beliefs and a higher lifetime rate of suicide attempts. Thus, adolescents with BDD have high levels of distress and rates of functional impairment, suicidal ideation, and suicide attempts. BDD’s clinical features in adolescents appear largely similar to those in adults. PMID:16499973

A Proposal for Overcoming Problems in Teaching Interviewing Skills to Medical Students

ERIC Educational Resources Information Center

Benbassat, Jochanan; Baumal, Reuben

2009-01-01

The objective of this paper is to draw attention to four features that distinguish the pedagogy of patient interviewing from the teaching of other clinical skills: (a) students are not naive to the skill to be learned, (b) they encounter role models with a wide variability in interviewing styles, (c) clinical teachers are not usually specialists…

Granulomatous lobular mastitis.

PubMed

Miliauskas, J R; Pieterse, A S; Williams, R S

1995-02-01

Two cases of benign lobular granulomatous mastitis, both clinically felt to be carcinoma, are reported. One patient was cured by local excision of the mass while the other was cured by oral prednisolone, demonstrating the variable ways to treat this entity. The clinical and histological features were similar to those noted in previous reports. Immunological studies revealed predominantly stromal T lymphocytes and only duct intra-epithelial T lymphocytes.

Breast cancer - one term, many entities?

PubMed

Bertos, Nicholas R; Park, Morag

2011-10-01

Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-intrinsic features, including classical histological and immunopathological classifications as well as more recently described molecular subtypes, separate breast tumors into multiple groups. Tumor-extrinsic features, including microenvironmental configuration, also have prognostic significance and further expand the list of tumor-defining variables. A better understanding of the features underlying heterogeneity, as well as of the mechanisms and consequences of their interactions, is essential to improve targeting of existing therapies and to develop novel agents addressing specific combinations of features.

P09.62 Towards individualized survival prediction in glioblastoma patients using machine learning methods

PubMed Central

Vera, L.; Pérez-Beteta, J.; Molina, D.; Borrás, J. M.; Benavides, M.; Barcia, J. A.; Velásquez, C.; Albillo, D.; Lara, P.; Pérez-García, V. M.

2017-01-01

Abstract Introduction: Machine learning methods are integrated in clinical research studies due to their strong capability to discover parameters having a high information content and their predictive combined potential. Several studies have been developed using glioblastoma patient’s imaging data. Many of them have focused on including large numbers of variables, mostly two-dimensional textural features and/or genomic data, regardless of their meaning or potential clinical relevance. Materials and methods: 193 glioblastoma patients were included in the study. Preoperative 3D magnetic resonance images were collected and semi-automatically segmented using an in-house software. After segmentation, a database of 90 parameters including geometrical and textural image-based measures together with patients’ clinical data (including age, survival, type of treatment, etc.) was constructed. The criterion for including variables in the study was that they had either shown individual impact on survival in single or multivariate analyses or have a precise clinical or geometrical meaning. These variables were used to perform several machine learning experiments. In a first set of computational cross-validation experiments based on regression trees, those attributes showing the highest information measures were extracted. In the second phase, more sophisticated learning methods were employed in order to validate the potential of the previous variables predicting survival. Concretely support vector machines, neural networks and sparse grid methods were used. Results: Variables showing high information measure in the first phase provided the best prediction results in the second phase. Specifically, patient age, Stupp regimen and a geometrical measure related with the irregularity of contrast-enhancing areas were the variables showing the highest information measure in the first stage. For the second phase, the combinations of patient age and Stupp regimen together with one tumor geometrical measure and one tumor heterogeneity feature reached the best quality prediction. Conclusions: Advanced machine learning methods identified the parameters with the highest information measure and survival predictive potential. The uninformed machine learning methods identified a novel feature measure with direct impact on survival. Used in combination with other previously known variables multi-indexes can be defined that can help in tumor characterization and prognosis prediction. Recent advances on the definition of those multi-indexes will be reported in the conference. Funding: James S. Mc. Donnell Foundation (USA) 21st Century Science Initiative in Mathematical and Complex Systems Approaches for Brain Cancer [Collaborative award 220020450 and planning grant 220020420], MINECO/FEDER [MTM2015-71200-R], JCCM [PEII-2014-031-P].

Salivary Parameters (Salivary Flow, pH and Buffering Capacity) in Stimulated Saliva of Mexican Elders 60 Years Old and Older

PubMed Central

Islas-Granillo, H; Borges-Yañez, SA; Medina-Solís, CE; Galan-Vidal, CA; Navarrete-Hernández, JJ; Escoffié-Ramirez, M; Maupomé, G

2014-01-01

ABSTRACT Objective: To compare a limited array of chewing-stimulated saliva features (salivary flow, pH and buffer capacity) in a sample of elderly Mexicans with clinical, sociodemographic and socio-economic variables. Subjects and Methods: A cross-sectional study was carried out in 139 adults, 60 years old and older, from two retirement homes and a senior day care centre in the city of Pachuca, Mexico. Socio-demographic, socio-economic and behavioural variables were collected through a questionnaire. A trained and standardized examiner obtained the oral clinical variables. Chewing-stimulated saliva (paraffin method) was collected and the salivary flow rate, pH and buffer capacity were measured. The analysis was performed using non-parametric tests in Stata 9.0. Results: Mean age was 79.1 ± 9.8 years. Most of the subjects included were women (69.1%). Mean chewing-stimulated salivary flow was 0.75 ± 0.80 mL/minute, and the pH and buffer capacity were 7.88 ± 0.83 and 4.20 ± 1.24, respectively. Mean chewing-stimulated salivary flow varied (p < 0.05) across type of retirement home, tooth brushing frequency, number of missing teeth and use of dental prostheses. pH varied across the type of retirement home (p < 0.05) and marginally by age (p = 0.087); buffer capacity (p < 0.05) varied across type of retirement home, tobacco consumption and the number of missing teeth. Conclusions: These exploratory data add to the body of knowledge with regard to chewing-stimulated salivary features (salivary flow rate, pH and buffer capacity) and outline the variability of those features across selected sociodemographic, socio-economic and behavioural variables in a group of Mexican elders. PMID:25867562

Salivary Parameters (Salivary Flow, pH and Buffering Capacity) in Stimulated Saliva of Mexican Elders 60 Years Old and Older.

PubMed

Islas-Granillo, H; Borges-Yañez, S A; Medina-Solís, C E; Galan-Vidal, C A; Navarrete-Hernández, J J; Escoffié-Ramirez, M; Maupomé, G

2014-12-01

To compare a limited array of chewing-stimulated saliva features (salivary flow, pH and buffer capacity) in a sample of elderly Mexicans with clinical, sociodemographic and socio-economic variables. A cross-sectional study was carried out in 139 adults, 60 years old and older, from two retirement homes and a senior day care centre in the city of Pachuca, Mexico. Sociodemographic, socio-economic and behavioural variables were collected through a questionnaire. A trained and standardized examiner obtained the oral clinical variables. Chewing-stimulated saliva (paraffin method) was collected and the salivary flow rate, pH and buffer capacity were measured. The analysis was performed using non-parametric tests in Stata 9.0. Mean age was 79.1 ± 9.8 years. Most of the subjects included were women (69.1%). Mean chewing-stimulated salivary flow was 0.75 ± 0.80 mL/minute, and the pH and buffer capacity were 7.88 ± 0.83 and 4.20 ± 1.24, respectively. Mean chewing-stimulated salivary flow varied (p < 0.05) across type of retirement home, tooth brushing frequency, number of missing teeth and use of dental prostheses. pH varied across the type of retirement home (p < 0.05) and marginally by age (p = 0.087); buffer capacity (p < 0.05) varied across type of retirement home, tobacco consumption and the number of missing teeth. These exploratory data add to the body of knowledge with regard to chewing-stimulated salivary features (salivary flow rate, pH and buffer capacity) and outline the variability of those features across selected sociodemographic, socio-economic and behavioural variables in a group of Mexican elders.

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.

Logic Learning Machine and standard supervised methods for Hodgkin's lymphoma prognosis using gene expression data and clinical variables.

PubMed

Parodi, Stefano; Manneschi, Chiara; Verda, Damiano; Ferrari, Enrico; Muselli, Marco

2018-03-01

This study evaluates the performance of a set of machine learning techniques in predicting the prognosis of Hodgkin's lymphoma using clinical factors and gene expression data. Analysed samples from 130 Hodgkin's lymphoma patients included a small set of clinical variables and more than 54,000 gene features. Machine learning classifiers included three black-box algorithms ( k-nearest neighbour, Artificial Neural Network, and Support Vector Machine) and two methods based on intelligible rules (Decision Tree and the innovative Logic Learning Machine method). Support Vector Machine clearly outperformed any of the other methods. Among the two rule-based algorithms, Logic Learning Machine performed better and identified a set of simple intelligible rules based on a combination of clinical variables and gene expressions. Decision Tree identified a non-coding gene ( XIST) involved in the early phases of X chromosome inactivation that was overexpressed in females and in non-relapsed patients. XIST expression might be responsible for the better prognosis of female Hodgkin's lymphoma patients.

Evaluation of Voice Acoustics as Predictors of Clinical Depression Scores.

PubMed

Hashim, Nik Wahidah; Wilkes, Mitch; Salomon, Ronald; Meggs, Jared; France, Daniel J

2017-03-01

The aim of the present study was to determine if acoustic measures of voice, characterizing specific spectral and timing properties, predict clinical ratings of depression severity measured in a sample of patients using the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI-II). This is a prospective study. Voice samples and clinical depression scores were collected prospectively from consenting adult patients who were referred to psychiatry from the adult emergency department or primary care clinics. The patients were audio-recorded as they read a standardized passage in a nearly closed-room environment. Mean Absolute Error (MAE) between actual and predicted depression scores was used as the primary outcome measure. The average MAE between predicted and actual HAMD scores was approximately two scores for both men and women, and the MAE for the BDI-II scores was approximately one score for men and eight scores for women. Timing features were predictive of HAMD scores in female patients while a combination of timing features and spectral features was predictive of scores in male patients. Timing features were predictive of BDI-II scores in male patients. Voice acoustic features extracted from read speech demonstrated variable effectiveness in predicting clinical depression scores in men and women. Voice features were highly predictive of HAMD scores in men and women, and BDI-II scores in men, respectively. The methodology is feasible for diagnostic applications in diverse clinical settings as it can be implemented during a standard clinical interview in a normal closed room and without strict control on the recording environment. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

Validity and clinical utility of the DSM-5 severity specifier for bulimia nervosa: results from a multisite sample of patients who received evidence-based treatment.

PubMed

Dakanalis, Antonios; Bartoli, Francesco; Caslini, Manuela; Crocamo, Cristina; Zanetti, Maria Assunta; Riva, Giuseppe; Clerici, Massimo; Carrà, Giuseppe

2017-12-01

A new "severity specifier" for bulimia nervosa (BN), based on the frequency of inappropriate weight compensatory behaviours (IWCBs), was added to the DSM-5 as a means of documenting heterogeneity and variability in the severity of the disorder. Yet, evidence for its validity in clinical populations, including prognostic significance for treatment outcome, is currently lacking. Existing data from 281 treatment-seeking patients with DSM-5 BN, who received the best available treatment for their disorder (manual-based cognitive behavioural therapy; CBT) in an outpatient setting, were re-analysed to examine whether these patients subgrouped based on the DSM-5 severity levels would show meaningful and consistent differences on (a) a range of clinical variables assessed at pre-treatment and (b) post-treatment abstinence from IWCBs. Results highlight that the mild, moderate, severe, and extreme severity groups were statistically distinguishable on 22 variables assessed at pre-treatment regarding eating disorder pathological features, maintenance factors of BN, associated (current) and lifetime psychopathology, social maladjustment and illness-specific functional impairment, and abstinence outcome. Mood intolerance, a maintenance factor of BN but external to eating disorder pathological features (typically addressed within CBT), emerged as the primary clinical variable distinguishing the severity groups showing a differential treatment response. Overall, the findings speak to the concurrent and predictive validity of the new DSM-5 severity criterion for BN and are important because a common benchmark informing patients, clinicians, and researchers about severity of the disorder and allowing severity fluctuation and patient's progress to be tracked does not exist so far. Implications for future research are outlined.

Formant Frequencies and Bandwidths in Relation to Clinical Variables in an Obstructive Sleep Apnea Population.

PubMed

Montero Benavides, Ana; Blanco Murillo, José Luis; Fernández Pozo, Rubén; Espinoza Cuadros, Fernando; Torre Toledano, Doroteo; Alcázar-Ramírez, José D; Hernández Gómez, Luis A

2016-01-01

We investigated whether differences in formants and their bandwidths, previously reported comparing small sample population of healthy individuals and patients with obstructive sleep apnea (OSA), are detected on a larger population representative of a clinical practice scenario. We examine possible indirect or mediated effects of clinical variables, which may shed some light on the connection between speech and OSA. In a retrospective study, 241 male subjects suspected to suffer from OSA were examined. The apnea-hypopnea index (AHI) was obtained for every subject using overnight polysomnography. Furthermore, the clinical variables usually reported as predictors of OSA, body mass index (BMI), cervical perimeter, height, weight, and age, were collected. Voice samples of sustained phonations of the vowels /a/, /e/, /i/, /o/, and /u/ were recorded. Formant frequencies F1, F2, and F3 and bandwidths BW1, BW2, and BW3 of the sustained vowels were determined using spectrographic analysis. Correlations among AHI, clinical parameters, and formants and bandwidths were determined. Correlations between AHI and clinical variables were stronger than those between AHI and voice features. AHI only correlates poorly with BW2 of /a/ and BW3 of /e/. A number of further weak but significant correlations have been detected between voice and clinical variables. Most of them were for height and age, with two higher values for age and F2 of /o/ and F2 of /u/. Only few very weak correlations were detected between voice and BMI, weight and cervical perimeter, wich are the clinical variables more correlated with AHI. No significant correlations were detected between AHI and formant frequencies and bandwidths. Correlations between voice and other clinical factors characterizing OSA are weak but highlight the importance of considering indirect or mediated effects of such clinical variables in any research on speech and OSA. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Bipolar mixed features - Results from the comparative effectiveness for bipolar disorder (Bipolar CHOICE) study.

PubMed

Tohen, Mauricio; Gold, Alexandra K; Sylvia, Louisa G; Montana, Rebecca E; McElroy, Susan L; Thase, Michael E; Rabideau, Dustin J; Nierenberg, Andrew A; Reilly-Harrington, Noreen A; Friedman, Edward S; Shelton, Richard C; Bowden, Charles L; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence A; Calabrese, Joseph R; Bobo, William V; McInnis, Melvin G

2017-08-01

DSM-5 changed the criteria from DSM-IV for mixed features in mood disorder episodes to include non-overlapping symptoms of depression and hypomania/mania. It is unknown if, by changing these criteria, the same group would qualify for mixed features. We assessed how those meeting DSM-5 criteria for mixed features compare to those meeting DSM-IV criteria. We analyzed data from 482 adult bipolar patients in Bipolar CHOICE, a randomized comparative effectiveness trial. Bipolar diagnoses were confirmed through the MINI International Neuropsychiatric Interview (MINI). Presence and severity of mood symptoms were collected with the Bipolar Inventory of Symptoms Scale (BISS) and linked to DSM-5 and DSM-IV mixed features criteria. Baseline demographics and clinical variables were compared between mood episode groups using ANOVA for continuous variables and chi-square tests for categorical variables. At baseline, the frequency of DSM-IV mixed episodes diagnoses obtained with the MINI was 17% and with the BISS was 20%. Using DSM-5 criteria, 9% of participants met criteria for hypomania/mania with mixed features and 12% met criteria for a depressive episode with mixed features. Symptom severity was also associated with increased mixed features with a high rate of mixed features in patients with mania/hypomania (63.8%) relative to those with depression (8.0%). Data on mixed features were collected at baseline only and thus do not reflect potential patterns in mixed features within this sample across the study duration. The DSM-5 narrower, non-overlapping definition of mixed episodes resulted in fewer patients who met mixed criteria compared to DSM-IV. Copyright © 2017. Published by Elsevier B.V.

Recursive feature elimination for biomarker discovery in resting-state functional connectivity.

PubMed

Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E

2016-08-01

Biomarker discovery involves finding correlations between features and clinical symptoms to aid clinical decision. This task is especially difficult in resting state functional magnetic resonance imaging (rs-fMRI) data due to low SNR, high-dimensionality of images, inter-subject and intra-subject variability and small numbers of subjects compared to the number of derived features. Traditional univariate analysis suffers from the problem of multiple comparisons. Here, we adopt an alternative data-driven method for identifying population differences in functional connectivity. We propose a machine-learning approach to down-select functional connectivity features associated with symptom severity in mild traumatic brain injury (mTBI). Using this approach, we identified functional regions with altered connectivity in mTBI. including the executive control, visual and precuneus networks. We compared functional connections at multiple resolutions to determine which scale would be more sensitive to changes related to patient recovery. These modular network-level features can be used as diagnostic tools for predicting disease severity and recovery profiles.

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Time series analysis as input for clinical predictive modeling: Modeling cardiac arrest in a pediatric ICU

PubMed Central

2011-01-01

Background Thousands of children experience cardiac arrest events every year in pediatric intensive care units. Most of these children die. Cardiac arrest prediction tools are used as part of medical emergency team evaluations to identify patients in standard hospital beds that are at high risk for cardiac arrest. There are no models to predict cardiac arrest in pediatric intensive care units though, where the risk of an arrest is 10 times higher than for standard hospital beds. Current tools are based on a multivariable approach that does not characterize deterioration, which often precedes cardiac arrests. Characterizing deterioration requires a time series approach. The purpose of this study is to propose a method that will allow for time series data to be used in clinical prediction models. Successful implementation of these methods has the potential to bring arrest prediction to the pediatric intensive care environment, possibly allowing for interventions that can save lives and prevent disabilities. Methods We reviewed prediction models from nonclinical domains that employ time series data, and identified the steps that are necessary for building predictive models using time series clinical data. We illustrate the method by applying it to the specific case of building a predictive model for cardiac arrest in a pediatric intensive care unit. Results Time course analysis studies from genomic analysis provided a modeling template that was compatible with the steps required to develop a model from clinical time series data. The steps include: 1) selecting candidate variables; 2) specifying measurement parameters; 3) defining data format; 4) defining time window duration and resolution; 5) calculating latent variables for candidate variables not directly measured; 6) calculating time series features as latent variables; 7) creating data subsets to measure model performance effects attributable to various classes of candidate variables; 8) reducing the number of candidate features; 9) training models for various data subsets; and 10) measuring model performance characteristics in unseen data to estimate their external validity. Conclusions We have proposed a ten step process that results in data sets that contain time series features and are suitable for predictive modeling by a number of methods. We illustrated the process through an example of cardiac arrest prediction in a pediatric intensive care setting. PMID:22023778

Time series analysis as input for clinical predictive modeling: modeling cardiac arrest in a pediatric ICU.

PubMed

Kennedy, Curtis E; Turley, James P

2011-10-24

Thousands of children experience cardiac arrest events every year in pediatric intensive care units. Most of these children die. Cardiac arrest prediction tools are used as part of medical emergency team evaluations to identify patients in standard hospital beds that are at high risk for cardiac arrest. There are no models to predict cardiac arrest in pediatric intensive care units though, where the risk of an arrest is 10 times higher than for standard hospital beds. Current tools are based on a multivariable approach that does not characterize deterioration, which often precedes cardiac arrests. Characterizing deterioration requires a time series approach. The purpose of this study is to propose a method that will allow for time series data to be used in clinical prediction models. Successful implementation of these methods has the potential to bring arrest prediction to the pediatric intensive care environment, possibly allowing for interventions that can save lives and prevent disabilities. We reviewed prediction models from nonclinical domains that employ time series data, and identified the steps that are necessary for building predictive models using time series clinical data. We illustrate the method by applying it to the specific case of building a predictive model for cardiac arrest in a pediatric intensive care unit. Time course analysis studies from genomic analysis provided a modeling template that was compatible with the steps required to develop a model from clinical time series data. The steps include: 1) selecting candidate variables; 2) specifying measurement parameters; 3) defining data format; 4) defining time window duration and resolution; 5) calculating latent variables for candidate variables not directly measured; 6) calculating time series features as latent variables; 7) creating data subsets to measure model performance effects attributable to various classes of candidate variables; 8) reducing the number of candidate features; 9) training models for various data subsets; and 10) measuring model performance characteristics in unseen data to estimate their external validity. We have proposed a ten step process that results in data sets that contain time series features and are suitable for predictive modeling by a number of methods. We illustrated the process through an example of cardiac arrest prediction in a pediatric intensive care setting.

Quantitative topographic differentiation of the neonatal EEG.

PubMed

Paul, Karel; Krajca, Vladimír; Roth, Zdenek; Melichar, Jan; Petránek, Svojmil

2006-09-01

To test the discriminatory topographic potential of a new method of the automatic EEG analysis in neonates. A quantitative description of the neonatal EEG can contribute to the objective assessment of the functional state of the brain, and may improve the precision of diagnosing cerebral dysfunctions manifested by 'disorganization', 'dysrhythmia' or 'dysmaturity'. 21 healthy, full-term newborns were examined polygraphically during sleep (EEG-8 referential derivations, respiration, ECG, EOG, EMG). From each EEG record, two 5-min samples (one from the middle of quiet sleep, the other from the middle of active sleep) were subject to subsequent automatic analysis and were described by 13 variables: spectral features and features describing shape and variability of the signal. The data from individual infants were averaged and the number of variables was reduced by factor analysis. All factors identified by factor analysis were statistically significantly influenced by the location of derivation. A large number of statistically significant differences were also established when comparing the effects of individual derivations on each of the 13 measured variables. Both spectral features and features describing shape and variability of the signal are largely accountable for the topographic differentiation of the neonatal EEG. The presented method of the automatic EEG analysis is capable to assess the topographic characteristics of the neonatal EEG, and it is adequately sensitive and describes the neonatal electroencephalogram with sufficient precision. The discriminatory capability of the used method represents a promise for their application in the clinical practice.

Appreciating the broad clinical features of SMAD4 mutation carriers: a multi-center chart review

PubMed Central

Wain, K.E.; Ellingson, M.S.; McDonald, J.; Gammon, A.; Roberts, M.; Pichurin, P.; Winship, I.; Riegert-Johnson, D.; Weitzel, J. N.; Lindor, N.M.

2014-01-01

Heterozygous loss-of-function (LOF) SMAD4 mutations are associated with juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT). Some carriers exhibit symptoms of both conditions, leading to the name JP-HHT syndrome. Three families have been reported with connective tissue abnormalities. In order to better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n=3), aortic and mitral insufficiency (n=2), aortic dissection (n=1), retinal detachment (n=1), brain aneurysms (n=1), lax skin and joints (n=1). JP-specific findings were almost uniformly present but variable. Ninety-seven percent had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent (15/31) had extensive gastric polyposis. HHT features were documented in 76% including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (AVM) (6/16, 38%), brain AVM (1/26, 4%), pulmonary AVM (9/17, 53%), and intrapulmonary shunting (14/23, 61%). SMAD4 carriers should be managed for JP and HHT, since symptoms of both are likely yet unpredictable. Connective tissue abnormalities are an emerging component of JP-HHT syndrome, and larger studies are needed to understand these manifestations. PMID:24525918

The Relative Importance of Family History, Gender, Mode of Onset, and Age at Onsetin Predicting Clinical Features of First-Episode Psychotic Disorders.

PubMed

Compton, Michael T; Berez, Chantal; Walker, Elaine F

Family history of psychosis, gender, mode of onset, and age at onset are considered prognostic factors important to clinicians evaluating first-episode psychosis; yet, clinicians have little guidance as to how these four factors differentially predict early-course substance abuse, symptomatology, and functioning. We conducted a "head-to-head comparison" of these four factors regarding their associations with key clinical features at initial hospitalization. We also assessed potential interactions between gender and family history with regard to age at onset of psychosis and symptom severity. Consecutively admitted first-episode patients (n=334) were evaluated in two studies that rigorously assessed a number of early-course variables. Associations among variables of interest were examined using Pearson correlations, χ 2 tests, Student's t-tests, and 2×2 factorial analyses of variance. Substance (nicotine, alcohol, and cannabis) abuse and positive symptom severity were predicted only by male gender. Negative symptom severity and global functioning impairments were predicted by earlier age at onset of psychosis. General psychopathology symptom severity was predicted by both mode of onset and age at onset. Interaction effects were not observed with regard to gender and family history in predicting age at onset or symptom severity. The four prognostic features have differential associations with substance abuse, domains of symptom severity, and global functioning. Gender and age at onset of psychosis appear to be more predictive of clinical features at the time of initial evaluation (and thus presumably longer term outcomes) than the presence of a family history of psychosis and a more gradual mode of onset.

Prevalence of suicide attempt and clinical characteristics of suicide attempters with obsessive-compulsive disorder: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

PubMed

Dell'Osso, Bernardo; Benatti, Beatrice; Arici, Chiara; Palazzo, Carlotta; Altamura, A Carlo; Hollander, Eric; Fineberg, Naomi; Stein, Dan J; Nicolini, Humberto; Lanzagorta, Nuria; Marazziti, Donatella; Pallanti, Stefano; van Ameringen, Michael; Lochner, Christine; Karamustafalioglu, Oguz; Hranov, Luchezar; Figee, Martijn; Drummond, Lynne; Rodriguez, Carolyn I; Grant, John; Denys, Damiaan; Menchon, Jose M; Zohar, Joseph

2018-02-01

Obsessive-compulsive disorder (OCD) is associated with variable risk of suicide and prevalence of suicide attempt (SA). The present study aimed to assess the prevalence of SA and associated sociodemographic and clinical features in a large international sample of OCD patients. A total of 425 OCD outpatients, recruited through the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network, were assessed and categorized in groups with or without a history of SA, and their sociodemographic and clinical features compared through Pearson's chi-squared and t tests. Logistic regression was performed to assess the impact of the collected data on the SA variable. 14.6% of our sample reported at least one SA during their lifetime. Patients with an SA had significantly higher rates of comorbid psychiatric disorders (60 vs. 17%, p<0.001; particularly tic disorder), medical disorders (51 vs. 15%, p<0.001), and previous hospitalizations (62 vs. 11%, p<0.001) than patients with no history of SA. With respect to geographical differences, European and South African patients showed significantly higher rates of SA history (40 and 39%, respectively) compared to North American and Middle-Eastern individuals (13 and 8%, respectively) (χ2=11.4, p<0.001). The logistic regression did not show any statistically significant predictor of SA among selected independent variables. Our international study found a history of SA prevalence of ~15% in OCD patients, with higher rates of psychiatric and medical comorbidities and previous hospitalizations in patients with a previous SA. Along with potential geographical influences, the presence of the abovementioned features should recommend additional caution in the assessment of suicide risk in OCD patients.

Heterogeneity in chronic fatigue syndrome - empirically defined subgroups from the PACE trial.

PubMed

Williams, T E; Chalder, T; Sharpe, M; White, P D

2017-06-01

Chronic fatigue syndrome is likely to be a heterogeneous condition. Previous studies have empirically defined subgroups using combinations of clinical and biological variables. We aimed to explore the heterogeneity of chronic fatigue syndrome. We used baseline data from the PACE trial, which included 640 participants with chronic fatigue syndrome. Variable reduction, using a combination of clinical knowledge and principal component analyses, produced a final dataset of 26 variables for 541 patients. Latent class analysis was then used to empirically define subgroups. The most statistically significant and clinically recognizable model comprised five subgroups. The largest, 'core' subgroup (33% of participants), had relatively low scores across all domains and good self-efficacy. A further three subgroups were defined by: the presence of mood disorders (21%); the presence of features of other functional somatic syndromes (such as fibromyalgia or irritable bowel syndrome) (21%); or by many symptoms - a group which combined features of both of the above (14%). The smallest 'avoidant-inactive' subgroup was characterized by physical inactivity, belief that symptoms were entirely physical in nature, and fear that they indicated harm (11%). Differences in the severity of fatigue and disability provided some discriminative validation of the subgroups. In addition to providing further evidence for the heterogeneity of chronic fatigue syndrome, the subgroups identified may aid future research into the important aetiological factors of specific subtypes of chronic fatigue syndrome and the development of more personalized treatment approaches.

Clinical and molecular characterization of duplications encompassing the human SHOX gene reveal a variable effect on stature.

PubMed

Thomas, N Simon; Harvey, John F; Bunyan, David J; Rankin, Julia; Grigelioniene, Giedre; Bruno, Damien L; Tan, Tiong Y; Tomkins, Susan; Hastings, Robert

2009-07-01

Deletions of the SHOX gene are well documented and cause disproportionate short stature and variable skeletal abnormalities. In contrast interstitial SHOX duplications limited to PAR1 appear to be very rare and the clinical significance of the only case report in the literature is unclear. Mapping of this duplication has now shown that it includes the entire SHOX gene but little flanking sequence and so will not encompass any of the long-range enhancers required for SHOX transcription. We now describe the clinical and molecular characterization of three additional cases. The duplications all included the SHOX coding sequence but varied in the amount of flanking sequence involved. The probands were ascertained for a variety of reasons: hypotonia and features of Asperger syndrome, Leri-Weill dyschondrosteosis (LWD), and a family history of cleft palate. However, the presence of a duplication did not correlate with any of these features or with evidence of skeletal abnormality. Remarkably, the proband with LWD had inherited both a SHOX deletion and a duplication. The effect of the duplications on stature was variable: height appeared to be elevated in some carriers, particularly in those with the largest duplications, but was still within the normal range. SHOX duplications are likely to be under ascertained and more cases need to be identified and characterized in detail in order to accurately determine their phenotypic consequences.

Clinical and Molecular Aspects of an Informative Family with Neurofibromatosis Type 1 and Noonan Phenotype

PubMed Central

Stevenson, David A.; Viskochil, David H.; Rope, Alan F.; Carey, John C.

2011-01-01

NF-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndromes, which are separate syndromes. Potential etiologies of NF-Noonan syndrome include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS. PMID:16542390

A Data Base Management System for Clinical and Epidemiologic Studies In Systemic Lupus Erythematosus: Design and Maintenance

PubMed Central

Kosmides, Victoria S.; Hochberg, Marc C.

1984-01-01

This report describes the development, design specifications, features and implementation of a data base management system (DBMS) for clinical and epidemiologic studies in SLE. The DBMS is multidimensional with arrays formulated across patients, studies and variables. The major impact of this DBMS has been to increase the efficiency of managing and analyzing vast amounts of clinical and laboratory data and, as a result, to allow for continued growth in research productivity in areas related to SLE.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

PubMed

Beukinga, Roelof J; Hulshoff, Jan Binne; Mul, Véronique E M; Noordzij, Walter; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Plukker, John T M

2018-06-01

Purpose To assess the value of baseline and restaging fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18 F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18 F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Is recurrence in major depressive disorder related to bipolarity and mixed features? Results from the BRIDGE-II-Mix study.

PubMed

Mazzarini, Lorenzo; Kotzalidis, Georgios D; Piacentino, Daria; Rizzato, Salvatore; Angst, Jules; Azorin, Jean-Michel; Bowden, Charles L; Mosolov, Sergey; Young, Allan H; Vieta, Eduard; Girardi, Paolo; Perugi, Giulio

2018-03-15

Current classifications separate Bipolar (BD) from Major Depressive Disorder (MDD) based on polarity rather than recurrence. We aimed to determine bipolar/mixed feature frequency in a large MDD multinational sample with (High-Rec) and without (Low-Rec) >3 recurrences, comparing the two subsamples. We measured frequency of bipolarity/hypomanic features during current depressive episodes (MDEs) in 2347 MDD patients from the BRIDGE-II-mix database, comparing High-Rec with Low-Rec. We used Bonferroni-corrected Student's t-test for continuous, and chi-squared test, for categorical variables. Logistic regression estimated the size of the association between clinical characteristics and High-Rec MDD. Compared to Low-Rec (n = 1084, 46.2%), High-Rec patients (n = 1263, 53.8%) were older, with earlier depressive onset, had more family history of BD, more atypical features, suicide attempts, hospitalisations, and treatment resistance and (hypo)manic switches when treated with antidepressants, higher comorbidity with borderline personality disorder, and more hypomanic symptoms during current MDE, resulting in higher rates of mixed depression according to both DSM-5 and research-based diagnostic (RBDC) criteria. Logistic regression showed age at first symptoms < 30 years, current MDE duration ≤ 1 month, hypomania/mania among first-degree relatives, past suicide attempts, treatment-resistance, antidepressant-induced swings, and atypical, mixed, or psychotic features during MDE to associate with High-Rec. Number of MDEs for defining recurrence was arbitrary; cross-sectionality did not allow assessment of conversion from MDD to BD. High-Rec MDD differed from Low-Rec group for several clinical/epidemiological variables, including bipolar/mixed features. Bipolarity specifier and RBDC were more sensitive than DSM-5 criteria in detecting bipolar and mixed features in MDD. Copyright © 2017. Published by Elsevier B.V.

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.

H syndrome: the first 79 patients.

PubMed

Molho-Pessach, Vered; Ramot, Yuval; Camille, Frances; Doviner, Victoria; Babay, Sofia; Luis, Siekavizza Juan; Broshtilova, Valentina; Zlotogorski, Abraham

2014-01-01

H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. We sought to investigate the clinical and molecular findings in 79 patients with this disorder. A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. In the 31 patients described by others, data were collected from the medical literature. H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Significance of the impact of motion compensation on the variability of PET image features

NASA Astrophysics Data System (ADS)

Carles, M.; Bach, T.; Torres-Espallardo, I.; Baltas, D.; Nestle, U.; Martí-Bonmatí, L.

2018-03-01

In lung cancer, quantification by positron emission tomography/computed tomography (PET/CT) imaging presents challenges due to respiratory movement. Our primary aim was to study the impact of motion compensation implied by retrospectively gated (4D)-PET/CT on the variability of PET quantitative parameters. Its significance was evaluated by comparison with the variability due to (i) the voxel size in image reconstruction and (ii) the voxel size in image post-resampling. The method employed for feature extraction was chosen based on the analysis of (i) the effect of discretization of the standardized uptake value (SUV) on complementarity between texture features (TF) and conventional indices, (ii) the impact of the segmentation method on the variability of image features, and (iii) the variability of image features across the time-frame of 4D-PET. Thirty-one PET-features were involved. Three SUV discretization methods were applied: a constant width (SUV resolution) of the resampling bin (method RW), a constant number of bins (method RN) and RN on the image obtained after histogram equalization (method EqRN). The segmentation approaches evaluated were 40% of SUVmax and the contrast oriented algorithm (COA). Parameters derived from 4D-PET images were compared with values derived from the PET image obtained for (i) the static protocol used in our clinical routine (3D) and (ii) the 3D image post-resampled to the voxel size of the 4D image and PET image derived after modifying the reconstruction of the 3D image to comprise the voxel size of the 4D image. Results showed that TF complementarity with conventional indices was sensitive to the SUV discretization method. In the comparison of COA and 40% contours, despite the values not being interchangeable, all image features showed strong linear correlations (r  >  0.91, p\\ll 0.001 ). Across the time-frames of 4D-PET, all image features followed a normal distribution in most patients. For our patient cohort, the compensation of tumor motion did not have a significant impact on the quantitative PET parameters. The variability of PET parameters due to voxel size in image reconstruction was more significant than variability due to voxel size in image post-resampling. In conclusion, most of the parameters (apart from the contrast of neighborhood matrix) were robust to the motion compensation implied by 4D-PET/CT. The impact on parameter variability due to the voxel size in image reconstruction and in image post-resampling could not be assumed to be equivalent.

Discrete subgroups of adolescents diagnosed with borderline personality disorder: a latent class analysis of personality features.

PubMed

Ramos, Vera; Canta, Guilherme; de Castro, Filipa; Leal, Isabel

2014-08-01

Research suggests that borderline personality disorder (BPD) can be diagnosed in adolescents and is marked by considerable heterogeneity. This study aimed to identify personality features characterizing adolescents with BPD and possible meaningful patterns of heterogeneity that could lead to personality subgroups. The authors analyzed data on 60 adolescents, ages 15 to 18 years, who met DSM criteria for a BPD diagnosis. The authors used latent class analysis (LCA) to identify subgroups based on the personality pattern scales from the Millon Adolescent Clinical Inventory (MACI). LCA indicated that the best-fitting solution was a two-class model, identifying two discrete subgroups of BPD adolescents that were described as internalizing and externalizing. The subgroups were then compared on clinical and sociodemographic variables, measures of personality dimensions, DSM BPD criteria, and perception of attachment styles. Adolescents with a BPD diagnosis constitute a heterogeneous group and vary meaningfully on personality features that can have clinical implications for treatment.

Clinical state assessment in bipolar patients by means of HRV features obtained with a sensorized T-shirt.

PubMed

Mariani, Sara; Migliorini, Matteo; Tacchino, Giulia; Gentili, Claudio; Bertschy, Gilles; Werner, Sandra; Bianchi, Anna M

2012-01-01

The aim of this study is to identify parameters extracted from the Heart Rate Variability (HRV) signal that correlate to the clinical state in patients affected by bipolar disorder. 25 ECG and activity recordings from 12 patients were obtained by means of a sensorized T-shirt and the clinical state of the subjects was assessed by a psychiatrist. Features in the time and frequency domain were extracted from each signal. HRV features were also used to automatically compute the sleep profile of each subject by means of an Artificial Neural Network, trained on a control group of healthy subjects. From the hypnograms, sleep-specific parameters were computed. All the parameters were compared with those computed on the control group, in order to highlight significant differences in their values during different stages of the pathology. The analysis was performed by grouping the subjects first on the basis of the depression-mania level and then on the basis of the anxiety level.

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

Cytokines Synergize to Combat Metastatic Neuroblastoma | Center for Cancer Research

Cancer.gov

Neuroblastoma is the most common extracranial solid tumor in children, and clinical outcomes of patients with this disease are quite variable. Prognosis is particularly poor for patients with high-risk tumors (classification based on patients’ age, extent of disease spread, and other biological features).

Machine Learning Approach for Classifying Multiple Sclerosis Courses by Combining Clinical Data with Lesion Loads and Magnetic Resonance Metabolic Features.

PubMed

Ion-Mărgineanu, Adrian; Kocevar, Gabriel; Stamile, Claudio; Sima, Diana M; Durand-Dubief, Françoise; Van Huffel, Sabine; Sappey-Marinier, Dominique

2017-01-01

Purpose: The purpose of this study is classifying multiple sclerosis (MS) patients in the four clinical forms as defined by the McDonald criteria using machine learning algorithms trained on clinical data combined with lesion loads and magnetic resonance metabolic features. Materials and Methods: Eighty-seven MS patients [12 Clinically Isolated Syndrome (CIS), 30 Relapse Remitting (RR), 17 Primary Progressive (PP), and 28 Secondary Progressive (SP)] and 18 healthy controls were included in this study. Longitudinal data available for each MS patient included clinical (e.g., age, disease duration, Expanded Disability Status Scale), conventional magnetic resonance imaging and spectroscopic imaging. We extract N -acetyl-aspartate (NAA), Choline (Cho), and Creatine (Cre) concentrations, and we compute three features for each spectroscopic grid by averaging metabolite ratios (NAA/Cho, NAA/Cre, Cho/Cre) over good quality voxels. We built linear mixed-effects models to test for statistically significant differences between MS forms. We test nine binary classification tasks on clinical data, lesion loads, and metabolic features, using a leave-one-patient-out cross-validation method based on 100 random patient-based bootstrap selections. We compute F1-scores and BAR values after tuning Linear Discriminant Analysis (LDA), Support Vector Machines with gaussian kernel (SVM-rbf), and Random Forests. Results: Statistically significant differences were found between the disease starting points of each MS form using four different response variables: Lesion Load, NAA/Cre, NAA/Cho, and Cho/Cre ratios. Training SVM-rbf on clinical and lesion loads yields F1-scores of 71-72% for CIS vs. RR and CIS vs. RR+SP, respectively. For RR vs. PP we obtained good classification results (maximum F1-score of 85%) after training LDA on clinical and metabolic features, while for RR vs. SP we obtained slightly higher classification results (maximum F1-score of 87%) after training LDA and SVM-rbf on clinical, lesion loads and metabolic features. Conclusions: Our results suggest that metabolic features are better at differentiating between relapsing-remitting and primary progressive forms, while lesion loads are better at differentiating between relapsing-remitting and secondary progressive forms. Therefore, combining clinical data with magnetic resonance lesion loads and metabolic features can improve the discrimination between relapsing-remitting and progressive forms.

Pediatric schwannomatosis, a rare but distinct form of neurofibromatosis.

PubMed

Thomas, Anna K; Egelhoff, John C; Curran, John G; Thomas, Bobby

2016-03-01

Schwannomatosis is the third major form of neurofibromatosis, distinct from neurofibromatosis type 2 (NF2) and type 1 (NF1). This condition is rare with a variable phenotypic presentation and complex molecular and genetic findings. In this case, a previously healthy teenager was found to have multiple spinal lesions and an enhancing right parotid mass on MRI. On extensive further work-up, this patient met the existing clinical criteria for schwannomatosis. This case report aims to review the clinical features and current diagnostic criteria for schwannomatosis and compare it to NF1 and NF2. Special emphasis will be placed on imaging features that should prompt the radiologist to suggest this rare diagnosis.

The motor and cognitive features of Parkinson's disease in patients with concurrent Gaucher disease over 2 years: a case series.

PubMed

Collins, Lucy M; Williams-Gray, Caroline H; Morris, Elizabeth; Deegan, Patrick; Cox, Timothy M; Barker, Roger A

2018-05-29

We report the cognitive features and progression of Parkinson's disease (PD) in five patients with concurrent Gaucher disease. The patients presented at an earlier age than patients with sporadic PD, as previously noted by others; but in contrast to many previous reports, our patients followed a variable clinical course. While two patients developed early cognitive deficits and dementia, three others remained cognitively intact over the follow-up period. Thus, in this small case series, PD in the context of GD more closely resembles idiopathic PD in terms of its clinical heterogeneity in contrast to PD associated with GBA heterozygote mutations.

Gastric adenocarcinoma in common variable immunodeficiency: features of cancer and associated gastritis may be characteristic of the condition.

PubMed

De Petris, Giovanni; Dhungel, Bal M; Chen, Longwen; Chang, Yu-Hui H

2014-10-01

Common variable immunodeficiency (CVID) is associated with an increased risk of gastric cancer. The aim of the study was to determine the morphological features of CVID-associated gastric adenocarcinoma (CAGA) and of the background gastritis. The population of gastric cancer patients with CVID of Mayo Clinic in the period 2000-2010 was studied; 6 cases of CVID (2 males, 4 females, average age 47 years, age range 26-71 years) were found in 5793 patients with gastric cancer in the study period. Each patient underwent gastric resection for which histology slides were reviewed. Chronic gastritis variables, CVID-related findings, and features of the adenocarcinoma were recorded. CAGA was of intestinal type, with high number of intratumoral lymphocytes (ITLs). Cancer was diagnosed in younger patients than in the overall population of gastric cancer. Severe atrophic metaplastic pangastritis with extensive dysplasia was present in the background in 4 cases, with features of lymphocytic gastritis in 2 cases. Features of CVID (plasma cells paucity in 4 of 6 cases, lymphoid nodules prominent in four cases) could be detected. In summary, gastric adenocarcinoma at young age with ITLs, accompanied by atrophic metaplastic pangastritis, should alert the pathologist of the possibility of CAGA. It follows that, in presence of those characteristics, the search of CVID-associated abnormalities should be undertaken in the nonneoplastic tissues. © The Author(s) 2014.

Clinical characteristics and medication use patterns among hospitalized patients admitted with psychotic vs nonpsychotic major depressive disorder.

PubMed

Gaudiano, Brandon A; Weinstock, Lauren M; Epstein-Lubow, Gary; Uebelacker, Lisa A; Miller, Ivan W

2016-02-01

In routine practice, major depressive disorder (MDD) with psychotic features often goes under-recognized and undertreated. Previous research has specified several demographic and clinical differences in MDD patients with psychotic features compared with those without psychosis in routine outpatient practice, but there is little systematic research in modern routine hospital settings. We conducted a retrospective electronic medical records chart review of 1,314 patients diagnosed with MDD who were admitted consecutively to a major psychiatric hospital over a 1-year period. We examined the prevalence of psychotic features in the sample and investigated the differences in demographic variables, clinical characteristics, and medication use patterns among patients with and without psychosis. The prevalence of psychotic features was 13.2% in the current hospital sample. Patients with psychotic depression were more likely to be older, male, a member of a racial/ethnic minority, and have more medical comorbidities and certain Axis I disorders compared with nonpsychotic patients. In addition, patients with psychotic depression were more likely to be prescribed antipsychotics and hypnotics before admission. Several demographic and clinical characteristics differentiate MDD patients with psychosis from those without psychosis in hospital settings that may be helpful in identifying these patients. Comparisons with outpatient samples and treatments implications are discussed.

Noonan syndrome and clinically related disorders

PubMed Central

Tartaglia, Marco; Gelb, Bruce D.; Zenker, Martin

2010-01-01

Noonan syndrome is a relatively common, clinically variable developmental disorder. Cardinal features include postnatally reduced growth, distinctive facial dysmorphism, congenital heart defects and hypertrophic cardiomyopathy, variable cognitive deficit and skeletal, ectodermal and hematologic anomalies. Noonan syndrome is transmitted as an autosomal dominant trait, and is genetically heterogeneous. So far, heterozygous mutations in nine genes (PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 and CBL) have been documented to underlie this disorder or clinically related phenotypes. Based on these recent discoveries, the diagnosis can now be confirmed molecularly in approximately 75% of affected individuals. Affected genes encode for proteins participating in the RAS-mitogen-activated protein kinases (MAPK) signal transduction pathway, which is implicated in several developmental processes controlling morphology determination, organogenesis, synaptic plasticity and growth. Here, we provide an overview of clinical aspects of this disorder and closely related conditions, the molecular mechanisms underlying pathogenesis, and major genotype-phenotype correlations. PMID:21396583

A diagnostic model for chronic hypersensitivity pneumonitis

PubMed Central

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2017-01-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature.

PubMed

Tadiotto, Elisa; Maines, Evelina; Degani, Daniela; Balter, Rita; Bordugo, Andrea; Cesaro, Simone

2018-04-01

Pearson syndrome (PS) is a rare mitochondrial disorder that usually presents with transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction, and lactic acidosis. Typical bone marrow (BM) features are vacuolization in hematopoietic progenitors, hypocellularity, and ringed sideroblasts. At the neonatal age, PS may have a variable clinical onset. Moreover, there is little information about BM features at this age and the timing of their presentation. We report a neonatal case of PS that presented with refractory anemia and atypical BM features. We reviewed the BM findings in neonatal-onset PS cases to stress the importance and limitations of BM evaluation at this age. © 2017 Wiley Periodicals, Inc.

Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

ERIC Educational Resources Information Center

Ouvrier, Robert; Grew, Simon

2010-01-01

Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

Immunopathology in Taenia solium neurocysticercosis.

PubMed

Fleury, A; Cardenas, G; Adalid-Peralta, L; Fragoso, G; Sciutto, E

2016-03-01

Neurocysticercosis is a clinically and radiologically heterogeneous disease, ranging from asymptomatic infection to a severe, potentially fatal clinical picture. The intensity and extension of the parasite-elicited inflammatory reaction is a key factor for such variability. The main features of the inflammatory process found in the brain and in the peripheral blood of neurocysticercosis patients will be discussed in this review, and the factors involved in its modulation will be herein presented. © 2015 John Wiley & Sons Ltd.

White matter involvement in a family with a novel PDGFB mutation.

PubMed

Biancheri, Roberta; Severino, Mariasavina; Robbiano, Angela; Iacomino, Michele; Del Sette, Massimo; Minetti, Carlo; Cervasio, Mariarosaria; Del Basso De Caro, Marialaura; Striano, Pasquale; Zara, Federico

2016-06-01

Primary familial brain calcification (PFBC) (formerly idiopathic basal ganglia calcification; Fahr disease) is an autosomal dominant cerebral microvascular calcifying disorder with variable clinical and imaging features.(1) Four causative genes have been identified: SLC20A2,(2) PDGFRB,(3) PDGFB,(4) and XPR1.(5).

Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review.

PubMed

Wain, Karen E; Ellingson, Marissa S; McDonald, Jamie; Gammon, Amanda; Roberts, Maegan; Pichurin, Pavel; Winship, Ingrid; Riegert-Johnson, Douglas L; Weitzel, Jeffrey N; Lindor, Noralane M

2014-08-01

Heterozygous loss-of-function SMAD4 mutations are associated with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia. Some carriers exhibit symptoms of both conditions, leading to juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome. Three families have been reported with connective tissue abnormalities. To better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent of the patients (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n = 3), aortic and mitral insufficiency (n = 2), aortic dissection (n = 1), retinal detachment (n = 1), brain aneurysms (n = 1), and lax skin and joints (n = 1). Juvenile polyposis-specific findings were almost uniformly present but variable. Ninety-seven percent of the patients had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent of the patients (15/31) had extensive gastric polyposis. Hereditary hemorrhagic telangiectasia features, including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (6/16, 38%), brain arteriovenous malformation (1/26, 4%), pulmonary arteriovenous malformation (9/17, 53%), and intrapulmonary shunting (14/23, 61%), were documented in 76% of the patients. SMAD4 carriers should be managed for juvenile polyposis and hereditary hemorrhagic telangiectasia because symptoms of both conditions are likely yet unpredictable. Connective tissue abnormalities are an emerging component of juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome, and larger studies are needed to understand these manifestations.

Features of Heart Rate Variability Capture Regulatory Changes During Kangaroo Care in Preterm Infants.

PubMed

Kommers, Deedee R; Joshi, Rohan; van Pul, Carola; Atallah, Louis; Feijs, Loe; Oei, Guid; Bambang Oetomo, Sidarto; Andriessen, Peter

2017-03-01

To determine whether heart rate variability (HRV) can serve as a surrogate measure to track regulatory changes during kangaroo care, a period of parental coregulation distinct from regulation within the incubator. Nurses annotated the starting and ending times of kangaroo care for 3 months. The pre-kangaroo care, during-kangaroo care, and post-kangaroo care data were retrieved in infants with at least 10 accurately annotated kangaroo care sessions. Eight HRV features (5 in the time domain and 3 in the frequency domain) were used to visually and statistically compare the pre-kangaroo care and during-kangaroo care periods. Two of these features, capturing the percentage of heart rate decelerations and the extent of heart rate decelerations, were newly developed for preterm infants. A total of 191 kangaroo care sessions were investigated in 11 preterm infants. Despite clinically irrelevant changes in vital signs, 6 of the 8 HRV features (SD of normal-to-normal intervals, root mean square of the SD, percentage of consecutive normal-to-normal intervals that differ by >50 ms, SD of heart rate decelerations, high-frequency power, and low-frequency/high-frequency ratio) showed a visible and statistically significant difference (P <.01) between stable periods of kangaroo care and pre-kangaroo care. HRV was reduced during kangaroo care owing to a decrease in the extent of transient heart rate decelerations. HRV-based features may be clinically useful for capturing the dynamic changes in autonomic regulation in response to kangaroo care and other changes in environment and state. Copyright © 2016 Elsevier Inc. All rights reserved.

Dental, dermatological and radiographic findings in a case of Gorlin-Goltz Syndrome: report and review.

PubMed

Nilesh, Kumar; Tewary, Shivsagar; Zope, Sameer; Patel, Jinesh; Vande, Aaditee

2017-01-01

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. Thus a multidisciplinary approach is required for its prompt clinical diagnosis and management of this condition. This paper highlights a case of GGS presenting in a young male patient with cranial, facial, dermatological, dental and skeletal involvement. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. A review of the diagnostic criteria is also presented.

Dental, dermatological and radiographic findings in a case of Gorlin-Goltz Syndrome: report and review

PubMed Central

Nilesh, Kumar; Tewary, Shivsagar; Zope, Sameer; Patel, Jinesh; Vande, Aaditee

2017-01-01

Gorlin-Goltz syndrome (GGS) is a rare autosomal dominant disorder. The disease shows multiple organ involvement with variable clinical presentation. Thus a multidisciplinary approach is required for its prompt clinical diagnosis and management of this condition. This paper highlights a case of GGS presenting in a young male patient with cranial, facial, dermatological, dental and skeletal involvement. The diagnosis of the syndrome was based on its clinical presentation, radiological features and histopathological findings. A review of the diagnostic criteria is also presented. PMID:28819517

Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

PubMed

Tüysüz, Beyhan; Collin, Anna; Arapoğlu, Müjde; Suyugül, Nezir

2009-10-01

Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4.

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.

Clinical Geneticists’ Views of VACTERL/VATER Association

PubMed Central

Solomon, Benjamin D.; Bear, Kelly A.; Kimonis, Virginia; de Klein, Annelies; Scott, Daryl A.; Shaw-Smith, Charles; Tibboel, Dick; Reutter, Heiko; Giampietro, Philip F.

2012-01-01

VACTERL association (sometimes termed “VATER association” depending on which component features are included) is typically defined by the presence of at least three of the following congenital malformations, which tend to statistically co-occur in affected individuals: Vertebral anomalies, Anal atresia, Cardiac malformations, Tracheo-Esophageal fistula, Renal anomalies, and Limb abnormalities. Although the clinical criteria for VACTERL association may appear to be straightforward, there is wide variability in the way clinical geneticists define the disorder and the genetic testing strategy they use when confronted with an affected patient. In order to describe this variability and determine the most commonly used definitions and testing modalities, we present the results of survey responses by 121 clinical geneticists. We discuss the results of the survey responses, provide a literature review and commentary from a group of physicians who are currently involved in clinical and laboratory-based research on VACTERL association, and offer an algorithm for genetic testing in patients with this association. PMID:23165726

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

PubMed Central

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

2015-01-01

Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

PubMed

Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

2015-08-01

Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

Identification of five chronic obstructive pulmonary disease subgroups with different prognoses in the ECLIPSE cohort using cluster analysis.

PubMed

Rennard, Stephen I; Locantore, Nicholas; Delafont, Bruno; Tal-Singer, Ruth; Silverman, Edwin K; Vestbo, Jørgen; Miller, Bruce E; Bakke, Per; Celli, Bartolomé; Calverley, Peter M A; Coxson, Harvey; Crim, Courtney; Edwards, Lisa D; Lomas, David A; MacNee, William; Wouters, Emiel F M; Yates, Julie C; Coca, Ignacio; Agustí, Alvar

2015-03-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that likely includes clinically relevant subgroups. To identify subgroups of COPD in ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) subjects using cluster analysis and to assess clinically meaningful outcomes of the clusters during 3 years of longitudinal follow-up. Factor analysis was used to reduce 41 variables determined at recruitment in 2,164 patients with COPD to 13 main factors, and the variables with the highest loading were used for cluster analysis. Clusters were evaluated for their relationship with clinically meaningful outcomes during 3 years of follow-up. The relationships among clinical parameters were evaluated within clusters. Five subgroups were distinguished using cross-sectional clinical features. These groups differed regarding outcomes. Cluster A included patients with milder disease and had fewer deaths and hospitalizations. Cluster B had less systemic inflammation at baseline but had notable changes in health status and emphysema extent. Cluster C had many comorbidities, evidence of systemic inflammation, and the highest mortality. Cluster D had low FEV1, severe emphysema, and the highest exacerbation and COPD hospitalization rate. Cluster E was intermediate for most variables and may represent a mixed group that includes further clusters. The relationships among clinical variables within clusters differed from that in the entire COPD population. Cluster analysis using baseline data in ECLIPSE identified five COPD subgroups that differ in outcomes and inflammatory biomarkers and show different relationships between clinical parameters, suggesting the clusters represent clinically and biologically different subtypes of COPD.

An exploratory study of clinical measures associated with subsyndromal pathological gambling in patients with binge eating disorder.

PubMed

Yip, Sarah W; White, Marney A; Grilo, Carlos M; Potenza, Marc N

2011-06-01

Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.

Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

PubMed

Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

2017-01-01

Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (<4000, 4001-7000 and >7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (<2 and ≥2 mg/dL), serum glutamic oxaloacetic transaminase (>200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Clinical, radiological, and physiological differences between obliterative bronchiolitis and problematic severe asthma in adolescents and young adults: the early origins of the overlap syndrome?

PubMed

Bandeira, Teresa; Negreiro, Filipa; Ferreira, Rosário; Salgueiro, Marisa; Lobo, Luísa; Aguiar, Pedro; Trindade, J C

2011-06-01

Few reports have compared chronic obstructive lung diseases (OLDs) starting in childhood. To describe functional, radiological, and biological features of obliterative bronchiolitis (OB) and further discriminate to problematic severe asthma (PSA) or to diagnose a group with overlapping features. Patients with OB showed a greater degree of obstructive lung defect and higher hyperinflation (P < 0.001). The most frequent high-resolution computed tomography (HRCT) features (increased lung volume, inspiratory decreased attenuation, mosaic pattern, and expiratory air trapping) showed significantly greater scores in OB patients. Patients with PSA have shown a higher frequency of atopy (P < 0.05). ROC curve analysis demonstrated discriminative power for the LF variables, HRCT findings and for atopy between diagnoses. Further analysis released five final variables more accurate for the identification of a third diagnostic group (FVC%t, post-bronchodilator ΔFEV(1) in ml, HRCT mosaic pattern, SPT, and D. pteronyssinus-specific IgE). We found that OB and PSA possess identifiable characteristic features but overlapping values may turn them undistinguishable. Copyright © 2011 Wiley-Liss, Inc.

Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype.

