A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

Directory of Open Access Journals (Sweden)

Warren D Anderson

2017-07-01

Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

Characteristics and heterogeneity of schizoaffective disorder compared with unipolar depression and schizophrenia - a systematic literature review and meta-analysis.

Science.gov (United States)

Rink, Lena; Pagel, Tobias; Franklin, Jeremy; Baethge, Christopher

2016-02-01

Comparisons of illness characteristics between patients with schizoaffective disorder (SAD) patients and unipolar depression (UD) are rare, even though UD is one of the most important differential diagnoses of SAD. Also, the variability of illness characteristics (heterogeneity) has not been compared. We compared illness characteristics and their heterogeneity among SAD, UD, and - as another important differential diagnosis - schizophrenia (S). In order to reduce sampling bias we systematically searched for studies simultaneously comparing samples of patients with SAD, UD, and S. Using random effects and Mantel-Haenszel models we estimated and compared demographic, illness course and psychopathology parameters, using pooled standard deviations as a measurement of heterogeneity. Out of 155 articles found by an earlier meta-analysis, 765 screened in Medline, 2738 screened in EMBASE, and 855 screened in PsycINFO we selected 24 studies, covering 3714 patients diagnosed according to RDC, DSM-III, DSM-IIIR, DSM-IV, or ICD-10. In almost all key characteristics, samples with schizoaffective disorders fell between unipolar depression and schizophrenia, with a tendency towards schizophrenia. On average, UD patients were significantly older at illness onset (33.0 years, SAD: 25.2, S: 23.4), more often women (59% vs. 57% vs. 39%) and more often married (53% vs. 39% vs. 27%). Their psychopathology was also less severe, as measured by BPRS, GAS, and HAMD. In demographic and clinical variables heterogeneity was roughly 5% larger in UD than in SAD, and samples of patients with schizophrenia had the lowest pooled heterogeneity. A similar picture emerged in a sensitivity analysis with coefficient of variation as the measurement of heterogeneity. Relative to bipolar disorder there are fewer studies including unipolar patients. No studies based on DSM-5 could be included. Regarding unipolar affective disorder this study confirms what we have shown for bipolar disorders in earlier

Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness

Directory of Open Access Journals (Sweden)

Bas C. T. van Bussel

2017-02-01

Full Text Available Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.

Multiorgan failure and antiphospholipid antibodies: the catastrophic antiphospholipid (Asherson's) syndrome.

Science.gov (United States)

Asherson, Ronald A

2005-01-01

A review of 250 patients with the catastrophic antiphospholipid (Asherson's) syndrome (CAPS) taken from the web site organized by the Europhospholipid Group (http://www.med.ub.es/MIMMUN/FORUM/CAPS.HTM) is presented in this paper. A short historical overview of the antiphospholipid syndrome (APS) is followed by a description of the "triggering" factors, associated autoimmune diseases, clinical presentation, presumed pathogenesis, prognosis, mode of death and suggested therapies. Triggering factors are present in approximately 50% of patients and consist predominantly of infections, trauma, including minor surgical procedures such as biopsies, obstetric-related multiorgan failure and malignancy-associated CAPS. The patients present mainly with multiorgan failure resulting from predominantly small vessel occlusions affecting mainly intra-abdominal organs such as bowel, liver, pancreas, and adrenals, although large vessel occlusions do occur and comprise mainly deep vein thromboses (DVT) of the veins of the lower limbs and arterial occlusions causing strokes and peripheral gangrene. They do not however dominate the clinical picture. The condition differs considerably from the simple/classic APS in several respects, viz. the rapid development of multiorgan failure following the above-mentioned identifiable precipitating factors, the involvement of unusual organs such as bowel, reproductive organs, and bone marrow, complicating features of disseminated intravascular coagulation in 20% of cases, the acute (adult) respiratory distress syndrome (ARDS) in one third of patients, and severe thrombocytopenia; these not being encountered in the simple/classic APS. Treatment consisting of regular and repeated plasma exchanges using fresh frozen plasma, and IV immunoglobulins in addition to parenteral steroids and anticoagulation are necessary to improve the survival in a condition where the mortality is still of the order of 50%. Treatment may have to be continued for several

Platelets and Multi-Organ Failure in Sepsis

Directory of Open Access Journals (Sweden)

Elisabetta Greco

2017-10-01

Full Text Available Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

Platelets and Multi-Organ Failure in Sepsis.

Science.gov (United States)

Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

2017-10-20

Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

Heterogeneity within autism spectrum disorders: what have we learned from neuroimaging studies?

Directory of Open Access Journals (Sweden)

Rhoshel Krystyna Lenroot

2013-10-01

Full Text Available Autism spectrum disorders (ASD display significant heterogeneity. Although most neuroimaging studies in ASD have been designed to identify commonalities among affected individuals, rather than differences, some studies have explored variation within ASD. There have been two general types of approaches used for this in the neuroimaging literature to date: comparison of subgroups within ASD, and analyses using dimensional measures to link clinical variation to brain differences. This review focuses on structural and functional magnetic resonance imaging studies that have used these approaches to begin to explore heterogeneity between individuals with ASD. Although this type of data is yet sparse, recognition is growing of the limitations of behaviourally defined categorical diagnoses for understanding neurobiology. Study designs that are more informative regarding the sources of heterogeneity in ASD have the potential to improve our understanding of the neurobiological processes underlying ASD.

Heterogeneity of executive functions among comorbid neurodevelopmental disorders

Science.gov (United States)

Dajani, Dina R.; Llabre, Maria M.; Nebel, Mary Beth; Mostofsky, Stewart H.; Uddin, Lucina Q.

2016-01-01

Executive functions (EFs) are used to set goals, plan for the future, inhibit maladaptive responses, and change behavior flexibly. Although some studies point to specific EF profiles in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) — prevalent and often highly comorbid neurodevelopmental disorders — others have not differentiated them. The objective of the current study was to identify distinct profiles of EF across typically developing (TD) children and children with ASD and ADHD. We employed a latent profile analysis using indicators of EF (e.g., working memory, inhibition, and flexibility) in a mixed group of 8–13 year-olds including TD children (n = 128), children with ASD without ADHD (n = 30), children with ADHD (n = 93), and children with comorbid ASD and ADHD (n = 66). Three EF classes emerged: “above average,” “average,” and “impaired.” EF classes did not reproduce diagnostic categories, suggesting that differences in EF abilities are present within the ASD and ADHD groups. Further, greater EF dysfunction predicted more severe socioemotional problems, such as anxiety/depression. These results highlight the heterogeneity of current diagnostic groups and identify an “impaired” EF group, consisting of children with both ASD and ADHD, which could specifically be targeted for EF intervention. PMID:27827406

Sepsis and multiorgan failure following TVT procedure.