PubMed

Tatton-Brown, Katrina; Murray, Anne; Hanks, Sandra; Douglas, Jenny; Armstrong, Ruth; Banka, Siddharth; Bird, Lynne M; Clericuzio, Carol L; Cormier-Daire, Valerie; Cushing, Tom; Flinter, Frances; Jacquemont, Marie-Line; Joss, Shelagh; Kinning, Esther; Lynch, Sally Ann; Magee, Alex; McConnell, Vivienne; Medeira, Ana; Ozono, Keiichi; Patton, Michael; Rankin, Julia; Shears, Debbie; Simon, Marleen; Splitt, Miranda; Strenger, Volker; Stuurman, Kyra; Taylor, Clare; Titheradge, Hannah; Van Maldergem, Lionel; Temple, I Karen; Cole, Trevor; Seal, Sheila; Rahman, Nazneen

2013-12-01

Weaver syndrome, first described in 1974, is characterized by tall stature, a typical facial appearance, and variable intellectual disability. In 2011, mutations in the histone methyltransferase, EZH2, were shown to cause Weaver syndrome. To date, we have identified 48 individuals with EZH2 mutations. The mutations were primarily missense mutations occurring throughout the gene, with some clustering in the SET domain (12/48). Truncating mutations were uncommon (4/48) and only identified in the final exon, after the SET domain. Through analyses of clinical data and facial photographs of EZH2 mutation-positive individuals, we have shown that the facial features can be subtle and the clinical diagnosis of Weaver syndrome is thus challenging, especially in older individuals. However, tall stature is very common, reported in >90% of affected individuals. Intellectual disability is also common, present in ~80%, but is highly variable and frequently mild. Additional clinical features which may help in stratifying individuals to EZH2 mutation testing include camptodactyly, soft, doughy skin, umbilical hernia, and a low, hoarse cry. Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes. As mutation testing becomes increasingly accessible and larger numbers of EZH2 mutation-positive individuals are identified, knowledge of the clinical spectrum and prognostic implications of EZH2 mutations should improve. © 2013 Wiley Periodicals, Inc.

Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

PubMed

Yu, Run; Jih, Lily; Zhai, Jing; Nissen, Nicholas N; Colquhoun, Steven; Wolin, Edward; Dhall, Deepti

2013-04-01

The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Five patients were identified. The median age at presentation was 74 years (range, 59-89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9-16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-04-01

To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.

The antigenic evolution of influenza: drift or thrift?

PubMed Central

Wikramaratna, Paul S.; Sandeman, Michi; Recker, Mario; Gupta, Sunetra

2013-01-01

It is commonly assumed that antibody responses against the influenza virus are polarized in the following manner: strong antibody responses are directed at highly variable antigenic epitopes, which consequently undergo ‘antigenic drift’, while weak antibody responses develop against conserved epitopes. As the highly variable epitopes are in a constant state of flux, current antibody-based vaccine strategies are focused on the conserved epitopes in the expectation that they will provide some level of clinical protection after appropriate boosting. Here, we use a theoretical model to suggest the existence of epitopes of low variability, which elicit a high degree of both clinical and transmission-blocking immunity. We show that several epidemiological features of influenza and its serological and molecular profiles are consistent with this model of ‘antigenic thrift’, and that identifying the protective epitopes of low variability predicted by this model could offer a more viable alternative to regularly update the influenza vaccine than exploiting responses to weakly immunogenic conserved regions. PMID:23382423

Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

PubMed

Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

2017-10-01

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

Predicting Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer with Textural Features Derived from Pretreatment 18F-FDG PET/CT Imaging.

PubMed

Beukinga, Roelof J; Hulshoff, Jan B; van Dijk, Lisanne V; Muijs, Christina T; Burgerhof, Johannes G M; Kats-Ugurlu, Gursah; Slart, Riemer H J A; Slump, Cornelis H; Mul, Véronique E M; Plukker, John Th M

2017-05-01

Adequate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (EC) patients is important in a more personalized treatment. The current best clinical method to predict pathologic complete response is SUV max in 18 F-FDG PET/CT imaging. To improve the prediction of response, we constructed a model to predict complete response to nCRT in EC based on pretreatment clinical parameters and 18 F-FDG PET/CT-derived textural features. Methods: From a prospectively maintained single-institution database, we reviewed 97 consecutive patients with locally advanced EC and a pretreatment 18 F-FDG PET/CT scan between 2009 and 2015. All patients were treated with nCRT (carboplatin/paclitaxel/41.4 Gy) followed by esophagectomy. We analyzed clinical, geometric, and pretreatment textural features extracted from both 18 F-FDG PET and CT. The current most accurate prediction model with SUV max as a predictor variable was compared with 6 different response prediction models constructed using least absolute shrinkage and selection operator regularized logistic regression. Internal validation was performed to estimate the model's performances. Pathologic response was defined as complete versus incomplete response (Mandard tumor regression grade system 1 vs. 2-5). Results: Pathologic examination revealed 19 (19.6%) complete and 78 (80.4%) incomplete responders. Least absolute shrinkage and selection operator regularization selected the clinical parameters: histologic type and clinical T stage, the 18 F-FDG PET-derived textural feature long run low gray level emphasis, and the CT-derived textural feature run percentage. Introducing these variables to a logistic regression analysis showed areas under the receiver-operating-characteristic curve (AUCs) of 0.78 compared with 0.58 in the SUV max model. The discrimination slopes were 0.17 compared with 0.01, respectively. After internal validation, the AUCs decreased to 0.74 and 0.54, respectively. Conclusion: The predictive values of the constructed models were superior to the standard method (SUV max ). These results can be considered as an initial step in predicting tumor response to nCRT in locally advanced EC. Further research in refining the predictive value of these models is needed to justify omission of surgery. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Sacro-anterior haemangiopericytoma: a case report

PubMed Central

Ge, Xiu-Hong; Liu, Shuai-Shuai; Shan, Hu-Sheng; Wang, Zhi-Min; Li, Qian-Wen

2014-01-01

Haemangiopericytoma (HPC) is a rare vascular tumor with borderline malignancy, considerable histological variability, and unpredictable clinical and biological behavior. HPC can present a diagnostic challenge because of its indeterminate clinical, radiological, and pathological features. HPC generally presents in adulthood and is equally frequent in both sexes. HPC can arise in any site in the body as a slowly growing and painless mass. The precise cell type origin of HPC is uncertain. One third of HPCs occur in the head and neck areas. Exceptional cases of hemangioblastoma arising outside the head and neck areas have been reported, but little is known about their clinicopathologic and immunohistochemical features. This study reports on a case of a large sacro-anterior HPC in a 65-year-old male. PMID:25009757

The variable presentations and broadening geographic distribution of hepatic fascioliasis.

PubMed

Rowan, Sarah E; Levi, Marilyn E; Youngwerth, Jean M; Brauer, Brian; Everson, Gregory T; Johnson, Steven C

2012-06-01

We report 2 unrelated cases of hepatic fascioliasis in travelers returning to the United States from Africa and the Middle East. The first case presented with acute infection. Prominent clinical features included abdominal pain, elevated liver transaminases, serpiginous hepatic lesions, pericapsular hematoma, and marked peripheral eosinophilia. The second case was diagnosed in the chronic stage of infection and presented with right upper quadrant abdominal pain, cystic hepatic lesions, and an adult fluke in the common bile duct. We review the life cycle of Fasciola species, the corresponding clinical features during the stages of human infection, diagnostic methods, and the evolving understanding of the epidemiology of human fascioliasis, particularly emphasizing fascioliasis in African countries. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Detection and evaluation of ventricular repolarization alternans: an approach to combined ECG, thoracic impedance, and beat-to-beat heart rate variability analysis.

PubMed

Kriščiukaitis, Algimantas; Šimoliūnienė, Renata; Macas, Andrius; Petrolis, Robertas; Drėgūnas, Kęstutis; Bakšytė, Giedrė; Pieteris, Linas; Bertašienė, Zita; Žaliūnas, Remigijus

2014-01-01

Beat-to-beat alteration in ventricles repolarization reflected by alternans of amplitude and/or shape of ECG S-T,T segment (TWA) is known as phenomena related with risk of severe arrhythmias leading to sudden cardiac death. Technical difficulties have caused limited its usage in clinical diagnostics. Possibilities to register and analyze multimodal signals reflecting heart activity inspired search for new technical solutions. First objective of this study was to test whether thoracic impedance signal and beat-to-beat heart rate reflect repolarization alternans detected as TWA. The second objective was revelation of multimodal signal features more comprehensively representing the phenomena and increasing its prognostic usefulness. ECG, and thoracic impedance signal recordings made during 24h follow-up of the patients hospitalized in acute phase of myocardial infarction were used for investigation. Signal morphology variations reflecting estimates were obtained by the principal component analysis-based method. Clinical outcomes of patients (survival and/or rehospitalization in 6 and 12 months) were compared to repolarization alternans and heart rate variability estimates. Repolarization alternans detected as TWA was also reflected in estimates of thoracic impedance signal shape and variation in beat-to-beat heart rate. All these parameters showed correlation with clinical outcomes of patients. The strongest significant correlation showed magnitude of alternans in estimates of thoracic impedance signal shape. The features of ECG, thoracic impedance signal and beat-to-beat variability of heart rate, give comprehensive estimates of repolarization alternans, which correlate, with clinical outcomes of the patients and we recommend using them to improve diagnostic reliability. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Could texture features from preoperative CT image be used for predicting occult peritoneal carcinomatosis in patients with advanced gastric cancer?

PubMed

Kim, Hae Young; Kim, Young Hoon; Yun, Gabin; Chang, Won; Lee, Yoon Jin; Kim, Bohyoung

2018-01-01

To retrospectively investigate whether texture features obtained from preoperative CT images of advanced gastric cancer (AGC) patients could be used for the prediction of occult peritoneal carcinomatosis (PC) detected during operation. 51 AGC patients with occult PC detected during operation from January 2009 to December 2012 were included as occult PC group. For the control group, other 51 AGC patients without evidence of distant metastasis including PC, and whose clinical T and N stage could be matched to those of the patients of the occult PC group, were selected from the period of January 2011 to July 2012. Each group was divided into test (n = 41) and validation cohort (n = 10). Demographic and clinical data of these patients were acquired from the hospital database. Texture features including average, standard deviation, kurtosis, skewness, entropy, correlation, and contrast were obtained from manually drawn region of interest (ROI) over the omentum on the axial CT image showing the omentum at its largest cross sectional area. After using Fisher's exact and Wilcoxon signed-rank test for comparison of the clinical and texture features between the two groups of the test cohort, conditional logistic regression analysis was performed to determine significant independent predictor for occult PC. Using the optimal cut-off value from receiver operating characteristic (ROC) analysis for the significant variables, diagnostic sensitivity and specificity were determined in the test cohort. The cut-off value of the significant variables obtained from the test cohort was then applied to the validation cohort. Bonferroni correction was used to adjust P value for multiple comparisons. Between the two groups, there was no significant difference in the clinical features. Regarding the texture features, the occult PC group showed significantly higher average, entropy, standard deviation, and significantly lower correlation (P value < 0.004 for all). Conditional logistic regression analysis demonstrated that entropy was significant independent predictor for occult PC. When the cut-off value of entropy (> 7.141) was applied to the validation cohort, sensitivity and specificity for the prediction of occult PC were 80% and 90%, respectively. For AGC patients whose PC cannot be detected with routine imaging such as CT, texture analysis may be a useful adjunct for the prediction of occult PC.

Effects of non-neuronal components for functional connectivity analysis from resting-state functional MRI toward automated diagnosis of schizophrenia

NASA Astrophysics Data System (ADS)

Kim, Junghoe; Lee, Jong-Hwan

2014-03-01

A functional connectivity (FC) analysis from resting-state functional MRI (rsfMRI) is gaining its popularity toward the clinical application such as diagnosis of neuropsychiatric disease. To delineate the brain networks from rsfMRI data, non-neuronal components including head motions and physiological artifacts mainly observed in cerebrospinal fluid (CSF), white matter (WM) along with a global brain signal have been regarded as nuisance variables in calculating the FC level. However, it is still unclear how the non-neuronal components can affect the performance toward diagnosis of neuropsychiatric disease. In this study, a systematic comparison of classification performance of schizophrenia patients was provided employing the partial correlation coefficients (CCs) as feature elements. Pair-wise partial CCs were calculated between brain regions, in which six combinatorial sets of nuisance variables were considered. The partial CCs were used as candidate feature elements followed by feature selection based on the statistical significance test between two groups in the training set. Once a linear support vector machine was trained using the selected features from the training set, the classification performance was evaluated using the features from the test set (i.e. leaveone- out cross validation scheme). From the results, the error rate using all non-neuronal components as nuisance variables (12.4%) was significantly lower than those using remaining combination of non-neuronal components as nuisance variables (13.8 ~ 20.0%). In conclusion, the non-neuronal components substantially degraded the automated diagnosis performance, which supports our hypothesis that the non-neuronal components are crucial in controlling the automated diagnosis performance of the neuropsychiatric disease using an fMRI modality.

Impact of Reconstruction Algorithms on CT Radiomic Features of Pulmonary Tumors: Analysis of Intra- and Inter-Reader Variability and Inter-Reconstruction Algorithm Variability.

PubMed

Kim, Hyungjin; Park, Chang Min; Lee, Myunghee; Park, Sang Joon; Song, Yong Sub; Lee, Jong Hyuk; Hwang, Eui Jin; Goo, Jin Mo

2016-01-01

To identify the impact of reconstruction algorithms on CT radiomic features of pulmonary tumors and to reveal and compare the intra- and inter-reader and inter-reconstruction algorithm variability of each feature. Forty-two patients (M:F = 19:23; mean age, 60.43±10.56 years) with 42 pulmonary tumors (22.56±8.51mm) underwent contrast-enhanced CT scans, which were reconstructed with filtered back projection and commercial iterative reconstruction algorithm (level 3 and 5). Two readers independently segmented the whole tumor volume. Fifteen radiomic features were extracted and compared among reconstruction algorithms. Intra- and inter-reader variability and inter-reconstruction algorithm variability were calculated using coefficients of variation (CVs) and then compared. Among the 15 features, 5 first-order tumor intensity features and 4 gray level co-occurrence matrix (GLCM)-based features showed significant differences (p<0.05) among reconstruction algorithms. As for the variability, effective diameter, sphericity, entropy, and GLCM entropy were the most robust features (CV≤5%). Inter-reader variability was larger than intra-reader or inter-reconstruction algorithm variability in 9 features. However, for entropy, homogeneity, and 4 GLCM-based features, inter-reconstruction algorithm variability was significantly greater than inter-reader variability (p<0.013). Most of the radiomic features were significantly affected by the reconstruction algorithms. Inter-reconstruction algorithm variability was greater than inter-reader variability for entropy, homogeneity, and GLCM-based features.

1.5Mb deletion of chromosome 4p16.3 associated with postnatal growth delay, psychomotor impairment, epilepsy, impulsive behavior and asynchronous skeletal development.

PubMed

Misceo, D; Barøy, T; Helle, J R; Braaten, O; Fannemel, M; Frengen, E

2012-10-01

Several Wolf-Hirschhorn syndrome patients have been studied, mouse models for a few candidate genes have been constructed and two WHS critical regions have been postulated, but the molecular basis of the syndrome remains poorly understood. Single gene contributions to phenotypes of microdeletion syndromes have often been based on the study of patients carrying small, atypical deletions. We report a 5-year-old girl harboring an atypical 1.5Mb del4p16.3 and review seven previously published patients carrying a similar deletion. They show a variable clinical presentation and the only consistent feature is post-natal growth delay. However, four of eight patients carry a ring (4), and ring chromosomes in general are associated with growth deficiency. The Greek helmet profile is absent, although a trend towards common dysmorphic features exists. Variable expressivity and incomplete penetrance might play a role in WHS, resulting in difficult clinical diagnosis and challenge in understanding of the genotype/phenotype correlation. Copyright © 2012 Elsevier B.V. All rights reserved.

Understanding the reliability of diagnostic variables in a Chinese Medicine examination.

PubMed

O'Brien, Kylie A; Abbas, Estelle; Zhang, Jiansheng; Guo, Zhi-Xin; Luo, Ruizhi; Bensoussan, Alan; Komesaroff, Paul A

2009-07-01

The question of the objectivity of the clinical examination has been raised in relation to Western and non-Western medical systems. Western practitioners are often skeptical about Traditional Chinese Medicine (TCM), on the basis that its diagnostic variables and subcategories of disease appear subjective and not repeatable. We conducted a study investigating the reproducibility of individual diagnostic observations within three of the four diagnostic methods used in a TCM examination: inspection, palpation, and auscultation. Three TCM practitioners participated in the study, and examined 45 adults who had mild-to-moderate hypercholesterolemia but were otherwise healthy. Results indicated that while there are certain features of the TCM system that are highly objective and repeatable, such as detection of the presence of shen, character of breath sounds, and pulse speed, there are other features that are subjective and unreliable, such as color under the eyes and tongue body color. This poses a challenge for TCM practitioners to improve their clinical practice and demonstrates to Western medical practitioners that TCM does in part rest on a rigorous and objective empirical basis.

R124C mutation of the betaIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1.

PubMed

Hellenbroich, Y; Tzivras, G; Neppert, B; Schwinger, E; Zühlke, C

2001-01-01

Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the betaIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the betaIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the betaIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course. Copyright 2001 S. Karger AG, Basel

Noonan Syndrome: An Underestimated Cause of Severe to Profound Sensorineural Hearing Impairment. Which Clues to Suspect the Diagnosis?

PubMed

Ziegler, Alban; Loundon, Natalie; Jonard, Laurence; Cavé, Hélène; Baujat, Geneviève; Gherbi, Souad; Couloigner, Vincent; Marlin, Sandrine

2017-09-01

To highlight Noonan syndrome as a clinically recognizable cause of severe to profound sensorineural hearing impairment. New clinical cases and review. Patients evaluated for etiological diagnosis by a medical geneticist in a reference center for hearing impairment. Five patients presenting with confirmed Noonan syndrome and profound sensorineural hearing impairment. Diagnostic and review of the literature. Five patients presented with profound sensorineural hearing impairment and molecularly confirmed Noonan syndrome. Sensorineural hearing impairment has been progressive for three patients. Cardiac echography identified pulmonary stenosis in two patients and was normal for the three other patients. Short stature was found in two patients. Mild intellectual disability was found in one patient. Inconspicuous clinical features as facial dysmorphism, cryptorchidism, or easy bruising were of peculiar interest to reach the diagnosis of Noonan syndrome. Profound sensorineural hearing impairment can be the main feature of Noonan syndrome. Associated features are highly variable; thus, detailed medical history and careful physical examination are mandatory to consider the diagnosis in case of a sensorineural hearing impairment.

Hubness of strategic planning and sociality influences depressive mood and anxiety in College Population.

PubMed

Yun, Je-Yeon; Choi, Yoobin; Kwon, Yoonhee; Lee, Hwa Young; Choi, Soo-Hee; Jang, Joon Hwan

2017-12-19

Depressive mood and anxiety can reduce cognitive performance. Conversely, the presence of a biased cognitive tendency may serve as a trigger for depressive mood-anxiety. Previous studies have largely focused on group-wise correlations between clinical-neurocognitive variables. Using network analyses for intra-individual covariance, we sought to decipher the most influential clinical-neurocognitive hub in the differential severity of depressive-anxiety symptoms in a college population. Ninety college students were evaluated for depressive-anxiety symptoms, Minnesota multiphasic personality inventory-2(MMPI-2), and neuro-cognition. Weighted and undirected version of the intra-individual covariance networks, comprised of 18 clinical-neurocognitive variables satisfied small-worldness and modular organization in the sparsity range of K = 0.20-0.21. Furthermore, betweenness centrality of perseverative error for the Wisconsin card sorting test was reduced in more depressive individuals; higher anxiety was related to the increased betweenness centrality of MMPI-2 clinical scale 0(Si). Elevated edge-betweenness centrality of covariance between the MMPI-2 clinical scale 7(Pt) versus commission error of the continuous performance test predicted more anxiety higher than depressive mood. With intra-individual covariance network of clinical-neurocognitive variables, this study demonstrated critical drivers of depressive mood[attenuated influence of strategic planning] or anxiety[domination of social introversion/extroversion, in addition to the influence of compulsivity-impulsivity covariance as a shortcut component among various clinical-neurocognitive features].

Clinical and radiological features of Marchiafava–Bignami disease

PubMed Central

Dong, Xiaoyu; Bai, Chaobo; Nao, Jianfei

2018-01-01

Abstract Marchiafava–Bignami disease (MBD) is a rare neurological disease usually associated with chronic alcoholism and characterized by demyelination and necrosis. Our aims were to describe the clinicoradiological features and identify factors that may affect the prognosis of patients with MBD. We examined clinical manifestations, laboratory results, and neuroradiological features of 9 patients with MBD. The patients were classified into 2 subgroups (favorable and poor outcome subgroups) based on the Modified Oxford Handicap Scale (MOSH). In addition, we compared the clinical and neuroimaging features between the 2 subgroups. Nine adult male patients (age of onset range 37–62 years, with a mean age of 47.00 ± 14.50 years) were included in this study. According to MOSH, 4 patients were placed in the poor outcome subgroup (MOHS ≥ 3), 5 patients were placed in the favorable outcome subgroup (MOHS ≤ 2). Relatively high score of MAST-C (≥6) (P = .008), extracallosal lesions (P = .048), GCS (P = .026), cerebral lobe impairment (P = .048) was significantly more common in the poor outcome subgroup. Clinical manifestations of MBD are variable and lack specificity. Early diagnosis by relatively specific performance of bisymmetric lesions in corpus callosum of diffusion-weighted imaging (DWI) may affect the prognosis. The prognosis of patients with severe disturbance of consciousness, heavy alcohol consumption, extracallosal lesions, cerebral lobe impairment is probably unfavorable. PMID:29384842

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.

Signs and genetics of rare cancer syndromes with gastroenterological features

PubMed Central

Bruno, William; Fornarini, Giuseppe; Ghiorzo, Paola

2015-01-01

Although the genetic bases of most hereditary cancer syndromes are known, and genetic tests are available for them, the incidence of the most rare of these syndromes is likely underestimated, partially because the clinical expression is neither fully understood nor easily diagnosed due to the variable and complex expressivity. The clinical features of a small pool of rare cancer syndromes include gastroenterological signs, though not necessarily tumors, that could require the intervention of a gastroenterologist during any of the phases of the clinical management. Herein we will attempt to spread the knowledge on these rare syndromes by summarizing the phenotype and genetic basis, and revising the peculiar gastroenterological signs whose underlying role in these rare hereditary cancer syndromes is often neglected. Close collaboration between geneticists and gastroenterologists could facilitate both the early identification of patients or relatives at-risk and the planning of multidisciplinary and tailored management of these subjects. PMID:26290627

Noonan syndrome: clinical features, diagnosis, and management guidelines.

PubMed

Romano, Alicia A; Allanson, Judith E; Dahlgren, Jovanna; Gelb, Bruce D; Hall, Bryan; Pierpont, Mary Ella; Roberts, Amy E; Robinson, Wanda; Takemoto, Clifford M; Noonan, Jacqueline A

2010-10-01

Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. Because of the variability in presentation and the need for multidisciplinary care, it is essential that the condition be identified and managed comprehensively. The Noonan Syndrome Support Group (NSSG) is a nonprofit organization committed to providing support, current information, and understanding to those affected by NS. The NSSG convened a conference of health care providers, all involved in various aspects of NS, to develop these guidelines for use by pediatricians in the diagnosis and management of individuals with NS and to provide updated genetic findings.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

PubMed

Chen, Zhi-Hai; Qin, Xin-Cheng; Song, Rui; Shen, Yi; Chen, Xiao-Ping; Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C; Zhang, Yong-Zhen

2014-01-01

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

Automated Detection of Actinic Keratoses in Clinical Photographs

PubMed Central

Hames, Samuel C.; Sinnya, Sudipta; Tan, Jean-Marie; Morze, Conrad; Sahebian, Azadeh; Soyer, H. Peter; Prow, Tarl W.

2015-01-01

Background Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. Objective The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. Methods Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist’s assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. Results The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist’s intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. Conclusions The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face. PMID:25615930

Clinical and Molecular Genetic Analysis in Three Children with Wolfram Syndrome: A Novel WFS1 Mutation (c.2534T>A)

PubMed Central

Çelmeli, Gamze; Türkkahraman, Doğa; Çürek, Yusuf; Houghton, Jayne; Akçurin, Sema; Bircan, İffet

2017-01-01

Wolfram syndrome (WS) is an autosomal recessive disorder caused by mutations in WFS1 gene. The clinical features include diabetes insipidus, diabetes mellitus (DM), optic atrophy, deafness, and other variable clinical manifestations. In this paper, we present the clinical and genetic characteristics of 3 WS patients from 3 unrelated Turkish families. Clinical characteristics of the patients and the age of onset of symptoms were quite different in each pedigree. The first two cases developed all symptoms of the disease in their first decade of life. The heterozygous father of case 2 was symptomatic with bilateral deafness. The first ocular finding of one patient (patient 3) was bilateral cataract which was accompanying DM as a first feature of the syndrome. In this patient’s family, there were two members with features suggestive of WS. Previously known homozygous mutations, c.460+1G>A in intron 4 and c.1885C>T in exon 8, were identified in these cases. A novel homozygous c.2534T>A mutation was also detected in the exon 8 of WFS1 gene. Because of the rarity and heterogeneity of WS, detection of specific and nonspecific clinical signs including ocular findings and family history in non-autoimmune, insulinopenic diabetes cases should lead to a tentative diagnosis of WS. Genetic testing is required to confirm the diagnosis. PMID:27468121

Poison ivy dermatitis. Nuances in treatment.

PubMed

Williford, P M; Sheretz, E F

1994-02-01

Acute allergic contact dermatitis due to poison ivy or poison oak is a common presenting complaint in the practices of many primary care physicians. While the clinical features are well described, reported treatment regimens vary in both topical and systemic therapies. We review herein the variability of presenting morphologic features of the disease and common treatment regimens, with attention given to complications of therapy. We also comment on the correct botanical designation, incidence, and immune mechanisms of the disease state and review measures to avoid allergic contact dermatitis due to poison ivy and poison oak.

Towards a clinically informed, data-driven definition of elderly onset epilepsy.

PubMed

Josephson, Colin B; Engbers, Jordan D T; Sajobi, Tolulope T; Jette, Nathalie; Agha-Khani, Yahya; Federico, Paolo; Murphy, William; Pillay, Neelan; Wiebe, Samuel

2016-02-01

Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy. We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time. We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons. This study provides an empirical, clinically informed definition of "elderly onset epilepsy." If validated, an age threshold of 65-70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis.

PubMed

Kelley, B P; Patel, S C; Marin, H L; Corrigan, J J; Mitsias, P D; Griffith, B

2017-06-01

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up. © 2017 by American Journal of Neuroradiology.

Culture as a variable in neuroscience and clinical neuropsychology: A comprehensive review

PubMed Central

Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira; Mansur, Letícia Lessa; Gauthier, Serge

2015-01-01

Culture is a dynamic system of bidirectional influences among individuals and their environment, including psychological and biological processes, which facilitate adaptation and social interaction. One of the main challenges in clinical neuropsychology involves cognitive, behavioral and functional assessment of people with different sociocultural backgrounds. In this review essay, examining culture from a historical perspective to ethical issues in cross-cultural research, including the latest significant and publications, the authors sought to explore the main features related to cultural variables in neuropsychological practice and to debate the challenges found regarding the operational methods currently in use. Literature findings suggest a more comprehensive approach in cognitive and behavioral neuroscience, including an interface between elementary disciplines and applied neuropsychology. Thus, as a basis for discussion on this issue, the authors analyzed key-topics related to the study of new trends in sociocultural neuroscience and the application of their concepts from a clinical perspective. PMID:29213964

A standardised protocol for texture feature analysis of endoscopic images in gynaecological cancer.

PubMed

Neofytou, Marios S; Tanos, Vasilis; Pattichis, Marios S; Pattichis, Constantinos S; Kyriacou, Efthyvoulos C; Koutsouris, Dimitris D

2007-11-29

In the development of tissue classification methods, classifiers rely on significant differences between texture features extracted from normal and abnormal regions. Yet, significant differences can arise due to variations in the image acquisition method. For endoscopic imaging of the endometrium, we propose a standardized image acquisition protocol to eliminate significant statistical differences due to variations in: (i) the distance from the tissue (panoramic vs close up), (ii) difference in viewing angles and (iii) color correction. We investigate texture feature variability for a variety of targets encountered in clinical endoscopy. All images were captured at clinically optimum illumination and focus using 720 x 576 pixels and 24 bits color for: (i) a variety of testing targets from a color palette with a known color distribution, (ii) different viewing angles, (iv) two different distances from a calf endometrial and from a chicken cavity. Also, human images from the endometrium were captured and analysed. For texture feature analysis, three different sets were considered: (i) Statistical Features (SF), (ii) Spatial Gray Level Dependence Matrices (SGLDM), and (iii) Gray Level Difference Statistics (GLDS). All images were gamma corrected and the extracted texture feature values were compared against the texture feature values extracted from the uncorrected images. Statistical tests were applied to compare images from different viewing conditions so as to determine any significant differences. For the proposed acquisition procedure, results indicate that there is no significant difference in texture features between the panoramic and close up views and between angles. For a calibrated target image, gamma correction provided an acquired image that was a significantly better approximation to the original target image. In turn, this implies that the texture features extracted from the corrected images provided for better approximations to the original images. Within the proposed protocol, for human ROIs, we have found that there is a large number of texture features that showed significant differences between normal and abnormal endometrium. This study provides a standardized protocol for avoiding any significant texture feature differences that may arise due to variability in the acquisition procedure or the lack of color correction. After applying the protocol, we have found that significant differences in texture features will only be due to the fact that the features were extracted from different types of tissue (normal vs abnormal).

Interrelationship of clinical, histomorphometric and immunohistochemical features of oral lesions in chronic paracoccidioidomycosis.

PubMed

de Abreu E Silva, Mariana À; Salum, Fernanda G; Figueiredo, Maria A; Lopes, Tiago G; da Silva, Vinicius D; Cherubini, Karen

2013-03-01

This study aimed to analyze the oral lesions of chronic paracoccidioidomycosis concerning their histomorphometric, immunohistochemical, and clinical features in a standardized sample. Fifty biopsy specimens of oral lesions of chronic paracoccidioidomycosis were submitted to hematoxylin and eosin (H&E), Grocott-Gomori and immunohistochemical staining. Data regarding disease duration and size and number of oral lesions, as well as erythrocytes, leukocytes, lymphocytes, hematocrit, hemoglobin, and erythrocyte sedimentation rate, were collected from medical charts. Granuloma density and number and diameter of buds and fungal cells, and IL-2, TNF-alpha and IFN-gamma expression, as well as clinical and hematological features, were quantified and correlated. Bud diameter was significantly greater in intermediate density granulomas compared to higher density granulomas. The other variables (number of buds, number and diameter of fungi, expression of IL-2, TNF-alpha and IFN-gamma, and clinical and hematological features) did not significantly change with the density of granulomas. There was a positive correlation between bud number and fungal cell number (r = 0.834), bud diameter and fungal cell diameter (r = 0.496), erythrocytes and number of fungi (r = 0.420), erythrocytes and bud number (r = 0.408), and leukocytes and bud number (r = 0.396). Negative correlation occurred between number and diameter of fungi (r = -0.419), bud diameter and granuloma density (r = -0.367), TNF-alpha expression and number of fungi (r = -0.372), and TNF-alpha expression and bud number (r = -0.300). The histological, immunological, and clinical features of oral lesions evaluated did not differ significantly between patients in our sample of chronic paracoccidioidomycosis. TNF-alpha levels were inversely correlated with intensity of infection. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Predictors of the development of myocarditis or acute renal failure in patients with leptospirosis: An observational study

PubMed Central

2012-01-01

Background Leptospirosis has a varied clinical presentation with complications like myocarditis and acute renal failure. There are many predictors of severity and mortality including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore recognizing the early predictors of the complications of leptospirosis is important in patient management. This study was aimed at determining the clinical and laboratory predictors of myocarditis or acute renal failure. Methods This was a prospective descriptive study carried out in the Teaching Hospital, Kandy, from 1st July 2007 to 31st July 2008. Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory measures done on admission were recorded. Patients were observed for the development of acute renal failure or myocarditis. Chi-square statistics, Fisher's exact test and Mann-Whitney U test were used to compare patients with and without complications. A logistic regression model was used to select final predictor variables. Results Sixty two confirmed leptospirosis patients were included in the study. Seven patients (11.3%) developed acute renal failure and five (8.1%) developed myocarditis while three (4.8%) had both acute renal failure and myocarditis. Conjunctival suffusion - 40 (64.5%), muscle tenderness - 28 (45.1%), oliguria - 20 (32.2%), jaundice - 12 (19.3%), hepatomegaly - 10 (16.1%), arrhythmias (irregular radial pulse) - 8 (12.9%), chest pain - 6 (9.7%), bleeding - 5 (8.1%), and shortness of breath (SOB) 4 (6.4%) were the common clinical features present among the patients. Out of these, only oliguria {odds ratio (OR) = 4.14 and 95% confidence interval (CI) 1.003-17.261}, jaundice (OR = 5.13 and 95% CI 1.149-28.003), and arrhythmias (OR = 5.774 and 95% CI 1.001-34.692), were predictors of myocarditis or acute renal failure and none of the laboratory measures could predict the two complications. Conclusions This study shows that out of clinical and laboratory variables, only oliguria, jaundice and arrhythmia are strong predictors of development of acute renal failure or myocarditis in patients with leptospirosis presented to Teaching Hospital of Kandy, Sri Lanka. PMID:22243770

Balance confidence is related to features of balance and gait in individuals with chronic stroke

PubMed Central

Schinkel-Ivy, Alison; Wong, Jennifer S.; Mansfield, Avril

2016-01-01

Reduced balance confidence is associated with impairments in features of balance and gait in individuals with sub-acute stroke. However, an understanding of these relationships in individuals at the chronic stage of stroke recovery is lacking. This study aimed to quantify relationships between balance confidence and specific features of balance and gait in individuals with chronic stroke. Participants completed a balance confidence questionnaire and clinical balance assessment (quiet standing, walking, and reactive stepping) at 6 months post-discharge from inpatient stroke rehabilitation. Regression analyses were performed using balance confidence as a predictor variable and quiet standing, walking, and reactive stepping outcome measures as the dependent variables. Walking velocity was positively correlated with balance confidence, while medio-lateral centre of pressure excursion (quiet standing) and double support time, step width variability, and step time variability (walking) were negatively correlated with balance confidence. This study provides insight into the relationships between balance confidence and balance and gait measures in individuals with chronic stroke, suggesting that individuals with low balance confidence exhibited impaired control of quiet standing as well as walking characteristics associated with cautious gait strategies. Future work should identify the direction of these relationships to inform community-based stroke rehabilitation programs for individuals with chronic stroke, and determine the potential utility of incorporating interventions to improve balance confidence into these programs. PMID:27955809

ZAP-70 staining in chronic lymphocytic leukemia.

PubMed

Villamor, Neus

2005-05-01

Chronic lymphocytic leukemia (CLL) is the most common chronic leukemia in Western countries. The disease has an extremely variable clinical course, and several prognostic features have been identified to assess individual risk. The configuration of the immunoglobulin variable heavy-chain gene (IgV(H)) is a strong predictor of the outcome. CLL patients with unmutated IgV(H) status have an aggressive clinical course and a short survival. Unfortunately, analysis of IgV(H) gene configuration is not available in most clinical laboratories. A small number of genes are differentially expressed between unmutated IgV(H) and mutated IgV(H) clinical forms of CLL. One of these genes is ZAP-70, which is detected in leukemic cells from patients with the unmutated IgV(H) form of CLL. Flow cytometry presents advantages over other methods to detect ZAP-70, and its quantification by flow cytometry has proved its predictive value. This unit focuses on protocols to quantify ZAP-70 by flow cytometry in CLL.

Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

PubMed Central

Inamura, Kentaro

2018-01-01

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

Integrated Analysis of Pharmacologic, Clinical, and SNP Microarray Data using Projection onto the Most Interesting Statistical Evidence with Adaptive Permutation Testing

PubMed Central

Pounds, Stan; Cao, Xueyuan; Cheng, Cheng; Yang, Jun; Campana, Dario; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

2010-01-01

Powerful methods for integrated analysis of multiple biological data sets are needed to maximize interpretation capacity and acquire meaningful knowledge. We recently developed Projection Onto the Most Interesting Statistical Evidence (PROMISE). PROMISE is a statistical procedure that incorporates prior knowledge about the biological relationships among endpoint variables into an integrated analysis of microarray gene expression data with multiple biological and clinical endpoints. Here, PROMISE is adapted to the integrated analysis of pharmacologic, clinical, and genome-wide genotype data that incorporating knowledge about the biological relationships among pharmacologic and clinical response data. An efficient permutation-testing algorithm is introduced so that statistical calculations are computationally feasible in this higher-dimension setting. The new method is applied to a pediatric leukemia data set. The results clearly indicate that PROMISE is a powerful statistical tool for identifying genomic features that exhibit a biologically meaningful pattern of association with multiple endpoint variables. PMID:21516175

Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype

PubMed Central

Martinelli, Simone; De Luca, Alessandro; Stellacci, Emilia; Rossi, Cesare; Checquolo, Saula; Lepri, Francesca; Caputo, Viviana; Silvano, Marianna; Buscherini, Francesco; Consoli, Federica; Ferrara, Grazia; Digilio, Maria C.; Cavaliere, Maria L.; van Hagen, Johanna M.; Zampino, Giuseppe; van der Burgt, Ineke; Ferrero, Giovanni B.; Mazzanti, Laura; Screpanti, Isabella; Yntema, Helger G.; Nillesen, Willy M.; Savarirayan, Ravi; Zenker, Martin; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco

2010-01-01

RAS signaling plays a key role in controlling appropriate cell responses to extracellular stimuli and participates in early and late developmental processes. Although enhanced flow through this pathway has been established as a major contributor to oncogenesis, recent discoveries have revealed that aberrant RAS activation causes a group of clinically related developmental disorders characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, ectodermal and musculoskeletal anomalies, and increased risk for certain malignancies. Here, we report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloid malignancies and encodes a multivalent adaptor protein with E3 ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), the most common condition of this disease family. Independent CBL mutations were identified in two sporadic cases and two families from among 365 unrelated subjects who had NS or suggestive features and were negative for mutations in previously identified disease genes. Phenotypic heterogeneity and variable expressivity were documented. Mutations were missense changes altering evolutionarily conserved residues located in the RING finger domain or the linker connecting this domain to the N-terminal tyrosine kinase binding domain, a known mutational hot spot in myeloid malignancies. Mutations were shown to affect CBL-mediated receptor ubiquitylation and dysregulate signal flow through RAS. These findings document that germline mutations in CBL alter development to cause a clinically variable condition that resembles NS and that possibly predisposes to malignancies. PMID:20619386

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.

MEN1, MEN4, and Carney Complex: Pathology and Molecular Genetics

PubMed Central

Schernthaner-Reiter, Marie Helene; Trivellin, Giampaolo; Stratakis, Constantine A.

2015-01-01

Pituitary adenomas are a common feature of a subset of endocrine neoplasia syndromes, which have otherwise highly variable disease manifestations. We provide here a review of the clinical features and human molecular genetics of multiple endocrine neoplasia type 1 and 4 (MEN1 and MEN4, respectively) and Carney complex (CNC). MEN1, MEN4 and CNC are hereditary autosomal dominant syndromes that can present with pituitary adenomas. MEN1 is caused by inactivating mutations in the MEN1 gene, whose product menin is involved in multiple intracellular pathways contributing to transcriptional control and cell proliferation. MEN1 clinical features include primary hyperparathyroidism, pancreatic neuroendocrine tumours and prolactinomas and other pituitary adenomas. A subset of patients with pituitary adenomas and other MEN1 features have mutations in the CDKN1B gene; their disease has been called MEN type 4 (MEN4). Inactivating mutations in the type 1α regulatory subunit of protein kinase A (PKA) (the PRKAR1A gene), that lead to dysregulation and activation of the PKA pathway, are the main genetic cause of CNC, which is clinically characterised by primary pigmented adrenocortical disease (PPNAD), spotty skin pigmentation (lentigines), cardiac and other myxomas and acromegaly due to somatotropinomas or somatotrope hyperplasia. PMID:25592387

Lumbar hernia in South Korea: different from that in foreign literature?

PubMed

Park, S H; Chung, H S; Song, S H

2015-10-01

This study aimed to analyze the clinical features of lumbar hernia reported in South Korea and compare these features with those reported in foreign literature. From January 1968 through December 2013, 13 cases reported in South Korea were included in the study. The variables compared were age, sex, main symptoms at hospital visit, etiology, location, herniated contents, lateralization, defect size, diagnostic methods, surgical methods, surgical opinions, and recurrence. In the South Korean cases, women outnumbered men (3.3:1) and no significant differences were found in the herniated side (left:right, 1.1:1). In contrast, in the foreign cases, men outnumbered women (3:1) and left-sided hernia was dominant (2:1). Moreover, in most of the foreign cases, patients were aged 50-70 years, whereas in the South Korean cases, none of the patients were in their 50 s. However, no substantial differences were found in etiology, anatomical locations, symptoms, and herniated contents. This research revealed that few clinical features of lumbar hernias in South Korea differ from those reported in foreign literature. Thirteen cases were analyzed in the present study, and results obtained from such a small sample size cannot be generalized with certainty. Therefore, more cases should be collected for a definitive analysis. Despite this limitation, this study is important because it is the first attempt to collect and analyze the clinical features of lumbar hernia in South Korea. This study will serve as a basis for future studies investigating the clinical features of lumbar hernia cases in South Korea.

Recurrent Deletions and Reciprocal Duplications of 10q11.21q11.23 Including CHAT and SLC18A3 are Likely Mediated by Complex Low-Copy Repeats

PubMed Central

Stankiewicz, Paweł; Kulkarni, Shashikant; Dharmadhikari, Avinash V.; Sampath, Srirangan; Bhatt, Samarth S.; Shaikh, Tamim H.; Xia, Zhilian; Pursley, Amber N.; Cooper, M. Lance; Shinawi, Marwan; Paciorkowski, Alex R.; Grange, Dorothy K.; Noetzel, Michael J.; Saunders, Scott; Simons, Paul; Summar, Marshall; Lee, Brendan; Scaglia, Fernando; Fellmann, Florence; Martinet, Danielle; Beckmann, Jacques S.; Asamoah, Alexander; Platky, Kathryn; Sparks, Susan; Martin, Ann S.; Madan-Khetarpal, Suneeta; Hoover, Jacqueline; Medne, Livija; Bonnemann, Carsten G.; Moeschler, John B.; Vallee, Stephanie E.; Parikh, Sumit; Irwin, Polly; Dalzell, Victoria P.; Smith, Wendy E.; Banks, Valerie C.; Flannery, David B.; Lovell, Carolyn M.; Bellus, Gary A.; Golden-Grant, Kathryn; Gorski, Jerome L.; Kussmann, Jennifer L.; McGregor, Tracy L.; Hamid, Rizwan; Pfotenhauer, Jean; Ballif, Blake C.; Shaw, Chad A.; Kang, Sung-Hae L.; Bacino, Carlos A.; Patel, Ankita; Rosenfeld, Jill A.; Cheung, Sau Wai; Shaffer, Lisa G.

2013-01-01

We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers. PMID:21948486

Orofacial functions and oral health associated with Treacher Collins syndrome.

PubMed

Asten, Pamela; Skogedal, Nina; Nordgarden, Hilde; Axelsson, Stefan; Akre, Harriet; Sjögreen, Lotta

2013-01-01

The aim of this study was to describe orofacial features and functions and oral health associated with Treacher Collins syndrome (TCS) in relation to the variable phenotypic expression of the condition. The Nordic Orofacial Test-Screening (NOT-S), MHC Questionnaire, MHC Observation chart and clinical examinations of nasal and pharyngeal conditions and chewing and swallowing function were used to assess 19 individuals aged 5-74 years (median 34 years). TCS severity scores were calculated by a clinical geneticist. Orofacial features characterizing the study group were altered profile, increased mandibular angle, narrow hypopharynx and facial asymmetry. Basic orofacial functions such as breathing, eating, facial expression and speech were affected in all subjects demonstrating orofacial dysfunction in at least two NOT-S domains (median NOT-S total score 4/12, range 2-7). Significant correlation was found between the TCS severity scores reflecting phenotypic expression and the NOT-S total scores reflecting orofacial function. Self-reported experience of dry oral mucosa was common. Overall, dental health was good with few carious lesions diagnosed, but considerable need for orthodontic treatment was documented. Altered orofacial features and functions in TCS are common and often persist into late adolescence and adulthood. The functional level was correlated with the phenotypic variability of the condition. The standard of oral health was satisfactory. The findings indicated that individuals with TCS are likely to require lifelong health services related to their oral condition.

Predictors of relapse in patients with major depressive disorder in a 52-week, fixed dose, double blind, randomized trial of selegiline transdermal system (STS).

PubMed

Jang, Saeheon; Jung, Sungwon; Pae, Chiun; Kimberly, Blanchard Portland; Craig Nelson, J; Patkar, Ashwin A

2013-12-01

We investigated patient and disease characteristics predictive of relapse of MDD during a 52-week placebo controlled trial of selegiline transdermal system (STS) to identify patient characteristics relevant for STS treatment. After 10 weeks of open-label stabilization with STS, 322 remitted patients with MDD were randomized to 52-weeks of double-blind treatment with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression Rating Scale (HAMD-17) score of ≥ 14 and a CGI-S score of ≥ 3 with at least 2-point increase from the beginning of the double blind phase on 2 consecutive visits. Cox's proportional hazards regression was used to examine the effect of potential predictors (age, sex, age at onset of first MDD, early response pattern, number of previous antidepressant trials, severity of index episode, number of previous episodes, melancholic features, atypical features and anxious feature) on outcome. Exploratory analyses examined additional clinical variables (medical history, other psychiatric history, and individual items of HAM-D 28) on relapse. For all predictor variables analyzed, treatment Hazard Ratio (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than PLB). Age of onset was significantly predictive of relapse. Type, duration, and severity of depressive episodes, previous antidepressant trials, or demographic variables did not predict relapse. In additional exploratory analysis, eating disorder history and suicidal ideation were significant predictors of relapse after controlling for the effect of treatment in individual predictor analysis. While age of onset, eating disorder history and suicidal ideation were significant predictors, the majority of clinical and demographic variables were not predictive of relapse. Given the post-hoc nature of analysis, the findings need confirmation from a prospective study. It appears that selegiline transdermal system was broadly effective in preventing relapse across different subtypes and symptoms clusters of MDD. © 2013 Published by Elsevier B.V.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed Central

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-01-01

OBJECTIVES: To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). METHODS: The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. RESULTS: Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). CONCLUSIONS: The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed. Images PMID:9120450

Incentive motivation deficits in schizophrenia reflect effort computation impairments during cost-benefit decision-making.

PubMed

Fervaha, Gagan; Graff-Guerrero, Ariel; Zakzanis, Konstantine K; Foussias, George; Agid, Ofer; Remington, Gary

2013-11-01

Motivational impairments are a core feature of schizophrenia and although there are numerous reports studying this feature using clinical rating scales, objective behavioural assessments are lacking. Here, we use a translational paradigm to measure incentive motivation in individuals with schizophrenia. Sixteen stable outpatients with schizophrenia and sixteen matched healthy controls completed a modified version of the Effort Expenditure for Rewards Task that accounts for differences in motoric ability. Briefly, subjects were presented with a series of trials where they may choose to expend a greater amount of effort for a larger monetary reward versus less effort for a smaller reward. Additionally, the probability of receiving money for a given trial was varied at 12%, 50% and 88%. Clinical and other reward-related variables were also evaluated. Patients opted to expend greater effort significantly less than controls for trials of high, but uncertain (i.e. 50% and 88% probability) incentive value, which was related to amotivation and neurocognitive deficits. Other abnormalities were also noted but were related to different clinical variables such as impulsivity (low reward and 12% probability). These motivational deficits were not due to group differences in reward learning, reward valuation or hedonic capacity. Our findings offer novel support for incentive motivation deficits in schizophrenia. Clinical amotivation is associated with impairments in the computation of effort during cost-benefit decision-making. This objective translational paradigm may guide future investigations of the neural circuitry underlying these motivational impairments. Copyright © 2013 Elsevier Ltd. All rights reserved.

Temperament and character profiles in bipolar I, bipolar II and major depressive disorder: Impact over illness course, comorbidity pattern and psychopathological features of depression.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Di Nicola, Marco; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Robert Cloninger, C; Serretti, Alessandro; Janiri, Luigi

2015-09-15

Studies comparing temperament and character traits between patients with mood disorders and healthy individuals have yielded variable results. The Temperament and Character Inventory (TCI) was administered to 101 bipolar I (BP-I), 96 bipolar II (BP-II), 123 major depressive disorder (MDD) patients, and 125 HS. A series of generalized linear models were performed in order to: (a) compare the TCI dimensions across groups; (b) test any effect of the TCI dimensions on clinical features of mood disorders; and (c) detect any association between TCI dimensions and the psychopathological features of a major depressive episode. Demographic and clinical variables were also included in the models as independent variables. Higher Harm Avoidance was found in BP-II and MDD, but not in BP-I. Higher Self-Transcendence was found in BP-I. Our models also showed higher Self-Directedness in HS, either vs MDD or BP-II. No association was found between any TCI dimension and the severity of symptoms. Conversely, a positive association was found between Harm Avoidance and the overall burden of depressive episodes during lifetime. The cross-sectional design and the heterogeneity of the sample may be the main limitations of our study. In general, our sample seems to support the view of a similar profile of temperament and character between MDD and BP-II, characterized by high Harm Avoidance and low Self-Directedness. In contrast, patients with BP-I only exhibit high Self-Transcendence, having a near-normal profile in terms of Harm Avoidance or Self-Directedness. Copyright © 2015 Elsevier B.V. All rights reserved.

The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO

PubMed Central

Fratter, C.; Gorman, G.S.; Stewart, J.D.; Buddles, M.; Smith, C.; Evans, J.; Seller, A.; Poulton, J.; Roberts, M.; Hanna, M.G.; Rahman, S.; Omer, S.E.; Klopstock, T.; Schoser, B.; Kornblum, C.; Czermin, B.; Lecky, B.; Blakely, E.L.; Craig, K.; Chinnery, P.F.; Turnbull, D.M.; Horvath, R.; Taylor, R.W.

2010-01-01

Background: Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting in the accumulation of multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)-deficient fibers in skeletal muscle secondary to a disorder of mtDNA maintenance. Patients typically present with isolated extraocular muscle involvement, with little apparent evidence of the clinical heterogeneity documented in other mtDNA maintenance disorders, in particular POLG-related disease. Methods: We reviewed the clinical, histochemical, and molecular genetics analysis of 33 unreported patients from 26 families together with all previous cases described in the literature to define the clinical phenotype associated with PEO1 mutations. Results: Ptosis and ophthalmoparesis were almost universal clinical features among this cohort, with 52% (17/33) reporting fatigue and 33% (11/33) having mild proximal myopathy. Features consistent with CNS involvement were rarely described; however, in 24% (8/33) of the patients, cardiac abnormalities were reported. Mitochondrial histochemical changes observed in muscle showed remarkable variability, as did the secondary mtDNA deletions, which in some patients were only detected by PCR-based assays and not Southern blotting. Moreover, we report 7 novel PEO1 variants. Conclusions: Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of adPEO may well be underestimated. Direct sequencing of the PEO1 gene should be considered in adPEO patients prior to muscle biopsy. GLOSSARY adPEO = autosomal dominant progressive external ophthalmoplegia; COX = cytochrome c oxidase; IOSCA = infantile-onset spinocerebellar ataxia; mtDNA = mitochondrial DNA; PEO = progressive external ophthalmoplegia; SANDO = sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; SDH = succinate dehydrogenase. PMID:20479361

Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

PubMed

Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

2016-02-01

The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dendritic cell and histiocytic neoplasms: biology, diagnosis, and treatment.

PubMed

Dalia, Samir; Shao, Haipeng; Sagatys, Elizabeth; Cualing, Hernani; Sokol, Lubomir

2014-10-01

Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma. A literature search for articles published between 1990 and 2013 was undertaken. Articles are reviewed and salient findings are systematically described. Patients with dendritic cell and histiocytic neoplasms have distinct but variable clinical presentations; however, because many tumors have recently been recognized, their true incidence is uncertain. Although the clinical features can present in many organs, most occur in the lymph nodes or skin. Most cases are unifocal and solitary presentations have good prognoses with surgical resection. The role of adjuvant therapy in these disorders remains unclear. In cases with disseminated disease, prognosis is poor and data on treatment options are limited, although chemotherapy and referral to a tertiary care center should be considered. Excisional biopsy is the preferred method of specimen collection for tissue diagnosis, and immunohistochemistry is the most important diagnostic method for differentiating these disorders from other entities. Dendritic cell and histiocytic cell neoplasms are rare hematological disorders with variable clinical presentations and prognoses. Immunohistochemistry remains important for diagnosis. Larger pooled analyses or clinical trials are needed to better understand optimal treatment options in these rare disorders. Whenever possible, patients should be referred to a tertiary care center for disease management.

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.

Computational phenotype discovery using unsupervised feature learning over noisy, sparse, and irregular clinical data.

PubMed

Lasko, Thomas A; Denny, Joshua C; Levy, Mia A

2013-01-01

Inferring precise phenotypic patterns from population-scale clinical data is a core computational task in the development of precision, personalized medicine. The traditional approach uses supervised learning, in which an expert designates which patterns to look for (by specifying the learning task and the class labels), and where to look for them (by specifying the input variables). While appropriate for individual tasks, this approach scales poorly and misses the patterns that we don't think to look for. Unsupervised feature learning overcomes these limitations by identifying patterns (or features) that collectively form a compact and expressive representation of the source data, with no need for expert input or labeled examples. Its rising popularity is driven by new deep learning methods, which have produced high-profile successes on difficult standardized problems of object recognition in images. Here we introduce its use for phenotype discovery in clinical data. This use is challenging because the largest source of clinical data - Electronic Medical Records - typically contains noisy, sparse, and irregularly timed observations, rendering them poor substrates for deep learning methods. Our approach couples dirty clinical data to deep learning architecture via longitudinal probability densities inferred using Gaussian process regression. From episodic, longitudinal sequences of serum uric acid measurements in 4368 individuals we produced continuous phenotypic features that suggest multiple population subtypes, and that accurately distinguished (0.97 AUC) the uric-acid signatures of gout vs. acute leukemia despite not being optimized for the task. The unsupervised features were as accurate as gold-standard features engineered by an expert with complete knowledge of the domain, the classification task, and the class labels. Our findings demonstrate the potential for achieving computational phenotype discovery at population scale. We expect such data-driven phenotypes to expose unknown disease variants and subtypes and to provide rich targets for genetic association studies.

Computational Phenotype Discovery Using Unsupervised Feature Learning over Noisy, Sparse, and Irregular Clinical Data

PubMed Central

Lasko, Thomas A.; Denny, Joshua C.; Levy, Mia A.

2013-01-01

Inferring precise phenotypic patterns from population-scale clinical data is a core computational task in the development of precision, personalized medicine. The traditional approach uses supervised learning, in which an expert designates which patterns to look for (by specifying the learning task and the class labels), and where to look for them (by specifying the input variables). While appropriate for individual tasks, this approach scales poorly and misses the patterns that we don’t think to look for. Unsupervised feature learning overcomes these limitations by identifying patterns (or features) that collectively form a compact and expressive representation of the source data, with no need for expert input or labeled examples. Its rising popularity is driven by new deep learning methods, which have produced high-profile successes on difficult standardized problems of object recognition in images. Here we introduce its use for phenotype discovery in clinical data. This use is challenging because the largest source of clinical data – Electronic Medical Records – typically contains noisy, sparse, and irregularly timed observations, rendering them poor substrates for deep learning methods. Our approach couples dirty clinical data to deep learning architecture via longitudinal probability densities inferred using Gaussian process regression. From episodic, longitudinal sequences of serum uric acid measurements in 4368 individuals we produced continuous phenotypic features that suggest multiple population subtypes, and that accurately distinguished (0.97 AUC) the uric-acid signatures of gout vs. acute leukemia despite not being optimized for the task. The unsupervised features were as accurate as gold-standard features engineered by an expert with complete knowledge of the domain, the classification task, and the class labels. Our findings demonstrate the potential for achieving computational phenotype discovery at population scale. We expect such data-driven phenotypes to expose unknown disease variants and subtypes and to provide rich targets for genetic association studies. PMID:23826094

Learning Optimal Individualized Treatment Rules from Electronic Health Record Data

PubMed Central

Wang, Yuanjia; Wu, Peng; Liu, Ying; Weng, Chunhua; Zeng, Donglin

2016-01-01

Medical research is experiencing a paradigm shift from “one-size-fits-all” strategy to a precision medicine approach where the right therapy, for the right patient, and at the right time, will be prescribed. We propose a statistical method to estimate the optimal individualized treatment rules (ITRs) that are tailored according to subject-specific features using electronic health records (EHR) data. Our approach merges statistical modeling and medical domain knowledge with machine learning algorithms to assist personalized medical decision making using EHR. We transform the estimation of optimal ITR into a classification problem and account for the non-experimental features of the EHR data and confounding by clinical indication. We create a broad range of feature variables that reflect both patient health status and healthcare data collection process. Using EHR data collected at Columbia University clinical data warehouse, we construct a decision tree for choosing the best second line therapy for treating type 2 diabetes patients. PMID:28503676

Report of Two Cases of Combined Odontogenic Tumors: Ameloblastoma with Odontogenic Keratocyst and Ameloblastic Fibroma with Calcifying Odontogenic Cyst.

PubMed

Neuman, Ashley Nicole; Montague, Lindsay; Cohen, Donald; Islam, Nadim; Bhattacharyya, Indraneel

2015-09-01

Combined odontogenic neoplasms have rarely been documented. Such tumors have also been described by other researchers as "hybrid" lesions. The histologic features are often identical to other individually well-established odontogenic neoplasms such as ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma (AF), and ameloblastic fibro-odontoma. Their clinical presentation is variable, ranging from cysts to neoplasms showing varying degrees of aggressive behavior. Most combined tumors contain features of one of the odontogenic tumors in combination with either a calcifying odontogenic cyst (COC) or a calcifying epithelial odontogenic tumor. We present two new cases of combined odontogenic tumors: an ameloblastoma with an odontogenic keratocyst and an AF with COC. Predicting clinical outcome is challenging when a combination tumor is encountered due to the paucity of such lesions. One must understand salient features of these entities and differentiate them from the more common conventional neoplasms to expand classification and provide prognostic criteria.

Gross feature recognition of Anatomical Images based on Atlas grid (GAIA): Incorporating the local discrepancy between an atlas and a target image to capture the features of anatomic brain MRI.

PubMed

Qin, Yuan-Yuan; Hsu, Johnny T; Yoshida, Shoko; Faria, Andreia V; Oishi, Kumiko; Unschuld, Paul G; Redgrave, Graham W; Ying, Sarah H; Ross, Christopher A; van Zijl, Peter C M; Hillis, Argye E; Albert, Marilyn S; Lyketsos, Constantine G; Miller, Michael I; Mori, Susumu; Oishi, Kenichi

2013-01-01

We aimed to develop a new method to convert T1-weighted brain MRIs to feature vectors, which could be used for content-based image retrieval (CBIR). To overcome the wide range of anatomical variability in clinical cases and the inconsistency of imaging protocols, we introduced the Gross feature recognition of Anatomical Images based on Atlas grid (GAIA), in which the local intensity alteration, caused by pathological (e.g., ischemia) or physiological (development and aging) intensity changes, as well as by atlas-image misregistration, is used to capture the anatomical features of target images. As a proof-of-concept, the GAIA was applied for pattern recognition of the neuroanatomical features of multiple stages of Alzheimer's disease, Huntington's disease, spinocerebellar ataxia type 6, and four subtypes of primary progressive aphasia. For each of these diseases, feature vectors based on a training dataset were applied to a test dataset to evaluate the accuracy of pattern recognition. The feature vectors extracted from the training dataset agreed well with the known pathological hallmarks of the selected neurodegenerative diseases. Overall, discriminant scores of the test images accurately categorized these test images to the correct disease categories. Images without typical disease-related anatomical features were misclassified. The proposed method is a promising method for image feature extraction based on disease-related anatomical features, which should enable users to submit a patient image and search past clinical cases with similar anatomical phenotypes.

Variability in CT lung-nodule quantification: Effects of dose reduction and reconstruction methods on density and texture based features.

PubMed

Lo, P; Young, S; Kim, H J; Brown, M S; McNitt-Gray, M F

2016-08-01

To investigate the effects of dose level and reconstruction method on density and texture based features computed from CT lung nodules. This study had two major components. In the first component, a uniform water phantom was scanned at three dose levels and images were reconstructed using four conventional filtered backprojection (FBP) and four iterative reconstruction (IR) methods for a total of 24 different combinations of acquisition and reconstruction conditions. In the second component, raw projection (sinogram) data were obtained for 33 lung nodules from patients scanned as a part of their clinical practice, where low dose acquisitions were simulated by adding noise to sinograms acquired at clinical dose levels (a total of four dose levels) and reconstructed using one FBP kernel and two IR kernels for a total of 12 conditions. For the water phantom, spherical regions of interest (ROIs) were created at multiple locations within the water phantom on one reference image obtained at a reference condition. For the lung nodule cases, the ROI of each nodule was contoured semiautomatically (with manual editing) from images obtained at a reference condition. All ROIs were applied to their corresponding images reconstructed at different conditions. For 17 of the nodule cases, repeat contours were performed to assess repeatability. Histogram (eight features) and gray level co-occurrence matrix (GLCM) based texture features (34 features) were computed for all ROIs. For the lung nodule cases, the reference condition was selected to be 100% of clinical dose with FBP reconstruction using the B45f kernel; feature values calculated from other conditions were compared to this reference condition. A measure was introduced, which the authors refer to as Q, to assess the stability of features across different conditions, which is defined as the ratio of reproducibility (across conditions) to repeatability (across repeat contours) of each feature. The water phantom results demonstrated substantial variability among feature values calculated across conditions, with the exception of histogram mean. Features calculated from lung nodules demonstrated similar results with histogram mean as the most robust feature (Q ≤ 1), having a mean and standard deviation Q of 0.37 and 0.22, respectively. Surprisingly, histogram standard deviation and variance features were also quite robust. Some GLCM features were also quite robust across conditions, namely, diff. variance, sum variance, sum average, variance, and mean. Except for histogram mean, all features have a Q of larger than one in at least one of the 3% dose level conditions. As expected, the histogram mean is the most robust feature in their study. The effects of acquisition and reconstruction conditions on GLCM features vary widely, though trending toward features involving summation of product between intensities and probabilities being more robust, barring a few exceptions. Overall, care should be taken into account for variation in density and texture features if a variety of dose and reconstruction conditions are used for the quantification of lung nodules in CT, otherwise changes in quantification results may be more reflective of changes due to acquisition and reconstruction conditions than in the nodule itself.

The clinical spectrum of late-onset Alexander disease: a systematic literature review.

PubMed

Balbi, Pietro; Salvini, Silvana; Fundarò, Cira; Frazzitta, Giuseppe; Maestri, Roberto; Mosah, Dibo; Uggetti, Carla; Sechi, GianPietro

2010-12-01

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

Feature-Based Correlation and Topological Similarity for Interbeat Interval Estimation Using Ultrawideband Radar.

PubMed

Sakamoto, Takuya; Imasaka, Ryohei; Taki, Hirofumi; Sato, Toru; Yoshioka, Mototaka; Inoue, Kenichi; Fukuda, Takeshi; Sakai, Hiroyuki

2016-04-01

The objectives of this paper are to propose a method that can accurately estimate the human heart rate (HR) using an ultrawideband (UWB) radar system, and to determine the performance of the proposed method through measurements. The proposed method uses the feature points of a radar signal to estimate the HR efficiently and accurately. Fourier- and periodicity-based methods are inappropriate for estimation of instantaneous HRs in real time because heartbeat waveforms are highly variable, even within the beat-to-beat interval. We define six radar waveform features that enable correlation processing to be performed quickly and accurately. In addition, we propose a feature topology signal that is generated from a feature sequence without using amplitude information. This feature topology signal is used to find unreliable feature points, and thus, to suppress inaccurate HR estimates. Measurements were taken using UWB radar, while simultaneously performing electrocardiography measurements in an experiment that was conducted on nine participants. The proposed method achieved an average root-mean-square error in the interbeat interval of 7.17 ms for the nine participants. The results demonstrate the effectiveness and accuracy of the proposed method. The significance of this study for biomedical research is that the proposed method will be useful in the realization of a remote vital signs monitoring system that enables accurate estimation of HR variability, which has been used in various clinical settings for the treatment of conditions such as diabetes and arterial hypertension.

Alexithymia in anorexia nervosa: the mediating role of depression.

PubMed

Torres, Sandra; Guerra, Marina Prista; Lencastre, Leonor; Miller, Kylee; Vieira, Filipa Mucha; Roma-Torres, António; Brandão, Isabel; Costa, Patrício

2015-01-30

The role of depression in the expression of alexithymia in anorexia nervosa (AN) has been controversially explained and several variables that may mask or increase the presence of emotional difficulties have scant examination in previous studies. This study aims to analyze the associations between alexithymia and state variables, such as age, BMI, illness duration, treatment duration, and medication status in AN participants, and to test the mediating role of depression in emotional difficulties. The Toronto Alexithymia Scale (TAS-20) and the Zung Self-Rating Depression Scale were administrated to 160 females: 80 participants with AN and 80 healthy controls. High levels of alexithymia were not a function of state variables. The mediating role of depression differed by the alexithymia dimension, with total mediation found for the TAS-DDF and partial mediation found for the TAS-DIF. Alexithymia is a relevant feature throughout the spectrum of AN and does not seem to be related to developmental maturation and some clinical features. Depression is probably the variable that best accounts for the variance in alexithymia, but is not a complete explanation for the known cognitive-affective disturbances in AN. Specific emotional competencies require scrutiny during psychiatric treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Propriospinal myoclonus

PubMed Central

van der Salm, Sandra M.A.; Erro, Roberto; Cordivari, Carla; Edwards, Mark J.; Koelman, Johannes H.T.M.; van den Ende, Tom; Bhatia, Kailash P.; van Rootselaar, Anne-Fleur; Brown, Peter

2014-01-01

Objective: Propriospinal myoclonus (PSM) is a rare disorder with repetitive, usually flexor arrhythmic brief jerks of the trunk, hips, and knees in a fixed pattern. It has a presumed generation in the spinal cord and diagnosis depends on characteristic features at polymyography. Recently, a historical paradigm shift took place as PSM has been reported to be a functional (or psychogenic) movement disorder (FMD) in most patients. This review aims to characterize the clinical features, etiology, electrophysiologic features, and treatment outcomes of PSM. Methods: Re-evaluation of all published PSM cases and systematic scoring of clinical and electrophysiologic characteristics in all published cases since 1991. Results: Of the 179 identified patients with PSM (55% male), the mean age at onset was 43 years (range 6–88 years). FMD was diagnosed in 104 (58%) cases. In 12 cases (26% of reported secondary cases, 7% of total cases), a structural spinal cord lesion was found. Clonazepam and botulinum toxin may be effective in reducing jerks. Conclusions: FMD is more frequent than previously assumed. Structural lesions reported to underlie PSM are scarce. Based on our clinical experience and the reviewed literature, we recommend polymyography to assess recruitment variability combined with a Bereitschaftspotential recording in all cases. PMID:25305154

Clinical implications of antimitochondrial antibody seropositivity in autoimmune hepatitis: a multicentre study.

PubMed

Muratori, Paolo; Efe, Cumali; Muratori, Luigi; Ozaslan, Ersan; Schiano, Thomas; Yoshida, Eric M; Heurgué-Berlot, Alexandra; Lalanne, Claudine; Lenzi, Marco; Wahlin, Staffan

2017-07-01

Antimitochondrial antibody (AMA) positivity is the serological marker of primary biliary cholangitis (PBC), but can also be sporadically detected in autoimmune hepatitis (AIH). Little is known about the clinical significance of AMA in AIH. We recruited 47 AMA-positive AIH cases from several centres and compared them with 264 well-characterized Italian AIH patients. Cases with any features of PBC were excluded. In univariate analysis, AMA-positive AIH patients were older (46 vs. 36, P=0.002) and more responsive to immunosuppression (74 vs. 59%, P=0.05), but no differences were observed between the two groups after logistic regression using AMA as a dependent variable. None of the AMA-positive AIH patients showed signs of evolving PBC features after a median follow-up of up 47 months. AMA was detected in combination with all serological AIH markers except antiliver kidney microsome type 1 and antiliver cytosol type 1. AMA was the only marker of autoimmunity in eight cases. We found no differences between AIH with and without AMA. The groups had similar clinical, biochemical and histological features. AMA-positive AIH patients did not evolve towards PBC. In some cases, AMA was the only autoantibody.

The prognostic impact of clinical and CT parameters in patients with pontine hemorrhage.

PubMed

Dziewas, Rainer; Kremer, Marion; Lüdemann, Peter; Nabavi, Darius G; Dräger, Bianca; Ringelstein, Bernd

2003-01-01

In patients with pontine hemorrhage (PH), an accurate prognostic assessment is critical for establishing a reasonable therapeutic approach. The initial clinical symptoms and computed tomography (CT) features were analyzed with multivariate regression analysis in 39 consecutive patients with PH. PHs were classified into three types: (1) large paramedian, (2) basal or basotegmental and (3) lateral tegmental, and the hematomas' diameters were measured. The patients' outcome was evaluated. Twenty-seven patients (69%) died and 12 (31%) survived for more than 1 year after PH. The symptom most predictive of death was coma on admission. The large paramedian type of PH predicted a poor prognosis, whereas the lateral tegmental type was associated with a favorable outcome. The transverse hematoma diameter was also related to outcome, with the threshold value found to be 20 mm. We conclude that PH outcome can be estimated best by combining the CT parameters 'large paramedian PH' and 'transverse diameter >/=20 mm' with the clinical variable 'coma on admission'. Survival is unlikely if all 3 features are present, whereas survival may be expected if only 1 or none of these features is found. Copyright 2003 S. Karger AG, Basel

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

PubMed

Dias, Olívia Meira; Baldi, Bruno Guedes; Pennati, Francesca; Aliverti, Andrea; Chate, Rodrigo Caruso; Sawamura, Márcio Valente Yamada; Carvalho, Carlos Roberto Ribeiro de; Albuquerque, André Luis Pereira de

2018-01-01

Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

Eosinophilic panniculitis.

PubMed

Samlaska, C P; de Lorimier, A J; Heldman, L S

1995-03-01

Eosinophillic panniculitis is a poorly defined entity with variable clinical features. We report a case of rapidly enlarging, asymptomatic subcutaneous scalp nodules in a 6-year-old black boy with atopic dermatitis. The nodules resolved spontaneously over two to three days. Biopsy specimens were remarkable for eosinophilic panniculitis without evidence of epidermal change or vasculitis. We believe that this is the youngest reported patient with this disorder.

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.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

PubMed

Poduri, Annapurna; Chitsazzadeh, Vida; D'Arrigo, Stefano; Fedrizzi, Ermellina; Pantaleoni, Chiara; Riva, Daria; Busse, Claudia; Küster, Helmut; Duplessis, Adre; Gaitanis, John; Sahin, Mustafa; Garganta, Cheryl; Topcu, Meral; Dies, Kira A; Barry, Brenda J; Partlow, Jennifer; Barkovich, A James; Walsh, Christopher A; Chang, Bernard S

2010-08-01

Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. Copyright 2009 Elsevier B.V. All rights reserved.

Variability in CKD stage in outpatients followed in two large renal clinics.

PubMed

Sikaneta, Tabo; Abdolell, Mohamed; Taskapan, Hulya; Roscoe, Janet; Fung, Jason; Nagai, Gordon; Ting, Robert H; Ng, Paul; Wu, George; Oreopoulos, Dimitrios; Tam, Paul Y

2012-10-01

Chronic kidney disease (CKD) is staged by glomerular filtration rate (GFR). CKD stages sometimes vary between routine office visits, and it is unknown if this impacts renal and patient survival separately from a cross-sectional CKD stage value. We quantified and categorized CKD stage variability in a large group of outpatients and correlated this with clinical and demographic features and with renal and patient survival. All estimated GFRs were staged in the first observation period. CKD stages were then categorized as static, improving, worsening, or fluctuating. Logistic regression analysis was performed to identify clinical variables associated with CKD stage variability. Death and dialysis progression rates were then collected and analyzed using Cox proportional regression. During a 1.1-year observation period, 1,262 patients (mean age 71.25 years) had a mean 5 eGFR's. CKD stages were static in 60.4%, worsened in 14.4%, improved in 7.4%, and fluctuated in 17.2% of patients. Secondary analysis revealed heavy proteinuria and East Asian ethnicity to be negatively, and diabetes mellitus and previous acute kidney injury to be positively associated with improving CKD stages. Cox proportional regression of 902 patients analyzed 2.3 years later revealed a negative association with improving CKD stage and subsequent need for dialysis. CKD stage changed in 40% of 1,262 elderly patients when determined 5 times in just over 1 year. Improving CKD stage was the only variability pattern significantly associated with any of the clinical outcomes when assessed 2.3 years later, being unlikely to be linked with subsequent need for dialysis.

Characterizing facial features in individuals with craniofacial microsomia: A systematic approach for clinical research.

PubMed

Heike, Carrie L; Wallace, Erin; Speltz, Matthew L; Siebold, Babette; Werler, Martha M; Hing, Anne V; Birgfeld, Craig B; Collett, Brent R; Leroux, Brian G; Luquetti, Daniela V

2016-11-01

Craniofacial microsomia (CFM) is a congenital condition with wide phenotypic variability, including hypoplasia of the mandible and external ear. We assembled a cohort of children with facial features within the CFM spectrum and children without known craniofacial anomalies. We sought to develop a standardized approach to assess and describe the facial characteristics of the study cohort, using multiple sources of information gathered over the course of this longitudinal study and to create case subgroups with shared phenotypic features. Participants were enrolled between 1996 and 2002. We classified the facial phenotype from photographs, ratings using a modified version of the Orbital, Ear, Mandible, Nerve, Soft tissue (OMENS) pictorial system, data from medical record abstraction, and health history questionnaires. The participant sample included 142 cases and 290 controls. The average age was 13.5 years (standard deviation, 1.3 years; range, 11.1-17.1 years). Sixty-one percent of cases were male, 74% were white non-Hispanic. Among cases, the most common features were microtia (66%) and mandibular hypoplasia (50%). Case subgroups with meaningful group definitions included: (1) microtia without other CFM-related features (n = 24), (2) microtia with mandibular hypoplasia (n = 46), (3) other combinations of CFM- related facial features (n = 51), and (4) atypical features (n = 21). We developed a standardized approach for integrating multiple data sources to phenotype individuals with CFM, and created subgroups based on clinically-meaningful, shared characteristics. We hope that this system can be used to explore associations between phenotype and clinical outcomes of children with CFM and to identify the etiology of CFM. Birth Defects Research (Part A) 106:915-926, 2016.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Constitutional trisomy 8 mosaicism syndrome: case report and review

PubMed Central

Udayakumar, Achandira M.; Al-Kindy, Adila

2013-01-01

Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder. PMID:27625859

Constitutional trisomy 8 mosaicism syndrome: case report and review.

PubMed

Udayakumar, Achandira M; Al-Kindy, Adila

2013-12-01

Trisomy 8 mosaicism (Warkany syndrome) is a rare viable condition with variable phenotypes, ranging from mild dysmorphic features to severe malformations. Karyotyping and fluorescence in-situ hybridization potentially help detecting this low mosaic clone to confirm the diagnosis of patients with classical and unusual clinical presentations. This report reviews few previous cases to describe our case - a boy who had trisomy 8 mosaicism with severe dysmorphic features, born to a consanguineous Arabic couple. This study concludes that careful cytogenetic diagnoses of trisomy 8 mosaicism is essential for appropriate management and follow up of this rare disorder.

Novel high-resolution computed tomography-based radiomic classifier for screen-identified pulmonary nodules in the National Lung Screening Trial.

PubMed

Peikert, Tobias; Duan, Fenghai; Rajagopalan, Srinivasan; Karwoski, Ronald A; Clay, Ryan; Robb, Richard A; Qin, Ziling; Sicks, JoRean; Bartholmai, Brian J; Maldonado, Fabien

2018-01-01

Optimization of the clinical management of screen-detected lung nodules is needed to avoid unnecessary diagnostic interventions. Herein we demonstrate the potential value of a novel radiomics-based approach for the classification of screen-detected indeterminate nodules. Independent quantitative variables assessing various radiologic nodule features such as sphericity, flatness, elongation, spiculation, lobulation and curvature were developed from the NLST dataset using 726 indeterminate nodules (all ≥ 7 mm, benign, n = 318 and malignant, n = 408). Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) method for variable selection and regularization in order to enhance the prediction accuracy and interpretability of the multivariate model. The bootstrapping method was then applied for the internal validation and the optimism-corrected AUC was reported for the final model. Eight of the originally considered 57 quantitative radiologic features were selected by LASSO multivariate modeling. These 8 features include variables capturing Location: vertical location (Offset carina centroid z), Size: volume estimate (Minimum enclosing brick), Shape: flatness, Density: texture analysis (Score Indicative of Lesion/Lung Aggression/Abnormality (SILA) texture), and surface characteristics: surface complexity (Maximum shape index and Average shape index), and estimates of surface curvature (Average positive mean curvature and Minimum mean curvature), all with P<0.01. The optimism-corrected AUC for these 8 features is 0.939. Our novel radiomic LDCT-based approach for indeterminate screen-detected nodule characterization appears extremely promising however independent external validation is needed.

MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features.

PubMed

Tonduti, Davide; Vanderver, Adeline; Berardinelli, Angela; Schmidt, Johanna L; Collins, Christin D; Novara, Francesca; Genni, Antonia Di; Mita, Alda; Triulzi, Fabio; Brunstrom-Hernandez, Janice E; Zuffardi, Orsetta; Balottin, Umberto; Orcesi, Simona

2013-06-01

Monocarboxylate transporter 8 (MCT8) deficiency is an X-linked disorder resulting from an impairment of the transcellular transportation of thyroid hormones. Within the central nervous system thyroid hormone transport is normally mediated by MCT8. Patients are described as affected by a static or slowly progressive clinical picture which consists of variable degrees of mental retardation, hypotonia, spasticity, ataxia and involuntary movements, occasionally paroxysmal. The authors describe the clinical and neuroradiological picture of 3 males patients with marked delayed brain myelination and in which the clinical picture was dominated by early onset nonparoxysmal extrapyramidal symptoms. In one subject a novel mutation is described.

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

PubMed

Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

2017-04-01

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

Phenotypic variability of the cat eye syndrome. Case report and review of the literature.

PubMed

Rosias, P R; Sijstermans, J M; Theunissen, P M; Pulles-Heintzberger, C F; De Die-Smulders, C E; Engelen, J J; Van Der Meer, S B

2001-01-01

We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. Cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.

Clinical predictors of high risk histopathology in retinoblastoma.

PubMed

Kashyap, Seema; Meel, Rachna; Pushker, Neelam; Sen, Seema; Bakhshi, Sameer; Sreenivas, Vishnubhatla; Sethi, Sumita; Chawla, Bhavna; Ghose, Supriyo

2012-03-01

Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma. We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF. Three hundred twenty-six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis. Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study. Copyright © 2011 Wiley Periodicals, Inc.

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

PubMed

Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

2018-03-01

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

Structures of the recurrence plot of heart rate variability signal as a tool for predicting the onset of paroxysmal atrial fibrillation.

PubMed

Mohebbi, Maryam; Ghassemian, Hassan; Asl, Babak Mohammadzadeh

2011-05-01

This paper aims to propose an effective paroxysmal atrial fibrillation (PAF) predictor which is based on the analysis of the heart rate variability (HRV) signal. Predicting the onset of PAF, based on non-invasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic interventions and to minimize the risks for the patients. This method consists of four steps: Preprocessing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In the next step, the recurrence plot (RP) of HRV signal is obtained and six features are extracted to characterize the basic patterns of the RP. These features consist of length of longest diagonal segments, average length of the diagonal lines, entropy, trapping time, length of longest vertical line, and recurrence trend. In the third step, these features are reduced to three features by the linear discriminant analysis (LDA) technique. Using LDA not only reduces the number of the input features, but also increases the classification accuracy by selecting the most discriminating features. Finally, a support vector machine-based classifier is used to classify the HRV signals. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database which consists of both 30-minutes ECG recordings end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, and positive predictivity were 96.55%, 100%, and 100%, respectively.

Imaging mass spectrometry data reduction: automated feature identification and extraction.

PubMed

McDonnell, Liam A; van Remoortere, Alexandra; de Velde, Nico; van Zeijl, René J M; Deelder, André M

2010-12-01

Imaging MS now enables the parallel analysis of hundreds of biomolecules, spanning multiple molecular classes, which allows tissues to be described by their molecular content and distribution. When combined with advanced data analysis routines, tissues can be analyzed and classified based solely on their molecular content. Such molecular histology techniques have been used to distinguish regions with differential molecular signatures that could not be distinguished using established histologic tools. However, its potential to provide an independent, complementary analysis of clinical tissues has been limited by the very large file sizes and large number of discrete variables associated with imaging MS experiments. Here we demonstrate data reduction tools, based on automated feature identification and extraction, for peptide, protein, and lipid imaging MS, using multiple imaging MS technologies, that reduce data loads and the number of variables by >100×, and that highlight highly-localized features that can be missed using standard data analysis strategies. It is then demonstrated how these capabilities enable multivariate analysis on large imaging MS datasets spanning multiple tissues. Copyright © 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

Clinical and Microbiological Features of HIV-Associated Tuberculous Meningitis in Vietnamese Adults

PubMed Central

Torok, M. Estee; Chau, Tran Thi Hong; Mai, Pham Phuong; Phong, Nguyen Duy; Dung, Nguyen Thi; Chuong, Ly Van; Lee, Sue J.; Caws, M.; de Jong, Menno D.; Hien, Tran Tinh; Farrar, Jeremy J.

2008-01-01

Methods The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death. Results The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm3. CSF findings were as follows: median leucocyte count 438×109cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003). Conclusions HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage. PMID:18350135

Expansion of the variable expression of Muenke syndrome: Hydrocephalus without craniosynostosis.

PubMed

González-Del Angel, Ariadna; Estandía-Ortega, Bernardette; Alcántara-Ortigoza, Miguel Angel; Martínez-Cruz, Víctor; Gutiérrez-Tinajero, Diana Judith; Rasmussen, Astrid; Gómez-González, Claudia Sofía

2016-12-01

Muenke syndrome (MS) is an autosomal dominant coronal craniosynostosis syndrome with variable extracranial anomalies. We studied 56 unrelated patients with non-syndromic uni- or bicoronal craniosynostosi to identify the frequency and clinical characteristics of MS in a cohort of Mexican childrens. The FGFR3 pathogenic variation p.Pro250Arg responsible for MS was characterized in all probands by PCR-restriction assay; available first-degree relatives (15 parents, 5 siblings) of the confirmed p.Pro250Arg carriers were also tested. All heterozygotes for p.Pro250Arg underwent clinical and audiologic assessment, as well as X-ray evaluations of hands and feet. Eight of 56 probands (14%) were found to carry the p.Pro250Arg variant and half of them were familial cases. Four p.Pro250Arg heterozygous familial members had been considered unaffected before the molecular testing. In one MS family, hydrocephalus without craniosynostosis, was documented as the only clinical manifestation in a previously undetected heterozygous male sibling. Hydrocephalus without craniosynostosis in a patient with the p.Pro250Arg variant suggests that some patients with MS might present only this manifestation; to our knowledge, hydrocephalus has not been described as isolated feature in MS, so we propose to consider this feature as an expansion of the MS phenotype rather than an unrelated finding. Our data also reinforce the notion that molecular testing of FGFR3 must be included in the diagnostic approach of coronal craniosynostosis. This will allow accurate genetic counseling and optimal management of MS, which might otherwise go undiagnosed because of mild manifestations and wide variability of expression. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The pathophysiology of migraine: implications for clinical management.

PubMed

Charles, Andrew

2018-02-01

The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Breast Cancer Subtypes: Morphologic and Biologic Characterization

PubMed Central

2016-01-01

Advances in basic science, technology and translational research have created a revolution in breast cancer diagnosis and therapy. Researchers' discoveries of genes defining variability in response to therapy and heterogeneity in clinical presentations and tumor biology are the foundation of the path to personalized medicine. The success of personalized breast cancer care depends on access to pertinent clinical information and risk factors, optimal imaging findings, well-established morphologic features, and traditional and contemporary prognostic/predictive testing. The integration of these entities provides an opportunity to identify patients who can benefit from specific therapies, and demonstrates the link between breast cancer subtypes and their association with different tumor biology. It is critical to recognize specific types of breast cancer in individual patients and design optimal personalized therapy. This article will highlight the roles of morphologic features and established tumor biomarkers on patient outcome. PMID:26756229

Twin infant with lymphatic dysplasia diagnosed with Noonan syndrome by molecular genetic testing.

PubMed

Mathur, Deepan; Somashekar, Santhosh; Navarrete, Cristina; Rodriguez, Maria M

2014-08-01

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

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

PubMed

Sólia-Nasser, L; de Aquino, S-N; Paranaíba, L-M R; Gomes, A; Dos-Santos-Neto, P; Coletta, R-D; Cardoso, A-F; Frota, A-C; Martelli-Júnior, H

2016-05-01

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. 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. 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. 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. 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.

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.

A diagnostic model for chronic hypersensitivity pneumonitis.

PubMed

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2016-10-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

PubMed Central

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Microcephaly, ectodermal dysplasia, multiple skeletal anomalies and distinctive facial appearance: delineation of cerebro-dermato-osseous-dysplasia.

PubMed

Castori, Marco; Pascolini, Giulia; Parisi, Valentina; Sana, Maria Elena; Novelli, Antonio; Nürnberg, Peter; Iascone, Maria; Grammatico, Paola

2015-04-01

In 1980, a novel multiple malformation syndrome has been described in a 17-year-old woman with micro- and turricephaly, intellectual disability, distinctive facial appearance, congenital atrichia, and multiple skeletal anomalies mainly affecting the limbs. Four further sporadic patients and a couple of affected sibs are also reported with a broad clinical variability. Here, we describe a 4-year-old girl strikingly resembling the original report. Phenotype comparison identified a recurrent pattern of multisystem features involving the central nervous system, and skin and bones in five sporadic patients (including ours), while the two sibs and a further sporadic case show significant phenotypic divergence. Marked clinical variability within the same entity versus syndrome splitting is discussed and the term "cerebro-dermato-osseous dysplasia" is introduced to define this condition. © 2015 Wiley Periodicals, Inc.

Self-Calibrating Wave-Encoded Variable-Density Single-Shot Fast Spin Echo Imaging.

PubMed

Chen, Feiyu; Taviani, Valentina; Tamir, Jonathan I; Cheng, Joseph Y; Zhang, Tao; Song, Qiong; Hargreaves, Brian A; Pauly, John M; Vasanawala, Shreyas S

2018-04-01

It is highly desirable in clinical abdominal MR scans to accelerate single-shot fast spin echo (SSFSE) imaging and reduce blurring due to T 2 decay and partial-Fourier acquisition. To develop and investigate the clinical feasibility of wave-encoded variable-density SSFSE imaging for improved image quality and scan time reduction. Prospective controlled clinical trial. With Institutional Review Board approval and informed consent, the proposed method was assessed on 20 consecutive adult patients (10 male, 10 female, range, 24-84 years). A wave-encoded variable-density SSFSE sequence was developed for clinical 3.0T abdominal scans to enable high acceleration (3.5×) with full-Fourier acquisitions by: 1) introducing wave encoding with self-refocusing gradient waveforms to improve acquisition efficiency; 2) developing self-calibrated estimation of wave-encoding point-spread function and coil sensitivity to improve motion robustness; and 3) incorporating a parallel imaging and compressed sensing reconstruction to reconstruct highly accelerated datasets. Image quality was compared pairwise with standard Cartesian acquisition independently and blindly by two radiologists on a scale from -2 to 2 for noise, contrast, confidence, sharpness, and artifacts. The average ratio of scan time between these two approaches was also compared. A Wilcoxon signed-rank tests with a P value under 0.05 considered statistically significant. Wave-encoded variable-density SSFSE significantly reduced the perceived noise level and improved the sharpness of the abdominal wall and the kidneys compared with standard acquisition (mean scores 0.8, 1.2, and 0.8, respectively, P < 0.003). No significant difference was observed in relation to other features (P = 0.11). An average of 21% decrease in scan time was achieved using the proposed method. Wave-encoded variable-density sampling SSFSE achieves improved image quality with clinically relevant echo time and reduced scan time, thus providing a fast and robust approach for clinical SSFSE imaging. 1 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2018;47:954-966. © 2017 International Society for Magnetic Resonance in Medicine.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.

PubMed

Escolà-Vergé, Laura; Pinal-Fernandez, Iago; Fernandez-Codina, Andreu; Callejas-Moraga, Eduardo L; Espinosa, Juan; Marin, Ana; Labrador-Horrillo, Moises; Selva-O'Callaghan, Albert

2017-04-01

Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

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.

Shoulder pain in primary care: diagnostic accuracy of clinical examination tests for non-traumatic acromioclavicular joint pain

PubMed Central

2013-01-01

Background Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. Methods Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics. Following a standardised clinical examination and diagnostic injection into the subacromial bursa, all participants received a fluoroscopically guided diagnostic block of 1% lidocaine hydrochloride (XylocaineTM) into the ACJ. Diagnostic accuracy statistics including sensitivity, specificity, predictive values, positive and negative likelihood ratios (LR+ and LR-) were calculated for traditional ACJ tests (Active Compression/O’Brien’s test, cross-body adduction, localised ACJ tenderness and Hawkins-Kennedy test), and for individual and combinations of clinical examination variables that were associated with a positive anaesthetic response (PAR) (P≤0.05) defined as 80% or more reduction in post-injection pain intensity during provocative clinical tests. Results Twenty two of 153 participants (14%) reported an 80% PAR. None of the traditional ACJ tests were associated with an 80% PAR (P<0.05) and combinations of traditional tests were not able to discriminate between a PAR and a negative anaesthetic response (AUC 0.507; 95% CI: 0.366, 0.647; P>0.05). Five clinical examination variables (repetitive mechanism of pain onset, no referred pain below the elbow, thickened or swollen ACJ, no symptom provocation during passive glenohumeral abduction and external rotation) were associated with an 80% PAR (P<0.05) and demonstrated an ability to accurately discriminate between an PAR and NAR (AUC 0.791; 95% CI 0.702, 0.880; P<0.001). Less than two positive clinical features resulted in 96% sensitivity (95% CI 0.78, 0.99) and a LR- 0.09 (95% CI 0.02, 0.41) and four positive clinical features resulted in 95% specificity (95% CI 0.90, 0.98) and a LR+ of 4.98 (95% CI 1.69, 13.84). Conclusions In this cohort of primary care patients with predominantly subacute or chronic ACJ pain of non-traumatic onset, traditional ACJ tests were of limited diagnostic value. Combinations of other history and physical examination findings were able to more accurately identify injection-confirmed ACJ pain in this cohort. PMID:23634871

Allelic and Phenotypic Heterogeneity in ABCA4 mutations

PubMed Central

Burke, Tomas R; Tsang, Stephen H

2011-01-01

Since the discovery of the ABCA4 gene as the cause of autosomal recessive Stargardt disease/fundus flavimaculatus much has been written of the phenotypic variability in ABCA4 retinopathy. In this review the authors discuss the findings seen on examination and the disease features detected using various clinical tests. Important differential diagnoses are presented and unusual presentations of ABCA4 disease highlighted. PMID:21510770

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome

PubMed Central

Willemsen, Marjolein H; Fernandez, Bridget A; Bacino, Carlos A; Gerkes, Erica; de Brouwer, Arjan PM; Pfundt, Rolph; Sikkema-Raddatz, Birgit; Scherer, Stephen W; Marshall, Christian R; Potocki, Lorraine; van Bokhoven, Hans; Kleefstra, Tjitske

2010-01-01

The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes. PMID:19920853

Do Psychosocial Factors Predict Muscle Strength, Pain, or Physical Performance in Patients With Knee Osteoarthritis?

PubMed

Baert, Isabel A C; Meeus, Mira; Mahmoudian, Armaghan; Luyten, Frank P; Nijs, Jo; Verschueren, Sabine M P

2017-09-01

The aim of this study was to examine the relationship of psychosocial factors, namely, pain catastrophizing, kinesiophobia, and maladaptive coping strategies, with muscle strength, pain, and physical performance in patients with knee osteoarthritis (OA)-related symptoms. A total of 109 women (64 with knee OA-related symptoms) with a mean age of 65.4 years (49-81 years) were recruited for this study. Psychosocial factors were quantified by the Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Pain Coping Inventory. Clinical features were assessed using isometric and isokinetic knee muscle strength measurements, visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, and functional tests. Associations were examined using correlation and regression analysis. In knee OA patients, pain catastrophizing, kinesiophobia, and coping strategy explained a significant proportion of the variability in isometric knee extension and flexion strength (6.3%-9.2%), accounting for more overall variability than some demographic and medical status variables combined. Psychosocial factors were not significant independent predictors of isokinetic strength, knee pain, or physical performance. In understanding clinical features related to knee OA, such as muscle weakness, pain catastrophizing, kinesiophobia, and coping strategy might offer something additional beyond what might be explained by traditional factors, underscoring the importance of a biopsychosocial approach in knee OA management. Further research on individual patient characteristics that mediate the effects of psychosocial factors is, however, required in order to create opportunities for more targeted, personalized treatment for knee OA.

Negative Mood and Obsessive-Compulsive Related Clinical Constructs: An Examination of Underlying Factors

PubMed Central

Britton, Gary I.; Davey, Graham C. L.

2017-01-01

Emerging evidence suggests that many of the clinical constructs used to help understand and explain obsessive-compulsive (OC) symptoms, and negative mood, may be causally interrelated. One approach to understanding this interrelatedness is a motivational systems approach. This approach suggests that rather than considering clinical constructs and negative affect as separable entities, they are all features of an integrated threat management system, and as such are highly coordinated and interdependent. The aim of the present study was to examine if clinical constructs related to OC symptoms and negative mood are best treated as separable or, alternatively, if these clinical constructs and negative mood are best seen as indicators of an underlying superordinate variable, as would be predicted by a motivational systems approach. A sample of 370 student participants completed measures of mood and the clinical constructs of inflated responsibility, intolerance of uncertainty, not just right experiences, and checking stop rules. An exploratory factor analysis suggested two plausible factor structures, one where all construct items and negative mood items loaded onto one underlying superordinate variable, and a second structure comprising of five factors, where each item loaded onto a factor representative of what the item was originally intended to measure. A confirmatory factor analysis showed that the five factor model was preferential to the one factor model, suggesting the four constructs and negative mood are best conceptualized as separate variables. Given the predictions of a motivational systems approach were not supported in the current study, other possible explanations for the causal interrelatedness between clinical constructs and negative mood are discussed. PMID:28959224

Is an Appreciation of Isomerism the Key to Unlocking the Mysteries of the Cardiac Findings in Heterotaxy?

PubMed

Anderson, Robert H; Spicer, Diane E; Loomba, Rohit

2018-02-06

Pediatric cardiologists treating patients with severe congenital cardiac defects define "visceral heterotaxy" on the basis of isomerism of the atrial appendages. The isomeric features represent an obvious manifestation of disruption of left-right asymmetry during embryonic development. Thus, there are two subsets of individuals within the overall syndrome, with features of either right or left isomerism. Within the heart, it is only the atrial appendages that are truly isomeric. The remainder of the cardiac components shows variable morphology, as does the arrangement of the remaining body organs. Order is provided in this potentially chaotic arrangement simply by describing the specific features of each of the systems. These features as defined by clinicians, however, seem less well recognized by those investigating the developmental origins of the disruption of symmetry. Developmental biologists place much greater emphasis on ventricular looping. Although the direction of the loop can certainly be interpreted as representing an example of asymmetry, it is not comparable to the isomeric features that underscore the clinical syndromes. This is because, thus far, there is no evidence of ventricular isomerism, with the ventricles distinguished one from the other on the basis of their disparate anatomical features. In similar fashion, some consider transposition to represent abnormal lateralization, but again, clinical diagnosis depends on recognition of the lateralized features. In this review, therefore, we discuss the key questions that currently underscore the mismatch in the approaches to "lateralization" as taken by clinicians and developmental biologists.

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

Clinical and Molecular Characterization of Osteogenesis Imperfecta Type V

PubMed Central

Brizola, Evelise; Mattos, Eduardo P.; Ferrari, Jessica; Freire, Patricia O.A.; Germer, Raquel; Llerena Jr, Juan C.; Félix, Têmis M.

2015-01-01

Osteogenesis imperfecta type V (OI-V) has a wide clinical variability, with distinct clinical/radiological features, such as calcification of the interosseous membrane (CIM) between the radius-ulna and/or tibia-fibula, hyperplastic callus (HPC) formation, dislocation of the radial head (DRH), and absence of dentinogenesis imperfecta (DI). Recently, a single heterozygous mutation (c.-14C>T) in the 5′UTR of the IFITM5 gene was identified to be causative for OI-V. Here, we describe 7 individuals from 5 unrelated families that carry the c.-14C>T IFITM5 mutation. The clinical findings in these cases are: absence of DI in all patients, presence of blue sclera in 2 cases, and 4 patients with DRH. Radiographic findings revealed HPC in 3 cases. All patients presented CIM between the radius and ulna, while 4 patients presented additional CIM between the tibia and fibula. Spinal fractures by vertebral compression were observed in all individuals. The proportion of cases identified with this mutation represents 4% of OI cases at our institution. The clinical identification of OI-V is crucial, as this mutation has an autosomal dominant inheritance with variable expressivity. PMID:26648832

MADRS symptom subtypes in ECT-treated depressed patients: relationship to response and subsequent ECT.

PubMed

Spashett, Renee; Fernie, Gordon; Reid, Ian C; Cameron, Isobel M

2014-09-01

This study aimed to explore the relationship of Montgomery-Åsberg Depression Rating Scale (MADRS) symptom subtypes with response to electroconvulsive therapy (ECT) and subsequent ECT treatment within 12 months. A consecutive sample of 414 patients with depression receiving ECT in the North East of Scotland was assessed by retrospective chart review. Response rate was defined as greater than or equal to 50% decrease in pretreatment total MADRS score or a posttreatment total MADRS less than or equal to 10. Principal component analyses were conducted on a sample with psychotic features (n = 124) and a sample without psychotic features (n = 290). Scores on extracted factor subscales, clinical and demographic characteristics were assessed for association with response and subsequent ECT treatment within 12 months. Where more than 1 variable was associated with response or subsequent ECT, logistic regression analysis was applied. MADRS symptom subtypes formed 3 separate factors in both samples. Logistic regression revealed older age and high "Despondency" subscale score predicted response in the nonpsychotic group. Older age alone predicted response in the group with psychotic features. Nonpsychotic patients subsequently re-treated with ECT were older than those not prescribed subsequent ECT. No association of variables emerged with subsequent ECT treatment in the group with psychotic features. Being of older age and the presence of psychotic features predicted response. Presence of psychotic features alone predicted subsequent retreatment. Subscale scores of the MADRS are of limited use in predicting which patients with depression will respond to ECT, with the exception of "Despondency" subscale scores in patients without psychotic features.

Clinical Factors Associated with PANDAS

PubMed Central

Murphy, Tanya K.; Storch, Eric A.; Lewin, Adam B.; Edge, Paula J.; Goodman, Wayne K.

2011-01-01

Objective To explore associated clinical factors in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS). Study design Children with tics and/or OCD (n = 109) were examined by personal and family history, diagnostic interview, physical examination, medical record review, and measurement of baseline levels of streptococcal antibodies. Results Significant group differences were found on several variables, such that those diagnosed with PANDAS (versus without PANDAS) were more likely to have had dramatic onset; definite remissions; remission of neuropsychiatric symptoms during antibiotic therapy; a history of tonsillectomies/adenoidectomies; evidence of GAS infection, and clumsiness. Conclusion The identification of clinical features associated with PANDAS should assist in delineating risks for this subtype of OCD/tics. PMID:21868033

Partial epilepsy and 47,XXX karyotype: report of four cases.

PubMed

Roubertie, Agathe; Humbertclaude, Véronique; Leydet, Julie; Lefort, Geneviève; Echenne, Bernard

2006-07-01

Epilepsy is a common finding in chromosomal imbalances, but only a few chromosome abnormalities have a characteristic electro-clinical pattern. Trisomy X is one of the most common sex chromosome abnormalities in females, and is associated with considerable phenotypic variability. This report describes four 47,XXX females with mental deficiency and epilepsy. Although a specific electro-clinical pattern could not be defined, the epileptic phenotypes of these patients share many features; we suggest that the association 47,XXX/epilepsy/mental retardation may not be coincidental. This report also enlarges the clinical spectrum of the 47,XXX phenotype. Moreover, these observations highlight the critical role of chromosome X in epilepsy and mental retardation.

Necrotizing fasciitis and its mimics: what radiologists need to know.

PubMed

Chaudhry, Ammar A; Baker, Kevin S; Gould, Elaine S; Gupta, Rajarsi

2015-01-01

The purpose of this article is to review the imaging features of necrotizing fasciitis and its potential mimics. Key imaging features are emphasized to enable accurate and efficient interpretation of variables that are essential in appropriate management. Necrotizing fasciitis is a medical emergency with potential lethal outcome. Dissecting gas along fascial planes in the absence of penetrating trauma (including iatrogenic) is essentially pathognomonic. However, the lack of soft-tissue emphysema does not exclude the diagnosis. Mimics of necrotizing fasciitis include nonnecrotizing fasciitis (eosinophilic, paraneoplastic, inflammatory (lupus myofasciitis, Churg-Strauss, nodular, or proliferative), myositis, neoplasm, myonecrosis, inflammatory myopathy, and compartment syndrome. Necrotizing fasciitis is a clinical diagnosis, and imaging can reveal nonspecific or negative findings (particularly during the early course of disease). One should be familiar with salient clinical and imaging findings of necrotizing fasciitis to facilitate a more rapid and accurate diagnosis and be aware that its diagnosis necessitates immediate discussion with the referring physician.

Trisomy 4p and deletion 4p- in a family having translocation, t(4p-; 12p+).

PubMed

Mortimer, J G; Chewings, W; Miethke, P; Smith, G F

1978-01-01

Chromosome studies on a newborn infant with the clinical features of 4p-syndrome revealed a 46,XY,4p-karyotype with deletion of bands distal to 4p14. Investigation of the family revealed normal chromosomes in the mother and a balanced translocation rcp(4;12) (p14;p13) in the father, the paternal grandfather and an uncle. A severely retarded and malformed aunt is a partial trismoy for the short arms of chromosome 4, with the unbalanced karyotype 45,XX,12p+. It appears that monosomy of bands 4p15 and 4p16 leads to the full clinical features of 4p-syndrome, while trisomy of this region causes disabilities consistent with the rather more variable 4p trisomy syndrome. From currently reported cases, a summary is presented of the results of pregnancies of both male and female translocation carriers.

Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature.

PubMed

Malinverni, Andréa C M; Yamashiro Coelho, Érika M; Chen, Kelin; Colovati, Mileny E; Soares Pinho Cernach, Mirlene C; Bragagnolo, Silvia; Melaragno, Maria Isabel

2017-01-01

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature. © 2017 S. Karger AG, Basel.

Somatoparaphrenia: evolving theories and concepts.

PubMed

Feinberg, Todd E; Venneri, Annalena

2014-12-01

Somatoparaphrenia, a syndrome that involves at a minimum unawareness of ownership of a body part, in addition involves productive features including delusional misidentification and confabulation. In this review we describe some of the clinical and neuroanatomical features of somatoparaphrenia highlighting its delusional and confabulatory aspects. Possible theoretical frameworks are reviewed taking into account cognitive, psychodynamic, and philosophical views. We suggest that future studies should approach this syndrome through investigations of structural and functional connectivity and focus on the possible interplay between alterations in major functional networks of the brain, such as the default mode and salience networks, but also take into account motivational variables. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multigenerational pedigree with STAR syndrome: A novel FAM58A variant and expansion of the phenotype.

PubMed

Boczek, Nicole J; Kruisselbrink, Teresa; Cousin, Margot A; Blackburn, Patrick R; Klee, Eric W; Gavrilova, Ralitza H; Lanpher, Brendan C

2017-05-01

STAR syndrome is a rare X-linked dominant disorder characterized by toe Syndactyly, Telecanthus, Anogenital malformations, and Renal malformations, and is caused by loss-of-function variants in FAM58A. Our proband presented with the hallmark features of STAR syndrome, as well as some additional less typical features including tethered cord and hearing loss. The proband's mother and maternal half-sister had similar clinical histories, but had variability in phenotypic severity. Clinical whole exome sequencing revealed a novel pathogenic nonsense variant, c.651G>A (p.Trp217X; NM_152274), in FAM58A in the proband, mother, and maternal half-sister. This pedigree represents the 11-13th patients described with STAR syndrome and the third instance of familial inheritance. To our knowledge, this is the first occurrence of a nonsense variant in FAM58A described in individuals with STAR syndrome and the phenotype in this pedigree suggests that tethered cord and hearing loss are features of STAR syndrome. © 2017 Wiley Periodicals, Inc.

Neurological manifestations of Ehlers-Danlos syndrome(s): A review

PubMed Central

Castori, Marco; C. Voermans, Nicol

2014-01-01

The term “Ehlers-Danlos syndrome” (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, dermal dysplasia with abnormal skin texture and repair, and variable range of the hollow organ and vascular dysfunctions. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been posed on neurological manifestations of EDSs, such as musculoskeletal pain, fatigue, headache, muscle weakness and paresthesias. Here, a comprehensive overview of neurological findings of these conditions is presented primarily intended for the clinical neurologist. Features are organized under various subheadings, including pain, fatigue, headache, stroke and cerebrovascular disease, brain and spine structural anomalies, epilepsy, muscular findings, neuropathy and developmental features. The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling. Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral. A set of basic tools for patient’s recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders. PMID:25632331

Diagnostic imaging features of normal anal sacs in dogs and cats.

PubMed

Jung, Yechan; Jeong, Eunseok; Park, Sangjun; Jeong, Jimo; Choi, Ul Soo; Kim, Min-Su; Kim, Namsoo; Lee, Kichang

2016-09-30

This study was conducted to provide normal reference features for canine and feline anal sacs using ultrasound, low-field magnetic resonance imaging (MRI) and radiograph contrast as diagnostic imaging tools. A total of ten clinically normal beagle dogs and eight clinically normally cats were included. General radiography with contrast, ultrasonography and low-field MRI scans were performed. The visualization of anal sacs, which are located at distinct sites in dogs and cats, is possible with a contrast study on radiography. Most surfaces of the anal sacs tissue, occasionally appearing as a hyperechoic thin line, were surrounded by the hypoechoic external sphincter muscle on ultrasonography. The normal anal sac contents of dogs and cats had variable echogenicity. Signals of anal sac contents on low-field MRI varied in cats and dogs, and contrast medium using T1-weighted images enhanced the anal sac walls more obviously than that on ultrasonography. In conclusion, this study provides the normal features of anal sacs from dogs and cats on diagnostic imaging. Further studies including anal sac evaluation are expected to investigate disease conditions.

Diagnostic imaging features of normal anal sacs in dogs and cats

PubMed Central

Jung, Yechan; Jeong, Eunseok; Park, Sangjun; Jeong, Jimo; Choi, Ul Soo; Kim, Min-Su; Kim, Namsoo

2016-01-01

This study was conducted to provide normal reference features for canine and feline anal sacs using ultrasound, low-field magnetic resonance imaging (MRI) and radiograph contrast as diagnostic imaging tools. A total of ten clinically normal beagle dogs and eight clinically normally cats were included. General radiography with contrast, ultrasonography and low-field MRI scans were performed. The visualization of anal sacs, which are located at distinct sites in dogs and cats, is possible with a contrast study on radiography. Most surfaces of the anal sacs tissue, occasionally appearing as a hyperechoic thin line, were surrounded by the hypoechoic external sphincter muscle on ultrasonography. The normal anal sac contents of dogs and cats had variable echogenicity. Signals of anal sac contents on low-field MRI varied in cats and dogs, and contrast medium using T1-weighted images enhanced the anal sac walls more obviously than that on ultrasonography. In conclusion, this study provides the normal features of anal sacs from dogs and cats on diagnostic imaging. Further studies including anal sac evaluation are expected to investigate disease conditions. PMID:26645338

Structures of the Recurrence Plot of Heart Rate Variability Signal as a Tool for Predicting the Onset of Paroxysmal Atrial Fibrillation

PubMed Central

Mohebbi, Maryam; Ghassemian, Hassan; Asl, Babak Mohammadzadeh

2011-01-01

This paper aims to propose an effective paroxysmal atrial fibrillation (PAF) predictor which is based on the analysis of the heart rate variability (HRV) signal. Predicting the onset of PAF, based on non-invasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic interventions and to minimize the risks for the patients. This method consists of four steps: Preprocessing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In the next step, the recurrence plot (RP) of HRV signal is obtained and six features are extracted to characterize the basic patterns of the RP. These features consist of length of longest diagonal segments, average length of the diagonal lines, entropy, trapping time, length of longest vertical line, and recurrence trend. In the third step, these features are reduced to three features by the linear discriminant analysis (LDA) technique. Using LDA not only reduces the number of the input features, but also increases the classification accuracy by selecting the most discriminating features. Finally, a support vector machine-based classifier is used to classify the HRV signals. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database which consists of both 30-minutes ECG recordings end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, and positive predictivity were 96.55%, 100%, and 100%, respectively. PMID:22606666

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.

Measuring the implementation of early childhood development programs.

PubMed

Aboud, Frances E; Prado, Elizabeth L

2018-05-01

In this paper we describe ways to measure variables of interest when evaluating the implementation of a program to improve early childhood development (ECD). The variables apply to programs delivered to parents in group sessions and home or clinic visits, as well as in early group care for children. Measurements for four categories of variables are included: training and assessment of delivery agents and supervisors; program features such as quality of delivery, reach, and dosage; recipients' acceptance and enactment; and stakeholders' engagement. Quantitative and qualitative methods are described, along with when measures might be taken throughout the processes of planning, preparing, and implementing. A few standard measures are available, along with others that researchers can select and modify according to their goals. Descriptions of measures include who might collect the information, from whom, and when, along with how information might be analyzed and findings used. By converging on a set of common methods to measure implementation variables, investigators can work toward improving programs, identifying gaps that impede the scalability and sustainability of programs, and, over time, ascertain program features that lead to successful outcomes. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer

PubMed Central

Bruegl, Amanda S.; Djordjevic, Bojana; Urbauer, Diana L.; Westin, Shannon N.; Soliman, Pamela T.; Lu, Karen H.; Luthra, Rajyalakshmi; Broaddus, Russell R.

2013-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients. PMID:23888949

Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

PubMed

Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

2014-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

Primary Sjogren's syndrome with central nervous system involvement.

PubMed

Alhomoud, Iftetah A; Bohlega, Saeed A; Alkawi, Mohammed Z; Alsemari, Abdulaziz M; Omer, Saleh M; Alsenani, Fahmi M

2009-08-01

To describe the clinical, laboratory, and radiological features of Primary Sjogren's syndrome (PSS) with central nervous system (CNS) involvement. A retrospective case series of 12 female patients with PSS and CNS involvement at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia from 1991-2009. The diagnosis of PSS is defined by the American-European Diagnostic Criteria. We analyzed the clinical, radiological, and immunological features. The mean age was 40 years (range 16-58 years); all patient were females and presented with active neurological symptoms. The neurological involvement preceded the classic sicca symptoms (33%). Eight patients (66%) presented with myelopathy, 9 patients (75%) had optic neuritis, and the rest had variable neurological signs. Immunological tests (anti-Sjogren's syndrome A and anti-Sjogren's syndrome B) were high in 7 patients (58%). Minor salivary gland biopsy revealed inflammatory cell infiltrate in 11 patients (92%). Brain MRI showed scattered white matter changes in 7 patients (58%). Spine MRI showed multiple foci of hyperintensity in T2-weighted image in 6 patients (50%), and long segment of hyperintensity at the cervical spinal cord in 2 patients (16%). Our findings demonstrate that CNS involvements in PSS have great clinical variability and could precede the classic sicca symptoms by years. Primary Sjogren's syndrome can mimic multiple sclerosis (primary progressive multiple sclerosis or relapsing remitting multiple sclerosis), therefore a screening test for PSS should be considered in suspected cases. A well-defined management protocol awaits studies with larger case numbers.

A comparison study of body dysmorphic disorder versus social phobia

PubMed Central

Kelly, Megan M.; Dalrymple, Kristy; Zimmerman, Mark; Phillips, Katharine A.

2012-01-01

Body dysmorphic disorder (BDD) shares many characteristics with social phobia (SP), including high levels of social anxiety and avoidance, but to our knowledge no studies have directly compared these disorders’ demographic and clinical features. Demographic and clinical features were compared in individuals with BDD (n=172), SP (n=644), and comorbid BDD/SP (n=125). SP participants had a significantly earlier age of onset and lower educational attainment than BDD participants. BDD participants were significantly less likely to ever be married than SP participants, had a greater likelihood of ever being psychiatrically hospitalized, and had significantly lower mean GAF scores than SP participants. The two groups had different comorbidity patterns, which included a greater likelihood for BDD participants to have comorbid obsessive-compulsive disorder (OCD) or an eating disorder, versus a greater likelihood for SP participants to have a comorbid non-OCD anxiety disorder. The comorbid BDD/SP group had significantly greater morbidity across several domains than the SP only group, but not the BDD only group. In summary, although BDD and SP were similar across many demographic and clinical features, they had important differences. Future studies are needed to confirm these findings and address similarities and differences between these disorders across a broader range of variables. PMID:22999105

Pruritus is a common feature in sheep infected with the BSE agent

PubMed Central

Konold, Timm; Bone, Gemma; Vidal-Diez, Alberto; Tortosa, Raul; Davis, Andrew; Dexter, Glenda; Hill, Peter; Jeffrey, Martin; Simmons, Marion M; Chaplin, Melanie J; Bellworthy, Susan J; Berthelin-Baker, Christine

2008-01-01

Background The variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (TSEs) in sheep, such as scrapie and bovine spongiform encephalopathy (BSE), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. The study aimed to describe the clinical signs in sheep infected with the BSE agent throughout its clinical course to determine whether the clinical signs were as variable as described for classical scrapie in sheep. The clinical signs were compared to BSE-negative sheep to assess if disease-specific clinical markers exist. Results Forty-seven (34%) of 139 sheep, which comprised 123 challenged sheep and 16 undosed controls, were positive for BSE. Affected sheep belonged to five different breeds and three different genotypes (ARQ/ARQ, VRQ/VRQ and AHQ/AHQ). None of the controls or BSE exposed sheep with ARR alleles were positive. Pruritus was present in 41 (87%) BSE positive sheep; the remaining six were judged to be pre-clinically infected. Testing of the response to scratching along the dorsum of a sheep proved to be a good indicator of clinical disease with a test sensitivity of 85% and specificity of 98% and usually coincided with weight loss. Clinical signs that were displayed significantly earlier in BSE positive cases compared to negative cases were behavioural changes, pruritic behaviour, a positive scratch test, alopecia, skin lesions, teeth grinding, tremor, ataxia, loss of weight and loss of body condition. The frequency and severity of each specific clinical sign usually increased with the progression of disease over a period of 16–20 weeks. Conclusion Our results suggest that BSE in sheep presents with relatively uniform clinical signs, with pruritus of increased severity and abnormalities in behaviour or movement as the disease progressed. Based on the studied sheep, these clinical features appear to be independent of breed, affected genotype, dose, route of inoculation and whether BSE was passed into sheep from cattle or from other sheep, suggesting that the clinical phenotype of BSE is influenced by the TSE strain more than by other factors. The clinical phenotype of BSE in the genotypes and breed studied was indistinguishable from that described for classical scrapie cases. PMID:18445253

Occlusal factors are not related to self-reported bruxism.