Science.gov (United States)

Stec, Piotr; Connell, Rowan

2014-04-01

Tension-free vaginal tape (TVT), is a commonly performed, low risk procedure for treatment of stress urinary incontinence (SUI). Severe complications are rare, but can be potentially life threatening. We present a case of 66 year old patient who sustained bladder perforation at the time of TVT procedure and subsequently developed sepsis rapidly leading to multi-organ failure and triggering sequence of serious complications. During her inpatient stay she required ITU admission, emergency laparotomy, TVT mesh removal, bowel resection due to ischemic colitis and anticoagulation for pulmonary embolism. Despite of clinical picture of sepsis her microbiology tests were almost consistently negative. This case emphasise importance of awareness and quick recognition of TVT related complications. Patient ultimately survived and recovered thanks to timely and coordinated management by the multidisciplinary team of doctors.

Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder.

Science.gov (United States)

Pavlovic, Sasha; Krunic, Aleksandar L; Bulj, Tanja K; Medenica, Maria M; Fong, Kenneth; Arita, Ken; McGrath, John A

2012-01-01

Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross-linking cornified cell envelope proteins. We report a new APSS pedigree from Jordan that contains at least 10 affected family members, although sequencing of the TGM5 gene failed to disclose any pathogenic mutation(s). On the basis of probable consanguinity, we performed homozygosity mapping and identified areas of homozygosity on chromosomes 1, 6, 10, 13, and 16, although none of the intervals contained genes of clear relevance to cornification. APSS is a clinically and genetically heterogeneous disorder, and this Jordanian pedigree underscores the likelihood of still further heterogeneity. © 2011 Wiley Periodicals, Inc.

Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse

DEFF Research Database (Denmark)

Schäfer, Carolyn; Guldager, Helle Skov; Jørgensen, H L

2011-01-01

and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency...

Research Review: Constraining Heterogeneity--The Social Brain and Its Development in Autism Spectrum Disorder

Science.gov (United States)

Pelphrey, Kevin A.; Shultz, Sarah; Hudac, Caitlin M.; Vander Wyk, Brent C.

2011-01-01

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved…

Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs.

Science.gov (United States)

Oleaga, Carlota; Bernabini, Catia; Smith, Alec S T; Srinivasan, Balaji; Jackson, Max; McLamb, William; Platt, Vivien; Bridges, Richard; Cai, Yunqing; Santhanam, Navaneetha; Berry, Bonnie; Najjar, Sarah; Akanda, Nesar; Guo, Xiufang; Martin, Candace; Ekman, Gail; Esch, Mandy B; Langer, Jessica; Ouedraogo, Gladys; Cotovio, Jose; Breton, Lionel; Shuler, Michael L; Hickman, James J

2016-02-03

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening.

Schizoaffective disorder diagnosed according to different diagnostic criteria--systematic literature search and meta-analysis of key clinical characteristics and heterogeneity.

Science.gov (United States)

Pagel, Tobias; Franklin, Jeremy; Baethge, Christopher

2014-03-01

Schizoaffective disorder is viewed as a heterogeneous diagnosis among psychotic illnesses. Different diagnostic systems differ in their definition with DSM (-IIIR, -IV, and -V) providing a narrower definition than RDC and ICD-10. It is unclear whether this difference is reflected in patient samples diagnosed according to different diagnostic systems. Exploratory study based on a systematic review of studies of schizoaffective disorder samples diagnosed by either RDC and ICD-10 (group of "broad criteria") or DSM-IIIR and -IV ("narrow criteria"); comparison (by Mann-Whitney-U-tests) of key characteristics, such as age, number of hospitalizations, or scores in psychometric tests, between more broadly and more narrowly defined schizoaffective disorder samples using standard deviations as a measurement of heterogeneity as well as weighted means and percentages. To reduce selection bias only studies including schizoaffective patient samples together with affective disorder and schizophrenia samples were selected. 55 studies were included, 14 employing RDC, 4 ICD-10, 20 DSM-IIIR, and 17 DSM-IV. Thirteen characteristics were compared: patients diagnosed according to broader criteria had fewer previous hospitalizations (2.2 vs. 5.4) and were both less often male (42 vs. 51%) and married (21 vs. 40%). Heterogeneity was similar in both groups but slightly higher in RDC and ICD-10 samples than in DSM-IIIR and -IV-samples: +4% regarding demographic and clinical course data and +13% regarding psychometric tests (pooled SD). Secular trends and different designs may have confounded the results and limit generalizability. Some comparisons were underpowered. Differences in diagnostic criteria are reflected in key characteristics of samples. The association of larger heterogeneity with wider diagnostic criteria supports employing standard deviations as a measurement of heterogeneity. Copyright © 2013 Elsevier B.V. All rights reserved.

Schizophrenia and bipolar disorder: The road from similarities and clinical heterogeneity to neurobiological types.

Science.gov (United States)

Dacquino, Claudia; De Rossi, Pietro; Spalletta, Gianfranco

2015-09-20

Although diagnosis is a central issue in medical care, in psychiatry its value is still controversial. The function of diagnosis is to indicate treatments and to help clinicians take better care of patients. The fundamental role of diagnosis is to predict outcome and prognosis. To date serious concern persists regarding the clinical utility and predictive validity of the diagnosis system in psychiatry, which is at the most syndromal. Schizophrenia and bipolar disorder, which nosologists consider two distinct disorders, are the most discussed psychiatric illnesses. Recent findings in different fields of psychiatric research, such as neuroimaging, neuropathology, neuroimmunology, neuropsychology and genetics, have led to other conceptualizations. Individuals with schizophrenia or bipolar disorder vary greatly with regard to symptoms, illness course, treatment response, cognitive and functional impairment and biological correlates. In fact, it is possible to find heterogeneous correlates even within the same syndrome, i.e., from one stage of the disorder to another. Thus, it is possible to identify different subsyndromes, which share some clinical and neurobiological characteristics. The main goal of modern psychiatry is to ovethrow these barriers and to obtain a better understanding of the biological profiles underlying heterogeneous clinical features and thus reduce the variance and lead to a homogeneous definition. The translational research model, which connects the basic neuroscience research field with clinical experience in psychiatry, aims to investigate different neurobiological features of syndromes and of the shared neurobiological features between two syndromes. In fact, this approach should help us to better understand the neurobiological pathways underlying clinical entities, and even to distinguish different, more homogeneous, diagnostic subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

Automatic abdominal multi-organ segmentation using deep convolutional neural network and time-implicit level sets.