PubMed

Manfredini, Daniele; Visscher, Corine M; Guarda-Nardini, Luca; Lobbezoo, Frank

2012-01-01

To estimate the contribution of various occlusal features of the natural dentition that may identify self-reported bruxers compared to nonbruxers. Two age- and sex-matched groups of self-reported bruxers (n = 67) and self-reported nonbruxers (n = 75) took part in the study. For each patient, the following occlusal features were clinically assessed: retruded contact position (RCP) to intercuspal contact position (ICP) slide length (< 2 mm was considered normal), vertical overlap (< 0 mm was considered an anterior open bite; > 4 mm, a deep bite), horizontal overlap (> 4 mm was considered a large horizontal overlap), incisor dental midline discrepancy (< 2 mm was considered normal), and the presence of a unilateral posterior crossbite, mediotrusive interferences, and laterotrusive interferences. A multiple logistic regression model was used to identify the significant associations between the assessed occlusal features (independent variables) and self-reported bruxism (dependent variable). Accuracy values to predict self-reported bruxism were unacceptable for all occlusal variables. The only variable remaining in the final regression model was laterotrusive interferences (P = .030). The percentage of explained variance for bruxism by the final multiple regression model was 4.6%. This model including only one occlusal factor showed low positive (58.1%) and negative predictive values (59.7%), thus showing a poor accuracy to predict the presence of self-reported bruxism (59.2%). This investigation suggested that the contribution of occlusion to the differentiation between bruxers and nonbruxers is negligible. This finding supports theories that advocate a much diminished role for peripheral anatomical-structural factors in the pathogenesis of bruxism.

SVM-RFE based feature selection and Taguchi parameters optimization for multiclass SVM classifier.

PubMed

Huang, Mei-Ling; Hung, Yung-Hsiang; Lee, W M; Li, R K; Jiang, Bo-Ru

2014-01-01

Recently, support vector machine (SVM) has excellent performance on classification and prediction and is widely used on disease diagnosis or medical assistance. However, SVM only functions well on two-group classification problems. This study combines feature selection and SVM recursive feature elimination (SVM-RFE) to investigate the classification accuracy of multiclass problems for Dermatology and Zoo databases. Dermatology dataset contains 33 feature variables, 1 class variable, and 366 testing instances; and the Zoo dataset contains 16 feature variables, 1 class variable, and 101 testing instances. The feature variables in the two datasets were sorted in descending order by explanatory power, and different feature sets were selected by SVM-RFE to explore classification accuracy. Meanwhile, Taguchi method was jointly combined with SVM classifier in order to optimize parameters C and γ to increase classification accuracy for multiclass classification. The experimental results show that the classification accuracy can be more than 95% after SVM-RFE feature selection and Taguchi parameter optimization for Dermatology and Zoo databases.

SVM-RFE Based Feature Selection and Taguchi Parameters Optimization for Multiclass SVM Classifier

PubMed Central

Huang, Mei-Ling; Hung, Yung-Hsiang; Lee, W. M.; Li, R. K.; Jiang, Bo-Ru

2014-01-01

Recently, support vector machine (SVM) has excellent performance on classification and prediction and is widely used on disease diagnosis or medical assistance. However, SVM only functions well on two-group classification problems. This study combines feature selection and SVM recursive feature elimination (SVM-RFE) to investigate the classification accuracy of multiclass problems for Dermatology and Zoo databases. Dermatology dataset contains 33 feature variables, 1 class variable, and 366 testing instances; and the Zoo dataset contains 16 feature variables, 1 class variable, and 101 testing instances. The feature variables in the two datasets were sorted in descending order by explanatory power, and different feature sets were selected by SVM-RFE to explore classification accuracy. Meanwhile, Taguchi method was jointly combined with SVM classifier in order to optimize parameters C and γ to increase classification accuracy for multiclass classification. The experimental results show that the classification accuracy can be more than 95% after SVM-RFE feature selection and Taguchi parameter optimization for Dermatology and Zoo databases. PMID:25295306

Clinical phenotypes and the biological parameters of Congolese patients suffering from sickle cell anemia: A first report from Central Africa.

PubMed

Mikobi, Tite M; Lukusa Tshilobo, Prosper; Aloni, Michel N; Akilimali, Pierre Z; Mvumbi-Lelo, Georges; Mbuyi-Muamba, Jean Marie

2017-11-01

The influence of phenotype on the clinical course and laboratory features of sickle cell anemia (SCA) is rarely described in sub-Saharan Africa. A cross-sectional study was conducted in Kinshasa. A clinical phenotype score was built up. The following definitions were applied: asymptomatic clinical phenotype (ACP; score≤5), moderate clinical phenotype (MCP; score between 6 and 15), and severe clinical phenotype (SCP; score≥16). ANOVA test were used to compare differences among categorical variables. We have studied 140 patients. The mean body mass index (BMI) value of three groups was lower (<25 kg/m 2 ) than the limit defining overweight. BMI of the subjects with ACP was significantly higher than those of other phenotypes (P<.05). Sickle cell patients with ACP have a high mean steady-state hemoglobin concentration compared to those with MCP and SCP (P<.001). A significant elevated baseline leukocyte count is associated with SCP (P<.001). Fetal Hemoglobin (HbF) was significantly higher in ACP. Significant elevation of alpha 1 and alpha 2 globulins in SCP were observed. In our study, fetal hemoglobin has an influence on the clinical severity and the biological parameters of SCA. The study provides data concerning the sickle cell anemia clinical and biological variability in our midst. © 2017 Wiley Periodicals, Inc.

X-linked juvenile retinoschisis (XLRS): a review of genotype-phenotype relationships.

PubMed

Kim, David Y; Mukai, Shizuo

2013-01-01

X-linked juvenile retinoschisis (XLRS) is one of the most common genetic causes of juvenile progressive retinal-vitreal degeneration in males. To date, more than 196 different mutations of the RS1 gene have been associated with XLRS. The mutation spectrum is large and the phenotype variable. This review will focus on the clinical features of XLRS and examine the relationship between phenotype and genotype.

Clinical and Immunological Features of Common Variable Immunodeficiency in China

PubMed Central

Lin, Lian-Jun; Wang, Yu-Chuan; Liu, Xin-Min

2015-01-01

Background: Common variable immunodeficiency (CVID) is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment. Methods: Clinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively. Results: The median age at onset was 11-year-old (range 4–51 years). The median age at diagnosis was 14.5-year-old (range 5–66 years). The average time of delay in diagnosis was 5.3 years (range 1–41 years). The most common main complaint was fever due to infections (35 cases, 87.5%). Pneumonia (28 cases, 70%) was the most common type of infections. Bronchiectasis was present in 6 patients (15%). Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3−/CD10+ B-cells were 1%–3.14%. Conclusions: Infection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig) and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended. PMID:25635425

Robinow syndrome: phenotypic variability in a family with a novel intragenic ROR2 mutation.

PubMed

Brunetti-Pierri, Nicola; Del Gaudio, Daniela; Peters, Hartmut; Justino, Henri; Ott, Claus-Eric; Mundlos, Stefan; Bacino, Carlos A

2008-11-01

Robinow syndrome comprises dysmorphic facial features, short stature, brachymesomelia, segmental spine defects, and genital hypoplasia. The range of severity in this disorder is broad. We report on the clinical and molecular findings of two sib pairs from the same extended family with Robinow syndrome due to a novel intragenic ROR2 deletion involving exons 6 and 7 that could not be detected by sequencing. The affected individuals exhibited variability with respect to the cleft lip, cleft palate, and cardiac findings and for the presence in one of the patients of syringomyelia, which has not been previously reported in Robinow syndrome. Copyright 2008 Wiley-Liss, Inc.

Differences in activation of MAP kinases and variability in the polyglutamine tract of Slt2 in clinical and non-clinical isolates of Saccharomyces cerevisiae.

PubMed

de Llanos, Rosa; Hernández-Haro, Carolina; Barrio, Eladio; Querol, Amparo; Fernández-Espinar, María Teresa; Molina, María

2010-08-01

The concept of Saccharomyces cerevisiae as an emerging opportunistic pathogen is relatively new and it is due to an increasing number of human infections during the past 20 years. There are still few studies addressing the mechanisms of infection of this yeast species. Moreover, little is known about how S. cerevisiae cells sense and respond to the harsh conditions imposed by the host, and whether this response is different between clinical isolates and non-pathogenic strains. In this regard, mitogen-activated protein kinase (MAPK) pathways constitute one of the major mechanisms for controlling transcriptional responses and, in some cases, virulence in fungi. Here we show differences among clinical and non-clinical isolates of S. cerevisiae in the level of activation of the MAPKs Kss1, which controls pseudohyphal and invasive growth, and Slt2, which is required for maintaining the integrity of the cell wall under stress conditions and in the absence of stimulating conditions. Moreover, we report for the first time the existence of length variability in SLT2 alleles of strains with a clinical origin. This is due to the expansion in the number of glutamine-encoding triplets in the microsatellite region coding for the polyglutamine (poly-Q) tract of this gene, which range from 12 to more than 38 repetitions. We suggest that this variability may influence biological features of the Slt2 protein, allowing it to adapt swiftly in order to survive in unusual environments. Copyright (c) 2010 John Wiley & Sons, Ltd.

Clinical status of comorbid bipolar disorder and borderline personality disorder.

PubMed

Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

2016-09-01

The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

Pediatric patients with common variable immunodeficiency: long-term follow-up.

PubMed

Mohammadinejad, P; Aghamohammadi, A; Abolhassani, H; Sadaghiani, M S; Abdollahzade, S; Sadeghi, B; Soheili, H; Tavassoli, M; Fathi, S M; Tavakol, M; Behniafard, N; Darabi, B; Pourhamdi, S; Rezaei, N

2012-01-01

Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. The study population comprised 69 individuals with CVID diagnosed during childhood. The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.

Maternal and neonatal epidemiological features in clinical subtypes of preterm-birth

PubMed Central

Gimenez, Lucas G.; Krupitzki, Hugo B.; Momany, Allison M.; Gili, Juan A.; Poletta, Fernando A.; Campaña, Hebe; Cosentino, Viviana R.; Saleme, César; Pawluk, Mariela; Murray, Jeffrey C.; Castilla, Eduardo E.; Gadow, Enrique C.; Lopez-Camelo, Jorge S.

2016-01-01

Objective This study was designed to characterize and compare the maternal and newborn epidemiological characteristics through analysis of environmental factors, socio-demographic characteristics, and clinical characteristics between the different clinical subtypes of preterm birth (PTB): Idiopathic (PTB-I), premature rupture of the membranes (PTB-PPROM) and medically indicated (PTB-M). The two subtypes PTB-I and PTB-PPROM grouped are called spontaneous preterm births (PTB-S). Methods A retrospective, observational study was conducted in 1.291 preterm non-malformed singleton live-born children to nulliparous and multiparous mother’s in Tucumán-Argentina between 2005 and 2010. Over 50 maternal variables and ten newborn variables were compared between the different clinical subtypes. The comparisons were done to identify heterogeneity between subtypes of preterm birth: (PTB-S) vs. (PTB-M), and within spontaneous subtype: (PTB-I) vs. (PTB-PPROM). In the same way, two conditional logistic multivariate regressions were used to compare the odds ratio (OR) between PTB-S and PTB-M, as well as PTB-I and PTB-PPROM. We matched for maternal age when comparing maternal variables and gestational age when comparing infant variables. Results The PTB-I subtype was characterized by younger mothers of lower socioeconomic status, PTB-PPROM was characterized by environmental factors resulting from inflammatory processes, and PTB-M was characterized by increased maternal or fetal risk pregnancies. Conclusions The main risk factor for PTB-I and PTB-M was having had a prior preterm delivery, however previous spontaneous abortion was not a risk factor, suggesting a reproductive selection mechanism. PMID:26701680

Histopathological characterization of corrosion product associated adverse local tissue reaction in hip implants: a study of 285 cases.

PubMed

Ricciardi, Benjamin F; Nocon, Allina A; Jerabek, Seth A; Wilner, Gabrielle; Kaplowitz, Elianna; Goldring, Steven R; Purdue, P Edward; Perino, Giorgio

2016-01-01

Adverse local tissue reaction (ALTR), characterized by a heterogeneous cellular inflammatory infiltrate and the presence of corrosion products in the periprosthetic soft tissues, has been recognized as a mechanism of failure in total hip replacement (THA). Different histological subtypes may have unique needs for longitudinal clinical follow-up and complication rates after revision arthroplasty. The purpose of this study was to describe the histological patterns observed in the periprosthetic tissue of failed THA in three different implant classes due to ALTR and their association with clinical features of implant failure. Consecutive patients presenting with ALTR from three major hip implant classes (N = 285 cases) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy. Clinical characteristics and features of synovial tissue analysis were compared between the three implant classes. Histological patterns of ALTR identified from our observations and the literature were used to classify each case. The association between implant class and histological patterns was compared. Our histological analysis demonstrates that ALTR encompasses three main histological patterns: 1) macrophage predominant, 2) mixed lymphocytic and macrophagic with or without features of associated with hypersensitivity/allergy or response to particle toxicity (eosinophils/mast cells and/or lymphocytic germinal centers), and 3) predominant sarcoid-like granulomas. Implant classification was associated with histological pattern of failure, and the macrophagic predominant pattern was more common in implants with metal-on-metal bearing surfaces (MoM HRA and MoM LHTHA groups). Duration of implantation and composition of periprosthetic cellular infiltrates was significantly different amongst the three implant types examined suggesting that histopathological features of ALTR may explain the variability of clinical implant performance in these cases. ALTR encompasses a diverse range of histological patterns, which are reflective of both the implant configuration independent of manufacturer and clinical features such as duration of implantation. The macrophagic predominant pattern and its mechanism of implant failure represent an important subgroup of ALTR which could become more prominent with increased length of implantation.

Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype.

PubMed

Hoppman-Chaney, N; Wain, K; Seger, P R; Superneau, D W; Hodge, J C

2013-04-01

The 15q13.3 microdeletion syndrome (OMIM #612001) is characterized by a wide range of phenotypic features, including intellectual disability, seizures, autism, and psychiatric conditions. This deletion is inherited in approximately 75% of cases and has been found in mildly affected and normal parents, consistent with variable expressivity and incomplete penetrance. The common deletion is approximately 2 Mb and contains several genes; however, the gene(s) responsible for the resulting clinical features have not been clearly defined. Recently, four probands were reported with small deletions including only the CHRNA7 gene. These patients showed a wide range of phenotypic features similar to those associated with the larger 15q13.3 microdeletion. To further correlate genotype and phenotype, we queried our database of >15,000 patients tested in the Mayo Clinic Cytogenetics Laboratory from 2008 to 2011 and identified 19 individuals (10 probands and 9 family members) with isolated heterozygous CHRNA7 gene deletions. All but two infants displayed multiple features consistent with 15q13.3 microdeletion syndrome. We also identified the first de novo deletion confined to CHRNA7 as well as the second known case with homozygous deletion of CHRNA7 only. These results provide further evidence implicating CHRNA7 as the gene responsible for the clinical findings associated with 15q13.3 microdeletion. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Clinical features of avian vacuolar myelinopathy in American coots

USGS Publications Warehouse

Larsen, R.S.; Nutter, F.B.; Augspurger, T.; Rocke, T.E.; Tomlinson, L.; Thomas, N.J.; Stoskopf, M.K.

2002-01-01

Objectivea??To characterize clinical features of avian vacuolar myelinopathy (AVM) in American coots. Designa??Case-control study. Animalsa??26 AVM-affected American coots and 12 unaffected coots. Proceduresa??Complete physical, neurologic, hematologic, and plasma biochemical evaluations were performed. Affected coots received supportive care. All coots died or were euthanatized, and AVM status was confirmed via histopathologic findings. Resultsa??3 severely affected coots were euthanatized immediately after examination. Seventeen affected coots were found dead within 7 days of admission, but 5 affected coots survived > 21 days and had signs of clinical recovery. Abnormal physical examination findings appeared to be related to general debilitation. Ataxia (88%), decreased withdrawal reflexes (88%), proprioceptive deficits (81%), decreased vent responses (69%), beak or tongue weakness (42%), and head tremors (31%), as well as absent pupillary light responses (46%), anisocoria (15%), apparent blindness (4%), nystagmus (4%), and strabismus (4%) were detected. Few gross abnormalities were detected at necropsy, but histologically, all AVM-affected coots had severe vacuolation of white matter of the brain. None of the control coots had vacuolation. Conclusions and Clinical Relevancea??Although there was considerable variability in form and severity of clinical neurologic abnormalities, clinical signs common in AVM-affected birds were identified. Clinical recovery of some AVM-affected coots can occur when supportive care is administered. Until the etiology is identified, caution should be exercised when rehabilitating and releasing coots thought to be affected by AVM.

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.

Tumour heterogeneity in glioblastoma assessed by MRI texture analysis: a potential marker of survival

PubMed Central

Pérez-Beteta, Julián; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Martino, Juan; Velasquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Martínez-González, Alicia; Pérez-Romasanta, Luis; Arana, Estanislao; Pérez-García, Víctor M

2016-01-01

Objective: The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. Methods: 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan–Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Results: Kaplan–Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Conclusion: Heterogeneity measures computed on the post-contrast pre-operative T1 weighted MR images of patients with GBM are predictors of survival. Advances in knowledge: Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour. PMID:27319577

Tumour heterogeneity in glioblastoma assessed by MRI texture analysis: a potential marker of survival.

PubMed

Molina, David; Pérez-Beteta, Julián; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Martino, Juan; Velasquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Martínez-González, Alicia; Pérez-Romasanta, Luis; Arana, Estanislao; Pérez-García, Víctor M

2016-07-04

The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T 1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan-Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Kaplan-Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Heterogeneity measures computed on the post-contrast pre-operative T 1 weighted MR images of patients with GBM are predictors of survival. Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour.

Anatomical Features and Early Outcomes of Endovascular Repair of Abdominal Aortic Aneurysm from a Korean Multicenter Registry.

PubMed

Kwon, Hyunwook; Lee, Do Yun; Choi, Soo Jin Na; Park, Ki Hyuk; Min, Seung-Kee; Chang, Jeong-Hwan; Huh, Seung; Jeon, Yong Sun; Won, Jehwan; Byun, Seung Jae; Park, Sang Jun; Jang, Lee Chan; Kwon, Tae-Won

2015-09-01

To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.

What to consider when pseudohypoparathyroidism is ruled out: iPPSD and differential diagnosis.

PubMed

Pereda, Arrate; Garin, Intza; Perez de Nanclares, Guiomar

2018-03-02

Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright's hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes.

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

Familial early-onset dementia with tau intron 10 + 16 mutation with clinical features similar to those of Alzheimer disease.

PubMed

Doran, Mark; du Plessis, Daniel G; Ghadiali, Eric J; Mann, David M A; Pickering-Brown, Stuart; Larner, Andrew J

2007-10-01

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) owing to the tau intron 10 + 16 mutation usually occurs with a prototypical frontotemporal dementia phenotype with prominent disinhibition and affective disturbances. To report a new FTDP-17 pedigree with the tau intron 10 + 16 mutation demonstrating a clinical phenotype suggestive of Alzheimer disease. Case reports. Regional neuroscience centers in northwest England. Patients We examined 4 members of a kindred in which 8 individuals were affected in 3 generations. All 4 patients reported memory difficulty. Marked anomia was also present, but behavioral disturbances were conspicuously absent in the early stages of disease. All patients had an initial clinical diagnosis of Alzheimer disease. No mutations were found in the presenilin or amyloid precursor protein genes. Pathologic examination of the proband showed features typical of FTDP-17, and tau gene analysis showed the intron 10 + 16 mutation. This pedigree illustrates the phenotypic variability of tau intron 10 + 16 mutations. In pedigrees with a clinical diagnosis of Alzheimer disease but without presenilin or amyloid precursor protein gene mutations, tau gene mutations may be found.

Evaluation of graphic cardiovascular display in a high-fidelity simulator.

PubMed

Agutter, James; Drews, Frank; Syroid, Noah; Westneskow, Dwayne; Albert, Rob; Strayer, David; Bermudez, Julio; Weinger, Matthew B

2003-11-01

"Human error" in anesthesia can be attributed to misleading information from patient monitors or to the physician's failure to recognize a pattern. A graphic representation of monitored data may provide better support for detection, diagnosis, and treatment. We designed a graphic display to show hemodynamic variables. Twenty anesthesiologists were asked to assume care of a simulated patient. Half the participants used the graphic cardiovascular display; the other half used a Datex As/3 monitor. One scenario was a total hip replacement with a transfusion reaction to mismatched blood. The second scenario was a radical prostatectomy with 1.5 L of blood loss and myocardial ischemia. Subjects who used the graphic display detected myocardial ischemia 2 min sooner than those who did not use the display. Treatment was initiated sooner (2.5 versus 4.9 min). There were no significant differences between groups in the hip replacement scenario. Systolic blood pressure deviated less from baseline, central venous pressure was closer to its baseline, and arterial oxygen saturation was higher at the end of the case when the graphic display was used. The study lends some support for the hypothesis that providing clinical information graphically in a display designed with emergent features and functional relationships can improve clinicians' ability to detect, diagnose, manage, and treat critical cardiovascular events in a simulated environment. A graphic representation of monitored data may provide better support for detection, diagnosis, and treatment. A user-centered design process led to a novel object-oriented graphic display of hemodynamic variables containing emergent features and functional relationships. In a simulated environment, this display appeared to support clinicians' ability to diagnose, manage, and treat a critical cardiovascular event in a simulated environment. We designed a graphic display to show hemodynamic variables. The study provides some support for the hypothesis that providing clinical information graphically in a display designed with emergent features and functional relationships can improve clinicians' ability to detect, diagnosis, mange, and treat critical cardiovascular events in a simulated environment.

Using automated texture features to determine the probability for masking of a tumor on mammography, but not ultrasound.

PubMed

Häberle, Lothar; Hack, Carolin C; Heusinger, Katharina; Wagner, Florian; Jud, Sebastian M; Uder, Michael; Beckmann, Matthias W; Schulz-Wendtland, Rüdiger; Wittenberg, Thomas; Fasching, Peter A

2017-08-30

Tumors in radiologically dense breast were overlooked on mammograms more often than tumors in low-density breasts. A fast reproducible and automated method of assessing percentage mammographic density (PMD) would be desirable to support decisions whether ultrasonography should be provided for women in addition to mammography in diagnostic mammography units. PMD assessment has still not been included in clinical routine work, as there are issues of interobserver variability and the procedure is quite time consuming. This study investigated whether fully automatically generated texture features of mammograms can replace time-consuming semi-automatic PMD assessment to predict a patient's risk of having an invasive breast tumor that is visible on ultrasound but masked on mammography (mammography failure). This observational study included 1334 women with invasive breast cancer treated at a hospital-based diagnostic mammography unit. Ultrasound was available for the entire cohort as part of routine diagnosis. Computer-based threshold PMD assessments ("observed PMD") were carried out and 363 texture features were obtained from each mammogram. Several variable selection and regression techniques (univariate selection, lasso, boosting, random forest) were applied to predict PMD from the texture features. The predicted PMD values were each used as new predictor for masking in logistic regression models together with clinical predictors. These four logistic regression models with predicted PMD were compared among themselves and with a logistic regression model with observed PMD. The most accurate masking prediction was determined by cross-validation. About 120 of the 363 texture features were selected for predicting PMD. Density predictions with boosting were the best substitute for observed PMD to predict masking. Overall, the corresponding logistic regression model performed better (cross-validated AUC, 0.747) than one without mammographic density (0.734), but less well than the one with the observed PMD (0.753). However, in patients with an assigned mammography failure risk >10%, covering about half of all masked tumors, the boosting-based model performed at least as accurately as the original PMD model. Automatically generated texture features can replace semi-automatically determined PMD in a prediction model for mammography failure, such that more than 50% of masked tumors could be discovered.

Young people with features of gender dysphoria: Demographics and associated difficulties.

PubMed

Holt, Vicky; Skagerberg, Elin; Dunsford, Michael

2016-01-01

This article presents the findings from a cross-sectional study on demographic variables and associated difficulties in 218 children and adolescents (Mean age = 14 years, SD = 3.08, range = 5-17 years), with features of gender dysphoria, referred to the Gender Identity Development Service (GIDS) in London during a 1-year period (1 January 2012-31 December 2012). Data were extracted from patient files (i.e. referral letters, clinical notes and clinician reports). The most commonly reported associated difficulties were bullying, low mood/depression and self-harming. There was a gender difference on some of the associated difficulties with reports of self-harm being significantly more common in the natal females and autism spectrum conditions being significantly more common in the natal males. The findings also showed that many of the difficulties increased with age. Findings regarding demographic variables, gender dysphoria, sexual orientation and family features are reported, and limitations and implications of the cross-sectional study are discussed. In conclusion, young people with gender dysphoria often present with a wide range of associated difficulties which clinicians need to take into account, and our article highlights the often complex presentations of these young people. © The Author(s) 2014.

Phenotypic variability in monozygotic twins with neurofibromatosis 2

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

Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affectedmore » organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.« less

Big Data Toolsets to Pharmacometrics: Application of Machine Learning for Time-to-Event Analysis.

PubMed

Gong, Xiajing; Hu, Meng; Zhao, Liang

2018-05-01

Additional value can be potentially created by applying big data tools to address pharmacometric problems. The performances of machine learning (ML) methods and the Cox regression model were evaluated based on simulated time-to-event data synthesized under various preset scenarios, i.e., with linear vs. nonlinear and dependent vs. independent predictors in the proportional hazard function, or with high-dimensional data featured by a large number of predictor variables. Our results showed that ML-based methods outperformed the Cox model in prediction performance as assessed by concordance index and in identifying the preset influential variables for high-dimensional data. The prediction performances of ML-based methods are also less sensitive to data size and censoring rates than the Cox regression model. In conclusion, ML-based methods provide a powerful tool for time-to-event analysis, with a built-in capacity for high-dimensional data and better performance when the predictor variables assume nonlinear relationships in the hazard function. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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.

[Reproductive variables and gynaecological service use in delusional disorder outpatients].

PubMed

González-Rodríguez, Alexandre; Molina-Andreu, Oriol; Penadés Rubio, Rafael; Catalán Campos, Rosa; Bernardo Arroyo, Miguel

2015-01-01

Oestrogens have been hypothesized to have a protective effect in psychotic disorders. Women with schizophrenia have a later age of menarche, fewer pregnancies and earlier age of menopause. However, little information is available focusing on delusional disorder (DD). We aimed to evaluate gynaecological variables and psychopathology, and rates of gynaecological service use in female DD outpatients. Fourty-six outpatients with DD (DSM-IV-TR) were attended at the Hospital Clinic of Barcelona, from 2008 to 2013. Demographic and clinical variables, as well as gynaecological features were recorded in twenty-five women with DD. Hamilton Rating Scale for Depression-17 for depression, Positive and Negative Syndrome Scale for psychopathology, Personal and Social Performance for functionality, and Columbia Suicide Severity Rating Scale were assessed. Mean age of menarche (SD) was 12.83(1.54) years, mean age of menopause 48.73(2.69), mean age at onset of DD was 48.70(13.03). 48% of the sample did not receive gynaecological attention in the last 2-3 years. No statistically significant correlations were found between age at menopause and age at onset of DD. Age at menopause showed a tendency to be negatively correlated with Personal and Social Performance total scores (r = -0.431; P = .074), and was positively associated with suicidal ideation intensity (r = 0.541; P = .038). However, after controlling for social support variables, this relationship was no longer significant. Although a small sample size, this is the first study to specifically examine gynaecological variables in DD. Low compliance rates in gynaecological service use were found. No correlations between age at menopause and clinical variables were statistically significant. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

Clinical features of progressive vacuolar hepatopathy in Scottish Terriers with and without hepatocellular carcinoma: 114 cases (1980-2013).

PubMed

Cortright, Catherine C; Center, Sharon A; Randolph, John F; McDonough, Sean P; Fecteau, Kellie A; Warner, Karen L; Chiapella, Ann M; Pierce, Rhonda L; Graham, A Heather; Wall, Linda J; Heidgerd, John H; Degen, Melisa A; Lucia, Patricia A; Erb, Hollis N

2014-10-01

To characterize signalment, clinical features, clinicopathologic variables, hepatic ultrasonographic characteristics, endocrinologic profiles, treatment response, and age at death of Scottish Terriers with progressive vacuolar hepatopathy (VH) with or without hepatocellular carcinoma (HCC). Retrospective case series. 114 Scottish Terriers with progressive VH. Electronic databases from 1980 to 2013 were searched for adult (age > 1 year) Scottish Terriers with histopathologic diagnoses of diffuse glycogen-like VH. Available sections of liver specimens were histologically reevaluated to confirm diffuse VH with or without HCC; 8 dogs with HCC only had neoplastic tissue available. Physical examination, clinicopathologic, treatment, and survival data were obtained. 39 of 114 (34%) dogs with VH had HCC detected at surgery or necropsy or by abdominal ultrasonography. Histologic findings indicated that HCC was seemingly preceded by dysplastic hepatocellular foci. No significant differences were found in clinicopathologic variables or age at death between VH-affected dogs with or without HCC. Fifteen of 26 (58%) dogs with high hepatic copper concentrations had histologic features consistent with copper-associated hepatopathy. Although signs consistent with hyperadrenocorticism were observed in 40% (46/114) of dogs, definitive diagnosis was inconsistently confirmed. Assessment of adrenal sex hormone concentrations before and after ACTH administration identified high progesterone and androstenedione concentrations in 88% (22/25) and 80% (20/25) of tested dogs, respectively. Results suggested that VH in Scottish Terriers may be linked to adrenal steroidogenesis and a predisposition to HCC. In dogs with VH, frequent serum biochemical analysis and ultrasonographic surveillance for early tumor detection are recommended.

Unveiling relevant non-motor Parkinson's disease severity symptoms using a machine learning approach.

PubMed

Armañanzas, Rubén; Bielza, Concha; Chaudhuri, Kallol Ray; Martinez-Martin, Pablo; Larrañaga, Pedro

2013-07-01

Is it possible to predict the severity staging of a Parkinson's disease (PD) patient using scores of non-motor symptoms? This is the kickoff question for a machine learning approach to classify two widely known PD severity indexes using individual tests from a broad set of non-motor PD clinical scales only. The Hoehn & Yahr index and clinical impression of severity index are global measures of PD severity. They constitute the labels to be assigned in two supervised classification problems using only non-motor symptom tests as predictor variables. Such predictors come from a wide range of PD symptoms, such as cognitive impairment, psychiatric complications, autonomic dysfunction or sleep disturbance. The classification was coupled with a feature subset selection task using an advanced evolutionary algorithm, namely an estimation of distribution algorithm. Results show how five different classification paradigms using a wrapper feature selection scheme are capable of predicting each of the class variables with estimated accuracy in the range of 72-92%. In addition, classification into the main three severity categories (mild, moderate and severe) was split into dichotomic problems where binary classifiers perform better and select different subsets of non-motor symptoms. The number of jointly selected symptoms throughout the whole process was low, suggesting a link between the selected non-motor symptoms and the general severity of the disease. Quantitative results are discussed from a medical point of view, reflecting a clear translation to the clinical manifestations of PD. Moreover, results include a brief panel of non-motor symptoms that could help clinical practitioners to identify patients who are at different stages of the disease from a limited set of symptoms, such as hallucinations, fainting, inability to control body sphincters or believing in unlikely facts. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute respiratory infection case definitions for young children: a systematic review of community-based epidemiologic studies in South Asia.

PubMed

Roth, Daniel E; Gaffey, Michelle F; Smith-Romero, Evelyn; Fitzpatrick, Tiffany; Morris, Shaun K

2015-12-01

To explore the variability in childhood acute respiratory infection case definitions for research in low-income settings where there is limited access to laboratory or radiologic investigations. We conducted a systematic review of community-based, longitudinal studies in South Asia published from January 1990 to August 2013, in which childhood acute respiratory infection outcomes were reported. Case definitions were classified by their label (e.g. pneumonia, acute lower respiratory infection) and clinical content 'signatures' (array of clinical features that would be always present, conditionally present or always absent among cases). Case definition heterogeneity was primarily assessed by the number of unique case definitions overall and by label. We also compared case definition-specific acute respiratory infection incidence rates for studies reporting incidence rates for multiple case definitions. In 56 eligible studies, we found 124 acute respiratory infection case definitions. Of 90 case definitions for which clinical content was explicitly defined, 66 (73%) were unique. There was a high degree of content heterogeneity among case definitions with the same label, and some content signatures were assigned multiple labels. Within studies for which incidence rates were reported for multiple case definitions, variation in content was always associated with a change in incidence rate, even when the content differed by a single clinical feature. There has been a wide variability in case definition label and content combinations to define acute upper and lower respiratory infections in children in community-based studies in South Asia over the past two decades. These inconsistencies have important implications for the synthesis and translation of knowledge regarding the prevention and treatment of childhood acute respiratory infection. © 2015 John Wiley & Sons Ltd.

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease.

PubMed

Cholerton, Brenna; Johnson, Catherine O; Fish, Brian; Quinn, Joseph F; Chung, Kathryn A; Peterson-Hiller, Amie L; Rosenthal, Liana S; Dawson, Ted M; Albert, Marilyn S; Hu, Shu-Ching; Mata, Ignacio F; Leverenz, James B; Poston, Kathleen L; Montine, Thomas J; Zabetian, Cyrus P; Edwards, Karen L

2018-05-01

Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD. Copyright © 2018 Elsevier Ltd. All rights reserved.

The utility of a classificatory decision tree approach to assist clinical differentiation of melancholic and non-melancholic depression.

PubMed

Parker, G; McCraw, S; Hadzi-Pavlovic, D

2015-07-15

Studies suggest that differentiating melancholic from non-melancholic depressive disorders is advanced by use of illness course as well as symptom variables but, in practice, potentially differentiating variables are generally positioned as having equal value. Judging that differentiating features are more likely to vary in their signal intensity, we sought to determine the number of features required to effect differentiation and their hierarchical order. The 24-item clinician-rated Sydney Melancholia Prototype Index (SMPI-CR) was completed for 364 unipolar depressed patients. The sample was divided into two cohorts according to the recruitment period. An RPART classification tree analysis identified the most discriminating SMPI items in the development sample of 197 patients, and examined the sensitivity and specificity of the diagnostic decisions, then sought to replicate findings in a validation sample of 169 patients. Independent analyses of putative SMPI items identified only seven items as required to discriminate those with clinically-diagnosed melancholic or non-melancholic depression when the conditions were examined separately. An RPART analysis considering differentiation of melancholic and non-melancholic depression in the total samples retained five of those items in the classification tree, three of which were non-symptom items, and with 92% sensitivity and 80% specificity in the development sample. This reduced item set showed 93% sensitivity and 82% specificity in the validation sample. Our clinical judgment of melancholic or non-melancholic depression may not correspond with the clinical logic employed by other clinicians. Only five SMPI items were required to derive a succinct and efficient decision tree, comprising high sensitivity and specificity in differentiating melancholic and non-melancholic depression. Current study findings provide an empirical model that could enrich clinicians׳ approach to differentiating melancholic and non-melancholic depression. Copyright © 2015 Elsevier B.V. All rights reserved.

TEPAPA: a novel in silico feature learning pipeline for mining prognostic and associative factors from text-based electronic medical records.

PubMed

Lin, Frank Po-Yen; Pokorny, Adrian; Teng, Christina; Epstein, Richard J

2017-07-31

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

Biochemical recurrence after radical prostatectomy: what does it mean?

PubMed Central

Tourinho-Barbosa, Rafael; Srougi, Victor; Nunes-Silva, Igor; Baghdadi, Mohammed; Rembeyo, Gregory; Eiffel, Sophie S.; Barret, Eric; Rozet, Francois; Galiano, Marc; Cathelineau, Xavier; Sanchez-Salas, Rafael

2018-01-01

ABSTRACT Background Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. Objective To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM. PMID:29039897

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

PubMed

Serretti, Alessandro; Chiesa, Alberto; Calati, Raffaella; Linotte, Sylvie; Sentissi, Othman; Papageorgiou, Konstantinos; Kasper, Siegfried; Zohar, Joseph; De Ronchi, Diana; Mendlewicz, Julien; Amital, Daniela; Montgomery, Stuart; Souery, Daniel

2013-03-01

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Masturbation in infancy and early childhood presenting as a movement disorder: 12 cases and a review of the literature.

PubMed

Yang, Michele L; Fullwood, Erika; Goldstein, Joshua; Mink, Jonathan W

2005-12-01

Infantile masturbation (gratification behavior) is not commonly identified as a cause of recurrent paroxysmal movements. Extensive and fruitless investigations may be pursued before establishing this diagnosis. Sparse literature is available regarding masturbatory behavior as a whole, but literature available as case reports describes common features. The purpose of this case series is to describe consistent features in young children with posturing accompanying masturbation. Twelve patients presenting to a pediatric movement disorders clinic with a suspected movement disorder were determined to have postures and movements associated with masturbation. We reviewed the clinical history, examination, and home videotapes of these patients. Our patients had several features in common: (1) onset after the age of 3 months and before 3 years; (2) stereotyped episodes of variable duration; (3) vocalizations with quiet grunting; (4) facial flushing with diaphoresis; (5) pressure on the perineum with characteristic posturing of the lower extremities; (6) no alteration of consciousness; (7) cessation with distraction; (8) normal examination; and (9) normal laboratory studies. The identification of these common features by primary care providers should assist in making this diagnosis and eliminate the need for extensive, unnecessary testing. Direct observation of the events is crucial, and the video camera is a useful tool that may help in the identification of masturbatory behavior.

Gender differences in older adults with chronic migraine in Turkey.

PubMed

Özge, Aynur; Uluduz, Derya; Selekler, Macit; Öztürk, Musa; Baykan, Betül; Çınar, Nilgün; Domaç, Füsun M; Zarifoğlu, Mehmet; Inan, Levent E; Akyol, Ali; Bolay, Hayrunnisa; Uzuner, Gülnur T; Erdemoğlu, Ali K; Oksuz, Nevra; Temel, Gulhan O

2015-05-01

Chronic migraine is a growing and disabling subtype of migraine with different risk factors and clinical features, even in older adults. We sought to define and differentiate clinical features of chronic migraine in older adults. We also aimed to compare major clinical features of chronic migraine in older adults with those in younger people of both sexes. We used electronic dataset (Turkish Headache Database) from 13 tertiary headache centers in Turkey. Electronic dataset included detailed headache-defining features according to ICHD-II criteria based on face-to-face interviews and examination by a headache specialist. Using statistical methods, clinical variables of chronic migraine in older adults were compared with those of younger adults. We included 915 patients with chronic migraine (mean age 43.80 ± 13.95 years); 83.3% were females. In total, 301 patients (32.9%) with chronic migraine aged >50 years were compared with 614 patients aged <50 years. There was no significant change in men with increasing age. However, duration of headache history, severity of attacks, previous histories of motion sickness and positive family history of headaches were significantly different in women with increasing age. Further sex-related differences have been shown in parameters such as attack duration, quality and associated nausea. Chronic migraine is an infrequent type of migraine and shows age-related changes in some phenotypic characteristics, such as severity of attacks, especially in women aged older than 50 years. Furthermore, positive family history of headaches and history of motion sickness increase the likelihood of developing chronic migraine in older women, indicating involvement of some gender-related, but as-yet unknown, genetic factors. © 2014 Japan Geriatrics Society.

Organization of care and diagnosed depression among women veterans.

PubMed

Sambamoorthi, Usha; Bean-Mayberry, Bevanne; Findley, Patricia A; Yano, Elizabeth M; Banerjea, Ranjana

2010-09-01

To analyze the association between the organizational features of integration of physical and mental healthcare in womens health clinics and the diagnosis of depression among women veterans with or at risk for cardiovascular conditions (ie, diabetes mellitus, heart disease, or hypertension). Retrospective and observational secondary data analyses. We studied 27,972 women veterans from 118 facilities with diagnosed cardiovascular conditions in fiscal year 2001 (FY2001) using merged Medicare claims and Veterans Health Administration (VHA) data merged with the 1999 VHA Survey of Primary Care Practices and the 2001 VHA Survey of Women Veterans Health Programs and Practices. The dependent variable was a binary indicator for diagnosed depression during FY2001 at the individual level. We used a multilevel logistic regression model to control for clustering of women veterans within facilities. Individual-level independent variables included demographics, socioeconomic characteristics, and chronic physical conditions. Overall, 27% of women veterans using the VHA were diagnosed as having depression in FY2001. Across facilities, rates of diagnosed depression varied from 13% to 41%. After controlling for individual-level and facility-level independent variables, women veterans who were served in separate women's health clinics with integrated physical and mental healthcare were more likely to have diagnosed depression. The adjusted odds ratio was 1.12 (95% confidence interval, 1.01-1.25). Existing women-specific VHA organizational features with integration of primary care and mental health seem effective in diagnosing depression. Emerging patient-centered medical home models may facilitate diagnosis and treatment of mental health issues among women with complex chronic conditions.

Magnetic resonance imaging features of dogs with incomplete recovery after acute, severe spinal cord injury

PubMed Central

Lewis, Melissa J.; Cohen, Eli B.; Olby, Natasha J.

2017-01-01

Study Design Retrospective case series Objectives Describe the magnetic resonance imaging (MRI) features of dogs chronically impaired after severe spinal cord injury (SCI) and investigate associations between imaging variables and residual motor function. Setting United States of America Methods Thoracolumbar MRI from dogs with incomplete recovery months to years after clinically complete (paralysis with loss of pain perception) thoracolumbar SCI were reviewed. Lesion features were described and quantified. Gait was quantified using an ordinal, open field scale (OFS). Associations between imaging features and gait scores, duration of injury (DOI) or SCI treatment were determined. Results 35 dogs were included. Median OFS was 2 (0–6), median DOI was 13 months (3–83) and intervertebral disc herniation was the most common diagnosis (n=27). Myelomalacia was the most common qualitative feature followed by cystic change; syringomyelia and fibrosis were uncommon. Lesion length corrected to L2 length (LL:L2) was variable (median LL:L2=3.5 (1.34–11.54)). Twenty-nine dogs had 100% maximum cross-sectional spinal cord compromise (MSCC) at the lesion epicenter and the length of 100% compromised area varied widely (median length 100% MSCC:L2=1.29 (0.39–7.64). Length 100% MSCC:L2 was associated with OFS (p=0.012). OFS was not associated with any qualitative features. DOI or treatment type were not associated with imaging features or lesion quantification. Conclusions Lesion characteristics on MRI in dogs with incomplete recovery after severe SCI were established. Length of 100% MSCC was associated with hind limb motor function. Findings demonstrate a spectrum of injury severity on MRI amongst severely affected dogs which is related to functional status. PMID:29057987

Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression.

PubMed

Brooks, Samira A; Khandani, Amir H; Fielding, Julia R; Lin, Weili; Sills, Tiffany; Lee, Yueh; Arreola, Alexandra; Milowsky, Mathew I; Wallen, Eric M; Woods, Michael E; Smith, Angie B; Nielsen, Mathew E; Parker, Joel S; Lalush, David S; Rathmell, W Kimryn

2016-06-15

Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans. ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis. Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype. Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia

PubMed Central

Gomperts, Stephen N.

2016-01-01

ABSTRACT Purpose of Review: This article provides an overview of the clinical features, neuropathologic findings, diagnostic criteria, and management of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), together known as the Lewy body dementias. Recent Findings: DLB and PDD are common, clinically similar syndromes that share characteristic neuropathologic changes, including deposition of α-synuclein in Lewy bodies and neurites and loss of tegmental dopamine cell populations and basal forebrain cholinergic populations, often with a variable degree of coexisting Alzheimer pathology. The clinical constellations of DLB and PDD include progressive cognitive impairment associated with parkinsonism, visual hallucinations, and fluctuations of attention and wakefulness. Current clinical diagnostic criteria emphasize these features and also weigh evidence for dopamine cell loss measured with single-photon emission computed tomography (SPECT) imaging and for rapid eye movement (REM) sleep behavior disorder, a risk factor for the synucleinopathies. The timing of dementia relative to parkinsonism is the major clinical distinction between DLB and PDD, with dementia arising in the setting of well-established idiopathic Parkinson disease (after at least 1 year of motor symptoms) denoting PDD, while earlier cognitive impairment relative to parkinsonism denotes DLB. The distinction between these syndromes continues to be an active research question. Treatment for these illnesses remains symptomatic and relies on both pharmacologic and nonpharmacologic strategies. Summary: DLB and PDD are important and common dementia syndromes that overlap in their clinical features, neuropathology, and management. They are believed to exist on a spectrum of Lewy body disease, and some controversy persists in their differentiation. Given the need to optimize cognition, extrapyramidal function, and psychiatric health, management can be complex and should be systematic. PMID:27042903

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

PubMed

Coulter, Tanya I; Chandra, Anita; Bacon, Chris M; Babar, Judith; Curtis, James; Screaton, Nick; Goodlad, John R; Farmer, George; Steele, Cathal Laurence; Leahy, Timothy Ronan; Doffinger, Rainer; Baxendale, Helen; Bernatoniene, Jolanta; Edgar, J David M; Longhurst, Hilary J; Ehl, Stephan; Speckmann, Carsten; Grimbacher, Bodo; Sediva, Anna; Milota, Tomas; Faust, Saul N; Williams, Anthony P; Hayman, Grant; Kucuk, Zeynep Yesim; Hague, Rosie; French, Paul; Brooker, Richard; Forsyth, Peter; Herriot, Richard; Cancrini, Caterina; Palma, Paolo; Ariganello, Paola; Conlon, Niall; Feighery, Conleth; Gavin, Patrick J; Jones, Alison; Imai, Kohsuke; Ibrahim, Mohammad A A; Markelj, Gašper; Abinun, Mario; Rieux-Laucat, Frédéric; Latour, Sylvain; Pellier, Isabelle; Fischer, Alain; Touzot, Fabien; Casanova, Jean-Laurent; Durandy, Anne; Burns, Siobhan O; Savic, Sinisa; Kumararatne, D S; Moshous, Despina; Kracker, Sven; Vanhaesebroeck, Bart; Okkenhaug, Klaus; Picard, Capucine; Nejentsev, Sergey; Condliffe, Alison M; Cant, Andrew James

2017-02-01

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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.

The Computer Book of the Internal Medicine Resident: competence acquisition and achievement of learning objectives.

PubMed

Oristrell, J; Oliva, J C; Casanovas, A; Comet, R; Jordana, R; Navarro, M

2014-01-01

The Computer Book of the Internal Medicine resident (CBIMR) is a computer program that was validated to analyze the acquisition of competences in teams of Internal Medicine residents. To analyze the characteristics of the rotations during the Internal Medicine residency and to identify the variables associated with the acquisition of clinical and communication skills, the achievement of learning objectives and resident satisfaction. All residents of our service (n=20) participated in the study during a period of 40 months. The CBIMR consisted of 22 self-assessment questionnaires specific for each rotation, with items on services (clinical workload, disease protocolization, resident responsibilities, learning environment, service organization and teamwork) and items on educational outcomes (acquisition of clinical and communication skills, achievement of learning objectives, overall satisfaction). Associations between services features and learning outcomes were analyzed using bivariate and multivariate analysis. An intense clinical workload, high resident responsibilities and disease protocolization were associated with the acquisition of clinical skills. High clinical competence and teamwork were both associated with better communication skills. Finally, an adequate learning environment was associated with increased clinical competence, the achievement of educational goals and resident satisfaction. Potentially modifiable variables related with the operation of clinical services had a significant impact on the acquisition of clinical and communication skills, the achievement of educational goals, and resident satisfaction during the specialized training in Internal Medicine. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Gorlin-Goltz Syndrome: An Uncommon Cause of Facial Pain and Asymmetry.

PubMed

Pickrell, Brent B; Nguyen, Harrison P; Buchanan, Edward P

2015-10-01

Gorlin-Goltz syndrome is an underdiagnosed autosomal dominant disorder with variable expressivity that is characterized by an increased predisposition to tumorigenesis of multiple types. The major clinical features include multiple basal cell carcinomas (BCCs) appearing in early childhood, palmar and plantar pits, odontogenic keratocysts of the oral cavity, skeletal defects, craniofacial dysmorphism, and ectopic intracranial calcification. The authors present the clinical course of a 12-year-old girl presenting with facial asymmetry and pain because of previously undiagnosed Gorlin-Goltz syndrome. Early diagnosis and attentive management by a multidisciplinary team are paramount to improving outcomes in patients with this disorder, and this report serves as a paradigm for maintaining a high clinical suspicion, which must be accompanied by an appropriate radiologic workup.

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.

Predicting clinical decline in progressive agrammatic aphasia and apraxia of speech.

PubMed

Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Clark, Heather M; Strand, Edythe A; Machulda, Mary M; Spychalla, Anthony J; Senjem, Matthew L; Jack, Clifford R; Josephs, Keith A

2017-11-28

To determine whether baseline clinical and MRI features predict rate of clinical decline in patients with progressive apraxia of speech (AOS). Thirty-four patients with progressive AOS, with AOS either in isolation or in the presence of agrammatic aphasia, were followed up longitudinally for up to 4 visits, with clinical testing and MRI at each visit. Linear mixed-effects regression models including all visits (n = 94) were used to assess baseline clinical and MRI variables that predict rate of worsening of aphasia, motor speech, parkinsonism, and behavior. Clinical predictors included baseline severity and AOS type. MRI predictors included baseline frontal, premotor, motor, and striatal gray matter volumes. More severe parkinsonism at baseline was associated with faster rate of decline in parkinsonism. Patients with predominant sound distortions (AOS type 1) showed faster rates of decline in aphasia and motor speech, while patients with segmented speech (AOS type 2) showed faster rates of decline in parkinsonism. On MRI, we observed trends for fastest rates of decline in aphasia in patients with relatively small left, but preserved right, Broca area and precentral cortex. Bilateral reductions in lateral premotor cortex were associated with faster rates of decline of behavior. No associations were observed between volumes and decline in motor speech or parkinsonism. Rate of decline of each of the 4 clinical features assessed was associated with different baseline clinical and regional MRI predictors. Our findings could help improve prognostic estimates for these patients. © 2017 American Academy of Neurology.

Modeling the acceptance of clinical information systems among hospital medical staff: an extended TAM model.

PubMed

Melas, Christos D; Zampetakis, Leonidas A; Dimopoulou, Anastasia; Moustakis, Vassilis

2011-08-01

Recent empirical research has utilized the Technology Acceptance Model (TAM) to advance the understanding of doctors' and nurses' technology acceptance in the workplace. However, the majority of the reported studies are either qualitative in nature or use small convenience samples of medical staff. Additionally, in very few studies moderators are either used or assessed despite their importance in TAM based research. The present study focuses on the application of TAM in order to explain the intention to use clinical information systems, in a random sample of 604 medical staff (534 physicians) working in 14 hospitals in Greece. We introduce physicians' specialty as a moderator in TAM and test medical staff's information and communication technology (ICT) knowledge and ICT feature demands, as external variables. The results show that TAM predicts a substantial proportion of the intention to use clinical information systems. Findings make a contribution to the literature by replicating, explaining and advancing the TAM, whereas theory is benefited by the addition of external variables and medical specialty as a moderator. Recommendations for further research are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk factors for autism: translating genomic discoveries into diagnostics.

PubMed

Scherer, Stephen W; Dawson, Geraldine

2011-07-01

Autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in communication and reciprocal social interaction, and the presence of restricted and repetitive behaviors. The spectrum of autistic features is variable, with severity of symptoms ranging from mild to severe, sometimes with poor clinical outcomes. Twin and family studies indicate a strong genetic basis for ASD susceptibility. Recent progress in defining rare highly penetrant mutations and copy number variations as ASD risk factors has prompted early uptake of these research findings into clinical diagnostics, with microarrays becoming a 'standard of care' test for any ASD diagnostic work-up. The ever-changing landscape of the generation of genomic data coupled with the vast heterogeneity in cause and expression of ASDs (further influenced by issues of penetrance, variable expressivity, multigenic inheritance and ascertainment) creates complexity that demands careful consideration of how to apply this knowledge. Here, we discuss the scientific, ethical, policy and communication aspects of translating the new discoveries into clinical and diagnostic tools for promoting the well-being of individuals and families with ASDs.

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute clinical recovery from sport-related concussion.

PubMed

Nelson, Lindsay D; Janecek, Julie K; McCrea, Michael A

2013-12-01

Concussion is a highly prevalent injury in contact and collision sports that has historically been poorly understood. An influx of sport-concussion research in recent years has led to a dramatic improvement in our understanding of the injury's defining characteristics and natural history of recovery. In this review, we discuss the current state of knowledge regarding the characteristic features of concussion and typical acute course of recovery, with an emphasis on the aspects of functioning most commonly assessed by clinicians and researchers (e.g., symptoms, cognitive deficits, postural stability). While prototypical clinical recovery is becoming better understood, questions remain regarding what factors (e.g., injury severity, demographic variables, history of prior concussions, psychological factors) may explain individual variability in recovery. Although research concerning individual differences in response to concussion is relatively new, and in many cases limited methodologically, we discuss the evidence about several potential moderators of concussion recovery and point out areas for future research. Finally, we describe how increased knowledge about the negative effects of and recovery following concussion has been translated into clinical guidelines for managing concussed athletes.

The Analytic Information Warehouse (AIW): a Platform for Analytics using Electronic Health Record Data

PubMed Central

Post, Andrew R.; Kurc, Tahsin; Cholleti, Sharath; Gao, Jingjing; Lin, Xia; Bornstein, William; Cantrell, Dedra; Levine, David; Hohmann, Sam; Saltz, Joel H.

2013-01-01

Objective To create an analytics platform for specifying and detecting clinical phenotypes and other derived variables in electronic health record (EHR) data for quality improvement investigations. Materials and Methods We have developed an architecture for an Analytic Information Warehouse (AIW). It supports transforming data represented in different physical schemas into a common data model, specifying derived variables in terms of the common model to enable their reuse, computing derived variables while enforcing invariants and ensuring correctness and consistency of data transformations, long-term curation of derived data, and export of derived data into standard analysis tools. It includes software that implements these features and a computing environment that enables secure high-performance access to and processing of large datasets extracted from EHRs. Results We have implemented and deployed the architecture in production locally. The software is available as open source. We have used it as part of hospital operations in a project to reduce rates of hospital readmission within 30 days. The project examined the association of over 100 derived variables representing disease and co-morbidity phenotypes with readmissions in five years of data from our institution’s clinical data warehouse and the UHC Clinical Database (CDB). The CDB contains administrative data from over 200 hospitals that are in academic medical centers or affiliated with such centers. Discussion and Conclusion A widely available platform for managing and detecting phenotypes in EHR data could accelerate the use of such data in quality improvement and comparative effectiveness studies. PMID:23402960

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

PubMed Central

Lee, Way Seah; Ng, Ruey Terng; Chan, Koon-Wing; Lau, Yu-Lung

2016-01-01

AIM Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn’s disease (CD). RESULTS Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified. CONCLUSION The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate. PMID:28082818

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort.

PubMed

Lee, Way Seah; Ng, Ruey Terng; Chan, Koon-Wing; Lau, Yu-Lung

2016-12-28

Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD. All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn's disease (CD). Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified. The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

Generalized overgrowth syndromes with prenatal onset.

PubMed

Yachelevich, Naomi

2015-04-01

Children with generalized overgrowth syndromes are large at birth, or have excessive postnatal growth. Many of these syndromes are associated with an increase in neoplasia. Consideration of the possibility of overgrowth syndrome in a pediatric patient who presents with increased growth parameters, variable malformations and neurodevelopmental phenotype, and distinctive features, is important for medical management, reproductive counseling, and tumor surveillance for some of the disorders. This review describes the clinical features and surveillance recommendations for the common generalized overgrowth syndromes the pediatrician may encounter. It also provides a glimpse into advances of recent years in understanding the molecular mechanisms responsible for the disrupted growth regulation in these disorders. Copyright © 2015 Mosby, Inc. All rights reserved.

Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.

PubMed

Aas, M; Henry, C; Bellivier, F; Lajnef, M; Gard, S; Kahn, J-P; Lagerberg, T V; Aminoff, S R; Bjella, T; Leboyer, M; Andreassen, O A; Melle, I; Etain, B

2017-04-01

Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro. Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset. Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.

Current situation of asthma-COPD overlap syndrome (ACOS) in Chinese patients older than 40 years with airflow limitation: rationale and design for a multicenter, cross-sectional trial (study protocol).

PubMed

Kang, Jian; Yao, Wanzhen; Cai, Baiqiang; Chen, Ping; Ling, Xia; Shang, Hongyan

2016-12-01

Asthma and chronic obstructive pulmonary disease (COPD) are the frequently occurring chronic airway diseases, and the overlapping syndrome observed in the majority of patients has been recently defined as asthma-COPD overlap syndrome (ACOS) by the Global Initiative for Chronic Obstructive Lung (GOLD, 2014) and Global initiative for Asthma (GINA, 2015). The proportion, features, and clinical practice of ACOS still remain elusive in China. We are conducting this multicenter, cross-sectional, observational study (NCT02600221) to investigate the distributions of chronic obstructive diseases in patients >40 years of age with chronic airflow limitation in China along with determination of the main clinical practice and features of these diseases. The study will also explore the factors that may influence the exacerbations and severity of ACOS in Chinese patients (>40 years of age). A total of 2,000 patients (age, ≥40 years; either sex) who are clinically diagnosed as having asthma, COPD/chronic bronchitis/emphysema, or ACOS for at least 12 months with airflow limitation [post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC): <0.7] will be enrolled from approximately 20 sites in China between December 2015 and December 2016. The proportion of ACOS among patients older than 40 years based on GINA 2015 and GOLD 2014 definitions is the primary variable. Following were the secondary variables: the proportions of COPD and asthma among the patients, distributions of the severity of airflow limitation, distribution of groups according to GOLD 2011 group definition (A, B, C, D), and the distribution of medication by drug class in patients with ACOS, asthma, and COPD. Acute exacerbation history, hospitalization, and severity of ACOS as evaluated using COPD Assessment Test, Asthma Control Questionnaire-5, and Modified British Medical Research Council in patients with ACOS were also assessed. This will be the first study to disseminate scientific knowledge on the current situation, main clinical practice, and features of ACOS, asthma, and COPD conditions in Chinese patients. The insights will be helpful in designing optimal management strategies for ACOS and redefining the healthcare development programs.

Genomic characterization of recurrent high-grade astroblastoma.

PubMed

Bale, Tejus A; Abedalthagafi, Malak; Bi, Wenya Linda; Kang, Yun Jee; Merrill, Parker; Dunn, Ian F; Dubuc, Adrian; Charbonneau, Sarah K; Brown, Loreal; Ligon, Azra H; Ramkissoon, Shakti H; Ligon, Keith L

2016-01-01

Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63)*, PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Magnitude and Temporal Variability of Inter-stimulus EEG Modulate the Linear Relationship Between Laser-Evoked Potentials and Fast-Pain Perception

PubMed Central

Li, Linling; Huang, Gan; Lin, Qianqian; Liu, Jia; Zhang, Shengli; Zhang, Zhiguo

2018-01-01

The level of pain perception is correlated with the magnitude of pain-evoked brain responses, such as laser-evoked potentials (LEP), across trials. The positive LEP-pain relationship lays the foundation for pain prediction based on single-trial LEP, but cross-individual pain prediction does not have a good performance because the LEP-pain relationship exhibits substantial cross-individual difference. In this study, we aim to explain the cross-individual difference in the LEP-pain relationship using inter-stimulus EEG (isEEG) features. The isEEG features (root mean square as magnitude and mean square successive difference as temporal variability) were estimated from isEEG data (at full band and five frequency bands) recorded between painful stimuli. A linear model was fitted to investigate the relationship between pain ratings and LEP response for fast-pain trials on a trial-by-trial basis. Then the correlation between isEEG features and the parameters of LEP-pain model (slope and intercept) was evaluated. We found that the magnitude and temporal variability of isEEG could modulate the parameters of an individual's linear LEP-pain model for fast-pain trials. Based on this, we further developed a new individualized fast-pain prediction scheme, which only used training individuals with similar isEEG features as the test individual to train the fast-pain prediction model, and obtained improved accuracy in cross-individual fast-pain prediction. The findings could help elucidate the neural mechanism of cross-individual difference in pain experience and the proposed fast-pain prediction scheme could be potentially used as a practical and feasible pain prediction method in clinical practice. PMID:29904336

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

Young Age at Diagnosis of Type 1 Diabetes Is Associated with the Development of Celiac Disease-Associated Antibodies in Children Living in Newfoundland and Labrador, Canada.

PubMed

Pall, Harpreet; Newhook, Leigh A; Aaron, Hillary; Curtis, Joseph; Randell, Ed

2015-10-14

The objectives of this study were to establish the prevalence of positive antibodies to endomysium (EMA) and tissue transglutaminase (tTG) in children with type 1 diabetes living in Newfoundland and Labrador (NL), and to examine clinical features associated with positive antibodies. Patients were recruited from the pediatric diabetes clinic. One hundred sixty-seven children with type 1 diabetes from the 280 children followed at the clinic were prospectively screened for celiac disease using EMA and tTG. The variables of Irish descent, age at onset of diabetes, duration of diabetes, sex, family history of celiac disease, hemoglobin A1C (A1C), ferritin, gastrointestinal symptoms, and body mass index were compiled for all patients. The group of patients with positive antibodies to EMA and/or tTG was compared to the group with negative antibodies. The prevalence of patients with positive antibodies to EMA and/or tTG was 16.8% (n = 28). One patient had also been previously diagnosed with symptomatic celiac disease. The two statistically significant variables with positive antibodies were an earlier age at onset of diabetes (Mann-Whitney U two-tailed test: mean difference 3.2 years, 95% CI 1.7-4.8 years, p < 0.0001) and longer duration of diabetes (Mann-Whitney U two-tailed test: mean difference 2.9 years, 95% CI 1.3-4.4 years, p < 0.0001). Irish descent was associated with positive antibodies but did not reach statistical significance. On logistic regression analysis performed with these three variables together, only age at onset of diabetes remained significant. There is a high prevalence of celiac disease-associated antibodies in children living in NL with type 1 diabetes. Unlike other clinical features, an earlier age at onset of diabetes was predictive for positive antibodies. As the majority of children with positive antibodies did not have signs or symptoms of celiac disease, routine screening for celiac disease in type 1 diabetes is recommended.

Observation of c.260A > G mutation in superoxide dismutase 1 that causes p.Asn86Ser in Iranian amyotrophic lateral sclerosis patient and absence of genotype/phenotype correlation.

PubMed

Khani, Marzieh; Alavi, Afagh; Nafissi, Shahriar; Elahi, Elahe

2015-07-06

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder in European populations. ALS can be sporadic ALS (SALS) or familial ALS (FALS). Among 20 known ALS genes, mutations in C9orf72 and superoxide dismutase 1 (SOD1) are the most common genetic causes of the disease. Whereas C9orf72 mutations are more common in Western populations, the contribution of SOD1 to ALS in Iran is more than C9orf72. At present, a clear genotype/phenotype correlation for ALS has not been identified. We aimed to perform mutation screening of SOD1 in a newly identified Iranian FALS patient and to assess whether a genotype/phenotype correlation for the identified mutation exists. The five exons of SOD1 and flanking intronic sequences of a FALS proband were screened for mutations by direct sequencing. The clinical features of the proband were assessed by a neuromuscular specialist (SN). The phenotypic presentations were compared to previously reported patients with the same mutation. Heterozygous c.260A > G mutation in SOD1 that causes Asn86Ser was identified in the proband. Age at onset was 34 years and site of the first presentation was in the lower extremities. Comparisons of clinical features of different ALS patients with the same mutation evidenced variable presentations. The c.260A > G mutation in SOD1 that causes Asn86Ser appears to cause ALS with variable clinical presentations.

Get the Picture: A Pilot Feasibility Study of Telemedical Wound Assessment Using a Mobile Phone in Cardiology Patients.

PubMed

de Heide, John; Vroegh, C J; Szili Torok, T; Gobbens, R J J; Zijlstra, F; Takens-Lameijer, M; Lenzen, M J; Yap, S C; Scholte Op Reimer, W J M

Postprocedural complications after elective cardiac interventions include hematomas and infections. Telemedical wound assessment using mobile phones with integrated cameras may improve quality of care and help reduce costs. We aimed to study the feasibility of telemedical wound assessment using a mobile phone. The primary aim was the number of patients who were able to upload their pictures. Secondary aims were image interpretability, agreement between nurse practitioners, and patient evaluation of the intervention. This is a prospective study of all consecutive patients who underwent an elective cardiac intervention. Patients were instructed to photograph their wound or puncture site after hospital discharge and upload the pictures to a secure email address 6 days after hospital discharge. Received photos were assessed by 2 nurse practitioners. The intervention was evaluated using a peer-reviewed questionnaire and photo assessment scheme. In total, 46 eligible patients were included in the study, with 5 screen failures (eg, clinical stay ≥ 6 days) and 1 patient lost to follow-up. Thirty-three of 40 patients (83%) were able to upload their pictures. Smartphone users were more successful in uploading their pictures compared with feature phone users (93% vs 55%, P < .01). Eighty-eight percent of the clinical pictures were interpretable. The interobserver variability had an agreement between 93% and 97%. Patients are able to take and upload the mobile clinical photos to the secure email address, and the vast majority was interpretable. Smartphone users were more successful than feature phone users in uploading their pictures. The interobserver variability was good.

Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation

PubMed Central

2011-01-01

Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4) due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity. PMID:21699693

X-linked adrenoleukodystrophy in heterozygous female patients: women are not just carriers.

PubMed

Lourenço, Charles Marques; Simão, Gustavo Novelino; Santos, Antonio Carlos; Marques, Wilson

2012-07-01

X-linked adrenoleukodystrophy (X-ALD) is a recessive X-linked disorder associated with marked phenotypic variability. Female carriers are commonly thought to be normal or only mildly affected, but their disease still needs to be better described and systematized. To review and systematize the clinical features of heterozygous women followed in a Neurogenetics Clinic. We reviewed the clinical, biochemical, and neuroradiological data of all women known to have X-ADL. The nine women identified were classified into three groups: with severe and aggressive diseases; with slowly progressive, spastic paraplegia; and with mildly decreased vibratory sensation, brisk reflexes, and no complaints. Many of these women did not have a known family history of X-ALD. Heterozygous women with X-ADL have a wide spectrum of clinical manifestations, ranging from mild to severe phenotypes.

Validity and Usefulness of `Wearable Blood Pressure Sensing' for Detection of Inappropriate Short-Term Blood Pressure Variability in the Elderly

NASA Astrophysics Data System (ADS)

Iijima, Katsuya; Kameyama, Yumi; Akishita, Masahiro; Ouchi, Yasuyoshi; Yanagimoto, Shintaro; Imai, Yasushi; Yahagi, Naoki; Lopez, Guillaume; Shuzo, Masaki; Yamada, Ichiro

An increase in short-term blood pressure (BP) variability is a characteristic feature in the elderly. It makes the management of hemodynamics more difficult, because it is frequently seen disturbed baro-reflex function and increased arterial stiffness, leading to isolated systolic hypertension. Large BP variability aggravates hypertensive target organ damage and is an independent risk factor for the cardiovascular (CV) events in elderly hypertensive patients. Therefore, appropriate control in BP is indispensable to manage lifestyle-related diseases and to prevent subsequent CV events. In addition, accumulating recent reports show that excessive BP variability is also associated with a decline in cognitive function and fall in the elderly. In the clinical settings, we usually evaluate their health condition, mainly with single point BP measurement using cuff inflation. However, unfortunately we are not able to find the close changes in BP by the traditional way. Here, we can show our advantageous approach of continuous BP monitoring using newly developing device `wearable BP sensing' without a cuff stress in the elderly. The new device could reflect systolic BP and its detailed changes, in consistent with cuff-based BP measurement. Our new challenge suggests new possibility of its clinical application with high accuracy.

Primary versus secondary hypertension in children followed up at an outpatient tertiary unit.

PubMed

Gomes, Romina S; Quirino, Isabel G; Pereira, Regina M; Vitor, Breno M; Leite, Alysson F; Oliveira, Eduardo A; Simões e Silva, Ana Cristina

2011-03-01

Childhood hypertension has classically been recognized as a secondary disease. However, primary hypertension also occurs in children. The aim of this study was to compare clinical features of pediatric patients with elevated blood pressure, which were referred to an outpatient tertiary unit, and to detect variables associated with the identification of primary hypertension. The records of 220 patients with hypertension followed between 1996 and 2006 were analyzed. The variable of interest was primary hypertension. Logistic regression analysis was applied to identify clinical variables that were independently associated with primary hypertension. Of 220 patients, 33 (15%) had primary hypertension, and 187 (85%) exhibited secondary hypertension. No statistically significant differences were detected in gender, race, age at diagnosis, and systolic/diastolic blood pressure levels between both groups. After adjustment, four variables at baseline remained independently associated with primary hypertension: absence of signs/symptoms (OR 18.87, 95% CI 6.32-56.29), normal serum creatinine (OR 0.02, 95% CI 0.00-0.27), family history of hypertension (OR 3.03, 95% CI 1.04-8.79), and elevated body weight (OR 1.06, 95% CI 1.02-1.10). The absence of signs/symptoms, normal serum creatinine, family history of hypertension, and overweight/obesity at admission are clues to diagnose primary hypertension in childhood.

Clinical variables and implications of the personality on the outcome of bipolar illness: a pilot study

PubMed Central

Casas-Barquero, Nieves; García-López, Olga; Fernández-Argüelles, Pedro; Camacho-Laraña, Manuel

2007-01-01

Outcome in bipolar patients is affected by comorbidity. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. This pilot study examined a series of 40 euthymic bipolar patients (DSM-IV criteria) (bipolar I disorder 31, bipolar II disorder 9) to assess the effect of clinical variables and the influence of comorbid personality on the clinical course of bipolar illness. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with “pure” bipolar patients (n = 10) with regard to demographic, clinical, and course of illness variables. Comorbid personality disorder was diagnosed in 75% of patients according to ICD-10 criteria, with obsessive-compulsive personality disorder being the most frequent type. Sixty-three per cent of subjects had more than one comorbid personality disorder. Bipolar patients with and without comorbid personality disorder showed no significant differences regarding features of the bipolar illness, although the group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness. In subjects with comorbid personality disorders, the number of hospitalizations correlated significantly with depressive episodes and there was an inverse correlation between age at the first episode and duration of bipolar illness. These findings, however, should be interpreted taking into account the preliminary nature of a pilot study and the contamination of the sample with too many bipolar II patients. PMID:19300559

Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1-T2N0 breast cancer.

PubMed

Bae, Min Sun; Shin, Sung Ui; Song, Sung Eun; Ryu, Han Suk; Han, Wonshik; Moon, Woo Kyung

2018-04-01

Background Most patients with early-stage breast cancer have clinically negative lymph nodes (LNs). However, 15-20% of patients have axillary nodal metastasis based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US) features of a primary tumor are associated with axillary LN metastasis in patients with clinical T1-T2N0 breast cancer. Material and Methods This retrospective study included 138 consecutive patients (median age = 51 years; age range = 27-78 years) who underwent breast surgery with axillary LN evaluation for clinically node-negative T1-T2 breast cancer. Three radiologists blinded to the axillary surgery results independently reviewed the US images. Tumor distance from the skin and distance from the nipple were determined based on the US report. Association between US features of a breast tumor and axillary LN metastasis was assessed using a multivariate logistic regression model after controlling for clinicopathologic variables. Results Of the 138 patients, 28 (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036), architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049) were associated with axillary LN metastasis. At multivariate analysis, shorter skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.01-16.19; P = 0.040) and masses with associated architectural distortion (OR = 3.80; 95% CI = 1.57-9.19; P = 0.003) were independent predictors of axillary LN metastasis. Conclusion US features of breast cancer can be promising factors associated with axillary LN metastasis in patients with clinically node-negative early-stage breast cancer.

Arrestin gene mutations in autosomal recessive retinitis pigmentosa.

PubMed

Nakazawa, M; Wada, Y; Tamai, M

1998-04-01

To assess the clinical and molecular genetic studies of patients with autosomal recessive retinitis pigmentosa associated with a mutation in the arrestin gene. Results of molecular genetic screening and case reports with DNA analysis and clinical features. University medical center. One hundred twenty anamnestically unrelated patients with autosomal recessive retinitis pigmentosa. DNA analysis was performed by single strand conformation polymorphism followed by nucleotide sequencing to search for a mutation in exon 11 of the arrestin gene. Clinical features were characterized by visual acuity slitlamp biomicroscopy, fundus examinations, fluorescein angiography, kinetic visual field testing, and electroretinography. We identified 3 unrelated patients with retinitis pigmentosa associated with a homozygous 1-base-pair deletion mutation in codon 309 of the arrestin gene designated as 1147delA. All 3 patients showed pigmentary retinal degeneration in the midperipheral area with or without macular involvement. Patient 1 had a sibling with Oguchi disease associated with the same mutation. Patient 2 demonstrated pigmentary retinal degeneration associated with a golden-yellow reflex in the peripheral fundus. Patients 1 and 3 showed features of retinitis pigmentosa without the golden-yellow fundus reflex. Although the arrestin 1147delA has been known as a frequent cause of Oguchi disease, this mutation also may be related to the pathogenesis of autosomal recessive retinitis pigmentosa. This phenomenon may provide evidence of variable expressivity of the mutation in the arrestin gene.

Impact of obsessive-compulsive disorder comorbidity on the sociodemographic and clinical features of patients with bipolar disorder.

PubMed

Koyuncu, Ahmet; Tükel, Raşit; Ozyildirim, Ilker; Meteris, Handan; Yazici, Olcay

2010-01-01

In this study, our aim is to determine the prevalence rates of obsessive-compulsive disorder (OCD) comorbidity and to assess the impact of OCD comorbidity on the sociodemographic and clinical features of patients with bipolar disorder (BD). Using the Yale-Brown Obsessive Compulsive Scale Symptom Checklist and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-IV/Clinical Version on bipolar patients, 2 groups, BD with OCD comorbidity (BD-OCD) and BD without OCD comorbidity, were formed. These groups were compared for sociodemographic and clinical variables. Of 214 patients with BD, 21.9% of them had obsession and/or compulsion symptoms and 16.3% had symptoms at the OCD level. Although there was no statistically significant difference between the frequency of comorbid OCD in BD-I (22/185, 11.9%) and BD-II (3/13, 23.1%) patients, but OCD was found to be significantly high in BD not otherwise specified (10/16, %62.5) patients than BD-I (P < .001) and BD-II (P = .03). Six patients (17.1%) of the BD-OCD group had chronic course (the presence of at least 1 mood disorder episode with a duration of longer than 2 years), whereas the BD without OCD group had none, which was statistically significant. There were no statistically significant differences between BD-OCD and BD without OCD groups in terms of age, sex, education, marital status, polarity, age of BD onset, presence of psychotic symptoms, presence of rapid cycling, history of suicide attempts, first episode type, and predominant episode type. Main limitation of our study was the assessment of some variables based on retrospective recall. Our study confirms the high comorbidity rates for OCD in BD patients. Future studies that examine the relationship between OCD and BD using a longitudinal design may be helpful in improving our understanding of the mechanism of this association. 2010 Elsevier Inc. All rights reserved.

EHR-based phenotyping: Bulk learning and evaluation.

PubMed

Chiu, Po-Hsiang; Hripcsak, George

2017-06-01

In data-driven phenotyping, a core computational task is to identify medical concepts and their variations from sources of electronic health records (EHR) to stratify phenotypic cohorts. A conventional analytic framework for phenotyping largely uses a manual knowledge engineering approach or a supervised learning approach where clinical cases are represented by variables encompassing diagnoses, medicinal treatments and laboratory tests, among others. In such a framework, tasks associated with feature engineering and data annotation remain a tedious and expensive exercise, resulting in poor scalability. In addition, certain clinical conditions, such as those that are rare and acute in nature, may never accumulate sufficient data over time, which poses a challenge to establishing accurate and informative statistical models. In this paper, we use infectious diseases as the domain of study to demonstrate a hierarchical learning method based on ensemble learning that attempts to address these issues through feature abstraction. We use a sparse annotation set to train and evaluate many phenotypes at once, which we call bulk learning. In this batch-phenotyping framework, disease cohort definitions can be learned from within the abstract feature space established by using multiple diseases as a substrate and diagnostic codes as surrogates. In particular, using surrogate labels for model training renders possible its subsequent evaluation using only a sparse annotated sample. Moreover, statistical models can be trained and evaluated, using the same sparse annotation, from within the abstract feature space of low dimensionality that encapsulates the shared clinical traits of these target diseases, collectively referred to as the bulk learning set. Copyright © 2017 Elsevier Inc. All rights reserved.

Waardenburg syndrome--a case report.

PubMed

Bansal, Yuvika; Jain, Parul; Goyal, Gaurav; Singh, Malvika; Mishra, Chittranjan

2013-02-01

Waardenburg syndrome is a rare genetic disorder characterized by varying degree of deafness associated with pigmentary anomaly and defects of neural crest cell derived structures. Four subtypes (I-IV) with variable penetrance and gene expression of different clinical features have been described. We report a patient showing constellation of complete heterochromia, dystopia canthorum, white forelock, and synophrys. Other affected family relatives with heterochromia have been depicted in pedigree. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Prognostic features and clinical presentation of acute idiopathic enterocolitis in horses

PubMed Central

Staempfli, Henry R.; Townsend, Hugh G.G.; Prescott, John F.

1991-01-01

Clinical and hematological changes observed on presentation of 47 horses referred to the Ontario Veterinary College with acute idiopathic colitis were analyzed for their prognostic features. Cases of acute enterocolitis were characterized by fever, dehydration, abnormalities of serum electrolyte concentrations, azotemia, hypoalbuminemia, and increased serum concentrations of muscle enzymes. Severely dehydrated horses were seven times more likely to die or be euthanized than those that were not dehydrated. Other factors associated with failure to survive included the following: increased hematocrit, increased number of band neutrophils, increased serum creatinine and urea concentrations, and decreased blood pH and increasingly negative base excess. The results of multivariate variable analysis (stepwise logistic regression) suggested that, among the variables tested, base excess was the best predictor of death or survival. Twenty of 47 horses died or were euthanized. Reasons for death or euthanasia included: severe disseminated intravascular coagulation, unresponsiveness of severe metabolic acidosis and hypoproteinemia to treatments, and severity of colonic lesions on exploratory laparotomy. Of the surviving horses, three developed chronic laminitis (two were destroyed) and five developed jugular vein thrombosis. Fourteen of 16 horses for which subsequent histories were available returned to normal function. Early recognition of the disease, combined with early and aggressive correction of dehydration and of acid-base imbalance, may be important determinants of survival in horses with acute idiopathic colitis. PMID:17423769

Obsessive-compulsive disorder versus body dysmorphic disorder: a comparison study of two possibly related disorders.

PubMed

Phillips, Katharine A; Pinto, Anthony; Menard, William; Eisen, Jane L; Mancebo, Maria; Rasmussen, Steven A

2007-01-01

The relationship between obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD) is unclear. BDD has been proposed to be an OCD-spectrum disorder or even a type of OCD. However, few studies have directly compared these disorders' clinical features. We compared characteristics of subjects with OCD (n=210), BDD (n=45), and comorbid BDD/OCD (n=40). OCD and BDD did not significantly differ in terms of demographic features, age of OCD or BDD onset, illness duration, and many other variables. However, subjects with BDD had significantly poorer insight than those with OCD and were more likely to be delusional. Subjects with BDD were also significantly more likely than those with OCD to have lifetime suicidal ideation, as well as lifetime major depressive disorder and a lifetime substance use disorder. The comorbid BDD/OCD group evidenced greater morbidity than subjects with OCD or BDD in a number of domains, but differences between the comorbid BDD/OCD group and the BDD group were no longer significant after controlling for BDD severity. However, differences between the comorbid BDD/OCD group and the OCD group remained significant after controlling for OCD severity. In summary, OCD and BDD did not significantly differ on many variables but did have some clinically important differences. These findings have implications for clinicians and for the classification of these disorders. (c) 2006 Wiley-Liss, Inc.

The impact of childhood traumas, depressive and anxiety symptoms on the relationship between borderline personality features and symptoms of adult attention deficit hyperactivity disorder in Turkish university students.

PubMed

Dalbudak, Ercan; Evren, Cuneyt

2015-01-01

Previous studies reported that there is a significant association between attention deficit hyperactivity disorder (ADHD) in childhood and borderline personality disorder (BPD) in adulthood. The aim of this study is to investigate the relationship of borderline personality features (BPF) and ADHD symptoms while controlling the effect of childhood traumas, symptoms of depression and anxiety in adulthood on this relationship in Turkish university students. A total of 271 Turkish university students participated in this study. The students were assessed through the Turkish version of the Borderline Personality Inventory (BPI), the Adult ADHD Self-Report Scale (ASRS), the Childhood Trauma Questionnaire (CTQ-28), the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Correlation analyses have revealed that severity of BPF is related with adult ADHD symptoms, emotional, physical abuse and depression scores. Hierarchical regression analysis has indicated that depressive symptoms, emotional and physical abuse and the severity of ADHD symptoms are the predictors for severity of BPF. Findings of the present study suggests that clinicians must carefully evaluate these variables and the relationship between them to understand BPF and ADHD symptoms in university students better. Together with depressive symptoms, emotional and physical abuse may play a mediator role on this relationship. Further studies are needed to evaluate causal relationship between these variables in both clinical and non-clinical populations.

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.

Automatic classification of written descriptions by healthy adults: An overview of the application of natural language processing and machine learning techniques to clinical discourse analysis.

PubMed

Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra

2014-01-01

Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. The aims were to describe how to:(i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and(ii) automatically identify the features that best distinguish the groups. The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described - simple or complex; presentation order - which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo 18 were used,which included 200 healthy Brazilians of both genders. A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods.

Clinical Management of Patients with ASXL1 Mutations and Bohring-Opitz Syndrome, Emphasizing the Need for Wilms Tumor Surveillance

PubMed Central

Russell, Bianca; Johnston, Jennifer J; Biesecker, Leslie G.; Kramer, Nancy; Pickart, Angela; Rhead, William; Tan, Wen-Hann; Brownstein, Catherine A; Clarkson, L Kate; Dobson, Amy; Rosenberg, Avi Z; Schrier Vergano, Samantha A.; Helm, Benjamin M.; Harrison, Rachel E; Graham, John M

2016-01-01

Bohring-Opitz syndrome is a rare genetic condition characterized by distinctive facial features, variable microcephaly, hypertrichosis, nevus flammeus, severe myopia, unusual posture (flexion at the elbows with ulnar deviation, and flexion of the wrists and metacarpophalangeal joints), severe intellectual disability, and feeding issues. Nine patients with Bohring-Opitz syndrome have been identified as having a mutation in ASXL1. We report on eight previously unpublished patients with Bohring-Opitz syndrome caused by an apparent or confirmed de novo mutation in ASXL1. Of note, two patients developed bilateral Wilms tumors. Somatic mutations in ASXL1 are associated with myeloid malignancies, and these reports emphasize the need for Wilms tumor screening in patients with ASXL1 mutations. We discuss clinical management with a focus on their feeding issues, cyclic vomiting, respiratory infections, insomnia, and tumor predisposition. Many patients are noted to have distinctive personalities (interactive, happy, and curious) and rapid hair growth; features not previously reported. PMID:25921057

Telangiectatic oncocytoma: a previously undescribed variant of renal oncocytoma.

PubMed

Xiao, Guang-Qian; Ko, Huai-Bin Mabel; Unger, Pamela

2013-07-01

To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.

Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia.

PubMed

Gagne, Katelyn E; Ghazvinian, Roxanne; Yuan, Daniel; Zon, Rebecca L; Storm, Kelsie; Mazur-Popinska, Magdalena; Andolina, Laura; Bubala, Halina; Golebiowska, Sydonia; Higman, Meghan A; Kalwak, Krzysztof; Kurre, Peter; Matysiak, Michal; Niewiadomska, Edyta; Pels, Salley; Petruzzi, Mary Jane; Pobudejska-Pieniazek, Aneta; Szczepanski, Tomasz; Fleming, Mark D; Gazda, Hanna T; Agarwal, Suneet

2014-07-17

Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early onset of severe anemia, variable nonhematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement. Because of the overlapping features and relative rarity of PS, we hypothesized that some patients in whom the leading clinical diagnosis is DBA actually have PS. Here, we evaluated patient DNA samples submitted for DBA genetic studies and found that 8 (4.6%) of 173 genetically uncharacterized patients contained large mtDNA deletions. Only 2 (25%) of the patients had been diagnosed with PS on clinical grounds subsequent to sample submission. We conclude that PS can be overlooked, and that mtDNA deletion testing should be performed in the diagnostic evaluation of patients with congenital anemia. © 2014 by The American Society of Hematology.

Computerized intrapartum electronic fetal monitoring: analysis of the decision to deliver for fetal distress.

PubMed

Georgieva, Antoniya; Payne, Stephen J; Moulden, Mary; Redman, Christopher W G

2011-01-01

We applied computerized methods to assess the Electronic Fetal Monitoring (EFM) in labor. We analyzed retrospectively the last hour of EFM for 1,370 babies, delivered by emergency Cesarean sections before the onset of pushing (data collected at the John Radcliffe Hospital, Oxford, UK). There were two cohorts according to the reason for intervention: (a) fetal distress, n(1) = 524 and (b) failure to progress and/or malpresentation, n(2) = 846. The cohorts were compared in terms of classical EFM features (baseline, decelerations, variability and accelerations), computed by a dedicated Oxford system for automated analysis--OxSys. In addition, OxSys was employed to simulate current clinical guidelines for the classification of fetal monitoring, i.e. providing in real time a three-tier grading system of the EFM (normal, indeterminate, or abnormal). The computerized features and the simulated guidelines corresponded well to the clinical management and to the actual labor outcome (measured by umbilical arterial pH).

Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

PubMed

Sturiale, C L; Rigante, L; Puca, A; Di Lella, G; Albanese, A; Marchese, E; Di Rocco, C; Maira, G; Colicchio, G

2013-05-01

Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P < 0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis. AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Differences in subependymal vein anatomy may predispose preterm infants to GMH-IVH.

PubMed

Tortora, Domenico; Severino, Mariasavina; Malova, Mariya; Parodi, Alessandro; Morana, Giovanni; Sedlacik, Jan; Govaert, Paul; Volpe, Joseph J; Rossi, Andrea; Ramenghi, Luca Antonio

2018-01-01

The anatomy of the deep venous system plays an important role in the pathogenesis of brain lesions in the preterm brain as shown by different histological studies. The aims of this study were to compare the subependymal vein anatomy of preterm neonates with germinal matrix haemorrhage-intraventricular haemorrhage (GMH-IVH), as evaluated by susceptibility-weighted imaging (SWI) venography, with a group of age-matched controls with normal brain MRI, and to explore the relationship between the anatomical features of subependymal veins and clinical risk factors for GMH-IVH. SWI venographies of 48 neonates with GMH-IVH and 130 neonates with normal brain MRI were retrospectively evaluated. Subependymal vein anatomy was classified into six different patterns: type 1 represented the classic pattern and types 2-6 were considered anatomic variants. A quantitative analysis of the venous curvature index was performed. Variables were analysed by using Mann-Whitney U and χ 2 tests, and a multiple logistic regression analysis was performed to evaluate the association between anatomical features, clinical factors and GMH-IVH. A significant difference was noticed among the six anatomical patterns according to the presence of GMH-IVH (χ 2 =14.242, p=0.014). Anatomic variants were observed with higher frequency in neonates with GMH-IVH than in controls (62.2% and 49.6%, respectively). Neonates with GMH-IVH presented a narrower curvature of the terminal portion of subependymal veins (p<0.05). These anatomical features were significantly associated with GMH-IVH (p<0.05). Preterm neonates with GMH-IVH show higher variability of subependymal veins anatomy confirming a potential role as predisposing factor for GMH-IVH. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Information Extraction for Clinical Data Mining: A Mammography Case Study

PubMed Central

Nassif, Houssam; Woods, Ryan; Burnside, Elizabeth; Ayvaci, Mehmet; Shavlik, Jude; Page, David

2013-01-01

Breast cancer is the leading cause of cancer mortality in women between the ages of 15 and 54. During mammography screening, radiologists use a strict lexicon (BI-RADS) to describe and report their findings. Mammography records are then stored in a well-defined database format (NMD). Lately, researchers have applied data mining and machine learning techniques to these databases. They successfully built breast cancer classifiers that can help in early detection of malignancy. However, the validity of these models depends on the quality of the underlying databases. Unfortunately, most databases suffer from inconsistencies, missing data, inter-observer variability and inappropriate term usage. In addition, many databases are not compliant with the NMD format and/or solely consist of text reports. BI-RADS feature extraction from free text and consistency checks between recorded predictive variables and text reports are crucial to addressing this problem. We describe a general scheme for concept information retrieval from free text given a lexicon, and present a BI-RADS features extraction algorithm for clinical data mining. It consists of a syntax analyzer, a concept finder and a negation detector. The syntax analyzer preprocesses the input into individual sentences. The concept finder uses a semantic grammar based on the BI-RADS lexicon and the experts’ input. It parses sentences detecting BI-RADS concepts. Once a concept is located, a lexical scanner checks for negation. Our method can handle multiple latent concepts within the text, filtering out ultrasound concepts. On our dataset, our algorithm achieves 97.7% precision, 95.5% recall and an F1-score of 0.97. It outperforms manual feature extraction at the 5% statistical significance level. PMID:23765123

Information Extraction for Clinical Data Mining: A Mammography Case Study.

PubMed

Nassif, Houssam; Woods, Ryan; Burnside, Elizabeth; Ayvaci, Mehmet; Shavlik, Jude; Page, David

2009-01-01

Breast cancer is the leading cause of cancer mortality in women between the ages of 15 and 54. During mammography screening, radiologists use a strict lexicon (BI-RADS) to describe and report their findings. Mammography records are then stored in a well-defined database format (NMD). Lately, researchers have applied data mining and machine learning techniques to these databases. They successfully built breast cancer classifiers that can help in early detection of malignancy. However, the validity of these models depends on the quality of the underlying databases. Unfortunately, most databases suffer from inconsistencies, missing data, inter-observer variability and inappropriate term usage. In addition, many databases are not compliant with the NMD format and/or solely consist of text reports. BI-RADS feature extraction from free text and consistency checks between recorded predictive variables and text reports are crucial to addressing this problem. We describe a general scheme for concept information retrieval from free text given a lexicon, and present a BI-RADS features extraction algorithm for clinical data mining. It consists of a syntax analyzer, a concept finder and a negation detector. The syntax analyzer preprocesses the input into individual sentences. The concept finder uses a semantic grammar based on the BI-RADS lexicon and the experts' input. It parses sentences detecting BI-RADS concepts. Once a concept is located, a lexical scanner checks for negation. Our method can handle multiple latent concepts within the text, filtering out ultrasound concepts. On our dataset, our algorithm achieves 97.7% precision, 95.5% recall and an F 1 -score of 0.97. It outperforms manual feature extraction at the 5% statistical significance level.

A Middle Eastern Founder Mutation Expands the Genotypic and Phenotypic Spectrum of Mitochondrial MICU1 Deficiency: A Report of 13 Patients.

PubMed

Musa, Sara; Eyaid, Wafaa; Kamer, Kimberli; Ali, Rehab; Al-Mureikhi, Mariam; Shahbeck, Noora; Al Mesaifri, Fatma; Makhseed, Nawal; Mohamed, Zakkiriah; AlShehhi, Wafaa Ali; Mootha, Vamsi K; Juusola, Jane; Ben-Omran, Tawfeg

2018-05-03

MICU1 encodes a Ca 2+ sensing, regulatory subunit of the mitochondrial uniporter, a selective calcium channel within the organelle's inner membrane. Ca 2+ entry into mitochondria helps to buffer cytosolic Ca 2+ transients and also activates ATP production within the organelle. Mutations in MICU1 have previously been reported in 17 children from nine families with muscle weakness, fatigue, normal lactate, and persistently elevated creatine kinase, as well as variable features that include progressive extrapyramidal signs, learning disabilities, nystagmus, and cataracts. In this study, we report the clinical features of an additional 13 patients from consanguineous Middle Eastern families with recessive mutations in MICU1. Of these patients, 12/13 are homozygous for a novel founder mutation c.553C>T (p.Q185*) that is predicted to lead to a complete loss of function of MICU1, while one patient is compound heterozygous for this mutation and an intragenic duplication of exons 9 and 10. The founder mutation occurs with a minor allele frequency of 1:60,000 in the ExAC database, but in ~1:500 individual in the Middle East. All 13 of these patients presented with developmental delay, learning disability, muscle weakness and easy fatigability, and failure to thrive, as well as additional variable features we tabulate. Consistent with previous cases, all of these patients had persistently elevated serum creatine kinase with normal lactate levels, but they also exhibited elevated transaminase enzymes. Our work helps to better define the clinical sequelae of MICU1 deficiency. Furthermore, our work suggests that targeted analysis of the MICU1 founder mutation in Middle Eastern patients may be warranted.

Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants.

PubMed

Hamilton, Eline M C; Tekturk, Pinar; Cialdella, Fia; van Rappard, Diane F; Wolf, Nicole I; Yalcinkaya, Cengiz; Çetinçelik, Ümran; Rajaee, Ahmad; Kariminejad, Ariana; Paprocka, Justyna; Yapici, Zuhal; Bošnjak, Vlatka Mejaški; van der Knaap, Marjo S

2018-04-17

To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Autoimmunity-Associated PTPN22 Polymorphisms in Latent Autoimmune Diabetes of the Adult Differ from Those of Type 1 Diabetes Patients.

PubMed

Heneberg, Petr; Kocková, Lucie; Čecháková, Marie; Daňková, Pavlína; Černá, Marie

2018-06-12

A portion of adults with humoral immune changes have clinical diabetes that is initially not insulin-requiring (latent autoimmune diabetes of the adult, LADA). One of the genes strongly associated with autoimmune diabetes is PTPN22. We hypothesized that the manifestation and clinical features of LADA are linked to functional variants of PTPN22. We genotyped allelic frequencies of 1 protective and 3 risk-associated PTPN22 variants in 156 Czech LADA patients, 194 type 2 diabetes mellitus patients with LADA-like progression to insulinotherapy and 324 type 1 diabetes mellitus patients, and subsequently examined the associations of PTPN22 variants with the expression of autoantibodies and other clinical features of LADA. We challenged the paradigm that stated that the PTPN22 c.1858T allele serves as a risk allele for LADA, although we confirmed its risk status in the geographically matched T1DM cohort. In contrast, the frequencies of other PTPN22 alleles (c.-1123C, c.788A and c.1970-852C) differed significantly from the healthy controls. We confirmed gender-related differences in the frequency of some PTPN22 polymorphisms (but not c.1858C>T) in LADA. The particular PTPN22 alleles and genotypes were associated with specific clinical features of the examined patients (autoantibodies, HbA1c and age at diagnosis of diabetes). The variability in PTPN22 haplotypes suggests that the genetic signature of LADA is independent and should not be considered a hybrid form of T1DM and T2DM. Further studies should elucidate the associations with clinical characteristics of the LADA patients and focus on the newly emerging types of diabetes with the disease onset in early to mid-adulthood. © 2018 S. Karger AG, Basel.

Quantitative image feature variability amongst CT scanners with a controlled scan protocol

NASA Astrophysics Data System (ADS)

Ger, Rachel B.; Zhou, Shouhao; Chi, Pai-Chun Melinda; Goff, David L.; Zhang, Lifei; Lee, Hannah J.; Fuller, Clifton D.; Howell, Rebecca M.; Li, Heng; Stafford, R. Jason; Court, Laurence E.; Mackin, Dennis S.

2018-02-01

Radiomics studies often analyze patient computed tomography (CT) images acquired from different CT scanners. This may result in differences in imaging parameters, e.g. different manufacturers, different acquisition protocols, etc. However, quantifiable differences in radiomics features can occur based on acquisition parameters. A controlled protocol may allow for minimization of these effects, thus allowing for larger patient cohorts from many different CT scanners. In order to test radiomics feature variability across different CT scanners a radiomics phantom was developed with six different cartridges encased in high density polystyrene. A harmonized protocol was developed to control for tube voltage, tube current, scan type, pitch, CTDIvol, convolution kernel, display field of view, and slice thickness across different manufacturers. The radiomics phantom was imaged on 18 scanners using the control protocol. A linear mixed effects model was created to assess the impact of inter-scanner variability with decomposition of feature variation between scanners and cartridge materials. The inter-scanner variability was compared to the residual variability (the unexplained variability) and to the inter-patient variability using two different patient cohorts. The patient cohorts consisted of 20 non-small cell lung cancer (NSCLC) and 30 head and neck squamous cell carcinoma (HNSCC) patients. The inter-scanner standard deviation was at least half of the residual standard deviation for 36 of 49 quantitative image features. The ratio of inter-scanner to patient coefficient of variation was above 0.2 for 22 and 28 of the 49 features for NSCLC and HNSCC patients, respectively. Inter-scanner variability was a significant factor compared to patient variation in this small study for many of the features. Further analysis with a larger cohort will allow more thorough analysis with additional variables in the model to truly isolate the interscanner difference.

Histological variability and the importance of clinicopathological correlation in cutaneous Rosai-Dorfman disease.

PubMed

Gameiro, Ana; Gouveia, Miguel; Cardoso, José Carlos; Tellechea, Oscar

2016-01-01

Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

HIV-associated salivary gland disease--clinical or imaging diagnosis?

PubMed

da Silva Rath, Inês Beatriz; Beltrame, Ana Paula C A; Carvalho, Aroldo P; Schaeffer, Marcela B; Almeida, Izabel C S

2015-07-01

This work aimed at studying the salivary gland disease (SGD) as it relates to associated factors, such as persistent generalised lymphadenopathy (PGL), lymphocytic interstitial pneumonia (LIP), clinical and immunological features of AIDS, and salivary flow rate and pH, as well as at exploring the relationship between the clinical diagnosis and the imaging diagnosis by ultrasound (US) examination of the parotid glands. Information regarding the observation of parotid gland enlargement, PGL, LIP, and clinical and immunological features of AIDS was gathered from medical records, and a saliva sample for unstimulated salivary flow rate and pH measurement was collected from 142 children aged 3 through 10 years treated at the Department of Infectious Diseases of Joana de Gusmão Children's Hospital, Florianópolis, SC, Brazil. High-resolution ultrasonography was performed in 58 children. Pearson's chi-square test and t-test were used to evaluate the association between the variables. A significant association was found between SGD and LIP. Ultrasound revealed a 50% higher incidence of SGD that was not reported in the patients' records. US examination proved to be essential for the correct diagnosis and monitoring of the progression of HIV/SGD. © 2014 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

JAG1 mutations are found in approximately one third of patients presenting with only one or two clinical features of Alagille syndrome.

PubMed

Guegan, K; Stals, K; Day, M; Turnpenny, P; Ellard, S

2012-07-01

Alagille syndrome is a multisystem disorder characterized by highly variable expressivity, most frequently caused by heterozygous JAG1 gene mutations. Classic diagnostic criteria combine the presence of bile duct paucity on liver biopsy with three of five systems affected; liver, heart, skeleton, eye and dysmorphic facies. The aim of this study was to determine the prevalence and distribution of JAG1 mutations in patients referred for routine clinical diagnostic testing. Clinical data were available for 241 patients from 135 families. The index cases were grouped according to the number of systems affected (heart, liver, skeletal, eye and facies) and the mutation frequency calculated for each group. JAG1 mutations were identified in 59/135 (44%) probands. The highest mutation detection rates were observed in patients with the most frequent presenting features of Alagille syndrome; ranging from 20% (one system) to 86% (five systems). The overall mutation pick-up rate in a clinical diagnostic setting was lower than in previous research studies. Identification of a JAG1 gene mutation is particularly useful for those patients with atypical or mild Alagille syndrome who do not meet classic diagnostic criteria as it provides a definite molecular diagnosis and allows accurate genetic counselling for the family. © 2011 John Wiley & Sons A/S.

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.

Clinical factors associated with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections.

PubMed

Murphy, Tanya K; Storch, Eric A; Lewin, Adam B; Edge, Paula J; Goodman, Wayne K

2012-02-01

To explore associated clinical factors in children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Children with tics, obsessive-compulsive disorder, or both (n=109) were examined with personal and family history, diagnostic interview, physical examination, medical record review, and measurement of baseline levels of streptococcal antibodies. Significant group differences were found on several variables, such that children in whom PANDAS (versus without PANDAS) were more likely to have had dramatic onset, definite remissions, remission of neuropsychiatric symptoms during antibiotic therapy, a history of tonsillectomies/adenoidectomies, evidence of group A streptococcal infection, and clumsiness. The identification of clinical features associated with PANDAS should assist in delineating risks for this subtype of obsessive-compulsive disorder/tics. Copyright © 2012 Mosby, Inc. All rights reserved.

An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1

PubMed Central

2010-01-01

Background HIV-1 can be inhibited by RNA interference in vitro through the expression of short hairpin RNAs (shRNAs) that target conserved genome sequences. In silico shRNA design for HIV has lacked a detailed study of virus variability constituting a possible breaking point in a clinical setting. We designed shRNAs against HIV-1 considering the variability observed in naïve and drug-resistant isolates available at public databases. Methods A Bioperl-based algorithm was developed to automatically scan multiple sequence alignments of HIV, while evaluating the possibility of identifying dominant and subdominant viral variants that could be used as efficient silencing molecules. Student t-test and Bonferroni Dunn correction test were used to assess statistical significance of our findings. Results Our in silico approach identified the most common viral variants within highly conserved genome regions, with a calculated free energy of ≥ -6.6 kcal/mol. This is crucial for strand loading to RISC complex and for a predicted silencing efficiency score, which could be used in combination for achieving over 90% silencing. Resistant and naïve isolate variability revealed that the most frequent shRNA per region targets a maximum of 85% of viral sequences. Adding more divergent sequences maintained this percentage. Specific sequence features that have been found to be related with higher silencing efficiency were hardly accomplished in conserved regions, even when lower entropy values correlated with better scores. We identified a conserved region among most HIV-1 genomes, which meets as many sequence features for efficient silencing. Conclusions HIV-1 variability is an obstacle to achieving absolute silencing using shRNAs designed against a consensus sequence, mainly because there are many functional viral variants. Our shRNA cocktail could be truly effective at silencing dominant and subdominant naïve viral variants. Additionally, resistant isolates might be targeted under specific antiretroviral selective pressure, but in both cases these should be tested exhaustively prior to clinical use. PMID:21172023

Clinical Significance of Mobile Health Assessed Sleep Duration and Variability in Bipolar Disorder

PubMed Central

Kaufmann, Christopher N.; Gershon, Anda; Eyler, Lisa T.; Depp, Colin A.

2016-01-01

OBJECTIVE Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect. METHODS Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect. RESULTS Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7-8 hours were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect. CONCLUSIONS Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. PMID:27451108

Clinical significance of mobile health assessed sleep duration and variability in bipolar disorder.

PubMed

Kaufmann, Christopher N; Gershon, Anda; Eyler, Lisa T; Depp, Colin A

2016-10-01

Sleep disturbances are prevalent, persistent, and impairing features of bipolar disorder. However, the near-term and cumulative impact of the severity and variability of sleep disturbances on symptoms and functioning remains unclear. We examined self-reported daily sleep duration and variability in relation to mood symptoms, medication adherence, cognitive functioning, and concurrent daily affect. Forty-one outpatients diagnosed with bipolar disorder were asked to provide daily reports of sleep duration and affect collected via ecological momentary assessment with smartphones over eleven weeks. Measures of depressive and manic symptoms, medication adherence, and cognitive function were collected at baseline and concurrent assessment of affect were collected daily. Analyses examined whether sleep duration or variability were associated with baseline measures and changes in same-day or next-day affect. Greater sleep duration variability (but not average sleep duration) was associated with greater depressive and manic symptom severity, and lower medication adherence at baseline, and with lower and more variable ratings of positive affect and higher ratings of negative affect. Sleep durations shorter than 7-8 h were associated with lower same-day ratings of positive and higher same-day ratings of negative affect, however this did not extend to next-day affect. Greater cumulative day-to-day sleep duration variability, but not average sleep duration, was related to more severe mood symptoms, lower self-reported medication adherence and higher levels of negative affect. Bouts of short- or long-duration sleep had transient impact on affect. Day-to-day sleep variability may be important to incorporate into clinical assessment of sleep disturbances in bipolar disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

NASA Astrophysics Data System (ADS)

El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

2006-11-01

Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

[Hepatic alterations in patients with dengue].

PubMed

Larreal, Yraima; Valero, Nereida; Estévez, Jesús; Reyes, Ivette; Maldonado, Mery; Espina, Luz Marina; Arias, Julia; Meleán, Eddy; Añez, German; Atencio, Ricardo

2005-06-01

Clinical features of Dengue are very variable due to multiple alterations induced by the virus in the organism. Increased levels of transaminases similar to those produced by the Hepatitis virus have been reported in patients with Dengue from hiperendemic zones in Asia. The objectives of this study were to determine alterations in the liver tests in patients with Dengue and to relate them to the disease, clinically and serologically. Clinical history, hemathological tests serum transaminases (ALT y AST) and bilirubin assays were performed in 62 patients with clinical and serological diagnosis of Dengue. According to clinical features 38.7% of the patients with classical (CD) and hemorrhagic (DHF) forms of Dengue reffered abdominal pain and 2 patients with DHF had ictericia and hepatomegaly. Laboratory test findings showed leucopenia in 72.5% in both forms of Dengue and of patients with DHF severe thrombocytopenia (< 50.000 platelets x mm3), long PT and PPT in 70.9%, 23.0% and 42.3%, respectively. Transaminase values five fold higher than the normal values (p < 0.005) were observed in 36.8% and 74.4% of patients with CD and DHF respectively; AST was predominant in both groups. Our results suggest liver damage during the course of Dengue. A differential diagnosis has to be done between the hepatic involvement of Dengue cases and others viral diseases with hepatic disfunctions.

Morphological comparison of archaic Homo sapiens crania from China and Africa.

PubMed

Wu, X; Bräuer, G

1993-12-01

Regional features play a great role in the analysis of the differentiations of Homo erectus and Homo sapiens. However, this poses the question how widespread and variable these features are. In order to examine this with regard to the features commonly seen in China their occurrence and variability were determined in Chinese as well as in African crania of archaic and late Pleistocene/Holocene modern Homo sapiens. Furthermore, some features known from Africa were examined with regard to their occurrence and variability in China. Although the variability might change due to new finds, the present results for some features point to larger morphological spectra in the African than in the Chinese archaic Homo sapiens. It is furthermore remarkable that the early modern Chinese in many features show deviations from the pattern of archaic Homo sapiens of this region and exhibit broader spectra similar to those seen in African archaic and early modern Homo sapiens.

Empirical Support for DSM-IV Schizoaffective Disorder: Clinical and Cognitive Validators from a Large Patient Sample

PubMed Central

DeRosse, Pamela; Burdick, Katherine E.; Lencz, Todd; Siris, Samuel G.; Malhotra, Anil K.

2013-01-01

Objective The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. Methods We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ−; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Results Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ− and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. Conclusions These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness. PMID:23737946

Empirical support for DSM-IV schizoaffective disorder: clinical and cognitive validators from a large patient sample.

PubMed

DeRosse, Pamela; Burdick, Katherine E; Lencz, Todd; Siris, Samuel G; Malhotra, Anil K

2013-01-01

The diagnosis of schizoaffective disorder has long maintained an uncertain status in psychiatric nosology. Studies comparing clinical and biological features of patients with schizoaffective disorder to patients with related disorders [e.g., schizophrenia and bipolar disorder] can provide an evidence base for judging the validity of the diagnostic category. However, because most prior studies of schizoaffective disorder have only evaluated differences between groups at a static timepoint, it is unclear how these disorders may be related when the entire illness course is taken into consideration. We ascertained a large cohort [N = 993] of psychiatric patients with a range of psychotic diagnoses including schizophrenia with no history of major affective episodes [SZ-; N = 371], schizophrenia with a superimposed mood syndrome [SZ+; N = 224], schizoaffective disorder [SAD; N = 129] and bipolar I disorder with psychotic features [BPD+; N = 269]. Using cross-sectional data we designed key clinical and neurocognitive dependent measures that allowed us to test longitudinal hypotheses about the differences between these diagnostic entities. Large differences between diagnostic groups on several demographic and clinical variables were observed. Most notably, groups differed on a putative measure of cognitive decline. Specifically, the SAD group demonstrated significantly greater post-onset cognitive decline compared to the BP+ group, with the SZ- and SZ+ group both exhibiting levels of decline intermediate to BPD+ and SAD. These results suggest that schizoaffective disorder may possess distinct features. Contrary to earlier formulations, schizoaffective disorder may be a more severe form of illness.

Complex psychotropic polypharmacy in bipolar disorder across varying mood polarities: A prospective cohort study of 2712 inpatients.

PubMed

Golden, Julia C; Goethe, John W; Woolley, Stephen B

2017-10-15

It is common for patients with bipolar disorder (BP) to receive multiple psychotropics, but few studies have assessed demographic and clinical features associated with risk for receiving complex psychotropic polypharmacy. This longitudinal cohort study examined 2712 inpatients with a DSM-IV clinical diagnosis of BP to assess associations between complex polypharmacy (defined as ≥4 psychotropics) and demographic and clinical features; associations with risk of rehospitalization were also examined. Logistic regressions were performed with the sample as a whole and with each of four DSM-IV BP subtypes individually. Complex polypharmacy was present in 21.0%. BP-I depressed patients were more likely to receive complex regimens than BP-I manic, BP-I mixed or BP-II patients. In the sample as a whole, variables significantly associated with complex polypharmacy included female, white, psychotic features and a co-diagnosis of borderline personality, post-traumatic stress or another anxiety disorder. The only examined medication not significantly associated with complex polypharmacy was lithium, although only in BP-I depressed and BP-I mixed. Complex polypharmacy was associated with rehospitalization in BP-I mania within 15 and 30days post index hospitalization. All data were from one clinical facility; results may not generalize to other settings and patient populations. BP-I depression may pose a greater treatment challenge than the other BP subtypes. Lithium may confer an overall advantage compared to other medications in BP-I depressed and BP-I mixed. Further research is needed to guide pharmacotherapy decisions in BP patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Constitutional trisomy 8 and Behçet syndrome.

PubMed

Becker, Kristin; Fitzgerald, Oliver; Green, Andrew J; Keogan, Mary; Newbury-Ecob, Ruth; Greenhalgh, Lynn; Withers, Stephen; Hollox, Edward J; Aldred, Patricia M R; Armour, John A L

2009-05-01

The characteristic clinical features of constitutional trisomy 8 include varying degrees of developmental delay, joint contractures and deep palmar and plantar creases. There is an established literature, which describes features of Behçet syndrome occurring in phenotypically normal individuals with myelodysplastic syndromes and trisomy 8 in their bone marrow. In this article, we describe four patients with constitutional trisomy 8, all with varying clinical phenotypes, who developed features of Behçet, in particular but not exclusively mucocutaneous ulceration. In addition, we examined gene copy numbers of the variable-number neutrophil defensin genes DEFA1A3 in one of the cases (case 1) and her parents, together with 14 cases of Behçet syndrome in comparison with 121 normal controls. The gene copy number was highest in case 1 (copy number 14) and was also increased in her parents (both copy number 9). However the mean copy number for DEFA1A3 among the 14 Behçet syndrome patients was actually lower (5.1) than among the controls (mean of 6.8 copies). Thus, we conclude that patients with constitutional trisomy 8 and those with trisomy 8 confined to the bone marrow are both at increased risk of developing features of Behçet syndrome. The mechanism may relate to increased chromosome 8 gene dosage with further analysis of candidate genes on chromosome 8 required.

Mosaic variegated aneuploidy associated with a dysmorphic syndrome and mental handicap

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

Mehta, L.; Babu, A.; Willner, J.

1994-09-01

A 41-year-old woman was evaluated for dysmorphic features and mental handicap. Prior karyotyping had revealed 7% mosaicism for trisomy 18 in skin fibroblasts with normal blood chromosomes. Clinical features consisted of short stature, mild mental retardation, sensorineural deafness and the following dysmorphic features: short, broad neck, low posterior hairline, small palpebral fissures with iris coloboma on the right, epicanthic folds, small mouth, high palate and prominent mandible, short metacarpals and digits, particularly the fifth, with bilateral simian creases. Medical problems included non-insulin dependent diabetes mellitus, hypertension, oligomenorrhea and recent onset of diabetic neuropathy and retinal exudates. Head size and brainmore » MRI were within normal limits. Peripheral blood chromosomes revealed: 46,XX (45 cells), 46,XX,t(7;16)(q21;q21) in 1 cell, 45,X (1 cell), 48,XXXX (1 cell), 47,XX,+mar (1 cell), 48,XX,+mar,+mar (1 cell). Skin fibroblasts revealed the following karyotypes: 46,XX (25 cells), 45,X (14 cells), 47,XX,+2 (10 cells) and 47,X,+2,+7 (1 cell). Previously reported cases of mosaic variegated aneuploidy include microcephaly as a prominent feature. Chromosomes involved in the abnormality are variable. Clinical presentations in such patients are not consistent and do not appear to correlate with specific chromosome defects. This patient represents an interesting example of probable mitotic instability disrupting normal developmental processes.« less

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Malignancy in Noonan syndrome and related disorders.

PubMed

Smpokou, P; Zand, D J; Rosenbaum, K N; Summar, M L

2015-12-01

Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen-activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feature-based Morphometry

PubMed Central

Toews, Matthew; Wells, William M.; Collins, Louis; Arbel, Tal

2013-01-01

This paper presents feature-based morphometry (FBM), a new, fully data-driven technique for identifying group-related differences in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between all subjects, FBM models images as a collage of distinct, localized image features which may not be present in all subjects. FBM thus explicitly accounts for the case where the same anatomical tissue cannot be reliably identified in all subjects due to disease or anatomical variability. A probabilistic model describes features in terms of their appearance, geometry, and relationship to sub-groups of a population, and is automatically learned from a set of subject images and group labels. Features identified indicate group-related anatomical structure that can potentially be used as disease biomarkers or as a basis for computer-aided diagnosis. Scale-invariant image features are used, which reflect generic, salient patterns in the image. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer’s (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and obtains an equal error classification rate of 0.78 on new subjects. PMID:20426102

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

PubMed Central

Vallance, Abigail E; Young, Alastair L; Macutkiewicz, Christian; Roberts, Keith J; Smith, Andrew M

2015-01-01

Background A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality. Method An electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool. Results Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50). Conclusion These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed. PMID:26456948

Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation.

PubMed

Kiely, Aoife P; Ling, Helen; Asi, Yasmine T; Kara, Eleanna; Proukakis, Christos; Schapira, Anthony H; Morris, Huw R; Roberts, Helen C; Lubbe, Steven; Limousin, Patricia; Lewis, Patrick A; Lees, Andrew J; Quinn, Niall; Hardy, John; Love, Seth; Revesz, Tamas; Houlden, Henry; Holton, Janice L

2015-08-27

We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.

Dupuytren disease: on our way to a cure?

PubMed

Degreef, Ilse; De Smet, Luc

2013-06-01

Despite its high prevalence, the clinical presentation and severity of Dupuytren disease is extremely variable. The disease features a broad spectrum of symptoms, from simple nodules without the slightest clinical impact towards an extremely disabling form requiring multiple surgical procedures, sometimes even partial hand amputations. Recurrence after surgery is considered a failure for both patient and surgeon, but its definition is vague. The term 'recontracture' was coined by a patient and reflects the disappointment of recurrent disease. Wether or not a treatment option will insure a definite result, may depend more on the severity of the disease, which is patient specific, than on the treatment method itself. If a patient presents with Dupuytren disease, one should not merely evaluate his hands. Different clinical and personal history features may uncover a severe fibrosis diathesis and both correct information to the patient and an individualized treatment plan are needed. In the near future, a simple genetic test may help to identify patients at risk. Similar to the evolving knowledge and treatment modalities seen in rheumatoid arthritis, treatment of Dupuytren disease is likely to advance in the direction of disease control with pharmacotherapy and single shot minimal invasive enzymatic fasciotomy with collagenase to correct established contractures.