Science.gov (United States)

Hu, Peijun; Wu, Fa; Peng, Jialin; Bao, Yuanyuan; Chen, Feng; Kong, Dexing

2017-03-01

Multi-organ segmentation from CT images is an essential step for computer-aided diagnosis and surgery planning. However, manual delineation of the organs by radiologists is tedious, time-consuming and poorly reproducible. Therefore, we propose a fully automatic method for the segmentation of multiple organs from three-dimensional abdominal CT images. The proposed method employs deep fully convolutional neural networks (CNNs) for organ detection and segmentation, which is further refined by a time-implicit multi-phase evolution method. Firstly, a 3D CNN is trained to automatically localize and delineate the organs of interest with a probability prediction map. The learned probability map provides both subject-specific spatial priors and initialization for subsequent fine segmentation. Then, for the refinement of the multi-organ segmentation, image intensity models, probability priors as well as a disjoint region constraint are incorporated into an unified energy functional. Finally, a novel time-implicit multi-phase level-set algorithm is utilized to efficiently optimize the proposed energy functional model. Our method has been evaluated on 140 abdominal CT scans for the segmentation of four organs (liver, spleen and both kidneys). With respect to the ground truth, average Dice overlap ratios for the liver, spleen and both kidneys are 96.0, 94.2 and 95.4%, respectively, and average symmetric surface distance is less than 1.3 mm for all the segmented organs. The computation time for a CT volume is 125 s in average. The achieved accuracy compares well to state-of-the-art methods with much higher efficiency. A fully automatic method for multi-organ segmentation from abdominal CT images was developed and evaluated. The results demonstrated its potential in clinical usage with high effectiveness, robustness and efficiency.

Neurobiological heterogeneity in ADHD

NARCIS (Netherlands)

de Zeeuw, P.

2011-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous disorder clinically. Symptoms take many forms, from subtle but pervasive attention problems or dreaminess up to disruptive and unpredictable behavior. Interestingly, early neuroscientific work on ADHD assumed either a

Heterogeneity in development of aspects of working memory predicts longitudinal attention deficit hyperactivity disorder symptom change.

Science.gov (United States)

Karalunas, Sarah L; Gustafsson, Hanna C; Dieckmann, Nathan F; Tipsord, Jessica; Mitchell, Suzanne H; Nigg, Joel T

2017-08-01

The role of cognitive mechanisms in the clinical course of neurodevelopmental disorders is poorly understood. Attention Deficit Hyperactivity Disorder (ADHD) is emblematic in that numerous alterations in cognitive development are apparent, yet how they relate to changes in symptom expression with age is unclear. To resolve the role of cognitive mechanisms in ADHD, a developmental perspective that takes into account expected within-group heterogeneity is needed. The current study uses an accelerated longitudinal design and latent trajectory growth mixture models in a sample of children ages 7-13 years carefully characterized as with (n = 437) and without (n = 297) ADHD to (a) identify heterogeneous developmental trajectories for response inhibition, visual spatial working memory maintenance, and delayed reward discounting and (b) to assess the relationships between these cognitive trajectories and ADHD symptom change. Best-fitting models indicated multiple trajectory classes in both the ADHD and typically developing samples, as well as distinct relationships between each cognitive process and ADHD symptom change. Developmental change in response inhibition and delayed reward discounting were unrelated to ADHD symptom change, while individual differences in the rate of visual spatial working memory maintenance improvement predicted symptom remission in ADHD. Characterizing heterogeneity in cognitive development will be crucial for clarifying mechanisms of symptom persistence and recovery. Results here suggest working memory maintenance may be uniquely related to ADHD symptom improvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Clinical and biochemical presentation of siblings with COG-7 deficiency, a lethal multiple O- and N-glycosylation disorder.

NARCIS (Netherlands)

Spaapen, L.J.; Bakker, J.A.; Meer, S.B. van der; Sijstermans, H.J.; Steet, R.A.; Wevers, R.A.; Jaeken, J.

2005-01-01

Congenital disorders of glycosylation (CDG) represent a group of inherited multiorgan diseases caused by defects in the biosynthesis of glycoproteins. We report on two dysmorphic siblings with severe liver disease who died at the age of a few weeks. Increased activities of lysosomal enzymes in

Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity.

Science.gov (United States)

Tordjman, S; Cohen, D; Coulon, N; Anderson, G M; Botbol, M; Canitano, R; Roubertoux, P L

2017-01-30

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2017. Published by Elsevier Ltd.

Majority rule on heterogeneous networks

International Nuclear Information System (INIS)

Lambiotte, R

2008-01-01

We focus on the majority rule (MR) applied on heterogeneous networks. When the underlying topology is homogeneous, the system is shown to exhibit a transition from an ordered regime to a disordered regime when the noise is increased. When the network exhibits modular structures, in contrast, the system may also exhibit an asymmetric regime, where the nodes in each community reach an opposite average opinion. Finally, the node degree heterogeneity is shown to play an important role by displacing the location of the order-disorder transition and by making the system exhibit non-equipartition of the average spin

A Case Against Fancy Decorated Drinks: Multi-Organ Failure After Drinking a Mojito Cocktail

Directory of Open Access Journals (Sweden)

Simon Bac

2016-09-01

Full Text Available We present the first case of gastro-intestinal perforation caused by a mint twig decorating a cocktail drink. A 76-year-old man was enjoying his Mojito cocktail on a cruise ship near Mexico when he accidently swallowed a mint twig, resulting in ileum perforation. This led to a cascade of events, eventually resulting in life-threatening multi-organ failure. Given this rare but potentially severe complication and the increasing popularity of decorated drinks, a less ‘fancy’ presentation for cocktails and similar drinks may be warranted.

Lemierre's Syndrome - A rare cause of disseminated sepsis requiring multi-organ support.