De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay.

PubMed

Yang, Hui; Douglas, Ganka; Monaghan, Kristin G; Retterer, Kyle; Cho, Megan T; Escobar, Luis F; Tucker, Megan E; Stoler, Joan; Rodan, Lance H; Stein, Diane; Marks, Warren; Enns, Gregory M; Platt, Julia; Cox, Rachel; Wheeler, Patricia G; Crain, Carrie; Calhoun, Amy; Tryon, Rebecca; Richard, Gabriele; Vitazka, Patrik; Chung, Wendy K

2015-10-01

Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors. Additional common clinical features include dysmorphic facial features and feeding difficulties associated with failure to thrive and short stature. The AHDC1 gene has only one coding exon, and the protein contains conserved regions including AT-hook motifs and a PDZ binding domain. We postulate that all seven variants detected in these patients result in a truncated protein missing critical functional domains, disrupting interactions with other proteins important for brain development. Our study demonstrates that truncating variants in AHDC1 are associated with ID and are primarily associated with a neurodevelopmental phenotype.

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.

Sporotrichosis: an update.

PubMed

Bonifaz, A; Vázquez-González, D

2010-10-01

Sporotrichosis is the most frequent and worldwide distributed subcutaneous mycoses. The aim of this article is to review the most recent aspects of sporotrichosis about its epidemiology, etiologic agents, mycologic characteristics, clinical features, diagnosis and treatment. The causative agents of sporotrichosis belong to five well defined species of dimorphic fungi of the called Sporothrix schenckii complex. Sporotrichosis and its etiologic agents have specific endemic areas, but it is possible to find epidemics of the disease in practically every continent, the entrance via is cutaneous due to the inoculation of the fungi into the skin after a traumatism and less frequent due to respiratory way. Clinical manifestations are widely variable, with important involvement of the skin and the superficial lymphatic system, but also with affection of the mucosa and some organs like lungs, bones and joints. Nowadays sporotrichosis is considered a true zoonosis with important changes related to the endemic areas and the ecologic features of the causative pathogens. The therapy of choice is the potassium iodide (KI), but other alternatives are itraconazole, terbinafine, thermotherapy and in severe cases amphotericin B. The importance of the recognition of the clinical manifestations of the disease in some non-endemic areas helps to challenge the diagnosis and give an accurate therapy.

Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?

PubMed Central

Hallett, Mark; Deuschl, Günther; Toni, Ivan; Bloem, Bastiaan R.

2012-01-01

Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed ‘dimmer-switch model’ that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression. PMID:22382359

Phenotypic variability of Cat-Eye syndrome.

PubMed

Berends, M J; Tan-Sindhunata, G; Leegte, B; van Essen, A J

2001-01-01

Cat-Eye syndrome (CES) is a disorder with a variable pattern of multiple congenital anomalies of which coloboma of the iris and anal atresia are the best known. CES is cytogenetically characterised by the presence of an extra bisatellited marker chromosome, which represents an inverted dicentric duplication of a part of chromosome 22 (inv dup(22)). We report on three CES-patients who carry an inv dup(22) diagnosed with FISH studies. They show remarkable phenotypic variability. The cause of this variability is unknown. Furthermore, we review clinical features of 71 reported patients. Only 41% of the CES-patients have the combination of iris coloboma, anal anomalies and pre-auricular anomalies. Therefore, almost 60% of the CES-patients are hard to recognize by their phenotype alone. Mild to moderate mental retardation was found in 32% (16/50) of the cases. Mental retardation occurs more frequently in male CES-patients. There is no apparent phenotypic difference between mentally retarded and mentally normal CES-patients.

Demographic and clinical features related to perceived discrimination in schizophrenia.

PubMed

Fresán, Ana; Robles-García, Rebeca; Madrigal, Eduardo; Tovilla-Zarate, Carlos-Alfonso; Martínez-López, Nicolás; Arango de Montis, Iván

2018-04-01

Perceived discrimination contributes to the development of internalized stigma among those with schizophrenia. Evidence on demographic and clinical factors related to the perception of discrimination among this population is both contradictory and scarce in low- and middle-income countries. Accordingly, the main purpose of this study is to determine the demographic and clinical factors predicting the perception of discrimination among Mexican patients with schizophrenia. Two hundred and seventeen adults with paranoid schizophrenia completed an interview on their demographic status and clinical characteristics. Symptom severity was assessed using the Positive and Negative Syndrome Scale; and perceived discrimination using 13 items from the King's Internalized Stigma Scale. Bivariate linear associations were determined to identify the variables of interest to be included in a linear regression analysis. Years of education, age of illness onset and length of hospitalization were associated with discrimination. However, only age of illness onset and length of hospitalization emerged as predictors of perceived discrimination in the final regression analysis, with longer length of hospitalization being the independent variable with the greatest contribution. Fortunately, this is a modifiable factor regarding the perception of discrimination and self-stigma. Strategies for achieving this as part of community-based mental health care are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Do ictal EEG characteristics predict treatment outcomes in schizophrenic patients undergoing electroconvulsive therapy?

PubMed

Simsek, Gulnihal Gokce; Zincir, Selma; Gulec, Huseyin; Eksioglu, Sevgin; Semiz, Umit Basar; Kurtulmus, Yasemin Sipka

2015-08-01

The aim of this study is to investigate the relationship between features of electroencephalography (EEG), including seizure time, energy threshold level and post-ictal suppression time, and clinical variables, including treatment outcomes and side-effects, among schizophrenia inpatients undergoing electroconvulsive therapy (ECT). This is a naturalistic follow-up study on schizophrenia patients, diagnosed using DSM-IV-TR criteria, treated by a psychosis inpatient service. All participants completed the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning (GAF) scale, the Frontal Assessment Battery (FAB) and a Data Collection Form. Assessments were made before treatment, during ECT and after treatment. Statistically significant improvements in both clinical and cognitive outcome were noted after ECT in all patients. Predictors of improvement were sought by evaluating electrophysiological variables measured at three time points (after the third, fifth and seventh ECT sessions). Logistic regression analysis showed that clinical outcome/improvement did not differ by seizure duration, threshold energy level or post-ictal suppression time. We found that ictal EEG parameters measured at several ECT sessions did not predict clinical recovery/outcomes. This may be because our centre defensively engages in "very specific patient selection" when ECT is contemplated. ECT does not cause short-term cognitive functional impairment and indeed improves cognition, because symptoms of the schizophrenic episode are alleviated.

Tics as an initial manifestation of juvenile Huntington's disease: case report and literature review.

PubMed

Cui, Shi-Shuang; Ren, Ru-Jing; Wang, Ying; Wang, Gang; Chen, Sheng-Di

2017-08-08

Huntington's disease (HD) is an autosomal dominant disorder, typically characterized by chorea due to a trinucleotide repeat expansion in the HTT gene, although the clinical manifestations of patients with juvenile HD (JHD) are atypical. A 17-year-old boy with initial presentation of tics attended our clinic and his DNA analysis demonstrated mutation in the HTT gene (49 CAG repeats). After treatment, his symptoms improved. Furthermore, we performed literature review through searching the databases and summarized clinical features in 33 JHD patients. The most prevalent symptoms are ataxia, and two cases reported that tics as initial and prominent manifestation in JHD. Among them, 88% patients carried CAG repeats beyond 60 and most of them have family history. This case here illustrates the variable range of clinical symptoms of JHD and the necessity of testing for the HD mutation in young patients with tics with symptoms unable to be explained by Tourette's syndrome (TS).

[Clinical features of focal brain lesions in the left-handed and ambidextrous].

PubMed

Chebysheva, L N; Bragina, N N; Dobrokhotova, T A

1977-01-01

On the basis of a study of 31 patients who demonstrated deviations from dextrality (Simistrals and ambidextrals) the authors describe some traits of the nervous and mental changes in focal brain lesions. There are insignificant correlations between the character of nervous and mental changes and the side of a brain lesion. The study demonstrated a wide variability of the clinical symptomatology, a peculiarity of each neurological and psychopathological phenomenon, distinguishing them from similar changes in dextrals. The studied contingent revealed prevalence of a disturbed sensory cognition in the clinical picture; the presence of special phenomena which most likely are not seen in dextrals and which are also related to a pathology of sensory cognition. It is being assumed that these clinical traits may testify to an insufficiency of speech lateralization in sinistrals and that an insufficient speech lateralization is accompanied by other than in dextrals organization of sensory processes.

Core Clinical Phenotypes in Myotonic Dystrophies

PubMed Central

Wenninger, Stephan; Montagnese, Federica; Schoser, Benedikt

2018-01-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) represent the most frequent multisystemic muscular dystrophies in adulthood. They are progressive, autosomal dominant diseases caused by an abnormal expansion of an unstable nucleotide repeat located in the non-coding region of their respective genes DMPK for DM1 and CNBP in DM2. Clinically, these multisystemic disorders are characterized by a high variability of muscular and extramuscular symptoms, often causing a delay in diagnosis. For both subtypes, many symptoms overlap, but some differences allow their clinical distinction. This article highlights the clinical core features of myotonic dystrophies, thus facilitating their early recognition and diagnosis. Particular attention will be given to signs and symptoms of muscular involvement, to issues related to respiratory impairment, and to the multiorgan involvement. This article is part of a Special Issue entitled “Beyond Borders: Myotonic Dystrophies—A European Perception.”

Mesomelic skeletal dysplasias.

PubMed

Kaitila, I; Leisti, J T; Rimoin, D L

1976-01-01

Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.

Primary Hepatic Malignant Fibrous Histiocytoma on PET/CT.

PubMed

Liu, Yachao; Xu, Baixuan

2018-06-01

Malignant fibrous histiocytoma is mainly presented in extremities, less commonly in posterior peritoneum, but primary presented in liver is very rare and often with a poor prognosis because of its high aggression. The features of clinical presentations and images are variable and the pre-operative diagnosis is difficult. Here, we report a primary hepatic malignant fibrous histiocytoma patient with no distant metastasis showed on pre-operative F-FDG PET/CT, however with many metastases showed on the post-operative F-FDG PET/CT.

A case of antenatal Bartter syndrome with sensorineural deafness.

PubMed

Lee, Hyun Seung; Cheong, Hae Il; Ki, Chang-Seok

2010-10-01

Bartter syndrome type IV, also known as Bartter syndrome with sensorineural deafness (BSND), is caused by loss-of-function mutations in the BSND gene, which encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Patients with BS IV have a highly variable clinical phenotype. This report concerns a Korean male patient with antenatal Bartter syndrome due to a homozygous BSND p.G47R mutation, who presented with severe perinatal symptoms followed by a relatively benign course with preserved renal function after early infancy. In addition, the clinical features and the laboratory data of the patient were compared with those of previously reported patients with the same mutation.

Clinical spectrum of anorexia nervosa in children.

PubMed

Atkins, D M; Silber, T J

1993-08-01

A retrospective review of 21 patients ages 12 years and younger (age of onset range 7 to 12 years) with anorexia nervosa showed diagnostic delay in the youngest ones, high incidence of family psychiatric history, a remarkable severity of illness, and positive response to intensive treatment. Additional findings included significant comorbidity, a distinct subgroup with personality disorder and another with features of the "vulnerable child syndrome." This broad clinical spectrum of anorexia nervosa in children may explain the great variability in outcome. The development of anorexia nervosa in children relates to a complex combination of etiological and trigger factors. Precipitants identified in this study were physical maturation, entry into junior high, loss, or some combination thereof.

Treacher Collins syndrome: clinical implications for the paediatrician--a new mutation in a severely affected newborn and comparison with three further patients with the same mutation, and review of the literature.

PubMed

Schlump, Jan-Ulrich; Stein, Anja; Hehr, Ute; Karen, Tanja; Möller-Hartmann, Claudia; Elcioglu, Nursel H; Bogdanova, Nadja; Woike, Hartmut Fritz; Lohmann, Dietmar R; Felderhoff-Mueser, Ursula; Linz, Annette; Wieczorek, Dagmar

2012-11-01

Treacher Collins syndrome (TCS) is the most common and well-known mandibulofacial dysostosis caused by mutations in at least three genes involved in pre-rRNA transcription, the TCOF1, POLR1D and POLR1C genes. We present a severely affected male individual with TCS with a heterozygous de novo frameshift mutation within the TCOF1 gene (c.790_791delAG,p.Ser264GlnfsX7) and compare the clinical findings with three previously unpublished, milder affected individuals from two families with the same mutation. We elucidate typical clinical features of TCS and its clinical implications for the paediatrician and mandibulofacial surgeon, especially in severely affected individuals and give a short review of the literature. The clinical data of these three families illustrate that the phenotype associated with this specific mutation has a wide intra- and interfamilial variability, which confirms that variable expressivity in carriers of TCOF1 mutations is not a simple consequence of the mutation but might be modified by the combination of genetic, environmental and stochastic factors. Being such a highly complex disease treatment of individuals with TCS should be tailored to the specific needs of each individual, preferably by a multidisciplinary team consisting of paediatricians, craniofacial surgeons and geneticists.

Evaluation of a Serum Lung Cancer Biomarker Panel.

PubMed

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.

Evaluation of a Serum Lung Cancer Biomarker Panel

PubMed Central

Mazzone, Peter J; Wang, Xiao-Feng; Han, Xiaozhen; Choi, Humberto; Seeley, Meredith; Scherer, Richard; Doseeva, Victoria

2018-01-01

Background: A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. Methods: The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. Results: The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. Conclusions: This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results. PMID:29371783

Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.

PubMed

Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T

2014-11-01

The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.

[CARDIOREABILITATION PECULIARITIES AND CORRECTION OF VIOLATIONS OF SISTOLIC, DIASOLIC FUNCTION AND HEART RATE VARIABILITY IN PATIENTS WITH ACUTE CORONARY SYNDROME AND CORONARY ARTERY REVASCULARIZATION].

PubMed

Shved, M; Tsuglevych, L; Kyrychok, I; Levytska, L; Boiko, T; Kitsak, Ya

2017-04-01

In patients with acute coronary syndrome (ACS) who underwent coronary arteries revascularization, violations of hemodynamics, metabolism and heart rate variability often develop in the postoperative period, therefore, the goal of the study was to establish the features of disturbances and the effectiveness of correction of left ventricular systolic and diastolic dysfunction and heart rate variability in stages of cardiorehabilitation in patients with acute coronary syndrome who underwent coronary arteries revascularization. The experimental group included 40 patients with ACS in the postoperative period who underwent balloon angioplasty and stenting of the coronary arteries (25 patients with ST-segment elevation ACS and 15 patients without ST-segment elevation ACS). The age of examined patients was 37 to 74 years, an average of 52.6±6.7 years. The control group consisted of 20 patients, comparable in age and clinico-laboratory manifestations of ACS, who underwent drug treatment with direct anticoagulants, double antiplatelet therapy, β-blockers, ACE inhibitors and statins. Clinical efficacy of cardiorespiratory process in patients of both groups was assessed by the dynamics of general clinical symptoms and parameters of natriuretic propeptide, systolic and diastolic function of the left ventricle and heart rate variability. In the initial state, clinical and laboratory-instrumental signs of myocardial ischemia disappear in patients with ACS undergoing surgical revascularization of the coronary arteries, but clinical and subclinical manifestations of heart failure were diagnosed. The use of the accelerated program of cardiac rehabilitation already during the first month of studies leads to a decreasement of the signs of systolic and diastolic dysfunction, the level of NT-proBNP and improve in the variability of the heart rhythm wich significantly improves the life quality of patients with ACS. To monitor the effectiveness and safety of cardiac rehabilitation in patients with ACS who underwent coronary arteries revascularization, in addition to the generally accepted methods (determination of heart rate, blood pressure, a 6-minute test), it is advisable to diagnose the subclinical stage of heart failure by determining the level of NT-proBNP, Doppler echocardiogram, parameters of the left ventricular systolic and diastolic function and heart rate variability.

Nonmetric traits of permanent posterior teeth in Kerala population: A forensic overview

PubMed Central

Baby, Tibin K; Sunil, S; Babu, Sharlene Sara

2017-01-01

Introduction: Dental morphology is a highly heritable characteristic which is stable with time and has a fairly high state of preservation. Nonmetric dental traits have crucial role in ethnic classifications of a population that helps in forensic racial identification purposes. Aims and Objectives: To determine the frequency and variability of possible nonmetric tooth traits using extracted permanent posterior teeth from Kerala population for discerning racial ethnicity. Materials and Methods: This qualitative, cross-sectional study was carried out using 1743 extracted intact permanent posterior teeth collected from different dental clinics situated all over Kerala. Results: The more common features on premolars were multiple lingual cusps (31.21%), distal accessary ridges (16.28%) and Tom's root (17.9%). In upper first molars, Carabelli trait expression was 17.78% and other common features included metaconulo, cusp 5 and enamel extensions. Conclusion: Posterior tooth traits had variable expression in the study population. Low prevalence rate of Carabelli trait in this study is characteristic of Asian population. This research explored new elements of invaluable tooth traits values to understand racial ethnicity of Kerala population. PMID:28932045

Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes.

PubMed

Torraco, Alessandra; Ardissone, Anna; Invernizzi, Federica; Rizza, Teresa; Fiermonte, Giuseppe; Niceta, Marcello; Zanetti, Nadia; Martinelli, Diego; Vozza, Angelo; Verrigni, Daniela; Di Nottia, Michela; Lamantea, Eleonora; Diodato, Daria; Tartaglia, Marco; Dionisi-Vici, Carlo; Moroni, Isabella; Farina, Laura; Bertini, Enrico; Ghezzi, Daniele; Carrozzo, Rosalba

2017-01-01

Defects of the Fe/S cluster biosynthesis represent a subgroup of diseases affecting the mitochondrial energy metabolism. In the last years, mutations in four genes (NFU1, BOLA3, ISCA2 and IBA57) have been related to a new group of multiple mitochondrial dysfunction syndromes characterized by lactic acidosis, hyperglycinemia, multiple defects of the respiratory chain complexes, and impairment of four lipoic acid-dependent enzymes: α-ketoglutarate dehydrogenase complex, pyruvic dehydrogenase, branched-chain α-keto acid dehydrogenase complex and the H protein of the glycine cleavage system. Few patients have been reported with mutations in IBA57 and with variable clinical phenotype. Herein, we describe four unrelated patients carrying novel mutations in IBA57. All patients presented with combined or isolated defect of complex I and II. Clinical features varied widely, ranging from fatal infantile onset of the disease to acute and severe psychomotor regression after the first year of life. Brain MRI was characterized by cavitating leukodystrophy. The identified mutations were never reported previously and all had a dramatic effect on IBA57 stability. Our study contributes to expand the array of the genotypic variation of IBA57 and delineates the leukodystrophic pattern of IBA57 deficient patients.

Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.

PubMed

Rochester, Lynn; Galna, Brook; Lord, Sue; Mhiripiri, Dadirayi; Eglon, Gail; Chinnery, Patrick F

2014-02-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no established treatment. Gait ataxia is a prominent feature causing substantial disability. Understanding the evolution of the gait disturbance is a key step in developing treatment strategies. We studied 9 gait variables in 24 SCA6 (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with clinical severity (presymptomatic and symptomatic). Discrete gait characteristics precede symptoms in SCA6 with significantly increased variability of step width and step time, whereas a more global gait deficit was evident in symptomatic individuals. Gait characteristics discriminated between presymptomatic and symptomatic individuals and were selectively associated with disease severity. This is the largest study to include a detailed characterization of gait in SCA6, including presymptomatic subjects, allowing changes across the disease spectrum to be compared. Selective gait disturbance is already present in SCA6 before clinical symptoms appear and gait characteristics are also sensitive to disease progression. Early gait disturbance likely reflects primary pathology distinct from secondary changes. These findings open the opportunity for early evaluation and sensitive measures of therapeutic efficacy using instrumented gait analysis which may have broader relevance for all degenerative ataxias. © 2013 Movement Disorder Society.

Incidence of positive surgical margins after robotic assisted radical prostatectomy: Does the surgeon's experience have an influence on all pathological stages?

PubMed

Villamil, A W; Costabel, J I; Billordo Peres, N; Martínez, P F; Giudice, C R; Damia, O H

2014-03-01

The aim of this study is to analyze the clinical and surgical features of patients who underwent robotic-assisted radical prostatectomy (RARP) at our institution, and the impact of the surgeon's experience in the oncological results related to pathological stage. An analysis of 300 RARP consecutively performed by the same urologist was conducted. Patients were divided into 3 groups of 100 patients in chronological order, according to surgery date. All patients had organ-confined clinical stage. Variables which could impact in positive margins rates were analyzed. Finally, positive surgical margins (PSM) in regard to pathological stage and surgeon's experience were compared and analyzed. No significant differences were found in variables which could impact in PSM rates. The overall PSM rate was 21%, with 28% in the first group, 20% in the second, and 16% in the third (P = .108). Significant lineal decreasing tendency was observed (P = .024). In pT2 patients, the overall PSM rate was 16.6%, with 27%, 13.8%, and 7.3% in each group respectively (P = .009). A significant difference was found between group 1 and group 3 (P = .004). In pT3 patients, the surgeon's experience was not significantly associated with margin reductions with an overall PSM rate of 27.7% (28.2%, 28.6%, and 26.7% in each group respectively). Clinical and surgical features in our patients did not vary over time. We found a significant reduction of PSM related to surgeon's experience in pT2 patients. Contrariwise, the margin status remained stable despite increasing experience in pT3 patients. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Body image dissatisfaction: clinical features, and psychosocial disability in inflammatory bowel disease.

PubMed

McDermott, Edel; Mullen, Georgina; Moloney, Jenny; Keegan, Denise; Byrne, Kathryn; Doherty, Glen A; Cullen, Garret; Malone, Kevin; Mulcahy, Hugh E

2015-02-01

Body image refers to a person's sense of their physical appearance and body function. A negative body image self-evaluation may result in psychosocial dysfunction. Crohn's disease and ulcerative colitis are associated with disabling features, and body image dissatisfaction is a concern for many patients with inflammatory bowel disease (IBD). However, no study has assessed body image and its comorbidities in patients with IBD using validated instruments. Our aim was to explore body image dissatisfaction in patients with IBD and assess its relationship with biological and psychosocial variables. We studied 330 patients (median age, 36 yr; range, 18-83; 169 men) using quantitative and qualitative methods. Patients completed a self-administered questionnaire that included a modified Hopwood Body Image Scale, the Cash Body Image Disturbance Questionnaire, and other validated instruments. Clinical and disease activity data were also collected. Body image dissatisfaction was associated with disease activity (P < 0.001) and steroid treatment (P = 0.03) but not with immunotherapy (P = 0.57) or biological (P = 0.55) therapy. Body image dissatisfaction was also associated with low levels of general (P < 0.001) and IBD-specific (P < 0.001) quality of life, self-esteem (P < 0.001), and sexual satisfaction (P < 0.001), and with high levels of anxiety (P < 0.001) and depression (P < 0.001). Qualitative analysis indicated that patients were concerned about both physical and psychosocial consequences of body image dissatisfaction, including steroid side effects and impaired work and social activities. Body image dissatisfaction is common in patients with IBD, relates to specific clinical variables and is associated with significant psychological dysfunction. Its measurement is warranted as part of a comprehensive patient-centered IBD assessment.

Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture.

PubMed

Zonana-Nacach, A; Roseman, J M; McGwin, G; Friedman, A W; Baethge, B A; Reveille, J D; Alarcón, G S

2000-01-01

To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.

Screening program for Waardenburg syndrome in Colombia: clinical definition and phenotypic variability.

PubMed

Tamayo, Marta L; Gelvez, Nancy; Rodriguez, Marcela; Florez, Silvia; Varon, Clara; Medina, David; Bernal, Jaime E

2008-04-15

A screening program to detect Waardenburg syndrome (WS) conducted between 2002 and 2005, among 1,763 deaf individuals throughout Columbia identified 95 affected individuals belonging to 95 families, giving a frequency of 5.38% of WS among the institutionalized deaf population. We confirmed the clinical diagnosis of WS in the 95 propositi and, through the family evaluation, we also identified 45 non-institutionalized affected relatives. Audiologic, ophthalmologic, and genetic studies were performed to confirm the diagnosis. Following the classification of the WS consortium, based on the Waardenburg Index (WI), to define the type of WS. We classified 62.1% of the propositi as WS2 and 37.9% as WS1. We present here the results of the study of clinical manifestations, analyzing the presence, severity, and symmetry of clinical findings among this affected population. Overall, among the 95 propositi, in addition to sensorineural deafness in all, the most frequent features were broad nasal root (58.9%), a first degree relative affected (37.9%), heterochromia irides (36.8%), skin hypopigmentation (31.6%), white forelock (28.0%), intense blue iris (27.4%), synophrys (12.6%), premature graying (10.5%), ptosis of the eyelids (9.5%), and hypoplasia alae nasi (1.1%). The majority of individuals had normal psychomotor development (87%), while the remaining 13% had developmental delay. Among the latter, 9.4% corresponded to WS2 and 3.6% to WS1. Our data confirm an interesting inter- and intrafamilial variability in the phenotypic manifestations as well as extremely variable expression. Copyright 2008 Wiley-Liss, Inc.

Levey-Jennings Analysis Uncovers Unsuspected Causes of Immunohistochemistry Stain Variability.

PubMed

Vani, Kodela; Sompuram, Seshi R; Naber, Stephen P; Goldsmith, Jeffrey D; Fulton, Regan; Bogen, Steven A

Almost all clinical laboratory tests use objective, quantitative measures of quality control (QC), incorporating Levey-Jennings analysis and Westgard rules. Clinical immunohistochemistry (IHC) testing, in contrast, relies on subjective, qualitative QC review. The consequences of using Levey-Jennings analysis for QC assessment in clinical IHC testing are not known. To investigate this question, we conducted a 1- to 2-month pilot test wherein the QC for either human epidermal growth factor receptor 2 (HER-2) or progesterone receptor (PR) in 3 clinical IHC laboratories was quantified and analyzed with Levey-Jennings graphs. Moreover, conventional tissue controls were supplemented with a new QC comprised of HER-2 or PR peptide antigens coupled onto 8 μm glass beads. At institution 1, this more stringent analysis identified a decrease in the HER-2 tissue control that had escaped notice by subjective evaluation. The decrement was due to heterogeneity in the tissue control itself. At institution 2, we identified a 1-day sudden drop in the PR tissue control, also undetected by subjective evaluation, due to counterstain variability. At institution 3, a QC shift was identified, but only with 1 of 2 controls mounted on each slide. The QC shift was due to use of the instrument's selective reagent drop zones dispense feature. None of these events affected patient diagnoses. These case examples illustrate that subjective QC evaluation of tissue controls can detect gross assay failure but not subtle changes. The fact that QC issues arose from each site, and in only a pilot study, suggests that immunohistochemical stain variability may be an underappreciated problem.

SU-F-R-42: Association of Radiomic and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme

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

Lopez, C; Nagornaya, N; Parra, N

Purpose: High-throughput extraction of imaging and metabolomic quantitative features from MRI and MR Spectroscopy Imaging (MRSI) of Glioblastoma Multiforme (GBM) results in tens of variables per patient. In radiotherapy (RT) of GBM, the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl Aspartate (NAA) and Choline (Cho). Corresponding Clinical Target Volumes (CTVs) for RT planning are based on Contrast Enhancing T1-weighted MRI (CE-T1w) and T2-weighted/Fluid Attenuated Inversion Recovery (FLAIR) MRI. The objective is to build a framework for investigation of associations between imaging, CTV, and MTV features better understanding of the underlying information in the CTVs andmore » dependencies between these volumes. Methods: Necrotic portions, enhancing lesion and edema were manually contoured on T1w/T2w images for 17 GBM patients. CTVs and MTVs for NAA (MTV{sub NAA}) and Cho (MTV{sub Cho}) were constructed. Tumors were scored categorically for ten semantic imaging traits by neuroradiologist. All features were investigated for redundancy. Two-way correlations between imaging and RT/MTV features were visualized as heat maps. Associations between MTV{sub NAA}, MTV{sub Cho} and imaging features were studied using Spearman correlation. Results: 39 imaging features were computed per patient. Half of the imaging traits were replaced with automatically extracted continuous variables. 21 features were extracted from MTVs/CTVs. There were a high number (43) of significant correlations of imaging with CTVs/MTV{sub NAA} while very few (10) significant correlations were with CTVs/MTV{sub Cho}. MTV{sub NAA} was found to be closely associated with MRI volumes, MTV{sub Cho} remains elusive for characterization with imaging. Conclusion: A framework for investigation of co-dependency between MRI and RT/metabolic features is established. A series of semantic imaging traits were replaced with automatically extracted continuous variables. The approach will allow for exploration of relationships between sizes and intersection of imaging features of tumors, RT volumes, metabolite concentrations and comparing those to therapy outcome, quality of life evaluation and overall survival rate. This publication was supported by Grant 10BN03 from Bankhead Coley Cancer Research Program, R01EB000822, R01EB016064, and R01CA172210 from the National Institutes of Health, and Indo-US Science & Technology Forum award #20-2009. Bhaswati Roy received financial assistance from University Grant Commission, New Delhi, India.« less

Clinical peripherality: development of a peripherality index for rural health services.

PubMed

Swan, Gillian M; Selvaraj, Sivasubramaniam; Godden, David J

2008-01-25

The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities.

Clinical peripherality: development of a peripherality index for rural health services

PubMed Central

Swan, Gillian M; Selvaraj, Sivasubramaniam; Godden, David J

2008-01-01

Background The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. Methods Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. Results Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. Conclusion Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities. PMID:18221533

Variability of textural features in FDG PET images due to different acquisition modes and reconstruction parameters.

PubMed

Galavis, Paulina E; Hollensen, Christian; Jallow, Ngoneh; Paliwal, Bhudatt; Jeraj, Robert

2010-10-01

Characterization of textural features (spatial distributions of image intensity levels) has been considered as a tool for automatic tumor segmentation. The purpose of this work is to study the variability of the textural features in PET images due to different acquisition modes and reconstruction parameters. Twenty patients with solid tumors underwent PET/CT scans on a GE Discovery VCT scanner, 45-60 minutes post-injection of 10 mCi of [(18)F]FDG. Scans were acquired in both 2D and 3D modes. For each acquisition the raw PET data was reconstructed using five different reconstruction parameters. Lesions were segmented on a default image using the threshold of 40% of maximum SUV. Fifty different texture features were calculated inside the tumors. The range of variations of the features were calculated with respect to the average value. Fifty textural features were classified based on the range of variation in three categories: small, intermediate and large variability. Features with small variability (range ≤ 5%) were entropy-first order, energy, maximal correlation coefficient (second order feature) and low-gray level run emphasis (high-order feature). The features with intermediate variability (10% ≤ range ≤ 25%) were entropy-GLCM, sum entropy, high gray level run emphsis, gray level non-uniformity, small number emphasis, and entropy-NGL. Forty remaining features presented large variations (range > 30%). Textural features such as entropy-first order, energy, maximal correlation coefficient, and low-gray level run emphasis exhibited small variations due to different acquisition modes and reconstruction parameters. Features with low level of variations are better candidates for reproducible tumor segmentation. Even though features such as contrast-NGTD, coarseness, homogeneity, and busyness have been previously used, our data indicated that these features presented large variations, therefore they could not be considered as a good candidates for tumor segmentation.

Variability of textural features in FDG PET images due to different acquisition modes and reconstruction parameters

PubMed Central

GALAVIS, PAULINA E.; HOLLENSEN, CHRISTIAN; JALLOW, NGONEH; PALIWAL, BHUDATT; JERAJ, ROBERT

2014-01-01

Background Characterization of textural features (spatial distributions of image intensity levels) has been considered as a tool for automatic tumor segmentation. The purpose of this work is to study the variability of the textural features in PET images due to different acquisition modes and reconstruction parameters. Material and methods Twenty patients with solid tumors underwent PET/CT scans on a GE Discovery VCT scanner, 45–60 minutes post-injection of 10 mCi of [18F]FDG. Scans were acquired in both 2D and 3D modes. For each acquisition the raw PET data was reconstructed using five different reconstruction parameters. Lesions were segmented on a default image using the threshold of 40% of maximum SUV. Fifty different texture features were calculated inside the tumors. The range of variations of the features were calculated with respect to the average value. Results Fifty textural features were classified based on the range of variation in three categories: small, intermediate and large variability. Features with small variability (range ≤ 5%) were entropy-first order, energy, maximal correlation coefficient (second order feature) and low-gray level run emphasis (high-order feature). The features with intermediate variability (10% ≤ range ≤ 25%) were entropy-GLCM, sum entropy, high gray level run emphsis, gray level non-uniformity, small number emphasis, and entropy-NGL. Forty remaining features presented large variations (range > 30%). Conclusion Textural features such as entropy-first order, energy, maximal correlation coefficient, and low-gray level run emphasis exhibited small variations due to different acquisition modes and reconstruction parameters. Features with low level of variations are better candidates for reproducible tumor segmentation. Even though features such as contrast-NGTD, coarseness, homogeneity, and busyness have been previously used, our data indicated that these features presented large variations, therefore they could not be considered as a good candidates for tumor segmentation. PMID:20831489

How People Use Social Information to Find out What to Want in the Paradigmatic Case of Inter-temporal Preferences

PubMed Central

Dolan, Raymond J.

2016-01-01

The weight with which a specific outcome feature contributes to preference quantifies a person’s ‘taste’ for that feature. However, far from being fixed personality characteristics, tastes are plastic. They tend to align, for example, with those of others even if such conformity is not rewarded. We hypothesised that people can be uncertain about their tastes. Personal tastes are therefore uncertain beliefs. People can thus learn about them by considering evidence, such as the preferences of relevant others, and then performing Bayesian updating. If a person’s choice variability reflects uncertainty, as in random-preference models, then a signature of Bayesian updating is that the degree of taste change should correlate with that person’s choice variability. Temporal discounting coefficients are an important example of taste–for patience. These coefficients quantify impulsivity, have good psychometric properties and can change upon observing others’ choices. We examined discounting preferences in a novel, large community study of 14–24 year olds. We assessed discounting behaviour, including decision variability, before and after participants observed another person’s choices. We found good evidence for taste uncertainty and for Bayesian taste updating. First, participants displayed decision variability which was better accounted for by a random-taste than by a response-noise model. Second, apparent taste shifts were well described by a Bayesian model taking into account taste uncertainty and the relevance of social information. Our findings have important neuroscientific, clinical and developmental significance. PMID:27447491

Collective feature selection to identify crucial epistatic variants.

PubMed

Verma, Shefali S; Lucas, Anastasia; Zhang, Xinyuan; Veturi, Yogasudha; Dudek, Scott; Li, Binglan; Li, Ruowang; Urbanowicz, Ryan; Moore, Jason H; Kim, Dokyoon; Ritchie, Marylyn D

2018-01-01

Machine learning methods have gained popularity and practicality in identifying linear and non-linear effects of variants associated with complex disease/traits. Detection of epistatic interactions still remains a challenge due to the large number of features and relatively small sample size as input, thus leading to the so-called "short fat data" problem. The efficiency of machine learning methods can be increased by limiting the number of input features. Thus, it is very important to perform variable selection before searching for epistasis. Many methods have been evaluated and proposed to perform feature selection, but no single method works best in all scenarios. We demonstrate this by conducting two separate simulation analyses to evaluate the proposed collective feature selection approach. Through our simulation study we propose a collective feature selection approach to select features that are in the "union" of the best performing methods. We explored various parametric, non-parametric, and data mining approaches to perform feature selection. We choose our top performing methods to select the union of the resulting variables based on a user-defined percentage of variants selected from each method to take to downstream analysis. Our simulation analysis shows that non-parametric data mining approaches, such as MDR, may work best under one simulation criteria for the high effect size (penetrance) datasets, while non-parametric methods designed for feature selection, such as Ranger and Gradient boosting, work best under other simulation criteria. Thus, using a collective approach proves to be more beneficial for selecting variables with epistatic effects also in low effect size datasets and different genetic architectures. Following this, we applied our proposed collective feature selection approach to select the top 1% of variables to identify potential interacting variables associated with Body Mass Index (BMI) in ~ 44,000 samples obtained from Geisinger's MyCode Community Health Initiative (on behalf of DiscovEHR collaboration). In this study, we were able to show that selecting variables using a collective feature selection approach could help in selecting true positive epistatic variables more frequently than applying any single method for feature selection via simulation studies. We were able to demonstrate the effectiveness of collective feature selection along with a comparison of many methods in our simulation analysis. We also applied our method to identify non-linear networks associated with obesity.

Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies

PubMed Central

Belaya, Katsiaryna; Rodríguez Cruz, Pedro M.; Liu, Wei Wei; Maxwell, Susan; McGowan, Simon; Farrugia, Maria E.; Petty, Richard; Walls, Timothy J.; Sedghi, Maryam; Basiri, Keivan; Yue, Wyatt W.; Sarkozy, Anna; Bertoli, Marta; Pitt, Matthew; Kennett, Robin; Schaefer, Andrew; Bushby, Kate; Parton, Matt; Lochmüller, Hanns; Palace, Jacqueline; Muntoni, Francesco

2015-01-01

Congenital myasthenic syndromes are inherited disorders that arise from impaired signal transmission at the neuromuscular junction. Mutations in at least 20 genes are known to lead to the onset of these conditions. Four of these, ALG2, ALG14, DPAGT1 and GFPT1, are involved in glycosylation. Here we identify a fifth glycosylation gene, GMPPB, where mutations cause congenital myasthenic syndrome. First, we identified recessive mutations in seven cases from five kinships defined as congenital myasthenic syndrome using decrement of compound muscle action potentials on repetitive nerve stimulation on electromyography. The mutations were present through the length of the GMPPB, and segregation, in silico analysis, exon trapping, cell transfection followed by western blots and immunostaining were used to determine pathogenicity. GMPPB congenital myasthenic syndrome cases show clinical features characteristic of congenital myasthenic syndrome subtypes that are due to defective glycosylation, with variable weakness of proximal limb muscle groups while facial and eye muscles are largely spared. However, patients with GMPPB congenital myasthenic syndrome had more prominent myopathic features that were detectable on muscle biopsies, electromyography, muscle magnetic resonance imaging, and through elevated serum creatine kinase levels. Mutations in GMPPB have recently been reported to lead to the onset of muscular dystrophy dystroglycanopathy. Analysis of four additional GMPPB-associated muscular dystrophy dystroglycanopathy cases by electromyography found that a defective neuromuscular junction component is not always present. Thus, we find mutations in GMPPB can lead to a wide spectrum of clinical features where deficit in neuromuscular transmission is the major component in a subset of cases. Clinical recognition of GMPPB-associated congenital myasthenic syndrome may be complicated by the presence of myopathic features, but correct diagnosis is important because affected individuals can respond to appropriate treatments. PMID:26133662

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.

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

Clinical features of the myasthenic syndrome arising from mutations in GMPPB.

PubMed

Rodríguez Cruz, Pedro M; Belaya, Katsiaryna; Basiri, Keivan; Sedghi, Maryam; Farrugia, Maria Elena; Holton, Janice L; Liu, Wei Wei; Maxwell, Susan; Petty, Richard; Walls, Timothy J; Kennett, Robin; Pitt, Matthew; Sarkozy, Anna; Parton, Matt; Lochmüller, Hanns; Muntoni, Francesco; Palace, Jacqueline; Beeson, David

2016-08-01

Congenital myasthenic syndrome (CMS) due to mutations in GMPPB has recently been reported confirming the importance of glycosylation for the integrity of neuromuscular transmission. Review of case notes of patients with mutations in GMPPB to identify the associated clinical, neurophysiological, pathological and laboratory features. In addition, serum creatine kinase (CK) levels within the Oxford CMS cohort were retrospectively analysed to assess its usefulness in the differential diagnosis of this new entity. All patients had prominent limb-girdle weakness with minimal or absent craniobulbar manifestations. Presentation was delayed beyond infancy with proximal muscle weakness and most patients recall poor performance in sports during childhood. Neurophysiology showed abnormal neuromuscular transmission only in the affected muscles and myopathic changes. Muscle biopsy showed dystrophic features and reduced α-dystroglycan glycosylation. In addition, myopathic changes were present on muscle MRI. CK was significantly increased in serum compared to other CMS subtypes. Patients were responsive to pyridostigimine alone or combined with 3,4-diaminopyridine and/or salbutamol. Patients with GMPPB-CMS have phenotypic features aligned with CMS subtypes harbouring mutations within the early stages of the glycosylation pathway. Additional features shared with the dystroglycanopathies include myopathic features, raised CK levels and variable mild cognitive delay. This syndrome underlines that CMS can occur in the absence of classic myasthenic manifestations such as ptosis and ophthalmoplegia or facial weakness, and links myasthenic disorders with dystroglycanopathies. This report should facilitate the recognition of this disorder, which is likely to be underdiagnosed and can benefit from symptomatic treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[18]Fluorodeoxyglucose Positron Emission Tomography for the Textural Features of Cervical Cancer Associated with Lymph Node Metastasis and Histological Type.

PubMed

Shen, Wei-Chih; Chen, Shang-Wen; Liang, Ji-An; Hsieh, Te-Chun; Yen, Kuo-Yang; Kao, Chia-Hung

2017-09-01

In this study, we investigated the correlation between the lymph node (LN) status or histological types and textural features of cervical cancers on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography. We retrospectively reviewed the imaging records of 170 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer. Four groups of textural features were studied in addition to the maximum standardized uptake value (SUV max ), metabolic tumor volume, and total lesion glycolysis (TLG). Moreover, we studied the associations between the indices and clinical parameters, including the LN status, clinical stage, and histology. Receiver operating characteristic curves were constructed to evaluate the optimal predictive performance among the various textural indices. Quantitative differences were determined using the Mann-Whitney U test. Multivariate logistic regression analysis was performed to determine the independent factors, among all the variables, for predicting LN metastasis. Among all the significant indices related to pelvic LN metastasis, homogeneity derived from the gray-level co-occurrence matrix (GLCM) was the sole independent predictor. By combining SUV max , the risk of pelvic LN metastasis can be scored accordingly. The TLG mean was the independent feature of positive para-aortic LNs. Quantitative differences between squamous and nonsquamous histology can be determined using short-zone emphasis (SZE) from the gray-level size zone matrix (GLSZM). This study revealed that in patients with cervical cancer, pelvic or para-aortic LN metastases can be predicted by using textural feature of homogeneity from the GLCM and TLG mean, respectively. SZE from the GLSZM is the sole feature associated with quantitative differences between squamous and nonsquamous histology.

Hand assessment in older adults with musculoskeletal hand problems: a reliability study.

PubMed

Myers, Helen L; Thomas, Elaine; Hay, Elaine M; Dziedzic, Krysia S

2011-01-07

Musculoskeletal hand pain is common in the general population. This study aims to investigate the inter- and intra-observer reliability of two trained observers conducting a simple clinical interview and physical examination for hand problems in older adults. The reliability of applying the American College of Rheumatology (ACR) criteria for hand osteoarthritis to community-dwelling older adults will also be investigated. Fifty-five participants aged 50 years and over with a current self-reported hand problem and registered with one general practice were recruited from a previous health questionnaire study. Participants underwent a standardised, structured clinical interview and physical examination by two independent trained observers and again by one of these observers a month later. Agreement beyond chance was summarised using Kappa statistics and intra-class correlation coefficients. Median values for inter- and intra-observer reliability for clinical interview questions were found to be "substantial" and "moderate" respectively [median agreement beyond chance (Kappa) was 0.75 (range: -0.03, 0.93) for inter-observer ratings and 0.57 (range: -0.02, 1.00) for intra-observer ratings]. Inter- and intra-observer reliability for physical examination items was variable, with good reliability observed for some items, such as grip and pinch strength, and poor reliability observed for others, notably assessment of altered sensation, pain on resisted movement and judgements based on observation and palpation of individual features at single joints, such as bony enlargement, nodes and swelling. Moderate agreement was observed both between and within observers when applying the ACR criteria for hand osteoarthritis. Standardised, structured clinical interview is reliable for taking a history in community-dwelling older adults with self reported hand problems. Agreement between and within observers for physical examination items is variable. Low Kappa values may have resulted, in part, from a low prevalence of clinical signs and symptoms in the study participants. The decision to use clinical interview and hand assessment variables in clinical practice or further research in primary care should include consideration of clinical applicability and training alongside reliability. Further investigation is required to determine the relationship between these clinical questions and assessments and the clinical course of hand pain and hand problems in community-dwelling older adults.

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

PubMed

Shashi, Vandana; Pena, Loren D M; Kim, Katherine; Burton, Barbara; Hempel, Maja; Schoch, Kelly; Walkiewicz, Magdalena; McLaughlin, Heather M; Cho, Megan; Stong, Nicholas; Hickey, Scott E; Shuss, Christine M; Freemark, Michael S; Bellet, Jane S; Keels, Martha Ann; Bonner, Melanie J; El-Dairi, Maysantoine; Butler, Megan; Kranz, Peter G; Stumpel, Constance T R M; Klinkenberg, Sylvia; Oberndorff, Karin; Alawi, Malik; Santer, Rene; Petrovski, Slavé; Kuismin, Outi; Korpi-Heikkilä, Satu; Pietilainen, Olli; Aarno, Palotie; Kurki, Mitja I; Hoischen, Alexander; Need, Anna C; Goldstein, David B; Kortüm, Fanny

2016-10-06

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes. Copyright © 2016. Published by Elsevier Inc.

Automatic classification of written descriptions by healthy adults: An overview of the application of natural language processing and machine learning techniques to clinical discourse analysis

PubMed Central

Toledo, Cíntia Matsuda; Cunha, Andre; Scarton, Carolina; Aluísio, Sandra

2014-01-01

Discourse production is an important aspect in the evaluation of brain-injured individuals. We believe that studies comparing the performance of brain-injured subjects with that of healthy controls must use groups with compatible education. A pioneering application of machine learning methods using Brazilian Portuguese for clinical purposes is described, highlighting education as an important variable in the Brazilian scenario. Objective The aims were to describe how to: (i) develop machine learning classifiers using features generated by natural language processing tools to distinguish descriptions produced by healthy individuals into classes based on their years of education; and (ii) automatically identify the features that best distinguish the groups. Methods The approach proposed here extracts linguistic features automatically from the written descriptions with the aid of two Natural Language Processing tools: Coh-Metrix-Port and AIC. It also includes nine task-specific features (three new ones, two extracted manually, besides description time; type of scene described – simple or complex; presentation order – which type of picture was described first; and age). In this study, the descriptions by 144 of the subjects studied in Toledo18 were used,which included 200 healthy Brazilians of both genders. Results and Conclusion A Support Vector Machine (SVM) with a radial basis function (RBF) kernel is the most recommended approach for the binary classification of our data, classifying three of the four initial classes. CfsSubsetEval (CFS) is a strong candidate to replace manual feature selection methods. PMID:29213908

The effects of variations in parameters and algorithm choices on calculated radiomics feature values: initial investigations and comparisons to feature variability across CT image acquisition conditions

NASA Astrophysics Data System (ADS)

Emaminejad, Nastaran; Wahi-Anwar, Muhammad; Hoffman, John; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael

2018-02-01

Translation of radiomics into clinical practice requires confidence in its interpretations. This may be obtained via understanding and overcoming the limitations in current radiomic approaches. Currently there is a lack of standardization in radiomic feature extraction. In this study we examined a few factors that are potential sources of inconsistency in characterizing lung nodules, such as 1)different choices of parameters and algorithms in feature calculation, 2)two CT image dose levels, 3)different CT reconstruction algorithms (WFBP, denoised WFBP, and Iterative). We investigated the effect of variation of these factors on entropy textural feature of lung nodules. CT images of 19 lung nodules identified from our lung cancer screening program were identified by a CAD tool and contours provided. The radiomics features were extracted by calculating 36 GLCM based and 4 histogram based entropy features in addition to 2 intensity based features. A robustness index was calculated across different image acquisition parameters to illustrate the reproducibility of features. Most GLCM based and all histogram based entropy features were robust across two CT image dose levels. Denoising of images slightly improved robustness of some entropy features at WFBP. Iterative reconstruction resulted in improvement of robustness in a fewer times and caused more variation in entropy feature values and their robustness. Within different choices of parameters and algorithms texture features showed a wide range of variation, as much as 75% for individual nodules. Results indicate the need for harmonization of feature calculations and identification of optimum parameters and algorithms in a radiomics study.

Clinical, radiographic, ultrasonographic and computed tomographic features of nonseptic osteitis of the axial border of the proximal sesamoid bones.

PubMed

Vanderperren, K; Bergman, H J; Spoormakers, T J P; Pille, F; Duchateau, L; Puchalski, S M; Saunders, J H

2014-07-01

Lysis of the axial aspect of equine proximal sesamoid bones (PSBs) is a rare condition reported to have septic or traumatic origins. Limited information exists regarding imaging of nonseptic axial osteitis of a PSB. To report the clinical, radiographic, ultrasonographic, computed tomographic and intra-arterial contrast-enhanced computed tomographic abnormalities in horses with axial nonseptic osteitis of a PSB. Retrospective clinical study. Eighteen horses diagnosed with nonseptic osteitis of the axial border of a PSB between 2007 and 2012 were reviewed retrospectively. Case details, clinical examination, radiographic, ultrasonographic, computed tomographic and intra-arterial/intra-articular contrast-enhanced computed tomographic features were recorded, when available. Radiographic, ultrasonographic and computed tomographic evaluations of the fetlock region had been performed on 18, 15 and 9 horses, respectively. The effect of the degree of lysis on the grade and duration of lameness was determined. All horses had chronic unilateral lameness, 4 with forelimb and 14 with hindlimb signs. On radiographs, lysis was identified in both PSBs in 14 horses, one PSB in 3 horses and in one horse no lysis was identified. The degree of osteolysis was variable. Ultrasonography identified variably sized irregularities of the bone surface and alteration in echogenicity of the palmar/plantar ligament (PL). All horses undergoing computed tomographic examination (n = 9) had biaxial lysis. The lesions were significantly longer and deeper on computed tomographic images compared with radiographic images. Intra-arterial contrast-enhanced computed tomography may reveal moderate to marked contrast enhancement of the PL. There was no significant effect of the degree of lysis on the grade and duration of lameness. Lesions of nonseptic axial osteitis of a PSB can be identified using a combination of radiography and ultrasonography. Computed tomography provides additional information regarding the extent of the pathology. © 2013 EVJ Ltd.

SU-F-R-30: Interscanner Variability of Radiomics Features in Computed Tomography (CT) Using a Standard ACR Phantom

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

Shafiq ul Hassan, M; Zhang, G; Moros, E

2016-06-15

Purpose: A simple approach to investigate Interscanner variability of Radiomics features in computed tomography (CT) using a standard ACR phantom. Methods: The standard ACR phantom was scanned on CT scanners from three different manufacturers. Scanning parameters of 120 KVp, 200 mA were used while slice thickness of 3.0 mm on two scanners and 3.27 mm on third scanner was used. Three spherical regions of interest (ROI) from water, medium density and high density inserts were contoured. Ninety four Radiomics features were extracted using an in-house program. These features include shape (11), intensity (22), GLCM (26), GLZSM (11), RLM (11), andmore » NGTDM (5) and 8 fractal dimensions features. To evaluate the Interscanner variability across three scanners, a coefficient of variation (COV) is calculated for each feature group. Each group is further classified according to the COV- by calculating the percentage of features in each of the following categories: COV less than 2%, between 2 and 10% and greater than 10%. Results: For all feature groups, similar trend was observed for three different inserts. Shape features were the most robust for all scanners as expected. 70% of the shape features had COV <2%. For intensity feature group, 2% COV varied from 9 to 32% for three scanners. All features in four groups GLCM, GLZSM, RLM and NGTDM were found to have Interscanner variability ≥2%. The fractal dimensions dependence for medium and high density inserts were similar while it was different for water inserts. Conclusion: We concluded that even for similar scanning conditions, Interscanner variability across different scanners was significant. The texture features based on GLCM, GLZSM, RLM and NGTDM are highly scanner dependent. Since the inserts of the ACR Phantom are not heterogeneous in HU values suggests that matrix based 2nd order features are highly affected by variation in noise. Research partly funded by NIH/NCI R01CA190105-01.« less

Aging and the Environment: Importance of Variability Issues in Understanding Risk

EPA Science Inventory

Of the many features of aging that could enhance susceptibility to environmental stressors, including toxic chemicals, the role of variability is arguably the least understood. This conclusion is surprising, since increased variability is a widely accepted feature of old age. In...

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

PubMed

García-Carbonero, R; Vilardell, F; Jiménez-Fonseca, P; González-Campora, R; González, E; Cuatrecasas, M; Capdevila, J; Aranda, I; Barriuso, J; Matías-Guiu, X

2014-03-01

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

LEPROSY NEPHROPATHY: A REVIEW OF CLINICAL AND HISTOPATHOLOGICAL FEATURES

PubMed Central

da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão

2015-01-01

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321

Machine learning approach for the outcome prediction of temporal lobe epilepsy surgery.

PubMed

Armañanzas, Rubén; Alonso-Nanclares, Lidia; Defelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G; Defelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery.

Machine Learning Approach for the Outcome Prediction of Temporal Lobe Epilepsy Surgery

PubMed Central

DeFelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G.; DeFelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery. PMID:23646148

A concentrated parameter model for the human cardiovascular system including heart valve dynamics and atrioventricular interaction.

PubMed

Korakianitis, Theodosios; Shi, Yubing

2006-09-01

Numerical modeling of the human cardiovascular system has always been an active research direction since the 19th century. In the past, various simulation models of different complexities were proposed for different research purposes. In this paper, an improved numerical model to study the dynamic function of the human circulation system is proposed. In the development of the mathematical model, the heart chambers are described with a variable elastance model. The systemic and pulmonary loops are described based on the resistance-compliance-inertia concept by considering local effects of flow friction, elasticity of blood vessels and inertia of blood in different segments of the blood vessels. As an advancement from previous models, heart valve dynamics and atrioventricular interaction, including atrial contraction and motion of the annulus fibrosus, are specifically modeled. With these improvements the developed model can predict several important features that were missing in previous numerical models, including regurgitant flow on heart valve closure, the value of E/A velocity ratio in mitral flow, the motion of the annulus fibrosus (called the KG diaphragm pumping action), etc. These features have important clinical meaning and their changes are often related to cardiovascular diseases. Successful simulation of these features enhances the accuracy of simulations of cardiovascular dynamics, and helps in clinical studies of cardiac function.

Mixed, melancholic, and anxious features in depression: a cross-sectional study of sociodemographic and clinical correlates.

PubMed

Zaninotto, Leonardo; Souery, Daniel; Calati, Raffaella; Scudellari, Paolo; Janiri, Luigi; Montgomery, Stuart; Kasper, Siegfried; Zohar, Joseph; Mendlewicz, Julien; Serretti, Alessandro

2014-11-01

Major depression (MD) is currently viewed as a heterogeneous condition, characterized by different psychopathological dimensions. Our sample was composed of 1,289 nonpsychotic bipolar/unipolar depressed patients. Participants were divided into mixed (MXD), melancholic (MEL), and anxious (ANX) depressed, according to a hierarchical functional model. Sociodemographic and clinical variables were compared across depressive subtypes by χ2 test and analysis of variance. The Young Mania Rating Scale (YMRS) and 2 subscales (melancholic [MEL-S] and psychic-somatic anxiety [PSOM-ANX]) from the Hamilton Depression Rating Scale also served as continuous outcome measures. MXD patients more frequently had bipolar I disorder (BD I), younger age of onset, and a higher familial load for mood disorders. MEL and ANX patients were more frequently diagnosed with major depressive disorder and reported a higher suicide risk. YMRS scores in depression was associated with BD I diagnosis (P < .0001) and manic polarity of the last episode (P < .0001), while a depressive polarity of the last episode (P < .0001) was associated with higher MEL-S score. No specific predictor was associated with PSOM-ANX score. Overall, our findings suggest that mixed depressive features are associated with significant hallmarks of bipolarity, and melancholic features may be influenced by previous depressive polarity. The symptom domain of anxiety appears to have no specific predictor.

Retrospective clinicopathological study of 418 odontogenic cysts.

PubMed

Nuñez-Urrutia, Sergio; Figueiredo, Rui; Gay-Escoda, Cosme

2010-09-01

To determine the relative incidence of odontogenic cysts and to identify the main clinicopathological features among patients treated in the Oral Surgery Department of the Dental Clinic of the University of Barcelona (Spain). A retrospective observational study was made of 418 odontogenic cysts diagnosed in 380 patients included in the database of 1235 histopathological diagnoses. The subjects were treated in the Master degree program of Oral Surgery and Implantology of the University of Barcelona in the period 1997-2006. The following variables were recorded: gender, age, clinical characteristics of the lesions (size and location), radiological features, duration, treatment, complications and relapses. A descriptive analysis was made of the study variables, using the SPSS version 15.0. The incidence of odontogenic cysts was 33.8%. The mean patient age at appearance of the lesion was 42 years (range 7-83). The cysts were slightly more prevalent in males (58.4%). The lesion size ranged from 2-60 mm, with a mean size of 18.4 mm. The most frequent diagnosis was radicular cyst (50.2%). The most common location of the odontogenic cysts was in the mandible (61.5%), particularly the lower third molar region (36.8%). The most frequently diagnosed lesion was the radicular cyst. Odontogenic cysts were seen to be slightly more prevalent in males, and showed a high mandibular incidence. Knowledge of the biological and histological behavior of odontogenic cysts and their frequency are key aspects for ensuring early detection and adequate treatment.

Submicroscopic deletions at 22q11.2: Variability of the clinical picture and delineation of a commonly deleted region

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

Lindsay, E.A.; Shaffer, L.G.; Greenberg, F.