Science.gov (United States)

Rae, John; Misselbrook, Katie

2017-11-01

Lemierre's syndrome is a rare complication of acute pharyngitis characterised by septicaemia with infective thrombophlebitis of the internal jugular vein, most commonly due to Fusobacterium necrophorum . It characteristically affects healthy young adults causing persistent pyrexia and systemic sepsis presenting several days after an initial pharyngitis. Septic emboli seed via the bloodstream to distant sites including the lung, joints, skin, liver, spleen and brain. Prolonged antimicrobial therapy is required and admission to intensive care common. This once rare condition is increasing in incidence but awareness amongst clinicians is low. We present a classic case in a young man who developed multi-organ failure requiring intensive care support and describe the epidemiology, pathophysiology, microbiology, clinical features and management of the disease.

Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

Directory of Open Access Journals (Sweden)

P Kasatkar

2013-01-01

Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

Repint of "Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity".

Science.gov (United States)

Tordjman, S; Cohen, D; Anderson, G M; Botbol, M; Canitano, R; Coulon, N; Roubertoux, P L

2018-06-01

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism. Copyright © 2018. Published by Elsevier Ltd.

Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

Science.gov (United States)

Schäfer, C N; Guldager, H; Jørgensen, H L

2011-01-01

A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

Heterogeneous continuous-time random walks

Science.gov (United States)

Grebenkov, Denis S.; Tupikina, Liubov

2018-01-01

We introduce a heterogeneous continuous-time random walk (HCTRW) model as a versatile analytical formalism for studying and modeling diffusion processes in heterogeneous structures, such as porous or disordered media, multiscale or crowded environments, weighted graphs or networks. We derive the exact form of the propagator and investigate the effects of spatiotemporal heterogeneities onto the diffusive dynamics via the spectral properties of the generalized transition matrix. In particular, we show how the distribution of first-passage times changes due to local and global heterogeneities of the medium. The HCTRW formalism offers a unified mathematical language to address various diffusion-reaction problems, with numerous applications in material sciences, physics, chemistry, biology, and social sciences.

Evaluating effect of symptoms heterogeneity on decision-making ability in obsessive-compulsive disorder.

Science.gov (United States)

Martoni, Riccardo Maria; Brombin, Chiara; Nonis, Alessandro; Salgari, Giulia Carlotta; Buongiorno, Angela; Cavallini, Maria Cristina; Galimberti, Elisa; Bellodi, Laura

2015-07-01

Despite having a univocal definition, obsessive-compulsive disorder (OCD) shows a remarkably phenotypic heterogeneity. The published reports show impaired decision-making in OCD patients, using tasks such as the Iowa Gambling Task (IGT). We wanted to verify the hypothesis of an IGT worse performance in a large sample of OCD patients and healthy control (HC) subjects and to examine the relation between neuropsychological performance in IGT and the OCD symptoms heterogeneity. Binary data from the Yale-Brown Obsessive Compulsive Scale collected on a large sample of OCD patients were analyzed using a multidimensional item response theory model to explore the underlying structure of data, thus revealing latent factors. Factor scores were categorized into quartiles. Then, for each factor, we identified patients respectively with the highest versus lowest score. We evaluated whether symptom dimensions affect the probability of a correct answer over time generalized, during IGT performance, fitting a generalized linear mixed model. We found a general deficit in ambiguous decision-making in OCD compared to HC. Moreover, our findings suggested that OCD symptoms heterogeneity affects decision-making learning abilities during IGT. In fact, while 'Symmetry' and 'Washing' patients showed a learning curve during the task, other subgroups did not. Our study confirmed previous findings suggesting that OCD is characterized by a deficit in decision-making under uncertainty. Moreover, our study gave evidence about biological specificity for each symptom dimension in OCD. Data were discussed in the context of the somatic marker hypothesis, which was hypothesized to be reduced in OCD patients. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Transmission of Angiosarcomas From a Common Multiorgan Donor to Four Transplant Recipients

DEFF Research Database (Denmark)

Thoning, J; Liu, Ying; Bistrup, C

2013-01-01

We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells...... confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared...... to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor...

Autistic disorder in 2 children with mitochondrial disorders.

Science.gov (United States)

Tsao, Chang-Yong; Mendell, Jerry R

2007-09-01

Autistic disorder is a heterogeneous disorder. The majority of the cases are idiopathic, and only a small number of the autistic children have associated secondary diagnosis. This article reports 2 children with mitochondrial disorders associated with autistic disorder fulfilling the diagnostic criteria of the American Psychiatric Association Manual of Psychiatric Diseases, 4th edition, and briefly reviews the literature on autistic disorder associated with mitochondrial disorders.

Heterogeneity in patterns of DSM-5 posttraumatic stress disorder and depression symptoms: Latent profile analyses.

Science.gov (United States)

Contractor, Ateka A; Roley-Roberts, Michelle E; Lagdon, Susan; Armour, Cherie

2017-04-01

Posttraumatic stress disorder (PTSD) and depression co-occur frequently following the experience of potentially traumatizing events (PTE; Morina et al., 2013). A person-centered approach to discern heterogeneous patterns of such co-occurring symptoms is recommended (Galatzer-Levy and Bryant, 2013). We assessed heterogeneity in PTSD and depression symptomatology; and subsequently assessed relations between class membership with psychopathology constructs (alcohol use, distress tolerance, dissociative experiences). The sample consisted of 268 university students who had experienced a PTE and susequently endorsed clinical levels of PTSD or depression severity. Latent profile analyses (LPA) was used to identify the best-fitting class solution accouring to recommended fit indices (Nylund et al., 2007a); and the effects of covariates was analyzed using a 3-step approach (Vermunt, 2010). Results of the LPA indicated an optimal 3-class solutions: high severity (Class 2), lower PTSD-higher depression (Class 1), and higher PTSD-lower depression (Class 3). Covariates of distress tolerance, and different kinds of dissociative experiences differentiated the latent classes. Use of self-report measure could lead to response biases; and the specific nature of the sample limits generalizability of results. We found evidence for a depressive subtype of PTSD differentiated from other classes in terms of lower distress tolerance and greater dissociative experiences. Thus, transdiagnostic treatment protocols may be most beneficial for these latent class members. Further, the distinctiveness of PTSD and depression at comparatively lower levels of PTSD severity was supported (mainly in terms of distress tolerance abilities); hence supporting the current classification system placement of these disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

Science.gov (United States)

Wang, Yumei; Yin, Xiaoling; Yang, Fang

2018-02-01

Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

Science.gov (United States)

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

Coding of time-dependent stimuli in homogeneous and heterogeneous neural populations.

Science.gov (United States)

Beiran, Manuel; Kruscha, Alexandra; Benda, Jan; Lindner, Benjamin

2018-04-01

We compare the information transmission of a time-dependent signal by two types of uncoupled neuron populations that differ in their sources of variability: i) a homogeneous population whose units receive independent noise and ii) a deterministic heterogeneous population, where each unit exhibits a different baseline firing rate ('disorder'). Our criterion for making both sources of variability quantitatively comparable is that the interspike-interval distributions are identical for both systems. Numerical simulations using leaky integrate-and-fire neurons unveil that a non-zero amount of both noise or disorder maximizes the encoding efficiency of the homogeneous and heterogeneous system, respectively, as a particular case of suprathreshold stochastic resonance. Our findings thus illustrate that heterogeneity can render similarly profitable effects for neuronal populations as dynamic noise. The optimal noise/disorder depends on the system size and the properties of the stimulus such as its intensity or cutoff frequency. We find that weak stimuli are better encoded by a noiseless heterogeneous population, whereas for strong stimuli a homogeneous population outperforms an equivalent heterogeneous system up to a moderate noise level. Furthermore, we derive analytical expressions of the coherence function for the cases of very strong noise and of vanishing intrinsic noise or heterogeneity, which predict the existence of an optimal noise intensity. Our results show that, depending on the type of signal, noise as well as heterogeneity can enhance the encoding performance of neuronal populations.

DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

OpenAIRE

Jelena Kostić; Milkica Nešić; Jasminka Marković; Miodrag Stanković

2015-01-01

Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to c...

Role of mediastinal and multi-organ CT scans in staging presumable surgical candidates with non-small-cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Osada, Hiroaki; Nakajima, Yasuo; Taira, Yasuhiko; Yokote, Kumio; Noguchi, Teruhiko

1987-09-01

In order to evaluate the role of CT scan and bone scan in staging patients with non-small-cell lung cancer presumably indicated for surgery, 70 consecutive patients who underwent thoracotomy were reviewed. Most of them received mediastinal and multi-organ (brain, liver and adrenal) CT scans and a bone scan. In the most recent 40 of the 70 patients, CT findings of the mediastinal lymph nodes were compared to the pathology following complete sampling. The overall accuracy of the mediastinal CT was 60.0 per cent (12 true positive and 12 true negative), but the negative predictable value was 12/(12 + 3) or 80.0 per cent, whereas 3 were false negatives though they showed an acceptable postoperative course. Sixteen out of 21 patients with one, or at the most, three enlarged nodes detected on CT also did well postoperatively and retrospectively, were considered not to have required mediastinoscopy. A group of patients showing no, or at the most, three enlarged mediastinal lymph nodes on CT may be considered as candidates for surgery even without mediastinoscopy. Multi-organ survey by means of CT was believed cost-ineffective and omittable. Bone scan however, retrospectively detected three true positives among 20 patients with a positive uptake, so that it cannot be omitted out of hand, though further examination of this point is required.

Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.

Directory of Open Access Journals (Sweden)

Seok-Hyung Kim

2013-06-01

Full Text Available Multiple Acyl-CoA Dehydrogenase Deficiency (MADD is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxa(vu463 that has an inactivating mutation in the etfa gene. dxa(vu463 recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxa(vu463 zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxa(vu463 zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1 with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity.

Fiber Bundle Model Under Heterogeneous Loading

Science.gov (United States)

Roy, Subhadeep; Goswami, Sanchari

2018-03-01

The present work deals with the behavior of fiber bundle model under heterogeneous loading condition. The model is explored both in the mean-field limit as well as with local stress concentration. In the mean field limit, the failure abruptness decreases with increasing order k of heterogeneous loading. In this limit, a brittle to quasi-brittle transition is observed at a particular strength of disorder which changes with k. On the other hand, the model is hardly affected by such heterogeneity in the limit where local stress concentration plays a crucial role. The continuous limit of the heterogeneous loading is also studied and discussed in this paper. Some of the important results related to fiber bundle model are reviewed and their responses to our new scheme of heterogeneous loading are studied in details. Our findings are universal with respect to the nature of the threshold distribution adopted to assign strength to an individual fiber.

DEVELOPMENTAL TAXONOMY OF CONDUCT DISORDER

Directory of Open Access Journals (Sweden)

Jelena Kostić

2015-12-01

Full Text Available Conduct disorder is a heterogeneous disorder in terms of etiology, course and prognosis, and currently, there is no singular model that would describe the development of the disorder. The results of empirical research on males confirm this heterogeneity, as they point out to two possible developmental pathways: childhood-onset and adolescentonset type. This paper presents the basic elements of developmental taxonomic theory which argues that there are two different developmental pathways to conduct disorder which have different causes and serve as the basis for the current typology of conduct disorders in the classification systems. Such a typology of conduct disorders in the diagnostic classification allows better understanding, prognosis and choice of treatment.

Heterogeneity of Loss Aversion in Pathological Gambling.

Science.gov (United States)

Takeuchi, Hideaki; Kawada, Ryosaku; Tsurumi, Kosuke; Yokoyama, Naoto; Takemura, Ariyoshi; Murao, Takuro; Murai, Toshiya; Takahashi, Hidehiko

2016-12-01

Pathological gambling (PG) is characterized by continual repeated gambling behavior despite negative consequences. PG is considered to be a disorder of altered decision-making under risk, and behavioral economics tools were utilized by studies on decision-making under risk. At the same time, PG was suggested to be a heterogeneous disorder in terms of personality traits as well as risk attitude. We aimed to examine the heterogeneity of PG in terms of loss aversion, which means that a loss is subjectively felt to be larger than the same amount of gain. Thirty-one male PG subjects and 26 male healthy control (HC) subjects underwent a behavioral economics task for estimation of loss aversion and personality traits assessment. Although loss aversion in PG subjects was not significantly different from that in HC subjects, distributions of loss aversion differed between PG and HC subjects. HC subjects were uniformly classified into three levels (low, middle, high) of loss aversion, whereas PG subjects were mostly classified into the two extremes, and few PG subjects were classified into the middle range. PG subjects with low and high loss aversion showed a significant difference in anxiety, excitement-seeking and craving intensity. Our study suggested that PG was a heterogeneous disorder in terms of loss aversion. This result might be useful for understanding cognitive and neurobiological mechanisms and the establishment of treatment strategies for PG.

Reliability and validity of the Persian lower extremity functional scale (LEFS) in a heterogeneous sample of outpatients with lower limb musculoskeletal disorders.