DiGeorge anomaly (DGA) and velo-cardio-facial syndrome (VCFS) are frequently associated with monosomy of chromosome region 22q11. Most patients have a submicroscopic deletion, recently estimated to be at least 1-2 Mb. It is not clear whether individuals who present with only some of the features of these conditions have the deletion, and if so, whether the size of the deletion varies from those with more classic phenotypes. We have used fluorescence in situ hybridization (FISH) to assess the deletion status of 85 individuals referred to us for molecular analysis, with a wide range of DGA-like or VCFS-like clinical features. The testmore » probe used was the cosmid sc11.1, which detects two loci about 2 Mb apart in 22q11.2. Twenty-four patients carried the deletion. Of the deleted patients, most had classic DGA or VCFS phenotypes, but 6 deleted patients had mild phenotypes, including 2 with minor facial anomalies and velopharyngeal incompetence as the only presenting signs. Despite the great phenotypic variability among the deleted patients, none had a deletion smaller than the 2-Mb region defined by sc11.1. Smaller deletions were not detected in patients with particularly suggestive phenotypes who were not deleted for sc11.1, even when tested with two other probes from the DGA/VCFS region. 24 refs., 2 figs., 2 tabs.« less

Free Interval Duration: Clinical Evidence of the Primary Role of Excitement in Bipolar Disorder.

PubMed

Sani, Gabriele; Simonetti, Alessio; Reginaldi, Daniela; Koukopoulos, Alexia E; Del Casale, Antonio; Manfredi, Giovanni; Kotzalidis, Georgios D; Girardi, Paolo

2017-04-01

Cyclicity is the essential feature of Bipolar disorder, but the effect of different cycle patterns on the clinical features is poorly understood. Moreover, no studies investigated the relationship between mania and depression inside the manic-depressive cycle. The aim of this study is to verify the presence of a relationship between the manic and the depressive phase during the course of bipolar disorder. 160 consecutive patients with BD type I were recruited and followed for a mean period of 10 years. During the follow-up period, four types of euthymic phases were collected: free intervals present between a depressive and a manic/hypomanic episode (D-M); free intervals present between a manic/hypomanic and a depressive episode (M-D); free intervals present between two depressive episodes (D-D); free intervals present between two manic/hypomanic episodes (M-M). One-way ANOVA using the groups as independent variable and the duration of the free intervals as dependent variables was used. Furthermore, ANOVA was followed by Fisher's Protected Least Significant Difference post-hoc test to measure between-group differences. M-D-free interval phases were shorter than D-M-free intervals. M-D intervals were the shortest ones, the D-D and D-M did not differ, and the M-M were the longest. The strict temporal link between manic and depressive phases supports the idea that the manic-depressive cycle usually begins with a manic episode, and that the subsequent depression is often the consequence of subsiding mania.

Mixed anxiety-depressive disorder and major depressive disorder: comparison of the severity of illness and biological variables.

PubMed

Kara, S; Yazici, K M; Güleç, C; Unsal, I

2000-04-24

Mixed anxiety-depressive disorder (MADD) is a new diagnostic category defining patients who suffer from both anxiety and depressive symptoms of limited and equal intensity accompanied by at least some autonomic features. Patients do not meet the criteria for specific anxiety or depressive disorders. The emergence of the symptoms is independent of stressful life events. There are many issues presently under investigation about the validity of this clinical entity. In this study, a group of 29 patients with MADD was compared with a group of 31 patients with major depressive disorder (MDD) to assess the differences and similarities between these two disease categories in terms of severity measures and biological variables. The dexamethasone suppression test (DST) was employed, and thyroid hormones and thyrotropin (TSH) levels were measured for the evaluation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes, respectively. The patients with MADD were found to be less depressive and more anxious compared to those with MDD. DST responses and thyroid functions were found to be similar in the two groups. When severity of depression was controlled, k(max) and 2300-h cortisol values were found to be significantly higher in the MADD group. Although the patients with MDD and MADD presented with relatively different clinical features, there is not enough biological evidence indicating that MADD represents a discrete diagnostic category. However, there may be relatively higher HPA activity in MADD patients.

Forecasting Daily Patient Outflow From a Ward Having No Real-Time Clinical Data

PubMed Central

Tran, Truyen; Luo, Wei; Phung, Dinh; Venkatesh, Svetha

2016-01-01

Background: Modeling patient flow is crucial in understanding resource demand and prioritization. We study patient outflow from an open ward in an Australian hospital, where currently bed allocation is carried out by a manager relying on past experiences and looking at demand. Automatic methods that provide a reasonable estimate of total next-day discharges can aid in efficient bed management. The challenges in building such methods lie in dealing with large amounts of discharge noise introduced by the nonlinear nature of hospital procedures, and the nonavailability of real-time clinical information in wards. Objective Our study investigates different models to forecast the total number of next-day discharges from an open ward having no real-time clinical data. Methods We compared 5 popular regression algorithms to model total next-day discharges: (1) autoregressive integrated moving average (ARIMA), (2) the autoregressive moving average with exogenous variables (ARMAX), (3) k-nearest neighbor regression, (4) random forest regression, and (5) support vector regression. Although the autoregressive integrated moving average model relied on past 3-month discharges, nearest neighbor forecasting used median of similar discharges in the past in estimating next-day discharge. In addition, the ARMAX model used the day of the week and number of patients currently in ward as exogenous variables. For the random forest and support vector regression models, we designed a predictor set of 20 patient features and 88 ward-level features. Results Our data consisted of 12,141 patient visits over 1826 days. Forecasting quality was measured using mean forecast error, mean absolute error, symmetric mean absolute percentage error, and root mean square error. When compared with a moving average prediction model, all 5 models demonstrated superior performance with the random forests achieving 22.7% improvement in mean absolute error, for all days in the year 2014. Conclusions In the absence of clinical information, our study recommends using patient-level and ward-level data in predicting next-day discharges. Random forest and support vector regression models are able to use all available features from such data, resulting in superior performance over traditional autoregressive methods. An intelligent estimate of available beds in wards plays a crucial role in relieving access block in emergency departments. PMID:27444059

Mid-infrared interferometric variability of DG Tau: implications for the inner-disk structure .

NASA Astrophysics Data System (ADS)

Ábrahám, P.; Varga, J.; Gabányi, K. É.; Chen, L.; Kóspál, Á.; Ratzka, Th.; van Boekel, R.; Mosoni, L.; Henning, Th.

DG Tau is a low-mass young star whose strongly accreting disk shows a variable 10 mu m silicate feature, that may even turn temporarily from emission to absorption. Aiming to find the physical reason of this variability, we analysed multiepoch VLTI/MIDI interferometric observations. We found that the inner disk within 3 au radius exhibits a 10 mu m absorption feature related to amorphous silicate grains, while the outer disk displays a variable crystalline feature in emission, similar in shape to the spectrum of comet Hale-Bopp. The variability may be related to a fluctuating amount of dusty material above the disk surface, possibly due to turbulence.

Accounting for disease modifying therapy in models of clinical progression in multiple sclerosis.

PubMed

Healy, Brian C; Engler, David; Gholipour, Taha; Weiner, Howard; Bakshi, Rohit; Chitnis, Tanuja

2011-04-15

Identifying predictors of clinical progression in patients with relapsing-remitting multiple sclerosis (RRMS) is complicated in the era of disease modifying therapy (DMT) because patients follow many different DMT regimens. To investigate predictors of progression in a treated RRMS sample, a cohort of RRMS patients was prospectively followed in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB). Enrollment criteria were exposure to either interferon-β (IFN-β, n=164) or glatiramer acetate (GA, n=114) for at least 6 months prior to study entry. Baseline demographic and clinical features were used as candidate predictors of longitudinal clinical change on the Expanded Disability Status Scale (EDSS). We compared three approaches to account for DMT effects in statistical modeling. In all approaches, we analyzed all patients together and stratified based on baseline DMT. Model 1 used all available longitudinal EDSS scores, even those after on-study DMT changes. Model 2 used only clinical observations prior to changing DMT. Model 3 used causal statistical models to identify predictors of clinical change. When all patients were considered using Model 1, patients with a motor symptom as the first relapse had significantly larger change in EDSS scores during follow-up (p=0.04); none of the other clinical or demographic variables significantly predicted change. In Models 2 and 3, results were generally unchanged. DMT modeling choice had a modest impact on the variables classified as predictors of EDSS score change. Importantly, however, interpretation of these predictors is dependent upon modeling choice. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterizing mammographic images by using generic texture features

PubMed Central

2012-01-01

Introduction Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design. Methods A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model. Results Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model. Conclusions Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy. PMID:22490545

Brachydactyly E: isolated or as a feature of a syndrome.

PubMed

Pereda, Arrate; Garin, Intza; Garcia-Barcina, Maria; Gener, Blanca; Beristain, Elena; Ibañez, Ane Miren; Perez de Nanclares, Guiomar

2013-09-12

Brachydactyly (BD) refers to the shortening of the hands, feet or both. There are different types of BD; among them, type E (BDE) is a rare type that can present as an isolated feature or as part of more complex syndromes, such as: pseudohypopthyroidism (PHP), hypertension with BD or Bilginturan BD (HTNB), BD with mental retardation (BDMR) or BDE with short stature, PTHLH type. Each syndrome has characteristic patterns of skeletal involvement. However, brachydactyly is not a constant feature and shows a high degree of phenotypic variability. In addition, there are other syndromes that can be misdiagnosed as brachydactyly type E, some of which will also be discussed. The objective of this review is to describe some of the syndromes in which BDE is present, focusing on clinical, biochemical and genetic characteristics as features of differential diagnoses, with the aim of establishing an algorithm for their differential diagnosis. As in our experience many of these patients are recruited at Endocrinology and/or Pediatric Endocrinology Services due to their short stature, we have focused the algorithm in those steps that could mainly help these professionals.

Brachydactyly E: isolated or as a feature of a syndrome

PubMed Central

2013-01-01

Brachydactyly (BD) refers to the shortening of the hands, feet or both. There are different types of BD; among them, type E (BDE) is a rare type that can present as an isolated feature or as part of more complex syndromes, such as: pseudohypopthyroidism (PHP), hypertension with BD or Bilginturan BD (HTNB), BD with mental retardation (BDMR) or BDE with short stature, PTHLH type. Each syndrome has characteristic patterns of skeletal involvement. However, brachydactyly is not a constant feature and shows a high degree of phenotypic variability. In addition, there are other syndromes that can be misdiagnosed as brachydactyly type E, some of which will also be discussed. The objective of this review is to describe some of the syndromes in which BDE is present, focusing on clinical, biochemical and genetic characteristics as features of differential diagnoses, with the aim of establishing an algorithm for their differential diagnosis. As in our experience many of these patients are recruited at Endocrinology and/or Pediatric Endocrinology Services due to their short stature, we have focused the algorithm in those steps that could mainly help these professionals. PMID:24028571

FFDM image quality assessment using computerized image texture analysis

NASA Astrophysics Data System (ADS)

Berger, Rachelle; Carton, Ann-Katherine; Maidment, Andrew D. A.; Kontos, Despina

2010-04-01

Quantitative measures of image quality (IQ) are routinely obtained during the evaluation of imaging systems. These measures, however, do not necessarily correlate with the IQ of the actual clinical images, which can also be affected by factors such as patient positioning. No quantitative method currently exists to evaluate clinical IQ. Therefore, we investigated the potential of using computerized image texture analysis to quantitatively assess IQ. Our hypothesis is that image texture features can be used to assess IQ as a measure of the image signal-to-noise ratio (SNR). To test feasibility, the "Rachel" anthropomorphic breast phantom (Model 169, Gammex RMI) was imaged with a Senographe 2000D FFDM system (GE Healthcare) using 220 unique exposure settings (target/filter, kVs, and mAs combinations). The mAs were varied from 10%-300% of that required for an average glandular dose (AGD) of 1.8 mGy. A 2.5cm2 retroareolar region of interest (ROI) was segmented from each image. The SNR was computed from the ROIs segmented from images linear with dose (i.e., raw images) after flat-field and off-set correction. Image texture features of skewness, coarseness, contrast, energy, homogeneity, and fractal dimension were computed from the Premium ViewTM postprocessed image ROIs. Multiple linear regression demonstrated a strong association between the computed image texture features and SNR (R2=0.92, p<=0.001). When including kV, target and filter as additional predictor variables, a stronger association with SNR was observed (R2=0.95, p<=0.001). The strong associations indicate that computerized image texture analysis can be used to measure image SNR and potentially aid in automating IQ assessment as a component of the clinical workflow. Further work is underway to validate our findings in larger clinical datasets.

Clinical significance and epidemiologic analyses of Mycobacterium avium and Mycobacterium intracellulare lung disease from post-marketing surveillance.

PubMed

Suzuki, Katsuhiro; Kurashima, Atsuyuki; Tatsuno, Kinji; Kadota, Jun-Ichi

2018-01-01

In Japan, nontuberculous mycobacterial lung disease is mostly attributable to Mycobacterium avium complex (MAC), i.e., M. avium or M. intracellulare. However, clinical features of the disease caused by these two pathogens have not been studied sufficiently yet. A post-marketing survey of clarithromycin was performed at 130 facilities across Japan. The data on patients with M. avium infection and patients with M. intracellulare infection were selected from this survey for comparison of background variables and clinical features of the two pathogens. Among the patients analyzed (n = 368), 67.4% had M. avium infection and 32.6% had M. intracellulare infection. Stratified analysis revealed no significant differences between the ratio of the two pathogens based on gender, disease type, complication, past medical history, or smoking history. However, the percentage of patients with M. intracellulare infection was significantly higher among those with underlying lung disease than among those without lung disease (p = 0.0217). The percentage of patients with M. intracellulare infection rose significantly with age (p = 0.0296). This age-related change was more significant in women (p = 0.0018). When district-wise analysis was performed for Japan, the percentage of M. intracellulare infection was higher in the Chugoku/Shikoku and Kyushu districts whereas the percentage of M. avium infection was higher in the other districts. This survey revealed some differences in the clinical and epidemiologic features of M. avium and M. intracellulare infection. The significant predominance of M. avium infection among relatively young women is suggestive of an increase in the M. avium/M. intracellulare infection ratio among women in the future. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

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.

Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

PubMed

Tobin, W Oliver; Guo, Yong; Krecke, Karl N; Parisi, Joseph E; Lucchinetti, Claudia F; Pittock, Sean J; Mandrekar, Jay; Dubey, Divyanshu; Debruyne, Jan; Keegan, B Mark

2017-09-01

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory syndrome predominantly affecting the brainstem, cerebellum, and spinal cord. Following its initial description, the salient features of CLIPPERS have been confirmed and expanded upon, but the lack of formalized diagnostic criteria has led to reports of patients with dissimilar features purported to have CLIPPERS. We evaluated clinical, radiological and pathological features of patients referred for suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were reviewed by experienced neuroradiologists and neuropathologists, respectively, both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23 patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis. CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72) and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS patients' median age of onset was 52 years (interquartile range, 39-59) and were followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical worsening occurred in all 12 CLIPPERS cases when corticosteroids were discontinued. Corticosteroid responsiveness was common but not universal in non-CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant perivascular gadolinium enhancing lesions on magnetic resonance imaging that were discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm in diameter without ring-enhancement or mass effect, and homogenous T2 signal abnormality not significantly exceeding the T1 enhancement. Brain neuropathology on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B-lymphocyte and moderate macrophage infiltrates, with perivascular predominance as well as diffuse parenchymal infiltration (14/14), present in meninges, white and grey matter, associated with variable tissue destruction, astrogliosis and secondary myelin loss. Clinical, radiological and pathological feature define CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by neuroradiological and neuropathological findings. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

PubMed

Zidan, Jamal; Karen, Drumea; Stein, Moshe; Rosenblatt, Edward; Basher, Walid; Kuten, Abraham

2003-03-01

The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically. Copyright 2003 American Cancer Society.

Phenotypic variability in Patau syndrome.

PubMed

Caba, Lavinia; Rusu, Cristina; Butnariu, Lacramioara; Panzaru, Monica; Braha, Elena; Volosciuc, M; Popescu, Roxana; Gramescu, Mihaela; Bujoran, C; Martiniuc, Violeta; Covic, M; Gorduza, E V

2013-01-01

Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

Plaque echodensity and textural features are associated with histologic carotid plaque instability.

PubMed

Doonan, Robert J; Gorgui, Jessica; Veinot, Jean P; Lai, Chi; Kyriacou, Efthyvoulos; Corriveau, Marc M; Steinmetz, Oren K; Daskalopoulou, Stella S

2016-09-01

Carotid plaque echodensity and texture features predict cerebrovascular symptomatology. Our purpose was to determine the association of echodensity and textural features obtained from a digital image analysis (DIA) program with histologic features of plaque instability as well as to identify the specific morphologic characteristics of unstable plaques. Patients scheduled to undergo carotid endarterectomy were recruited and underwent carotid ultrasound imaging. DIA was performed to extract echodensity and textural features using Plaque Texture Analysis software (LifeQ Medical Ltd, Nicosia, Cyprus). Carotid plaque surgical specimens were obtained and analyzed histologically. Principal component analysis (PCA) was performed to reduce imaging variables. Logistic regression models were used to determine if PCA variables and individual imaging variables predicted histologic features of plaque instability. Image analysis data from 160 patients were analyzed. Individual imaging features of plaque echolucency and homogeneity were associated with a more unstable plaque phenotype on histology. These results were independent of age, sex, and degree of carotid stenosis. PCA reduced 39 individual imaging variables to five PCA variables. PCA1 and PCA2 were significantly associated with overall plaque instability on histology (both P = .02), whereas PCA3 did not achieve statistical significance (P = .07). DIA features of carotid plaques are associated with histologic plaque instability as assessed by multiple histologic features. Importantly, unstable plaques on histology appear more echolucent and homogeneous on ultrasound imaging. These results are independent of stenosis, suggesting that image analysis may have a role in refining the selection of patients who undergo carotid endarterectomy. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2.24-31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence interval 2.24–31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. PMID:25281868

Characterization of PET/CT images using texture analysis: the past, the present… any future?

PubMed

Hatt, Mathieu; Tixier, Florent; Pierce, Larry; Kinahan, Paul E; Le Rest, Catherine Cheze; Visvikis, Dimitris

2017-01-01

After seminal papers over the period 2009 - 2011, the use of texture analysis of PET/CT images for quantification of intratumour uptake heterogeneity has received increasing attention in the last 4 years. Results are difficult to compare due to the heterogeneity of studies and lack of standardization. There are also numerous challenges to address. In this review we provide critical insights into the recent development of texture analysis for quantifying the heterogeneity in PET/CT images, identify issues and challenges, and offer recommendations for the use of texture analysis in clinical research. Numerous potentially confounding issues have been identified, related to the complex workflow for the calculation of textural features, and the dependency of features on various factors such as acquisition, image reconstruction, preprocessing, functional volume segmentation, and methods of establishing and quantifying correspondences with genomic and clinical metrics of interest. A lack of understanding of what the features may represent in terms of the underlying pathophysiological processes and the variability of technical implementation practices makes comparing results in the literature challenging, if not impossible. Since progress as a field requires pooling results, there is an urgent need for standardization and recommendations/guidelines to enable the field to move forward. We provide a list of correct formulae for usual features and recommendations regarding implementation. Studies on larger cohorts with robust statistical analysis and machine learning approaches are promising directions to evaluate the potential of this approach.

Predictors and moderators of response to cognitive behavioral therapy and medication for the treatment of binge eating disorder.

PubMed

Grilo, Carlos M; Masheb, Robin M; Crosby, Ross D

2012-10-01

To examine predictors and moderators of response to cognitive behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout, and posttreatment. Demographic factors, psychiatric and personality disorder comorbidity, eating disorder psychopathology, psychological features, and 2 subtyping methods (negative affect, overvaluation of shape/weight) were tested as predictors and moderators for the primary outcome of remission from binge eating and 4 secondary dimensional outcomes (binge-eating frequency, eating disorder psychopathology, depression, and body mass index). Mixed-effects models analyzed all available data for each outcome variable. In each model, effects for baseline value and treatment were included with tests of both prediction and moderator effects. Several demographic and clinical variables significantly predicted and/or moderated outcomes. One demographic variable signaled a statistical advantage for medication only (younger participants had greater binge-eating reductions), whereas several demographic and clinical variables (lower self-esteem, negative affect, and overvaluation of shape/weight) signaled better improvements if receiving CBT. Overvaluation was the most salient predictor/moderator of outcomes. Overvaluation significantly predicted binge-eating remission (29% of participants with vs. 57% of participants without overvaluation remitted). Overvaluation was especially associated with lower remission rates if receiving medication only (10% vs. 42% for participants without overvaluation). Overvaluation moderated dimensional outcomes: Participants with overvaluation had significantly greater reductions in eating disorder psychopathology and depression levels if receiving CBT. Overvaluation predictor/moderator findings persisted after controlling for negative affect. Our findings have clinical utility for prescription of CBT and medication and implications for refinement of the BED diagnosis. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Predictors and Moderators of Response to Cognitive Behavioral Therapy and Medication for the Treatment of Binge Eating Disorder

PubMed Central

Grilo, Carlos. M.; Masheb, Robin M.; Crosby, Ross D.

2012-01-01

Objective To examine predictors and moderators of response to cognitive-behavioral therapy (CBT) and medication treatments for binge-eating disorder (BED). Method 108 BED patients in a randomized double-blind placebo-controlled trial testing CBT and fluoxetine treatments were assessed prior, throughout-, and post-treatment. Demographic factors, psychiatric and personality-disorder co-morbidity, eating-disorder psychopathology, psychological features, and two sub-typing methods (negative-affect, overvaluation of shape/weight) were tested as predictors and moderators for the primary outcome of remission from binge-eating and four secondary dimensional outcomes (binge-eating frequency, eating-disorder psychopathology, depression, and body mass index). Mixed-effects-models analyzed all available data for each outcome variable. In each model, effects for baseline value and treatment were included with tests of both prediction and moderator effects. Results Several demographic and clinical variables significantly predicted and/or moderated outcomes. One demographic variable signaled a statistical advantage for medication-only (younger participants had greater binge-eating reductions) whereas several demographic and clinical variables (lower self-esteem, negative-affect, and overvaluation of shape/weight) signaled better improvements if receiving CBT. Overvaluation was the most salient predictor/moderator of outcomes. Overvaluation significantly predicted binge-eating remission (29% of participants with versus 57% of participants without overvaluation remitted). Overvaluation was especially associated with lower remission rates if receiving medication-only (10% versus 42% for participants without overvaluation). Overvaluation moderated dimensional outcomes: participants with overvaluation had significantly greater reductions in eating-disorder psychopathology and depression levels if receiving CBT. Overvaluation predictor/moderator findings persisted after controlling for negative-affect. Conclusions Our findings have clinical utility for prescription of CBT and medication and implications for refinement of the BED diagnosis. PMID:22289130

The role of psychological processes in estimates of stuttering severity.

PubMed

Manning, Walter; Gayle Beck, J

2013-12-01

To examine the associations of trait anxiety (STAI), social anxiety (SIAS), depression (BDI-II), and personality features (ADP-IV) with three measures of stuttering severity: %SS, Stuttering Severity, Instrument, and the Overall Assessment of the Speaker's Experience of Stuttering. Fifty adults with a history of stuttering served as participants. Participant scores on trait, anxiety, social anxiety, depression, and personality features were entered into a regression analysis, with the criterion variables (DVs) being: %SS, SSI-3, OASES total score. In order to explore the OASES, further, each of the four OASES subscales were also examined. A separate regression was conducted for, each dependent variable. The OASES total score model was significant (p<.0001) and revealed that social anxiety and, trait anxiety were the only significant predictors, with medium effect sizes noted for both variables. In contrast, percent syllables stuttered and the SSI were not significantly associated with psychological, variables, suggesting that anxiety may not always be related to overt indicators of stuttering. Depression and personality dysfunction were not significantly associated with any measure of, stuttering severity. Anxiety in the form of social and trait anxiety are significantly associated with stuttering, severity as indicated by the OASES. Traditional procedures for assigning severity ratings to individuals, who stutter based on percent syllables stuttered and the Stuttering Severity Instrument are not, significantly related to psychological processes central to the stuttering experience. Depression and, personality characteristics do not meaningfully account for stuttering. The reader will be able to: (a) differentiate forms of anxiety that are likely to be associated with stuttering (b) understand the importance of determining features of stuttering that go beyond the obvious, surface characteristics of stuttering frequency, and (c) discuss the important clinical and theoretical implications for understanding the degree of psychological dysfunction that is likely to be characteristic of those who stutter. Copyright © 2013 Elsevier Inc. All rights reserved.

Vegetation-terrain feature relationships in southeast Arizona

NASA Technical Reports Server (NTRS)

Schrumpf, B. J. (Principal Investigator); Mouat, D. A.

1972-01-01

There are no author-identified significant results in this report. Studies of relationships of vegetation distribution to geomorphic characteristics of the landscape and of plant phenological patterns to vegetation identification of satellite imagery indicate that there exists positive relationships between certain plant species and certain terrain features. Not all species were found to exhibit positive relationships with all terrain feature variables, but enough positive relationships seem to exist to indicate that terrain feature variable-vegetation relationship studies have a definite place in plant ecological investigations. Even more importantly, the vegetation groups examined appeared to be successfully discriminated by the terrain feature variables. This would seem to indicate that spatial interpretations of vegetation groups may be possible. While vegetational distributions aren't determined by terrain feature differences, terrain features do mirror factors which directly influence vegetational response and hence distribution. As a result, those environmental features which can be readily and rapidly ascertained on relatively small-scale imagery may prove to be valuable indicators of vegetation distribution.

[Myofibrillar myopaathy].

PubMed

Hayashi, Yukiko

2013-01-01

Myofibrillar myopathy (MFM) is a group of hereditary disorders pathologically characterized by focal disorganizations of myofibril structures with cytoplasmic inclusions. Most of the diseases so-called desmin-related or storage myopathy, cytoplasmic body myopathy, spheroid body myopathy, reducing body myopathy, and hyaline body myopathy are included in MFM. Several causative genes have been identified such as DES, CRYAB, MYOT, ZASP, BAG3, FLNC, DNAJB6, FHL1, TTN, and VCP. Most of these genes encode Z-line related proteins or proteins associated with protein quality control. Since MFM is the name from pathological characteristics, clinical features of the patients including the age at disease onset, affected muscles, disease course, and complications are quite variable. In this paper, characteristic clinical and pathological features of each causative gene are summarized. Unexpectedly, hereditary myopathy with early respiratory failure (HMERF) caused by mutation in the A-band region of TTN is the most common cause of MFM in our cohort. Despite of intensive mutation screening, the causative gene of more than 60% of MFM patients is still unknown. Further identification of novel causative genes and elucidate pathomechanisms of protein aggregation in necessary.

[Clinical and neuropsychological characteristics in congenital central hypoventilation syndrome].

PubMed

Seijas-Gomez, R; Esteso-Orduna, B; Melero-Llorente, J; Fournier-Del Castillo, M C

2018-05-01

Congenital central hypoventilation syndrome (CCHS) syndrome is a rare disease caused by mutations in the PHOX2B gene. Patients show a reduced response to hypercapnia and hypoxia accompanied by diffuse disturbances of the autonomic nervous system and occasionaly also disturbances in neuroimaging. A specific neuropsychological profile has not been described in children and adolescents with CCHS. We describe three cases (aged between 4 and 19 years) with different profiles of affectation in cognitive and functionality. These profiles are compared with the features described in the literature about neuropsychology in CCHS. The profile of functional impairment in the CCHS is variable: in case 1, a severe global developmental delay with autistic features and marked functional involvement is described. In case 2, bilateral atrophy of the hippocampus is associated with involvement in social cognition and in executive functions with moderate functional repercussion. Case 3 shows difficulties in some cognitive executive functions (planning and non-verbal fluency), but without functional repercussion. Neuropsychological assessment can help in the clinical management of these patients by determining and guiding the need for rehabilitation treatments.

Corticobasal degeneration.

PubMed

Stover, N P; Watts, R L

2001-01-01

Corticobasal degeneration (CBG) is an increasingly recognized neurodegenerative disease with both motor and cognitive dysfunction. The diagnosis is probably underestimated because of the heterogeneity of clinical features, overlap with symptoms, and pathologic findings of other neurodegenerative diseases. The most characteristic initial motor symptoms are akinesia, rigidity, and apraxia. Dystonia and alien limb phenomena are frequently observed. There is often a parkinsonian picture with failure or lack of efficacy of dopaminergic medical therapy. Cognitive decline, prompting the diagnosis of dementia, may be the most common presentation of CBD that is misdiagnosed. Pathology is characterized by an asymmetric frontoparietal neuronal loss and gliosis with ballooned, achromatic cortical neurons, nigral degeneration, and variable subcortical involvement. Neuroimaging and electrophysiologic studies may help with the diagnosis but are not specific. Treatment is primarily symptomatic and minimally effective, especially after the first several years of symptoms. CBD should be considered in the differential diagnosis of patients with motor and cognitive dysfunction presenting with cortical and subcortical features. Further studies to elucidate molecular abnormalities and biological markers associated with CBD are needed to improve clinical diagnosis and treatment of patients with this disorder.

Variation in and risk factors for paediatric inpatient all-cause mortality in a low income setting: data from an emerging clinical information network.

PubMed

Gathara, David; Malla, Lucas; Ayieko, Philip; Karuri, Stella; Nyamai, Rachel; Irimu, Grace; van Hensbroek, Michael Boele; Allen, Elizabeth; English, Mike

2017-04-05

Hospital mortality data can inform planning for health interventions and may help optimize resource allocation if they are reliable and appropriately interpreted. However such data are often not available in low income countries including Kenya. Data from the Clinical Information Network covering 12 county hospitals' paediatric admissions aged 2-59 months for the periods September 2013 to March 2015 were used to describe mortality across differing contexts and to explore whether simple clinical characteristics used to classify severity of illness in common treatment guidelines are consistently associated with inpatient mortality. Regression models accounting for hospital identity and malaria prevalence (low or high) were used. Multiple imputation for missing data was based on a missing at random assumption with sensitivity analyses based on pattern mixture missing not at random assumptions. The overall cluster adjusted crude mortality rate across hospitals was 6 · 2% with an almost 5 fold variation across sites (95% CI 4 · 9 to 7 · 8; range 2 · 1% - 11 · 0%). Hospital identity was significantly associated with mortality. Clinical features included in guidelines for common diseases to assess severity of illness were consistently associated with mortality in multivariable analyses (AROC =0 · 86). All-cause mortality is highly variable across hospitals and associated with clinical risk factors identified in disease specific guidelines. A panel of these clinical features may provide a basic common data framework as part of improved health information systems to support evaluations of quality and outcomes of care at scale and inform health system strengthening efforts.

Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features.

PubMed

Bellissimo-Rodrigues, Fernando; Bollela, Valdes Roberto; Da Fonseca, Benedito Antônio Lopes; Martinez, Roberto

2013-04-01

Paracoccidioidomycosis (PCM) is a systemic fungal disease endemic to Latin America and characterized by two clinical presentations, i.e., patients develop either acute/subacute or chronic clinical manifestations. The differences in clinical presentations are mainly dependent on the host immune response, but may also be related to demographic characteristics of some patients. In this retrospective study, 1,219 PCM cases treated between 1970 and 2009 in a university medical center, located in southeastern Brazil, were analyzed according to their clinical and demographic features. The most affected anatomical sites were lungs (63.8%) and oral mucosa (50.0%), with increasing involvement of these sites in accord with the age of the patients. Generalized lymphadenopathy (28.1%) and skin lesions (29.6%) were more frequent on the first decades of life. Involvement of the larynx (16.1%), gut (7.5%), spleen (4.7%), central nervous system (3.4%), bones and joints (2.2%), and adrenal (2.1%) were also variable according to the age of the host. The acute/subacute form of the disease accounted for 26.4% of PCM cases and, on a multivariate analysis, was inversely associated with aging (OR = 0.8 per year, P < 0.001), and directly associated with female sex (OR = 7.2, P < 0.001), mixed black and white racial background (OR = 2.3, P < 0.001) or black skin color (OR = 4.6, P < 0.001). Based on these findings, we have shown that host immune response, as well as age, gender and ethnicity may influence the clinical presentation of PCM.

Mining Feature of Data Fusion in the Classification of Beer Flavor Information Using E-Tongue and E-Nose

PubMed Central

Men, Hong; Shi, Yan; Fu, Songlin; Jiao, Yanan; Qiao, Yu; Liu, Jingjing

2017-01-01

Multi-sensor data fusion can provide more comprehensive and more accurate analysis results. However, it also brings some redundant information, which is an important issue with respect to finding a feature-mining method for intuitive and efficient analysis. This paper demonstrates a feature-mining method based on variable accumulation to find the best expression form and variables’ behavior affecting beer flavor. First, e-tongue and e-nose were used to gather the taste and olfactory information of beer, respectively. Second, principal component analysis (PCA), genetic algorithm-partial least squares (GA-PLS), and variable importance of projection (VIP) scores were applied to select feature variables of the original fusion set. Finally, the classification models based on support vector machine (SVM), random forests (RF), and extreme learning machine (ELM) were established to evaluate the efficiency of the feature-mining method. The result shows that the feature-mining method based on variable accumulation obtains the main feature affecting beer flavor information, and the best classification performance for the SVM, RF, and ELM models with 96.67%, 94.44%, and 98.33% prediction accuracy, respectively. PMID:28753917

Multilocus variable-number tandem-repeat analysis of clinical isolates of Aspergillus flavus from Iran reveals the first cases of Aspergillus minisclerotigenes associated with human infection

PubMed Central

2014-01-01

Background Aspergillus flavus is intensively studied for its role in infecting crop plants and contaminating produce with aflatoxin, but its role as a human pathogen is less well understood. In parts of the Middle East and India, A. flavus surpasses A. fumigatus as a cause of invasive aspergillosis and is a significant cause of cutaneous, sinus, nasal and nail infections. Methods A collection of 45 clinical and 10 environmental A. flavus isolates from Iran were analysed using Variable-Number Tandem-Repeat (VNTR) markers with MICROSAT and goeBURST to determine their genetic diversity and their relatedness to clinical and environmental A. flavus isolates from Australia. Phylogeny was assessed using partial β-tubulin and calmodulin gene sequencing, and mating type was determined by PCR. Antifungal susceptibility testing was performed on selected isolates using a reference microbroth dilution method. Results There was considerable diversity in the A. flavus collection, with no segregation on goeBURST networks according to source or geographic location. Three Iranian isolates, two from sinus infections and one from a paranasal infection grouped with Aspergillus minisclerotigenes, and all produced B and G aflatoxin. Phylogenic analysis using partial β-tubulin and calmodulin sequencing confirmed two of these as A. minisclerotigenes, while the third could not be differentiated from A. flavus and related species within Aspergillus section flavi. Based on epidemiological cut-off values, the A. minisclerotigens and A. flavus isolates tested were susceptible to commonly used antifungal drugs. Conclusions This is the first report of human infection due to A. minisclerotigenes, and it raises the possiblity that other species within Aspergillus section flavi may also cause clinical disease. Clinical isolates of A. flavus from Iran are not distinct from Australian isolates, indicating local environmental, climatic or host features, rather than fungal features, govern the high incidence of A. flavus infection in this region. The results of this study have important implications for biological control strategies that aim to reduce aflatoxin by the introduction of non-toxigenic strains, as potentially any strain of A. flavus, and closely related species like A. minisclerotigenes, might be capable of human infection. PMID:24986045

Association of T and B Cells Infiltrating Orbital Tissues With Clinical Features of Graves Orbitopathy.

PubMed

Rotondo Dottore, Giovanna; Torregrossa, Liborio; Caturegli, Patrizio; Ionni, Ilaria; Sframeli, Angela; Sabini, Elena; Menconi, Francesca; Piaggi, Paolo; Sellari-Franceschini, Stefano; Nardi, Marco; Latrofa, Francesco; Vitti, Paolo; Marcocci, Claudio; Basolo, Fulvio; Marinò, Michele

2018-06-01

Graves orbitopathy (GO) responds to immunosuppressive treatments when clinically active but poorly when inactive. In other autoimmune diseases, response has been ascribed to a reduction in lymphocytes infiltrating the target organ. It is not known whether active vs inactive GO differs in this regard, which would help in understanding the link between GO immunologic features and clinical behavior. To investigate the association between orbital lymphocytic infiltrate and GO clinical features. A cohort study aimed at assessing the extent and immunohistochemical phenotype of orbital lymphocytes and associating it with the ophthalmologic features of GO, especially its clinical activity score (CAS), was conducted at a tertiary referral center. Twenty consecutive patients with GO who underwent orbital decompression were included. The study was conducted from January 1 to May 31, 2017. Orbital tissue histology and immunohistochemistry testing as well as ophthalmologic evaluation. Association between CAS and orbital lymphocytes, analyzed as total number of lymphocytes and main lymphoid subsets. The patient population included 8 men and 12 women, all of white race, with a mean (SD) age of 46 (13) years. With an established cutoff value of 300 lymphoid cells per tissue sample, lymphocytes above this value were found in orbital tissues of 9 of 20 patients (45%), often organized into distinct foci. The lymphocytes comprised a mixture of T (CD3-positive) and B (CD20-positive) cells, suggesting a mature, polyclonal autoimmune response. In a simple linear regression model, the total number of lymphocytes, as well as the number of CD3- and CD20-positive subsets, correlated with CAS (R = 0.63; 95% CI, 0.27-0.84; P = .003; R = 0.59; 95% CI, 0.20-0.82; P = .006; and R = 0.65; 95% CI, 0.30-0.85; P = .002, respectively). In a multiple linear regression model, lymphocytes maintained their effect on CAS when adjusted for 2 additional variables that were correlated with CAS-smoking and GO duration-highlighting even more the important role of orbital lymphocytes in affecting CAS (total number: R = 0.58; 95% CI, 0.18-0.82; P = .01; CD3-positive: R = 0.58; 95% CI, 0.17-0.82; P = .01; and CD20-positive: R = 0.59; 95% CI, 0.19-0.83; P = .01). This study shows a correlation between T and B lymphocytes infiltrating orbital tissues and the activity of GO, possibly enhancing our understanding of the association between GO immunologic features and clinical expression.

Deep-learning derived features for lung nodule classification with limited datasets

NASA Astrophysics Data System (ADS)

Thammasorn, P.; Wu, W.; Pierce, L. A.; Pipavath, S. N.; Lampe, P. D.; Houghton, A. M.; Haynor, D. R.; Chaovalitwongse, W. A.; Kinahan, P. E.

2018-02-01

Only a few percent of indeterminate nodules found in lung CT images are cancer. However, enabling earlier diagnosis is important to avoid invasive procedures or long-time surveillance to those benign nodules. We are evaluating a classification framework using radiomics features derived with a machine learning approach from a small data set of indeterminate CT lung nodule images. We used a retrospective analysis of 194 cases with pulmonary nodules in the CT images with or without contrast enhancement from lung cancer screening clinics. The nodules were contoured by a radiologist and texture features of the lesion were calculated. In addition, sematic features describing shape were categorized. We also explored a Multiband network, a feature derivation path that uses a modified convolutional neural network (CNN) with a Triplet Network. This was trained to create discriminative feature representations useful for variable-sized nodule classification. The diagnostic accuracy was evaluated for multiple machine learning algorithms using texture, shape, and CNN features. In the CT contrast-enhanced group, the texture or semantic shape features yielded an overall diagnostic accuracy of 80%. Use of a standard deep learning network in the framework for feature derivation yielded features that substantially underperformed compared to texture and/or semantic features. However, the proposed Multiband approach of feature derivation produced results similar in diagnostic accuracy to the texture and semantic features. While the Multiband feature derivation approach did not outperform the texture and/or semantic features, its equivalent performance indicates promise for future improvements to increase diagnostic accuracy. Importantly, the Multiband approach adapts readily to different size lesions without interpolation, and performed well with relatively small amount of training data.

[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options].

PubMed

Martos-Moreno, Gabriel A; Calzada, Joan; Couce, María L; Argente, Jesús

2018-06-01

Hypophosphatasia is a very rare bone metabolism disorder caused by a deficiency in alkaline phosphatase activity, due to mutations in the ALPL gene. Its clinical hallmark is the impairment of skeletal and teeth mineralisation, although extra-skeletal manifestations are frequent. Its phenotypic spectrum is widely variable from a subtype with exclusive odontological impairment (odontohypophosphatasia) to five subtypes with systemic involvement, classified according to the age at the onset of the first symptoms (four of them in the paediatric age range: perinatal lethal, perinatal benign, infant and childhood hypophosphatasia). Those subtypes of hypophosphatasia with an earliest onset usually involve a worse prognosis, due to the risk of developing potentially lethal complications, such as seizures or severe respiratory insufficiency, secondary to rib cage malformations. Due to the extremely low prevalence of the severe forms of hypophosphatasia, its clinical variability and overlapping phenotypic features with several more prevalent conditions, the diagnosis of hypophosphatasia in the clinical setting is challenging. However, its potential lethality and impact on the patient's quality of life, along with the recent availability of an enzyme replacement therapy, increases the relevance of the early and accurate identification of patients affected with hypophosphatasia. On the basis of published evidence and clinical experience, this article suggests an algorithm with practical recommendations for the differential diagnosis of childhood hypophosphatasia, as well as an updated review of current therapeutic options. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Genotype- phenotype correlation in trisomy X: a retrospective study of a selected group of 36 patients and review of literature.

PubMed

Butnariu, Lăcrămioara; Rusu, Cristina; Caba, Lavinia; Pânzaru, Monica; Braha, Elena; Grămescu, Mihaela; Popescu, Roxana; Bujoranu, C; Gorduza, E V

2013-01-01

Trisomy X (47,XXX) is a gonosomal aneuploidy characterized by the presence of an extra X chromosome in a female person. Usually the diagnosis is established made postnatally by chromosome analysis in patients with suggestive clinical signs. Clinical signs vary by age. In prepubertal patients have a growth retardation associated with uncharacteristic facial dysmorphism, mild mental retardation with behavioral disorders, plus clinical signs of ovarian dysgenesis, postpubertal. We analyzed retrospectively the genotype - phenotype correlations for a selected group of 36 patients diagnosed with trisomy X (homogeneous or mosaic) by cytogenetic methods (X chromatin and karyotype). Analysis of the clinical data of 36 patients diagnosed with trisomy X and correlation with the results of X chromatin and karyotype. Clinical signs detected in patients with homogeneous trisomy X 47,XXX (22.22%), mosaic 46,XX/47,XXX (16.66%) or 47,XXX/48,XXXX (5.55%) were prepubertal, growth retardation associated with dysmorphic facial (upslanted palpebral fissure, epichantus, thin lips) and postpubertal, signs of ovarian dysgenesis (secondary amenorrhea, early menopause). The phenotype of patients with different gonosomal mosaic corresponding to Turner syndrome, incorporating a cell line with trisomy X (55.55%) was variable, correlated with the type of chromosomal abnormalities detected. The results of our study are similar to those obtained in other studies and emphasizes that phenotypic variability of patients with trisomy X feature makes it difficult to genotype - phenotype correlations.

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.

Diabetes mellitus in a girl with thyroid hormone resistance syndrome: a little recognized interaction between the two diseases.

PubMed

Stagi, Stefano; Manoni, Cristina; Cirello, Valentina; Covelli, Danila; Giglio, Sabrina; Chiarelli, Francesco; Seminara, Salvatore; de Martino, Maurizio

2014-01-01

The syndrome of resistance to thyroid hormone (RTH) is characterized by elevated serum free thyroid hormones (FT4 and FT3) in the presence of unsuppressed TSH levels, reflecting resistance to the normal negative feedback mechanisms in the hypothalamus and pituitary. The degree of resistance within peripheral tissues determines whether thyrotoxic clinical features are associated with this condition. Classic features include attention deficit hyperactivity disorder, growth delay, tachycardia, and goiter. However, other features, such as frequent ear, nose and throat infections, hearing deficit, and decreased bone mass have recently been recognized. The phenotype of RTH is variable, with most patients presenting with mild to moderate symptoms. In this report we describe a girl with familiar RTH and diabetes mellitus. This is, to our knowledge, the first report regarding this association. Nearly one year after long-term triiodothyroacetic acid (Triac) therapy, we observed a reduction of thyroid hormone levels with an amelioration of insulin resistance. The possible interactions between these disorders are discussed.

Stress assessment based on EEG univariate features and functional connectivity measures.

PubMed

Alonso, J F; Romero, S; Ballester, M R; Antonijoan, R M; Mañanas, M A

2015-07-01

The biological response to stress originates in the brain but involves different biochemical and physiological effects. Many common clinical methods to assess stress are based on the presence of specific hormones and on features extracted from different signals, including electrocardiogram, blood pressure, skin temperature, or galvanic skin response. The aim of this paper was to assess stress using EEG-based variables obtained from univariate analysis and functional connectivity evaluation. Two different stressors, the Stroop test and sleep deprivation, were applied to 30 volunteers to find common EEG patterns related to stress effects. Results showed a decrease of the high alpha power (11 to 12 Hz), an increase in the high beta band (23 to 36 Hz, considered a busy brain indicator), and a decrease in the approximate entropy. Moreover, connectivity showed that the high beta coherence and the interhemispheric nonlinear couplings, measured by the cross mutual information function, increased significantly for both stressors, suggesting that useful stress indexes may be obtained from EEG-based features.

Clustering of metabolic and cardiovascular risk factors in the polycystic ovary syndrome: a principal component analysis.

PubMed

Stuckey, Bronwyn G A; Opie, Nicole; Cussons, Andrea J; Watts, Gerald F; Burke, Valerie

2014-08-01

Polycystic ovary syndrome (PCOS) is a prevalent condition with heterogeneity of clinical features and cardiovascular risk factors that implies multiple aetiological factors and possible outcomes. To reduce a set of correlated variables to a smaller number of uncorrelated and interpretable factors that may delineate subgroups within PCOS or suggest pathogenetic mechanisms. We used principal component analysis (PCA) to examine the endocrine and cardiometabolic variables associated with PCOS defined by the National Institutes of Health (NIH) criteria. Data were retrieved from the database of a single clinical endocrinologist. We included women with PCOS (N = 378) who were not taking the oral contraceptive pill or other sex hormones, lipid lowering medication, metformin or other medication that could influence the variables of interest. PCA was performed retaining those factors with eigenvalues of at least 1.0. Varimax rotation was used to produce interpretable factors. We identified three principal components. In component 1, the dominant variables were homeostatic model assessment (HOMA) index, body mass index (BMI), high density lipoprotein (HDL) cholesterol and sex hormone binding globulin (SHBG); in component 2, systolic blood pressure, low density lipoprotein (LDL) cholesterol and triglycerides; in component 3, total testosterone and LH/FSH ratio. These components explained 37%, 13% and 11% of the variance in the PCOS cohort respectively. Multiple correlated variables from patients with PCOS can be reduced to three uncorrelated components characterised by insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia. Clustering of risk factors is consistent with different pathogenetic pathways within PCOS and/or differing cardiometabolic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Organization of managed clinical networking for home parenteral nutrition.

PubMed

Baxter, Janet P; McKee, Ruth F

2006-05-01

Home parenteral nutrition (HPN) is an established treatment for intestinal failure, and organization of HPN is variable throughout the UK and Europe. Managed clinical networking is the single most important feature of the UK National Health Service strategy for acute services in Scotland and has the potential to improve the management of HPN patients. This review addresses the role of managed clinical networking in HPN and compares outcome data between centres. The Scottish HPN Managed Clinical Network has published the main body of the current literature supporting the concept of managed clinical networking in this context. The Network is responsible for the organization and quality assurance of HPN provision in Scotland, and has been established for 5 years. It has captured significant patient data for the purpose of clinical audit and illustrates that this is an effective model for the management of this patient population. This review provides advice for other areas wishing to improve equity of access, and to smooth the patient journey between primary, secondary and tertiary health care in the context of artificial nutrition support.

Birt-Hogg-Dubé Syndrome.

PubMed

Gupta, Nishant; Sunwoo, Bernie Y; Kotloff, Robert M

2016-09-01

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the Folliculin gene and is characterized by the formation of fibrofolliculomas, early onset renal cancers, pulmonary cysts, and spontaneous pneumothoraces. The exact pathogenesis of tumor and lung cyst formation in BHD remains unclear. There is great phenotypic variability in the clinical features of BHD, and patients can present with any combination of skin, pulmonary, or renal findings. More than 80% of adult patients with BHD have pulmonary cysts on high-resolution computed tomography scan of the chest. Published by Elsevier Inc.

SAPHO: What radiologists should know.

PubMed

Depasquale, R; Kumar, N; Lalam, R K; Tins, B J; Tyrrell, P N M; Singh, J; Cassar-Pullicino, V N

2012-03-01

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an umbrella acronym for inflammatory clinical conditions whose common denominator is aseptic osteoarticular involvement with characteristic skin lesions. It involves all ages, can involve any skeletal site, and has variable imaging appearances depending on the stage/age of the lesion and imaging method. It mimics important differentials including infection and neoplasia. Awareness of the imaging features, especially in the spine, facilitates early diagnosis, prevents repeated biopsies, and avoids unnecessary surgery, while initiating appropriate treatment. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection.

PubMed

Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

2017-01-01

Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B , thus diagnosing this patient with Cabezas syndrome.

Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection

PubMed Central

Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

2017-01-01

Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome. PMID:28144446

Hypophosphatemic rickets associated with epidermal nevus syndrome and giant hairy nevus.

PubMed

Chou, Yen-Yin; Chao, Sheau-Chiou; Shiue, Chiou-Nan; Tsai, Wen-Hui; Lin, Shio-Jean

2005-01-01

The association of hypophosphatemic rickets and epidermal nevus or giant hairy nevus is rare. We report two patients with hypophosphatemic rickets, one associated with epidermal nevus syndrome and the other with giant hairy nevus, and describe their clinical features and variable response to treatment. The abnormal nevus tissue may have contributed to the pathogenesis of hypophosphatemic rickets. We did not find a PHEX gene mutation in these two patients, and the mechanism for their rickets may be different from that in X-linked hypophosphatemic rickets.

Poland's syndrome and military personnel.

PubMed

Phaltankar, P M; Langdon, J; Clasper, J

2003-12-01

We describe three cases of undiagnosed Poland's syndrome in Army personnel and discuss their fitness according to the PULHHEEMS system. This syndrome has variable clinical features that include unilateral chest wall and upper limb abnormalities. The syndrome is not hereditary and is of unknown origin. If the syndrome was diagnosed prior to enlistment the potential recruit would normally be graded P8, and unfit to enlist. However, these individuals had managed to pass routine medical examination as well as successfully complete basic training. The suitability of continuation in the army of personnel with Poland's syndrome is discussed.

An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Septic Shock Patients Stratified for Mortality.

PubMed

Cambiaghi, Alice; Díaz, Ramón; Martinez, Julia Bauzá; Odena, Antonia; Brunelli, Laura; Caironi, Pietro; Masson, Serge; Baselli, Giuseppe; Ristagno, Giuseppe; Gattinoni, Luciano; de Oliveira, Eliandre; Pastorelli, Roberta; Ferrario, Manuela

2018-04-27

In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Classification and clinical behavior of blastic plasmacytoid dendritic cell neoplasms according to their maturation-associated immunophenotypic profile

PubMed Central

Martín-Martín, Lourdes; López, Antonio; Vidriales, Belén; Caballero, María Dolores; Rodrigues, António Silva; Ferreira, Silvia Inês; Lima, Margarida; Almeida, Sérgio; Valverde, Berta; Martínez, Pilar; Ferrer, Ana; Candeias, Jorge; Ruíz-Cabello, Francisco; Buadesa, Josefa Marco; Sempere, Amparo; Villamor, Neus

2015-01-01

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56− phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment. PMID:26056082

Pleuroparenchymal fibroelastosis: is it also an idiopathic entity?

PubMed

Portillo, Karina; Guasch Arriaga, Ignasi; Ruiz-Manzano, Juan

2015-10-01

Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that has been recently included in the updated consensus on idiopathic interstitial pneumonias. It shares some clinical features with other chronic interstitial pneumonias (dyspnea, dry cough), and is radiologically characterized by pleural and subpleural parenchymal fibrosis and elastosis, mainly in the upper lobes. The main histological findings include pleural fibrosis and prominent subpleural and parenchymal fibroelastosis. Its characterization is based on the increasing number of cases reported in the literature, so several aspects of the etiology, pathogenesis and natural history are still unknown. Although some cases have been described as idiopathic, PPFE has been reported as a complication after bone marrow transplantation, lung transplantation and chemotherapy, especially with alkylating agents.Spontaneous or iatrogenic pneumothorax is a frequently reported complication of invasive diagnostic tests for identifying PPFE. The disease course is variable, ranging from slow progression to rapid clinical deterioration. No treatment has shown evidence of efficacy, and lung transplantation remains the only option for patients who fulfill the diagnostic criteria for this option. Recognizing and disseminating the specific features of PPFE is essential to raise the level of clinical suspicion for this entity, and to implement appropriate multidisciplinary diagnostic management. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.

Dosage changes of a segment at 17p13.1 lead to intellectual disability and microcephaly as a result of complex genetic interaction of multiple genes.

PubMed

Carvalho, Claudia M B; Vasanth, Shivakumar; Shinawi, Marwan; Russell, Chad; Ramocki, Melissa B; Brown, Chester W; Graakjaer, Jesper; Skytte, Anne-Bine; Vianna-Morgante, Angela M; Krepischi, Ana C V; Patel, Gayle S; Immken, LaDonna; Aleck, Kyrieckos; Lim, Cynthia; Cheung, Sau Wai; Rosenberg, Carla; Katsanis, Nicholas; Lupski, James R

2014-11-06

The 17p13.1 microdeletion syndrome is a recently described genomic disorder with a core clinical phenotype of intellectual disability, poor to absent speech, dysmorphic features, and a constellation of more variable clinical features, most prominently microcephaly. We identified five subjects with copy-number variants (CNVs) on 17p13.1 for whom we performed detailed clinical and molecular studies. Breakpoint mapping and retrospective analysis of published cases refined the smallest region of overlap (SRO) for microcephaly to a genomic interval containing nine genes. Dissection of this phenotype in zebrafish embryos revealed a complex genetic architecture: dosage perturbation of four genes (ASGR1, ACADVL, DVL2, and GABARAP) impeded neurodevelopment and decreased dosage of the same loci caused a reduced mitotic index in vitro. Moreover, epistatic analyses in vivo showed that dosage perturbations of discrete gene pairings induce microcephaly. Taken together, these studies support a model in which concomitant dosage perturbation of multiple genes within the CNV drive the microcephaly and possibly other neurodevelopmental phenotypes associated with rearrangements in the 17p13.1 SRO. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Real-time, non-invasive microscopic confirmation of clinical diagnosis of bullous pemphigoid using in vivo reflectance confocal microscopy.

PubMed

Ardigò, M; Agozzino, M; Amorosi, B; Moscarella, E; Cota, C; de Abreu, L; Berardesca, E

2014-05-01

Bullous pemphigoid is an autoimmune disease affecting prevalently the elder. In vivo reflectance confocal microscopy is a non-invasive technique for real-time imaging of the skin with cellular-level resolution. No previous data has been reported about confocal microscopy of bullous pemphigoid. Aim of this preliminary study is the evaluation of the potential of in vivo reflectance confocal microscopy for real-time, microscopical confirmation of clinical bullous pemphigoid diagnosis. A total of nine lesions from patients affected by pemphigoid underwent in vivo reflectance confocal microscopy before histological examination. In our preliminary study, confocal microscopy showed high grade of correspondence to histopathology. In particular, presence of sub-epidermal cleft and variable amount of oedema of the upper dermis associated with inflammatory cells infiltration were seen as prevalent confocal features in the bullous lesions considered. Differently, in urticarial lesions, no specific features could be appreciated at confocal analysis beside the presence of signs of spongiosis and perivascular inflammation. Confocal microscopy seems to be useful for in vivo, microscopical confirmation of the clinical suspect of bullous pemphigoid and for biopsy site selection in urticarial lesions to obtain a more significant specimen for histopathological examination. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Childhood trauma, depression, and sleep quality and their association with psychotic symptoms and suicidality in schizophrenia.

PubMed

Kilicaslan, Esin Evren; Esen, Asli Tugba; Kasal, Meltem Izci; Ozelci, Erdal; Boysan, Murat; Gulec, Mustafa

2017-12-01

This study involved the examination of the relationship between childhood trauma and both psychotic symptoms and suicidality in patients with schizophrenia after controlling for the possible confounding factors, such as clinical features, depression, and sleep quality. The Childhood Trauma Questionnaire-Short Form, Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Pittsburgh Sleep Quality Index (PSQI), and the suicidality subscale of Mini-International Neuropsychiatric Interview (MINI) were administered to 199 patients with schizophrenia. We used sequential multiple stepwise regression analyses in which positive symptoms, negative symptoms, overall psychopathology, total symptoms of schizophrenia, and suicidality were dependent variables. Depressive symptomatology and childhood physical abuse significantly contributed to positive, negative, general psychopathology, and global schizophrenia symptomatology. Interestingly, general psychopathology scores were negatively associated with childhood physical neglect. Also, subjective sleep quality significantly contributed to positive schizophrenia symptoms. Although prior suicide attempts and depression were significant antecedents of suicidal ideation, no association between suicidality and both childhood trauma and sleep was found. Childhood physical abuse could have an impact on psychopathology in schizophrenia. In addition to childhood trauma, depression, sleep disturbances, and clinical features should be considered and inquired about in the course of clinical care of schizophrenia patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Suicide attempts in major depressive episode: evidence from the BRIDGE-II-Mix study.