Science.gov (United States)

Negahban, Hossein; Hessam, Masumeh; Tabatabaei, Saeid; Salehi, Reza; Sohani, Soheil Mansour; Mehravar, Mohammad

2014-01-01

The aim was to culturally translate and validate the Persian lower extremity functional scale (LEFS) in a heterogeneous sample of outpatients with lower extremity musculoskeletal disorders (n = 304). This is a prospective methodological study. After a standard forward-backward translation, psychometric properties were assessed in terms of test-retest reliability, internal consistency, construct validity, dimensionality, and ceiling or floor effects. The acceptable level of intraclass correlation coefficient >0.70 and Cronbach's alpha coefficient >0.70 was obtained for the Persian LEFS. Correlations between Persian LEFS and Short-Form 36 Health Survey (SF-36) subscales of Physical Health component (rs range = 0.38-0.78) were higher than correlations between Persian LEFS and SF-36 subscales of Mental Health component (rs range = 0.15-0.39). A corrected item--total correlation of >0.40 (Spearman's rho) was obtained for all items of the Persian LEFS. Horn's parallel analysis detected a total of two factors. No ceiling or floor effects were detected for the Persian LEFS. The Persian version of the LEFS is a reliable and valid instrument that can be used to measure functional status in Persian-speaking patients with different musculoskeletal disorders of the lower extremity. Implications for Rehabilitation The Persian lower extremity functional scale (LEFS) is a reliable, internally consistent and valid instrument, with no ceiling or floor effects, to determine functional status of heterogeneous patients with musculoskeletal disorders of the lower extremity. The Persian version of the LEFS can be used in clinical and research settings to measure function in Iranian patients with different musculoskeletal disorders of the lower extremity.

Multiorgan fungal infection caused by Microsporum canis in a green iguana (Iguana iguana).

Science.gov (United States)

Chung, Tae-Ho; Kim, Eun-Ju; Choi, Ul Soo

2014-06-01

Multiple organ invasion by keratinophilic fungi in the green iguana (Iguana iguana) has not been previously reported. In this case, a 1-yr-old female green iguana presented with a nodular, darkly discolored skin lesion surrounded by necrosis in the right ventral abdominal region. A cytologic examination of the fine needle aspiration of the lesion revealed an exuberant proliferation of fibroblasts, macrophages, and multinucleated cells along with frequent filamentous structures consistent with hyphal elements. The necropsy revealed diffuse infiltration of the liver, lung, and cardiac apex with white nodules. A histopathologic examination of the lesions also confirmed a fungal infection associated with granulomatous inflammation. Rapid polymerase chain reaction (PCR) analysis of the chitin synthase 1 gene was conducted for rapid direct detection, and inter-simple sequence repeat fingerprinting was conducted to classify the infectious origin. The PCR analysis definitively demonstrated representative Microsporum canis fungus. The present report is the first case of disseminated M. canis infection with multiorgan involvement in a green iguana.

Eating disorders in children: is avoidant-restrictive food intake disorder a feeding disorder or an eating disorder and what are the implications for treatment?

Science.gov (United States)

Kennedy, Grace A; Wick, Madeline R; Keel, Pamela K

2018-01-01

Avoidant-restrictive food intake disorder (ARFID) is a current diagnosis in the "Feeding and Eating Disorders" section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) and captures a heterogeneous presentation of eating disturbances. In recent years, ARFID has been studied primarily within the context of eating disorders despite having historical roots as a feeding disorder. The following review examines ARFID's similarities with and differences from feeding disorders and eating disorders, focusing on research published within the last three years. Implications of this differentiation for treatment are discussed.

Alstrom syndrome: A rare genetic disorder and its anaesthetic significance

Directory of Open Access Journals (Sweden)

Akhilesh Tiwari

2010-01-01

Full Text Available Alstrom syndrome is a rare autosomal recessive disorder that was first described in 1959, by Carl Henry Alstrom, characterised by multiorgan system involvement ranging from ocular, aural, endocrinal, hepatorenal, gastrointestinal, respiratory and cardiac to the musculoskeletal system, among many others. It exposes the patient to various risks ranging from pulmonary aspiration and increased cardiac morbidity to separational anxiety, and may necessitate postoperative elective ventilation. We hereby present the successful management of one such diagnosed case in a 12-year-old boy, who presented to us for incision and drainage of an abscess present over the nape of his neck, along with foreign body removal from his right ear.

Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

Science.gov (United States)

Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

2017-01-01

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

Directory of Open Access Journals (Sweden)

R A Misgar

2017-01-01

Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

Comorbid Social Anxiety Disorder in Adults with Autism Spectrum Disorder

Science.gov (United States)

Maddox, Brenna B.; White, Susan W.

2015-01-01

Social anxiety symptoms are common among cognitively unimpaired youth with autism spectrum disorder (ASD). Few studies have investigated the co-occurrence of social anxiety disorder (SAD) in adults with ASD, although identification may aid access to effective treatments and inform our scientific efforts to parse heterogeneity. In this preliminary…

Eating disorders in children: is avoidant-restrictive food intake disorder a feeding disorder or an eating disorder and what are the implications for treatment? [version 1; referees: 2 approved

OpenAIRE

Grace A. Kennedy; Madeline R. Wick; Pamela K. Keel

2018-01-01

Avoidant-restrictive food intake disorder (ARFID) is a current diagnosis in the “Feeding and Eating Disorders” section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition) and captures a heterogeneous presentation of eating disturbances. In recent years, ARFID has been studied primarily within the context of eating disorders despite having historical roots as a feeding disorder. The following review examines ARFID’s similarities with and differences from feeding disord...

Are autism spectrum disorder and attention-deficit/hyperactivity disorder different manifestations of one overarching disorder? : Cognitive and symptom evidence from a clinical and population-based sample

NARCIS (Netherlands)

van der Meer, Jolanda M J; Oerlemans, Anoek M; van Steijn, Daphne J; Lappenschaar, Martijn G A; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2012-01-01

OBJECTIVE: Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Given the heterogeneity of both disorders, several more homogeneous ASD-ADHD comorbidity subgroups may exist. The current study examined whether such subgroups exist, and whether their

Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.

Science.gov (United States)

Zouboulis, Christos C; Lippert, Undine; Karagiannidis, Ioannis

2014-01-01

Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases. © 2014 S. Karger AG, Basel.

Advances in esophageal motor disorders.

Science.gov (United States)

Smout, André Jpm

2008-07-01

Esophageal motor disorders, often leading to dysphagia and chest pain, continue to pose diagnostic and therapeutic problems. In the past 12 months important new information regarding esophageal motor disorders was published. This information will be reviewed in this paper. A number of studies have addressed the issue of heterogeneity in achalasia, the best defined esophageal motility disorder. The spastic esophageal motility disorders nutcracker esophagus and diffuse esophageal spasm may coexist with gastroesophageal reflux disease, which has consequences for the management of patients with these disorders. The entity labelled ineffective esophageal motility is associated with reflux esophagitis, but also with morbid obesity. For the detection of disordered transit caused by ineffective esophageal motility, application of intraluminal impedance monitoring in conjunction with manometry leads to improved diagnosis. New data on the effect of Nissen fundoplication on esophageal motility were published during the last year. Recent knowledge on the heterogeneity of achalasia and the association of spastic esophageal motor disorders and ineffective motility with reflux disease will help the clinician in the management of patients with these disorders.

Clinical heterogeneity in Fabry disease

Directory of Open Access Journals (Sweden)

G. N. Salogub

2015-01-01

Full Text Available Fabry disease is an X-linked, lysosomal storage disease (OMIM: 301500, caused by α-galactosidase A deficiency, resulting in accumulation of its substrates, glycosphingolipids, primarily – globotriaosylceramide, in the lysosomes of multiple cell types with multi-system clinical manifestations, even within the same family, including abnormalities of the central and peripheral nervous system, kidneys, heart, gastrointestinal tract, lungs, organ of vision. Clinical heterogeneity is often the reason of the delayed diagnosis. Nowadays enzyme replacement therapy has proved its efficiency in the treatment of Fabry disease. Including Fabry disease in the differential diagnosis of a large range of disorders is important because of its wide clinical heterogeneity and the possibility of an earlier intervention with a beneficial treatment.

Are Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder Different Manifestations of One Overarching Disorder? Cognitive and Symptom Evidence from a Clinical and Population-Based Sample

Science.gov (United States)

van der Meer, Jolanda M. J.; Oerlemans, Anoek M.; van Steijn, Daphne J.; Lappenschaar, Martijn G. A.; de Sonneville, Leo M. J.; Buitelaar, Jan K.; Rommelse, Nanda N. J.

2012-01-01

Objective: Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Given the heterogeneity of both disorders, several more homogeneous ASD-ADHD comorbidity subgroups may exist. The current study examined whether such subgroups exist, and whether their overlap or distinctiveness in associated…

Neuropsychological heterogeneity in executive functioning in autism spectrum disorders

NARCIS (Netherlands)

Geurts, H.; Sinzig, J.; Booth, R.; Happé, F.

2014-01-01

In most research it is common to report results on a group level. For example, various studies report that children and adults with autism show executive function deficits. However, studies often differ in the pattern of findings. We believe this might be partly due to the heterogeneity of the

Maternal Preeclampsia and Neonatal Outcomes

Directory of Open Access Journals (Sweden)

Carl H. Backes

2011-01-01

Full Text Available Preeclampsia is a multiorgan, heterogeneous disorder of pregnancy associated with significant maternal and neonatal morbidity and mortality. Optimal strategies in the care of the women with preeclampsia have not been fully elucidated, leaving physicians with incomplete data to guide their clinical decision making. Because preeclampsia is a progressive disorder, in some circumstances, delivery is needed to halt the progression to the benefit of the mother and fetus. However, the need for premature delivery has adverse effects on important neonatal outcomes not limited to the most premature infants. Late-preterm infants account for approximately two thirds of all preterm deliveries and are at significant risk for morbidity and mortality. Reviewed is the current literature in the diagnosis and obstetrical management of preeclampsia, the outcomes of late-preterm infants, and potential strategies to optimize fetal outcomes in pregnancies complicated by preeclampsia.

Eating disorders in children: is avoidant-restrictive food intake disorder a feeding disorder or an eating disorder and what are the implications for treatment? [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Grace A. Kennedy

2018-01-01

Full Text Available Avoidant-restrictive food intake disorder (ARFID is a current diagnosis in the “Feeding and Eating Disorders” section of the Diagnostic and Statistical Manual of Mental Disorders (fifth edition and captures a heterogeneous presentation of eating disturbances. In recent years, ARFID has been studied primarily within the context of eating disorders despite having historical roots as a feeding disorder. The following review examines ARFID’s similarities with and differences from feeding disorders and eating disorders, focusing on research published within the last three years. Implications of this differentiation for treatment are discussed.

Lyme disease and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS: an overview

Directory of Open Access Journals (Sweden)

Rhee H

2012-02-01

Full Text Available Hanna Rhee1, Daniel J Cameron21Medicine, San Diego, CA, 2Northern Westchester Hospital, Mount Kisco, NY, USAAbstract: Lyme disease (LD is a complex, multisystemic illness. As the most common vector-borne disease in the United States, LD is caused by bacterial spirochete Borrelia burgdorferi sensu stricto, with potential coinfections from agents of anaplasmosis, babesiosis, and ehrlichiosis. Persistent symptoms and clinical signs reflect multiorgan involvement with episodes of active disease and periods of remission, not sparing the coveted central nervous system. The capability of microorganisms to cause and exacerbate various neuropsychiatric pathology is also seen in pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS, a recently described disorder attributed to bacterium Streptococcus pyogenes of group A beta-hemolytic streptococcus in which neurologic tics and obsessive-compulsive disorders are sequelae of the infection. In the current overview, LD and PANDAS are juxtaposed through a review of their respective infectious etiologies, clinical presentations, mechanisms of disease development, courses of illness, and treatment options. Future directions related to immunoneuropsychiatry are also discussed.Keywords: neuroborreliosis, infection, obsessive-compulsive disorder, tic disorder, Borrelia burgdorferi, strep throat

Psychogenetics of post-traumatic stress disorder: a short review

Directory of Open Access Journals (Sweden)

Ahmed Rady

2010-11-01

Full Text Available Ahmed Rady, Adel Elsheshai, Osama Elkholy, Heba Abou el WafaDepartment of Psychiatry, Alexandria University, Alexandria, EgyptAbstract: Post-traumatic stress disorder is a commonly overlooked psychiatric disorder due to the heterogeneity of symptoms that may simulate many other psychiatric disorders. Such heterogeneity of manifestations may be explained by the multifaceted nature of the different neurotransmitters, endocrinologic axis, and their genetic basis, that are implicated in the etiology. Although this disorder has been studied from many different perspectives, its etiology is still enigmatic. This minireview demonstrates, in brief, that different susceptibility genes are associated with post traumatic stress disorder.Keywords: trauma, post traumatic stress disorder, psychogenetic, stress response, neurobiology

Heterogeneity of late-life depression : relationship with cognitive functioning

NARCIS (Netherlands)

Korten, Nicole C M; Penninx, Brenda W J H; Kok, Rob M; Stek, Max L; Oude Voshaar, Richard C; Deeg, Dorly J H; Comijs, Hannie C

BACKGROUND: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. METHODS: Cross-sectional data of

Heterogeneity of late-life depression : relationship with cognitive functioning

NARCIS (Netherlands)

Korten, Nicole C. M.; Penninx, Brenda W. J. H.; Kok, Rob M.; Stek, Max L.; Oude Voshaar, Richard; Deeg, Dorly J. H.; Comijs, Hannie C.