PubMed

Popovic, Dina; Vieta, Eduard; Azorin, Jean-Michel; Angst, Jules; Bowden, Charles L; Mosolov, Sergey; Young, Allan H; Perugi, Giulio

2015-11-01

The Bipolar Disorders: Improving Diagnosis, Guidance, and Education (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as suicidality. A total of 2,811 subjects were enrolled in this multicenter cross-sectional study. Psychiatric symptoms, and sociodemographic and clinical variables were collected. The analysis compared the characteristics of patients with MDE with (MDE-SA group) and without (MDE-NSA) a history of suicide attempts. The history of suicide attempts was registered in 628 patients (22.34%). In the MDE-SA group, women (72.5%, p = 0.028), (hypo)mania in first-degree relatives (20.5%, p < 0.0001), psychotic features (15.1%, p < 0.0001), and atypical features (9.2%, p = 0.009) were more prevalent. MDE-SA patients' previous responses to treatment with antidepressants included more (hypo)manic switches [odds ratio (OR) = 1.97, 95% confidence interval (CI): 1.58-2.44, p < 0.0001], treatment resistance (OR = 2.07, 95% CI: 1.72-2.49, p < 0.0001), mood lability (OR = 1.98, 95% CI: 1.65-2.39, p < 0.0001), and irritability (OR = 1.80, 95% CI: 1.48-2.17, p < 0.0001). Multivariate analysis evidenced that risky behavior, psychomotor agitation and impulsivity, and borderline personality and substance use disorders were the variables most frequently associated with previous suicide attempts. In the MDE-SA group, 75 patients (11.9%) fulfilled Diagnostic and Statistical Manual (DSM)-5 criteria for MDE with mixed features, and 250 patients (39.8%) fulfilled research-based diagnostic criteria for a mixed depressive episode. Important differences between MDE-SA and MDE-NSA patients have emerged. Early identification of symptoms such as risky behavior, psychomotor agitation, and impulsivity in patients with MDE, and treatment of mixed depressive states could represent a major step in suicide prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

From vital signs to clinical outcomes for patients with sepsis: a machine learning basis for a clinical decision support system

PubMed Central

Gultepe, Eren; Green, Jeffrey P; Nguyen, Hien; Adams, Jason; Albertson, Timothy; Tagkopoulos, Ilias

2014-01-01

Objective To develop a decision support system to identify patients at high risk for hyperlactatemia based upon routinely measured vital signs and laboratory studies. Materials and methods Electronic health records of 741 adult patients at the University of California Davis Health System who met at least two systemic inflammatory response syndrome criteria were used to associate patients’ vital signs, white blood cell count (WBC), with sepsis occurrence and mortality. Generative and discriminative classification (naïve Bayes, support vector machines, Gaussian mixture models, hidden Markov models) were used to integrate heterogeneous patient data and form a predictive tool for the inference of lactate level and mortality risk. Results An accuracy of 0.99 and discriminability of 1.00 area under the receiver operating characteristic curve (AUC) for lactate level prediction was obtained when the vital signs and WBC measurements were analysed in a 24 h time bin. An accuracy of 0.73 and discriminability of 0.73 AUC for mortality prediction in patients with sepsis was achieved with only three features: median of lactate levels, mean arterial pressure, and median absolute deviation of the respiratory rate. Discussion This study introduces a new scheme for the prediction of lactate levels and mortality risk from patient vital signs and WBC. Accurate prediction of both these variables can drive the appropriate response by clinical staff and thus may have important implications for patient health and treatment outcome. Conclusions Effective predictions of lactate levels and mortality risk can be provided with a few clinical variables when the temporal aspect and variability of patient data are considered. PMID:23959843

Characterization and genetic variability of feed-borne and clinical animal/human Aspergillus fumigatus strains using molecular markers.

PubMed

Pena, Gabriela A; Coelho, Irene; Reynoso, María M; Soleiro, Carla; Cavaglieri, Lilia R

2015-09-01

Aspergillus fumigatus, the major etiological agent of human and animal aspergillosis, is a toxigenic fungus largely regarded as a single species by macroscopic and microscopic features. However, molecular studies have demonstrated that several morphologically identified A. fumigatus strains might be genetically distinct. This work was aimed to apply PCR-restriction length fragment polymorphisms (PCR-RFLP) and random amplification of polymorphic DNA (RAPD) molecular markers to characterize a set of feed-borne and clinical A. fumigatus sensu lato strains isolated from Argentina and Brazil and to determine and compare their genetic variability. All A. fumigatus strains had the same band profile and those typical of A. fumigatus sensu stricto positive controls by PCR-RFLP. Moreover, all Argentinian and Brazilian strains typified by RAPD showed similar band patterns to each other and to A. fumigatus sensu stricto reference strains regardless of their isolation source (animal feeds or human/animal clinical cases) and geographic origin. Genetic similarity coefficients ranged from 0.61 to 1.00, but almost all isolates showed 78% of genetic similarly suggesting that genetic variability was found at intraspecific level. Finally, benA sequencing confirmed its identification as A. fumigatus sensu stricto species. These results suggest that A. fumigatus sensu stricto is a predominant species into Aspergillus section Fumigati found in animal environments as well as in human/animal clinical cases, while other species may be rarely isolated. The strains involved in human and animal aspergillosis could come from the environment where this fungus is frequently found. Rural workers and animals would be constantly exposed. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Automated retrieval of forest structure variables based on multi-scale texture analysis of VHR satellite imagery

NASA Astrophysics Data System (ADS)

Beguet, Benoit; Guyon, Dominique; Boukir, Samia; Chehata, Nesrine

2014-10-01

The main goal of this study is to design a method to describe the structure of forest stands from Very High Resolution satellite imagery, relying on some typical variables such as crown diameter, tree height, trunk diameter, tree density and tree spacing. The emphasis is placed on the automatization of the process of identification of the most relevant image features for the forest structure retrieval task, exploiting both spectral and spatial information. Our approach is based on linear regressions between the forest structure variables to be estimated and various spectral and Haralick's texture features. The main drawback of this well-known texture representation is the underlying parameters which are extremely difficult to set due to the spatial complexity of the forest structure. To tackle this major issue, an automated feature selection process is proposed which is based on statistical modeling, exploring a wide range of parameter values. It provides texture measures of diverse spatial parameters hence implicitly inducing a multi-scale texture analysis. A new feature selection technique, we called Random PRiF, is proposed. It relies on random sampling in feature space, carefully addresses the multicollinearity issue in multiple-linear regression while ensuring accurate prediction of forest variables. Our automated forest variable estimation scheme was tested on Quickbird and Pléiades panchromatic and multispectral images, acquired at different periods on the maritime pine stands of two sites in South-Western France. It outperforms two well-established variable subset selection techniques. It has been successfully applied to identify the best texture features in modeling the five considered forest structure variables. The RMSE of all predicted forest variables is improved by combining multispectral and panchromatic texture features, with various parameterizations, highlighting the potential of a multi-resolution approach for retrieving forest structure variables from VHR satellite images. Thus an average prediction error of ˜ 1.1 m is expected on crown diameter, ˜ 0.9 m on tree spacing, ˜ 3 m on height and ˜ 0.06 m on diameter at breast height.

Comparison of Feature Selection Techniques in Machine Learning for Anatomical Brain MRI in Dementia.

PubMed

Tohka, Jussi; Moradi, Elaheh; Huttunen, Heikki

2016-07-01

We present a comparative split-half resampling analysis of various data driven feature selection and classification methods for the whole brain voxel-based classification analysis of anatomical magnetic resonance images. We compared support vector machines (SVMs), with or without filter based feature selection, several embedded feature selection methods and stability selection. While comparisons of the accuracy of various classification methods have been reported previously, the variability of the out-of-training sample classification accuracy and the set of selected features due to independent training and test sets have not been previously addressed in a brain imaging context. We studied two classification problems: 1) Alzheimer's disease (AD) vs. normal control (NC) and 2) mild cognitive impairment (MCI) vs. NC classification. In AD vs. NC classification, the variability in the test accuracy due to the subject sample did not vary between different methods and exceeded the variability due to different classifiers. In MCI vs. NC classification, particularly with a large training set, embedded feature selection methods outperformed SVM-based ones with the difference in the test accuracy exceeding the test accuracy variability due to the subject sample. The filter and embedded methods produced divergent feature patterns for MCI vs. NC classification that suggests the utility of the embedded feature selection for this problem when linked with the good generalization performance. The stability of the feature sets was strongly correlated with the number of features selected, weakly correlated with the stability of classification accuracy, and uncorrelated with the average classification accuracy.

Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

NASA Astrophysics Data System (ADS)

Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

2016-07-01

Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

Post-marketing survey on clinical response to interferon beta in relapsing multiple sclerosis: the Roman experience.

PubMed

Pozzilli, C; Prosperini, L; Sbardella, E; De Giglio, L; Onesti, E; Tomassini, V

2005-12-01

Safety, tolerability and efficacy profiles of interferon beta (IFNbeta) therapy in relapsing multiple sclerosis (MS) has been widely verified both in trial settings and in daily clinical practice. However, for a variable percentage of treated patients, it remains only partially effective. In this study, we reported the post-marketing experience of the efficacy of IFNbeta therapy for a large cohort of MS patients regularly attending the MS Outpatient Clinic of "La Sapienza University" in Rome. In this cohort we also sought clinical and paraclinical variables responsible for the clinical course of MS during IFNbeta therapy. Patients that received treatment with one of the IFNbeta formulations for at least 1 year were included. Clinical outcomes (i. e., relapses and disability score) were monitored throughout the entire study period. Magnetic resonance imaging (MRI) scans were performed twice for each subject: at baseline and after 1 year of therapy. The occurrence of more than one relapse during the study period or a sustained disability progression in the Expanded Disability Status Scale (EDSS) score were considered as criteria for the definition of suboptimal clinical response to IFNbeta therapy. During IFNbeta therapy (number of patients 242, mean length of treatment 4.3+/-2.3 years) a reduction in the annualised relapse rate of 59% (p<0.001) was observed. Eighty-six patients (35%) fulfilled the criterion for defining "suboptimal responder" on the basis of relapses, and 69 (28.5%) did the same on the basis of EDSS sustained progression. Twenty-seven (11.1%) patients showed both an EDSS progression and two or more relapses. The presence of T1-enhancing lesions and new T2 hyperintense lesions on the scan performed after the first year of therapy were the best MRI features associated with both the occurrence of relapses during the treatment period (OR for enhancing lesions and relapses 3.6; OR for new T2 lesion and relapses 2.8). The present post-marketing experience confirms the efficacy of IFNbeta in modifying the natural course of MS and encourages the use of paraclinical variables measuring subclinical disease activity as surrogate markers to monitor the clinical course of MS during IFNbeta therapy.

Complex systems and the technology of variability analysis

PubMed Central

Seely, Andrew JE; Macklem, Peter T

2004-01-01

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients. PMID:15566580

Defining new guidelines for screening the 22q11.2 deletion based on a clinical and dysmorphologic evaluation of 194 individuals and review of the literature.

PubMed

Monteiro, Fabíola P; Vieira, Társis P; Sgardioli, Ilária C; Molck, Miriam C; Damiano, Ana Paula; Souza, Josiane; Monlleó, Isabella L; Fontes, Marshall I B; Fett-Conte, Agnes C; Félix, Têmis M; Leal, Gabriela F; Ribeiro, Erlane M; Banzato, Claudio E M; Dantas, Clarissa de R; Lopes-Cendes, Iscia; Gil-da-Silva-Lopes, Vera Lúcia

2013-07-01

The 22q11.2 deletion is the most frequent interstitial deletion in humans and presents a wide phenotypic spectrum, with over 180 clinical manifestations described. Distinct studies have detected frequencies of the deletion ranging from 0 % to 75 %, depending on the studied population and selection criteria adopted. Due to the lack of consensus in this matter, several studies have been conducted aiming to define which patients would be eligible for screening; however, the issue is still up for debate. In order to contribute to the delineation of possible clinical and dysmorphologic guidelines to optimize decision making in the clinical setting, 194 individuals with variable features of the 22q11.2 deletion syndromes (22q11.2DS) were evaluated. Group I, clinical suspicion of 22q11.2DS with palatal anomalies; Group II, clinical suspicion without palatal anomalies; Group III, cardiac malformations associated with the 22q11.2DS; and Group IV, juvenile-onset schizophrenia. Multiplex ligation-dependent probe amplification was used for screening the 22q11.2 deletion, which was detected in 45 patients (23.2 %), distributed as such: Group I, 35/101 (34.7 %); Group II, 4/18 (22.2 %); Group III, 6/52 (11.5 %); and Group IV, 0/23 (0 %). Clinical data were analyzed by frequency distribution and statistically. Based on the present results and on the review of the literature, we propose a set of guidelines for screening patients with distinct manifestations of the 22q11.2DS in order to maximize resources. In addition, we report the dysmorphic features which we found to be statistically correlated with the presence of the 22q11.2DS.

Newly Identified Gait Patterns in Patients With Multiple Sclerosis May Be Related to Push-off Quality.

PubMed

Kempen, Jiska C E; Doorenbosch, Caroline A M; Knol, Dirk L; de Groot, Vincent; Beckerman, Heleen

2016-11-01

Limited walking ability is an important problem for patients with multiple sclerosis. A better understanding of how gait impairments lead to limited walking ability may help to develop more targeted interventions. Although gait classifications are available in cerebral palsy and stroke, relevant knowledge in MS is scarce. The aims of this study were: (1) to identify distinctive gait patterns in patients with MS based on a combined evaluation of kinematics, gait features, and muscle activity during walking and (2) to determine the clinical relevance of these gait patterns. This was a cross-sectional study of 81 patients with MS of mild-to-moderate severity (Expanded Disability Status Scale [EDSS] median score=3.0, range=1.0-7.0) and an age range of 28 to 69 years. The patients participated in 2-dimensional video gait analysis, with concurrent measurement of surface electromyography and ground reaction forces. A score chart of 73 gait items was used to rate each gait analysis. A single rater performed the scoring. Latent class analysis was used to identify gait classes. Analysis of the 73 gait variables revealed that 9 variables could distinguish 3 clinically meaningful gait classes. The 9 variables were: (1) heel-rise in terminal stance, (2) push-off, (3) clearance in initial swing, (4) plantar-flexion position in mid-swing, (5) pelvic rotation, (6) arm-trunk movement, (7) activity of the gastrocnemius muscle in pre-swing, (8) M-wave, and (9) propulsive force. The EDSS score and gait speed worsened in ascending classes. Most participants had mild-to-moderate limitations in walking ability based on their EDSS scores, and the number of walkers who were severely limited was small. Based on a small set of 9 variables measured with 2-dimensional clinical gait analysis, patients with MS could be divided into 3 different gait classes. The gait variables are suggestive of insufficient ankle push-off. © 2016 American Physical Therapy Association.

The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance

PubMed Central

Schnitt, Stuart J

2003-01-01

Flat epithelial atypia is a descriptive term that encompasses lesions of the breast terminal duct lobular units in which variably dilated acini are lined by one to several layers of epithelial cells, which are usually columnar in shape and which display low-grade cytologic atypia. Observational studies have suggested that at least some of these lesions may represent either a precursor of ductal carcinoma in situ (DCIS) or the earliest morphological manifestation of DCIS. In contrast, the limited available clinical follow-up data suggest that the risk of both local recurrence and progression of these lesions to invasive cancer is extremely low, supporting the notion that categorizing such lesions as 'clinging carcinoma' and managing them as if they were fully developed DCIS will result in overtreatment of many patients. Additional studies are needed to better understand the biological nature and clinical significance of these lesions. PMID:12927037

Phosphatase and tensin homolog (PTEN) gene mutations and autism: literature review and a case report of a patient with Cowden syndrome, autistic disorder, and epilepsy.

PubMed

Conti, Sara; Condò, Maria; Posar, Annio; Mari, Francesca; Resta, Nicoletta; Renieri, Alessandra; Neri, Iria; Patrizi, Annalisa; Parmeggiani, Antonia

2012-03-01

Phosphatase and tensin homolog (PTEN) gene mutations are associated with a spectrum of clinical disorders characterized by skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Autism has rarely been described in association with these variable clinical features. At present, 24 patients with phosphatase and tensin homolog gene mutation, autism, macrocephaly, and some clinical findings described in phosphatase and tensin homolog syndromes have been reported in the literature. We describe a 14-year-old boy with autistic disorder, focal epilepsy, severe and progressive macrocephaly, and multiple papular skin lesions and palmoplantar punctate keratoses, characteristic of Cowden syndrome. The boy has a de novo phosphatase and tensin homolog gene mutation. Our patient is the first case described to present a typical Cowden syndrome and autism associated with epilepsy.

Interstitial granulomatous dermatitis with arthritis.

PubMed

Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F

1996-06-01

Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Recent biologic and genetic advances in neuroblastoma: Implications for diagnostic, risk stratification, and treatment strategies.

PubMed

Newman, Erika A; Nuchtern, Jed G

2016-10-01

Neuroblastoma is an embryonic cancer of neural crest cell lineage, accounting for up to 10% of all pediatric cancer. The clinical course is heterogeneous ranging from spontaneous regression in neonates to life-threatening metastatic disease in older children. Much of this clinical variance is thought to result from distinct pathologic characteristics that predict patient outcomes. Consequently, many research efforts have been focused on identifying the underlying biologic and genetic features of neuroblastoma tumors in order to more clearly define prognostic subgroups for treatment stratification. Recent technological advances have placed emphasis on the integration of genetic alterations and predictive biologic variables into targeted treatment approaches to improve patient survival outcomes. This review will focus on these recent advances and the implications they have on the diagnostic, staging, and treatment approaches in modern neuroblastoma clinical management. Copyright © 2016 Elsevier Inc. All rights reserved.

Orthodontically induced eruption of a horizontally impacted maxillary central incisor.

PubMed

Rizzatto, Susana Maria Deon; de Menezes, Luciane Macedo; Allgayer, Susiane; Batista, Eraldo Luiz; Freitas, Maria Perpétua Mota; Loro, Raphael Carlos Drumond

2013-07-01

This case report presents the clinical features and periodontal findings in a patient with a horizontally impacted maxillary central incisor that had been exposed and aligned after a closed-eruption surgical technique. By combining 3 treatment stages-maxillary expansion, crown exposure surgery, and induced eruption-the horizontally impacted incisor was successfully moved into proper position. The patient finished treatment with a normal and stable occlusion between the maxillary and mandibular arches, and an adequate width of attached gingiva, even in the area surrounding the crown. The 5-year follow-up of stability and periodontal health demonstrated esthetic and functional outcomes after orthodontically induced tooth eruption. Clinical evaluation showed that the treated central incisor had periodontal clinical variables related to visible plaque, bleeding on probing, width of attached gingiva, and crown length that resembled the contralateral incisor. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

PubMed Central

Aygun, Meral Gunay-; Hildebrandt, Friedhelm

2011-01-01

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases. PMID:21926397

Why did bluetongue spread the way it did? Environmental factors influencing the velocity of bluetongue virus serotype 8 epizootic wave in France.

PubMed

Pioz, Maryline; Guis, Hélène; Crespin, Laurent; Gay, Emilie; Calavas, Didier; Durand, Benoît; Abrial, David; Ducrot, Christian

2012-01-01

Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007-2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread.

Why Did Bluetongue Spread the Way It Did? Environmental Factors Influencing the Velocity of Bluetongue Virus Serotype 8 Epizootic Wave in France

PubMed Central

Pioz, Maryline; Guis, Hélène; Crespin, Laurent; Gay, Emilie; Calavas, Didier; Durand, Benoît; Abrial, David; Ducrot, Christian

2012-01-01

Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007–2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread. PMID:22916249

Variable clinical presentations of secondary delusional infestation: an experience of six cases from a psychodermatology clinic.

PubMed

Altunay, Ilknur K; Ates, Bilge; Mercan, Sibel; Demirci, Gulsen Tukenmez; Kayaoglu, Semra

2012-01-01

Delusional Infestation (DI) is a relatively rare condition with a fixed belief of being infested with living organisms, despite a lack of medical evidence of such infestation. Although it seems to be a psychiatric disease, patients commonly are admitted to dermatology clinics because of skin findings. Psychiatrists can underestimate its prevalance, whereas dermatologists can miss the diagnosis. It should be managed as a psychodermatological disease. Our aim in the study was to evaluate six patients with different clinical presentations of DI and to emphasize some clinical features. All patients were internalized in the psychodermatology clinic for this study. Medical history and clinical data from dermatologic and psychiatric examinations were noted; Mini International Neuropsychiatric Interview (MINI-Plus) and laboratory investigations including blood and urine analyses, microscopic analysis of so-called pathogens, and skin biopsy if needed, were performed. The diagnosis was made based on detailed history, dermatologic and psychiatric examinations, and laboratory investigations. All patients had symptoms of itching, burning, or crawling sensations dermatologically and thus were admitted to dermatology clinic. They were all considered secondary DI to another medical condition or to psychiatric illness. Vitamin B12 deficiency, diabetes, and hypothyroidism were the underlying medical conditions. Related psychiatric illnesses were trichotillomania and schizoaffective disorder, schizophrenia, shared pychotic disorder, and brief psychotic disorder. Two patients had delusions of inanimate materials; four patients had partial and complete remissions; and two patients have dropped out. Each patient had different clinical characteristics creating diagnostic challenges. All complaints were related to the infestation of the skin. The presence of different psychiatric comorbidities is remarkable. It seems that both psychiatrists and dermatologists can face diagnostic and therapeutic challenges of this complex disease in clinical settings, particularly if there are unusual clinical features of DI. Therefore, both psychiatrists and dermatologists should be well aware of DI.

Variability in the prescription of non-biologic disease-modifying antirheumatic drugs for the treatment of spondyloarthritis in Spain.

PubMed

Silva-Fernández, Lucía; Pérez-Vicente, Sabina; Martín-Martínez, María Auxiliadora; López-González, Ruth

2015-06-01

To describe the variability in the prescription of non-biologic disease-modifying antirheumatic drugs (nbDMARDs) for the treatment of spondyloarthritis (SpA) in Spain and to explore which factors relating to the disease, patient, physician, and/or center contribute to these variations. A retrospective medical record review was performed using a probabilistic sample of 1168 patients with SpA from 45 centers distributed in 15/19 regions in Spain. The sociodemographic and clinical features and the use of drugs were recorded following a standardized protocol. Logistic regression, with nbDMARDs prescriptions as the dependent variable, was used for bivariable analysis. A multilevel logistic regression model was used to study variability. The probability of receiving an nbDMARD was higher in female patients [OR = 1.548; 95% confidence interval (CI): 1.208-1.984], in those with elevated C-reactive protein (OR = 1.039; 95% CI: 1.012-1.066) and erythrocyte sedimentation rate (OR = 1.012; 95% CI: 1.003-1.021), in those with a higher number of affected peripheral joints (OR = 12.921; 95% CI: 2.911-57.347), and in patients with extra-articular manifestations like dactylitis (OR = 2.997; 95% CI: 1.868-4.809), psoriasis (OR = 2.601; 95% CI: 1.870-3.617), and enthesitis (OR = 1.717; 95% CI: 1.224-2.410). There was a marked variability in the prescription of nbDMARDs for SpA patients, depending on the center (14.3%; variance 0.549; standard error 0.161; median odds ratio 2.366; p < 0.001). After adjusting for patient and center variables, this variability fell to 3.8%. A number of factors affecting variability in clinical practice, and which are independent of disease characteristics, are associated with the probability of SpA patients receiving nbDMARDs in Spain. Copyright © 2015 Elsevier Inc. All rights reserved.

Influences on choice of surgery as a career: a study of consecutive cohorts in a medical school.

PubMed

Sobral, Dejano T

2006-06-01

To examine the differential impact of person-based and programme-related features on graduates' dichotomous choice between surgical or non-surgical field specialties for first-year residency. A 10-year cohort study was conducted, following 578 students (55.4% male) who graduated from a university medical school during 1994-2003. Data were collected as follows: at the beginning of medical studies, on career preference and learning frame; during medical studies, on academic achievement, cross-year peer tutoring and selective clinical traineeship, and at graduation, on the first-year residency selected. Contingency and logistic regression analyses were performed, with graduates grouped by the dichotomous choice of surgery or not. Overall, 23% of graduates selected a first-year residency in surgery. Seven time-steady features related to this choice: male sex, high self-confidence, option of surgery at admission, active learning style, preference for surgery after Year 1, peer tutoring on clinical surgery, and selective training in clinical surgery. Logistic regression analysis, including all features, predicted 87.1% of the graduates' choices. Male sex, updated preference, peer tutoring and selective training were the most significant predictors in the pathway to choice. The relative roles of person-based and programme-related factors in the choice process are discussed. The findings suggest that for most students the choice of surgery derives from a temporal summation of influences that encompass entry and post-entry factors blended in variable patterns. It is likely that sex-unbiased peer tutoring and selective training supported the students' search process for personal compatibility with specialty-related domains of content and process.

Variable Selection for Road Segmentation in Aerial Images

NASA Astrophysics Data System (ADS)

Warnke, S.; Bulatov, D.

2017-05-01

For extraction of road pixels from combined image and elevation data, Wegner et al. (2015) proposed classification of superpixels into road and non-road, after which a refinement of the classification results using minimum cost paths and non-local optimization methods took place. We believed that the variable set used for classification was to a certain extent suboptimal, because many variables were redundant while several features known as useful in Photogrammetry and Remote Sensing are missed. This motivated us to implement a variable selection approach which builds a model for classification using portions of training data and subsets of features, evaluates this model, updates the feature set, and terminates when a stopping criterion is satisfied. The choice of classifier is flexible; however, we tested the approach with Logistic Regression and Random Forests, and taylored the evaluation module to the chosen classifier. To guarantee a fair comparison, we kept the segment-based approach and most of the variables from the related work, but we extended them by additional, mostly higher-level features. Applying these superior features, removing the redundant ones, as well as using more accurately acquired 3D data allowed to keep stable or even to reduce the misclassification error in a challenging dataset.

Distinct phenotype clusters in childhood inflammatory brain diseases: implications for diagnostic evaluation.

PubMed

Cellucci, Tania; Tyrrell, Pascal N; Twilt, Marinka; Sheikh, Shehla; Benseler, Susanne M

2014-03-01

To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted. Copyright © 2014 by the American College of Rheumatology.

Management of refractory pityriasis rubra pilaris: challenges and solutions

PubMed Central

Moretta, Gaia; De Luca, Erika V; Di Stefani, Alessandro

2017-01-01

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory papulosquamous skin disease. Its clinical presentation and evolution is very variable. The most frequent clinical features are follicular papules, progressing to yellow-orange erythroderma with round small areas of normal skin and the well-demarcated palmoplantar keratoderma. Actually, six different types of PRP have been described based on clinical characteristics, age of onset, and prognosis. The pathogenesis is still unknown, and treatment can be challenging. Available treatments are mainly based on case reports or case series of clinical experience because no controlled randomized trials have never been performed because of the rarity of the condition. Traditional systemic treatment consists in retinoids, which are actually considered as first-line therapy, but refractory cases that do not respond or relapse after drug interruption do exist. In recent years, numerous reports have demonstrated the efficacy of new agents such as biological drugs. This article is an overview on available therapeutic options, in particular for refractory forms of PRP. PMID:29184428

[Attention deficit hyperactivity disorder: from a neurodevelopmental perspective].

PubMed

Fernandez-Jaen, A; Lopez-Martin, S; Albert, J; Martin Fernandez-Mayoralas, D; Fernandez-Perrone, A L; Calleja-Perez, B; Lopez-Arribas, S

2017-02-24

Neurodevelopmental disorders cover a heterogeneous group of disorders such as intellectual disability, autism spectrum disorders or specific learning difficulties, among others. The neurobiological and clinical variables seem to clearly justify the recent inclusion of attention deficit hyperactivity disorder (ADHD) as a neurodevelopmental disorder in the international classifications. Neurodevelopmental disorders are characterised by their dimensional nature and the distribution of the different symptoms in the population. These aspects are reviewed, specifically from the perspective of the clinical features and the neuropsychology of ADHD. The dimensional symptomatic nature of ADHD contrasts with the diagnostic criteria of this disorder according to different classifications or clinical guidelines. It also contrasts with the data collected by means of different complementary examinations (scales, tests, etc.). It is essential to understand the clinical continuum within each neurodevelopmental disorder (including ADHD), among the different neurodevelopmental disorders, and among the neurodevelopmental disorders and normality for their research, diagnosis and management. The development of instruments that provide support for this dimensional component is equally significant.

Should learners reason one step at a time? A randomised trial of two diagnostic scheme designs.

PubMed

Blissett, Sarah; Morrison, Deric; McCarty, David; Sibbald, Matthew

2017-04-01

Making a diagnosis can be difficult for learners as they must integrate multiple clinical variables. Diagnostic schemes can help learners with this complex task. A diagnostic scheme is an algorithm that organises possible diagnoses by assigning signs or symptoms (e.g. systolic murmur) to groups of similar diagnoses (e.g. aortic stenosis and aortic sclerosis) and provides distinguishing features to help discriminate between similar diagnoses (e.g. carotid pulse). The current literature does not identify whether scheme layouts should guide learners to reason one step at a time in a terminally branching scheme or weigh multiple variables simultaneously in a hybrid scheme. We compared diagnostic accuracy, perceptual errors and cognitive load using two scheme layouts for cardiac auscultation. Focused on the task of identifying murmurs on Harvey, a cardiopulmonary simulator, 86 internal medicine residents used two scheme layouts. The terminally branching scheme organised the information into single variable decisions. The hybrid scheme combined single variable decisions with a chart integrating multiple distinguishing features. Using a crossover design, participants completed one set of murmurs (diastolic or systolic) with either the terminally branching or the hybrid scheme. The second set of murmurs was completed with the other scheme. A repeated measures manova was performed to compare diagnostic accuracy, perceptual errors and cognitive load between the scheme layouts. There was a main effect of the scheme layout (Wilks' λ = 0.841, F 3,80 = 5.1, p = 0.003). Use of a terminally branching scheme was associated with increased diagnostic accuracy (65 versus 53%, p = 0.02), fewer perceptual errors (0.61 versus 0.98 errors, p = 0.001) and lower cognitive load (3.1 versus 3.5/7, p = 0.023). The terminally branching scheme was associated with improved diagnostic accuracy, fewer perceptual errors and lower cognitive load, suggesting that terminally branching schemes are effective for improving diagnostic accuracy. These findings can inform the design of schemes and other clinical decision aids. © 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Infrastructure features outperform environmental variables explaining rabbit abundance around motorways.

PubMed

Planillo, Aimara; Malo, Juan E

2018-01-01

Human disturbance is widespread across landscapes in the form of roads that alter wildlife populations. Knowing which road features are responsible for the species response and their relevance in comparison with environmental variables will provide useful information for effective conservation measures. We sampled relative abundance of European rabbits, a very widespread species, in motorway verges at regional scale, in an area with large variability in environmental and infrastructure conditions. Environmental variables included vegetation structure, plant productivity, distance to water sources, and altitude. Infrastructure characteristics were the type of vegetation in verges, verge width, traffic volume, and the presence of embankments. We performed a variance partitioning analysis to determine the relative importance of two sets of variables on rabbit abundance. Additionally, we identified the most important variables and their effects model averaging after model selection by AICc on hypothesis-based models. As a group, infrastructure features explained four times more variability in rabbit abundance than environmental variables, being the effects of the former critical in motorway stretches located in altered landscapes with no available habitat for rabbits, such as agricultural fields. Model selection and Akaike weights showed that verge width and traffic volume are the most important variables explaining rabbit abundance index, with positive and negative effects, respectively. In the light of these results, the response of species to the infrastructure can be modulated through the modification of motorway features, being some of them manageable in the design phase. The identification of such features leads to suggestions for improvement through low-cost corrective measures and conservation plans. As a general indication, keeping motorway verges less than 10 m wide will prevent high densities of rabbits and avoid the unwanted effects that rabbit populations can generate in some areas.

Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution

PubMed Central

Rule, Michael E.; Vargas-Irwin, Carlos; Donoghue, John P.; Truccolo, Wilson

2015-01-01

Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band-pass filtered (δ,θ,α,β) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (<100 ms) spiking history. Overall, information in multiband LFP features, although predictive of single-neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID:26157365

A novel DNMT1 mutation associated with early onset hereditary sensory and autonomic neuropathy, cataplexy, cerebellar atrophy, scleroderma, endocrinopathy, and common variable immune deficiency.

PubMed

Fox, Robin; Ealing, John; Murphy, Helen; Gow, David P; Gosal, David

2016-09-01

DNA methyltransferase 1 (DNMT1) is an enzyme which has a role in methylation of DNA, gene regulation, and chromatin stability. Missense mutations in the DNMT1 gene have been previously associated with two neurological syndromes: hereditary sensory and autonomic neuropathy type 1 with dementia and deafness (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). We report a case showing overlap of both of these syndromes plus associated clinical features of common variable immune deficiency, scleroderma, and endocrinopathy that could also be mutation associated. Our patient was found to be heterozygous for a previously unreported frameshift mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. This case displays both the first frameshift mutation described in the literature which is associated with a phenotype with a high degree of overlap between HSAN1E and ADCA-DN and early age of onset (c. 8 years). Our case is also of interest as the patient displays a number of new non-neurological features, which could also be DNMT1 mutation related. © 2016 Peripheral Nerve Society.

Subtle imitation behaviour in convenience samples of normal, demented, and currently depressed elderly subjects.

PubMed

von Gunten, Armin; Duc, René

2007-06-01

The clinical significance of imitation behaviour (IB) is unclear. The aim of this study was to investigate the prevalence of subtle naïve and obstinate IB in convenience samples of normal elderly, demented, and depressed subjects. Subtle IB was assessed using a protocol constructed ad hoc in 146 patients, consecutively referred to a memory clinic having received an ICD-10 diagnosis of either dementia or depression, and in 241 healthy subjects. The prevalence of IB in the three groups was determined and the association with possible demographic, cognitive, and non-cognitive variables analysed. Subtle naïve IB was frequent in the elderly with dementia, intermediate in the depressed, and rare in the normal elderly except that the latter frequently stretched out their arms. Obstinate IB never occurred in the normal elderly. IB was predicted by none of the variables used. The groups included were convenience samples with the depressed being a small group precluding further distinction of depressive subtypes. Although naïve IB is a frequent clinical feature in the demented, it also accompanies depressive disorders in the elderly. It can be observed as context-specific IB in the normal elderly. Obstinate IB does not occur in the normal elderly. Copyright 2006 John Wiley & Sons, Ltd.

Computational methods using genome-wide association studies to predict radiotherapy complications and to identify correlative molecular processes

NASA Astrophysics Data System (ADS)

Oh, Jung Hun; Kerns, Sarah; Ostrer, Harry; Powell, Simon N.; Rosenstein, Barry; Deasy, Joseph O.

2017-02-01

The biological cause of clinically observed variability of normal tissue damage following radiotherapy is poorly understood. We hypothesized that machine/statistical learning methods using single nucleotide polymorphism (SNP)-based genome-wide association studies (GWAS) would identify groups of patients of differing complication risk, and furthermore could be used to identify key biological sources of variability. We developed a novel learning algorithm, called pre-conditioned random forest regression (PRFR), to construct polygenic risk models using hundreds of SNPs, thereby capturing genomic features that confer small differential risk. Predictive models were trained and validated on a cohort of 368 prostate cancer patients for two post-radiotherapy clinical endpoints: late rectal bleeding and erectile dysfunction. The proposed method results in better predictive performance compared with existing computational methods. Gene ontology enrichment analysis and protein-protein interaction network analysis are used to identify key biological processes and proteins that were plausible based on other published studies. In conclusion, we confirm that novel machine learning methods can produce large predictive models (hundreds of SNPs), yielding clinically useful risk stratification models, as well as identifying important underlying biological processes in the radiation damage and tissue repair process. The methods are generally applicable to GWAS data and are not specific to radiotherapy endpoints.

The Massachusetts abscess rule: a clinical decision rule using ultrasound to identify methicillin-resistant Staphylococcus aureus in skin abscesses.

PubMed

Gaspari, Romolo J; Blehar, David; Polan, David; Montoya, Anthony; Alsulaibikh, Amal; Liteplo, Andrew

2014-05-01

Treatment failure rates for incision and drainage (I&D) of skin abscesses have increased in recent years and may be attributable to an increased prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Previous authors have described sonographic features of abscesses, such as the presence of interstitial fluid, characteristics of abscess debris, and depth of abscess cavity. It is possible that the sonographic features are associated with MRSA and can be used to predict the presence of MRSA. The authors describe a potential clinical decision rule (CDR) using sonographic images to predict the presence of CA-MRSA. This was a pilot CDR derivation study using databases from two emergency departments (EDs) of patients presenting to the ED with uncomplicated skin abscesses who underwent I&D and culture of the abscess contents. Patients underwent ultrasound (US) imaging of the abscesses prior to I&D. Abscess contents were sent for culture and sensitivity. Two independent physicians experienced in soft tissue US blinded to the culture results and clinical data reviewed the images in a standardized fashion for the presence or absence of the predetermined image characteristics. In the instance of a disagreement between the initial two investigators, a third reviewer adjudicated the findings prior to analysis. The association between the primary outcome (presence of MRSA) and each sonographic feature was assessed using univariate and multivariate analysis. The reliability of each sonographic feature was measured by calculating the kappa (κ) coefficient of interobserver agreement. The decision tree model for the CDR was created with recursive partitioning using variables that were both reliable and strongly associated with MRSA. Of the total of 2,167 patients who presented with skin and soft tissue infections during the study period, 605 patients met inclusion criteria with US imaging and culture and sensitivity of purulence. Among the pathogenic organisms, MRSA was the most frequently isolated, representing 50.1% of all patients. Six of the sonographic features were associated with the presence of MRSA, but only four of these features were reliable using the kappa analysis. Recursive partitioning identified three independent variables that were both associated with MRSA and reliable: 1) the lack of a well-defined edge, 2) small volume, and 3) irregular or indistinct shape. This decision rule demonstrates a sensitivity of 89.2% (95% confidence interval [CI] = 84.7% to 92.7%), a specificity of 44.7% (95% CI = 40.9% to 47.8%), a positive predictive value of 57.9 (95% CI = 55.0 to 60.2), a negative predictive value of 82.9 (95% CI = 75.9 to 88.5), and an odds ratio (OR) of 7.0 (95% CI = 4.0 to 12.2). According to our putative CDR, patients with skin abscesses that are small, irregularly shaped, or indistinct, with ill-defined edges, are seven times more likely to demonstrate MRSA on culture. © 2014 by the Society for Academic Emergency Medicine.

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.

Mortality Prediction Model of Septic Shock Patients Based on Routinely Recorded Data

PubMed Central

Carrara, Marta; Baselli, Giuseppe; Ferrario, Manuela

2015-01-01

We studied the problem of mortality prediction in two datasets, the first composed of 23 septic shock patients and the second composed of 73 septic subjects selected from the public database MIMIC-II. For each patient we derived hemodynamic variables, laboratory results, and clinical information of the first 48 hours after shock onset and we performed univariate and multivariate analyses to predict mortality in the following 7 days. The results show interesting features that individually identify significant differences between survivors and nonsurvivors and features which gain importance only when considered together with the others in a multivariate regression model. This preliminary study on two small septic shock populations represents a novel contribution towards new personalized models for an integration of multiparameter patient information to improve critical care management of shock patients. PMID:26557154

[Myotonic dystrophy - a new insight into a well-known disease].

PubMed

Lusakowska, Anna; Sułek-Piatkowska, Anna

2010-01-01

Myotonic dystrophy (DM), the most common dystrophy in adults, is an autosomal dominant disease characterized by a variety of multisystemic features. Two genetically distinct forms of DM are identified - type 1 (DM1), the classic form first described by Steinert, and type 2 (DM2), identified by Ricker. DM1 is caused by trinucleotide expansion of CTG in the myotonic dystrophy protein kinase gene, whereas in DM2 the expansion of tetranucleotide repeats (CCTG) in the zinc finger protein 9 gene was identified. Both mutations are dynamic and are located in non-coding parts of the genes. Phenotype variability of DM1 and DM2 is caused by a molecular mechanism due to mutated RNA toxicity. This paper reviews the clinical features of both types of myotonic dystrophies and summarizes current views on pathogenesis of myotonic dystrophy.

A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

PubMed Central

2009-01-01

Background Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. Results We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight diferent datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical. Conclusion Feature variability can have a strong impact on breast cancer signature composition, as well as the classification of individual patient samples. We therefore strongly recommend that feature variability is considered in analyzing data from microarray breast cancer expression profiling experiments. PMID:19941644

Interobserver variability in identification of breast tumors in MRI and its implications for prognostic biomarkers and radiogenomics

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

Saha, Ashirbani, E-mail: as698@duke.edu; Grimm, La

Purpose: To assess the interobserver variability of readers when outlining breast tumors in MRI, study the reasons behind the variability, and quantify the effect of the variability on algorithmic imaging features extracted from breast MRI. Methods: Four readers annotated breast tumors from the MRI examinations of 50 patients from one institution using a bounding box to indicate a tumor. All of the annotated tumors were biopsy proven cancers. The similarity of bounding boxes was analyzed using Dice coefficients. An automatic tumor segmentation algorithm was used to segment tumors from the readers’ annotations. The segmented tumors were then compared between readersmore » using Dice coefficients as the similarity metric. Cases showing high interobserver variability (average Dice coefficient <0.8) after segmentation were analyzed by a panel of radiologists to identify the reasons causing the low level of agreement. Furthermore, an imaging feature, quantifying tumor and breast tissue enhancement dynamics, was extracted from each segmented tumor for a patient. Pearson’s correlation coefficients were computed between the features for each pair of readers to assess the effect of the annotation on the feature values. Finally, the authors quantified the extent of variation in feature values caused by each of the individual reasons for low agreement. Results: The average agreement between readers in terms of the overlap (Dice coefficient) of the bounding box was 0.60. Automatic segmentation of tumor improved the average Dice coefficient for 92% of the cases to the average value of 0.77. The mean agreement between readers expressed by the correlation coefficient for the imaging feature was 0.96. Conclusions: There is a moderate variability between readers when identifying the rectangular outline of breast tumors on MRI. This variability is alleviated by the automatic segmentation of the tumors. Furthermore, the moderate interobserver variability in terms of the bounding box does not translate into a considerable variability in terms of assessment of enhancement dynamics. The authors propose some additional ways to further reduce the interobserver variability.« less

US-guided percutaneous cholecystostomy: features predicting culture-positive bile and clinical outcome.

PubMed

Sosna, Jacob; Kruskal, Jonathan B; Copel, Laurian; Goldberg, S Nahum; Kane, Robert A

2004-03-01

To assess sonographic and clinical features that might be used to predict infected bile and/or patient outcome from ultrasonography (US)-guided percutaneous cholecystostomy. Between February 1997 and August 2002 at one institution, 112 patients underwent US-guided percutaneous cholecystostomy (59 men, 53 women; average age, 69.3 years). All US images were scored on a defined semiquantitative scale according to preset parameters: (a) gallbladder distention, (b) sludge and/or stones, (c) wall appearance, (d) pericholecystic fluid, and (e) common bile duct size and/or choledocholithiasis. Separate and total scores were generated. Retrospective evaluation of (a) the bacteriologic growth of aspirated bile and its color and (b) clinical indices (fever, white blood cell count, bilirubin level, liver function test results) was conducted by reviewing medical records. For each patient, the clinical manifestation was classified into four groups: (a) localized right upper quadrant symptoms, (b) generalized abdominal symptoms, (c) unexplained sepsis, or (d) sepsis with other known infection. Logistic regression models, exact Wilcoxon-Mann-Whitney test, and the Kruskal-Wallis test were used. Forty-seven (44%) of 107 patients had infected bile. A logistic regression model showed that wall appearance, distention, bile color, and pericholecystic fluid were not individually significant predictors for culture-positive bile, leaving sludge and/or stones (P =.003, odds ratio = 1.647), common bile duct status (P =.02, odds ratio = 2.214), and total score (P =.007, odds ratio = 1.267). No US covariates or clinical indices predicted clinical outcome. Clinical manifestation was predictive of clinical outcome (P =.001) and aspirating culture-positive bile (P =.008); specifically, 30 (86%) of 35 patients with right upper quadrant symptoms had their condition improve, compared with one (7%) of 15 asymptomatic patients with other known causes of infection. US variables can be used to predict culture-positive bile but not patient outcome. Clinical manifestation is important because patients with right upper quadrant symptoms have the best clinical outcome. Copyright RSNA, 2004

Richer concepts are better remembered: number of features effects in free recall

PubMed Central

Hargreaves, Ian S.; Pexman, Penny M.; Johnson, Jeremy C.; Zdrazilova, Lenka

2012-01-01

Many models of memory build in a term for encoding variability, the observation that there can be variability in the richness or extensiveness of processing at encoding, and that this variability has consequences for retrieval. In four experiments, we tested the expectation that encoding variability could be driven by the properties of the to-be-remembered item. Specifically, that concepts associated with more semantic features would be better remembered than concepts associated with fewer semantic features. Using feature listing norms we selected sets of items for which people tend to list higher numbers of features (high NoF) and items for which people tend to list lower numbers of features (low NoF). Results showed more accurate free recall for high NoF concepts than for low NoF concepts in expected memory tasks (Experiments 1–3) and also in an unexpected memory task (Experiment 4). This effect was not the result of associative chaining between study items (Experiment 3), and can be attributed to the amount of item-specific processing that occurs at study (Experiment 4). These results provide evidence that stimulus-specific differences in processing at encoding have consequences for explicit memory retrieval. PMID:22514526

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

PubMed

Leigh, Margaret W; Ferkol, Thomas W; Davis, Stephanie D; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D; Sagel, Scott D; Milla, Carlos; Olivier, Kenneth N; Sullivan, Kelli M; Zariwala, Maimoona A; Pittman, Jessica E; Shapiro, Adam J; Carson, Johnny L; Krischer, Jeffrey; Hazucha, Milan J; Knowles, Michael R

2016-08-01

Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as "definite PCD" (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), "probable/possible PCD" (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and "other diagnosis or undefined." Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. From 534 participants 18 years of age and younger, 205 were identified as having "definite PCD" (including 164 with two mutations in a PCD-associated gene), 187 were categorized as "other diagnosis or undefined," and 142 were defined as having "probable/possible PCD." Participants with "definite PCD" were compared with the "other diagnosis or undefined" group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167).

Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

PubMed Central

Díez-Noguera, Antoni

2018-01-01

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients frequently show autonomic symptoms which may be associated with a hypothalamic dysfunction. This study aimed to explore circadian rhythm patterns in rest and activity and distal skin temperature (DST) and their association with self-reported outcome measures, in CFS/ME patients and healthy controls at two different times of year. Ten women who met both the 1994 CDC/Fukuda definition and 2003 Canadian criteria for CFS/ME were included in the study, along with ten healthy controls matched for age, sex and body mass index. Self-reported measures were used to assess fatigue, sleep quality, anxiety and depression, autonomic function and health-related quality of life. The ActTrust actigraph was used to record activity, DST and light intensity, with data intervals of one minute over seven consecutive days. Sleep variables were obtained through actigraphic analysis and from subjective sleep diary. The circadian variables and the spectral analysis of the rhythms were calculated. Linear regression analysis was used to evaluate the relationship between the rhythmic variables and clinical features. Recordings were taken in the same subjects in winter and summer. Results showed no differences in rhythm stability, sleep latency or number of awakenings between groups as measured with the actigraph. However, daily activity, the relative amplitude and the stability of the activity rhythm were lower in CFS/ME patients than in controls. DST was sensitive to environmental temperature and showed lower nocturnal values in CFS/ME patients than controls only in winter. A spectral analysis showed no differences in phase or amplitude of the 24h rhythm, but the power of the second harmonic (12h), revealed differences between groups (controls showed a post-lunch dip in activity and peak in DST, while CFS/ME patients did not) and correlated with clinical features. These findings suggest that circadian regulation and skin vasodilator responses may play a role in CFS/ME. PMID:29874259

Stabilometric parameters are affected by anthropometry and foot placement.

PubMed

Chiari, Lorenzo; Rocchi, Laura; Cappello, Angelo

2002-01-01

To recognize and quantify the influence of biomechanical factors, namely anthropometry and foot placement, on the more common measures of stabilometric performance, including new-generation stochastic parameters. Fifty normal-bodied young adults were selected in order to cover a sufficiently wide range of anthropometric properties. They were allowed to choose their preferred side-by-side foot position and their quiet stance was recorded with eyes open and closed by a force platform. biomechanical factors are known to influence postural stability but their impact on stabilometric parameters has not been extensively explored yet. Principal component analysis was used for feature selection among several biomechanical factors. A collection of 55 stabilometric parameters from the literature was estimated from the center-of-pressure time series. Linear relations between stabilometric parameters and selected biomechanical factors were investigated by robust regression techniques. The feature selection process returned height, weight, maximum foot width, base-of-support area, and foot opening angle as the relevant biomechanical variables. Only eleven out of the 55 stabilometric parameters were completely immune from a linear dependence on these variables. The remaining parameters showed a moderate to high dependence that was strengthened upon eye closure. For these parameters, a normalization procedure was proposed, to remove what can well be considered, in clinical investigations, a spurious source of between-subject variability. Care should be taken when quantifying postural sway through stabilometric parameters. It is suggested as a good practice to include some anthropometric measurements in the experimental protocol, and to standardize or trace foot position. Although the role of anthropometry and foot placement has been investigated in specific studies, there are no studies in the literature that systematically explore the relationship between such BF and stabilometric parameters. This knowledge may contribute to better defining the experimental protocol and improving the functional evaluation of postural sway for clinical purposes, e.g. by removing through normalization the spurious effects of body properties and foot position on postural performance.

Limited Documentation and Treatment Quality of Glycemic Inpatient Care in Relation to Structural Deficits of Heterogeneous Insulin Charts at a Large University Hospital.

PubMed

Kopanz, Julia; Lichtenegger, Katharina M; Sendlhofer, Gerald; Semlitsch, Barbara; Cuder, Gerald; Pak, Andreas; Pieber, Thomas R; Tax, Christa; Brunner, Gernot; Plank, Johannes

2018-02-09

Insulin charts represent a key component in the inpatient glycemic management process. The aim was to evaluate the quality of structure, documentation, and treatment of diabetic inpatient care to design a new standardized insulin chart for a large university hospital setting. Historically grown blank insulin charts in use at 39 general wards were collected and evaluated for quality structure features. Documentation and treatment quality were evaluated in a consecutive snapshot audit of filled-in charts. The primary end point was the percentage of charts with any medication error. Overall, 20 different blank insulin charts with variable designs and significant structural deficits were identified. A medication error occurred in 55% of the 102 audited filled-in insulin charts, consisting of prescription and management errors in 48% and 16%, respectively. Charts of insulin-treated patients had more medication errors relative to patients treated with oral medication (P < 0.01). Chart design did support neither clinical authorization of individual insulin prescription (10%), nor insulin administration confirmed by nurses' signature (25%), nor treatment of hypoglycemia (0%), which resulted in a reduced documentation and treatment quality in clinical practice 7%, 30%, 25%, respectively. A multitude of charts with variable design characteristics and structural deficits were in use across the inpatient wards. More than half of the inpatients had a chart displaying a medication error. Lack of structure quality features of the charts had an impact on documentation and treatment quality. Based on identified deficits and international standards, a new insulin chart was developed to overcome these quality hurdles.

Characteristics of motivation and their impacts on the functional outcomes in patients with schizophrenia.

PubMed

Tobe, Miki; Nemoto, Takahiro; Tsujino, Naohisa; Yamaguchi, Taiju; Katagiri, Naoyuki; Fujii, Chiyo; Mizuno, Masafumi

2016-02-01

Deficits of motivation have been considered to be a core feature of schizophrenia, and recent studies have begun to reveal the biological and psychological characteristics and mechanisms underlying the deficits in motivation in schizophrenia patients. The aims of the present study were to investigate the characteristics of motivation in schizophrenia patients using the General Causality Orientations Scale (GCOS), and the impacts of motivational orientations on the functional outcomes in schizophrenia patients. A total of 53 outpatients with schizophrenia and 38 healthy controls were recruited for this study. The GCOS was used to assess individual tendencies in respect of three different motivational orientations: the autonomy, controlled, and impersonal orientations, corresponding to intrinsic motivation, extrinsic motivation, and amotivation, respectively. The cognitive functioning, psychiatric symptoms, social functioning, and quality of life of the subjects were also assessed. The score for autonomy orientation was significantly lower in the patient group than that in the control group, while no significant differences were found between the two groups in respect of the scores for the other two orientations. The autonomy orientation was associated with various clinical variables, and regression analysis identified as one of the variables with the highest predictive accuracy for social functioning. Intrinsic motivation measured by the GCOS in schizophrenia patients was significantly lower than that in healthy controls. The deficits of intrinsic motivation were broadly associated with the clinical features and were a determinant of social functioning. Development of treatments for enhancing intrinsic motivation would be essential for functional recovery in schizophrenia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Subtypes of depression and their overlap in a naturalistic inpatient sample of major depressive disorder.

PubMed

Musil, Richard; Seemüller, Florian; Meyer, Sebastian; Spellmann, Ilja; Adli, Mazda; Bauer, Michael; Kronmüller, Klaus-Thomas; Brieger, Peter; Laux, Gerd; Bender, Wolfram; Heuser, Isabella; Fisher, Robert; Gaebel, Wolfgang; Schennach, Rebecca; Möller, Hans-Jürgen; Riedel, Michael

2018-03-01

Subtyping depression is important in order to further delineate biological causes of depressive syndromes. The aim of this study was to evaluate clinical and outcome characteristics of distinct subtypes of depression and to assess proportion and features of patients fulfilling criteria for more than one subtype. Melancholic, atypical and anxious subtypes of depression were assessed in a naturalistic sample of 833 inpatients using DSM-IV specifiers based on operationalized criteria. Baseline characteristics and outcome criteria at discharge were compared between distinct subtypes and their overlap. A substantial proportion of patients (16%) were classified with more than one subtype of depression, 28% were of the distinct anxious, 7% of the distinct atypical and 5% of the distinct melancholic subtype. Distinct melancholic patients had shortest duration of episode, highest baseline depression severity, but were more often early improvers; distinct anxious patients had higher NEO-Five Factor Inventory (NEO-FFI) neuroticism scores compared with patients with unspecific subtype. Melancholic patients with overlap of anxious features had worse treatment outcome compared to distinct melancholic and distinct anxious subtype. Distinct subtypes differed in only few variables and patients with overlap of depression subtypes may have independent clinical and outcome characteristics. Studies investigating biological causes of subtypes of depression should take influence of features of other subtypes into account. Copyright © 2017 John Wiley & Sons, Ltd.

Majewski osteodysplastic primordial dwarfism type II (MOPD II): natural history and clinical findings.

PubMed

Hall, Judith G; Flora, Christina; Scott, Charles I; Pauli, Richard M; Tanaka, Kimi I

2004-09-15

A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family. Copyright 2004 Wiley-Liss, Inc.

Cloud structure of the nearest brown dwarfs. II: High-amplitude variability for Luhman 16 A and B in and out of the 0.99 μm FeH feature

DOE PAGES

Buenzli, Esther; Marley, Mark S.; Apai, Daniel; ...

2015-10-20

The re-emergence of the 0.99 μm FeH feature in brown dwarfs of early- to mid-T spectral type has been suggested as evidence for cloud disruption where flux from deep, hot regions below the Fe cloud deck can emerge. The same mechanism could account for color changes at the L/T transition and photometric variability. We present the first observations of spectroscopic variability of brown dwarfs covering the 0.99 μm FeH feature. We observed the spatially resolved very nearby brown dwarf binary WISE J104915.57–531906.1 (Luhman 16AB), a late-L and early-T dwarf, with Hubble Space Telescope/WFC3 in the G102 grism at 0.8–1.15 μm.more » We find significant variability at all wavelengths for both brown dwarfs, with peak-to-valley amplitudes of 9.3% for Luhman 16B and 4.5% for Luhman 16A. This represents the first unambiguous detection of variability in Luhman 16A. We estimate a rotational period between 4.5 and 5.5 hr, very similar to Luhman 16B. Variability in both components complicates the interpretation of spatially unresolved observations. The probability for finding large amplitude variability in any two brown dwarfs is less than 10%. Our finding may suggest that a common but yet unknown feature of the binary is important for the occurrence of variability. For both objects, the amplitude is nearly constant at all wavelengths except in the deep K i feature below 0.84 μm. No variations are seen across the 0.99 μm FeH feature. The observations lend strong further support to cloud height variations rather than holes in the silicate clouds, but cannot fully rule out holes in the iron clouds. Here, we re-evaluate the diagnostic potential of the FeH feature as a tracer of cloud patchiness.« less

Variable density thinning promotes variable structural responses 14 years after treatment in the Pacific Northwest

Treesearch

John L. Willis; Scott D. Roberts; Constance A. Harrington

2018-01-01

Young stands are commonly assumed to require centuries to develop into late-successional forest habitat. This viewpoint reflects the fact that young stands often lack many of the structural features that define late-successional habitat, and that these features derive from complex stand dynamics that are difficult to mimic with forest management. Variable density...

Is age of onset associated with severity, prognosis, and clinical features in bipolar disorder? A meta-analytic review.

PubMed

Joslyn, Cassandra; Hawes, David J; Hunt, Caroline; Mitchell, Philip B

2016-08-01

To identify clinical characteristics and adverse outcomes associated with an earlier age of onset of bipolar disorder. A comprehensive search yielded 15 empirical papers comparing clinical presentation and outcomes in individuals with bipolar disorder grouped according to age of onset (total N=7370). The following variables were examined to determine odds ratios (ORs) and 95% confidence intervals (CIs): presence of Axis I comorbidity, rapid cycling, psychotic symptoms, mixed episodes (DSM-IV), lifetime suicide attempts, lifetime alcohol and substance abuse, symptom severity, and treatment delay. Early age of onset was found to be associated with longer delay to treatment (Hedges' g=0.39, P=.001), greater severity of depression (Hedges' g=0.42, P<.001), and higher levels of comorbid anxiety (OR=2.34, P<.001) and substance use (OR=1.80, P<.001). Surprisingly, no association was found between early age of onset and clinical characteristics such as psychotic symptoms or mixed episodes as defined by DSM-IV. Earlier age of onset of bipolar disorder is associated with factors that can negatively impact long-term outcomes such as increased comorbidity. However, no association was found between early onset and indicators of severity or treatment resistance such as psychotic symptoms. Clinical features found to have the strongest relationship with early age of onset were those potentially amenable to pharmacological and psychological treatment. Results highlight the importance of early identification and provide potential areas of focus for the development of early intervention in bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.