Background: Late-life depression is a heterogeneous disorder, whereby cognitive impairments are often observed. This study examines which clinical characteristics and symptom dimensions of late-life depression are especially impacting on specific cognitive domains. Methods: Cross-sectional data of

Diagnostic heterogeneity in psychiatry : towards an empirical solution

NARCIS (Netherlands)

Wardenaar, Klaas J; de Jonge, Peter

2013-01-01

The launch of the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has sparked a debate about the current approach to psychiatric classification. The most basic and enduring problem of the DSM is that its classifications are heterogeneous clinical descriptions rather

Multi-organ damage induced by anabolic steroid supplements: a case report and literature review

Directory of Open Access Journals (Sweden)

Samaha Ali A

2008-10-01

Full Text Available Abstract Introduction The use of anabolic supplements and other related drugs for body building and to enhance athletic performance is nowadays widespread and acutely pervasive all around the world. This alarming increase in the use of anabolic and amino acid supplements has been linked to a diverse array of pathologies. As previously reported, the abuse of androgenic steroids is not without severe physiological, psychiatric and physical costs. The case we report here describes multi-organ damage resulting from the abuse and uncontrolled use of anabolic steroid supplements, mainly testosterone. Case presentation A 24-year-old white man presented with abdominal pain concomitant with nausea and vomiting. Laboratory analysis revealed hypercalcemia, elevated liver enzymes and high levels of amylase, lipase and creatine protein kinase. Conclusion Amino acid as well as anabolic supplements may lead to abnormal functioning of many organs, which could be fatal in some instances. This mandates worldwide and concerted efforts to educate the public, especially the youth, about the dangers of these increasingly abused drugs.

Development of Multiorgan Finite Element-Based Prostate Deformation Model Enabling Registration of Endorectal Coil Magnetic Resonance Imaging for Radiotherapy Planning

International Nuclear Information System (INIS)

Hensel, Jennifer M.; Menard, Cynthia; Chung, Peter W.M.; Milosevic, Michael F.; Kirilova, Anna; Moseley, Joanne L.; Haider, Masoom A.; Brock, Kristy K.

2007-01-01

Purpose: Endorectal coil (ERC) magnetic resonance imaging (MRI) provides superior visualization of the prostate compared with computed tomography at the expense of deformation. This study aimed to develop a multiorgan finite element deformable method, Morfeus, to accurately co-register these images for radiotherapy planning. Methods: Patients with prostate cancer underwent fiducial marker implantation and computed tomography simulation for radiotherapy planning. A series of axial MRI scans were acquired with and without an ERC. The prostate, bladder, rectum, and pubic bones were manually segmented and assigned linear elastic material properties. Morfeus mapped the surface of the bladder and rectum between two imaged states, calculating the deformation of the prostate through biomechanical properties. The accuracy of deformation was measured as fiducial marker error and residual surface deformation between the inferred and actual prostate. The deformation map was inverted to deform from 100 cm 3 to no coil. Results: The data from 19 patients were analyzed. Significant prostate deformation occurred with the ERC (mean intrapatient range, 0.88 ± 0.25 cm). The mean vector error in fiducial marker position (n = 57) was 0.22 ± 0.09 cm, and the mean vector residual surface deformation (n = 19) was 0.15 ± 0.06 cm for deformation from no coil to 100-cm 3 ERC, with an image vector resolution of 0.22 cm. Accurately deformed MRI scans improved soft-tissue resolution of the anatomy for radiotherapy planning. Conclusions: This method of multiorgan deformable registration enabled accurate co-registration of ERC-MRI scans with computed tomography treatment planning images. Superior structural detail was visible on ERC-MRI, which has potential for improving target delineation

EARLY DIAGNOSIS OF IMMUNE DISTURBANCES AND ITS CORRECTION IN THE TREATMENT OF MULTIORGAN FAILURE AND SEPTIC COMPLICATIONS AFTER OPERATIONS WITH ARTIFICIAL AND ASSIST CIRCULATION

Directory of Open Access Journals (Sweden)

V. S. Suskova

2009-01-01

Full Text Available The study has shown that early diagnosis of the type and degree of immune disturbances in preparation for the operation and the first signs of multiorgan failure and septic complications in the postoperative period in cardiac surgery patients were the rationale for the earlier substitution immunocorrection by immunomodulators of cytokine nature and intravenous immunoglobulin. It allowed increasing the efficiency of the treatment of postoperative complications and lower mortality after operations with artificial and assist circulation. 

Family Studies of Sensorimotor and Neurocognitive Heterogeneity Spectrum Disorders (ASD)

Science.gov (United States)

2012-09-01

attention deficit / hyperactivity disorder ( ADHD ) behaviors in individuals ages 18 and older. ii. Conners 3rd Edition (Conners 3) is a screening...questionnaire that uses observer and self-report ratings to assess attention deficit / hyperactivity disorder ( ADHD ) and evaluate problem behavior in... deficits in these disorders . II: BODY a. Overall Progress. We have successfully completed each of the first year tasks laid out in our original

Co-occurring manic symptomatology as a dimension which may help explaining heterogeneity of depression

NARCIS (Netherlands)

Jabben, Nienke; Penninx, Brenda; Beekman, Aartjan T. F.; Smit, Johannes H.; Nolen, Willem A.

Background: The dichotomous distinction between unipolar and bipolar disorders may be challenged by heterogeneity within diagnoses and overlap between different diagnoses. A broad mood disorder category in which patients differ as a result of variation along separate manic and depressive mood

Characterizing heterogeneous dynamics at hydrated electrode surfaces

Science.gov (United States)

Willard, Adam P.; Limmer, David T.; Madden, Paul A.; Chandler, David

2013-05-01

In models of Pt 111 and Pt 100 surfaces in water, motions of molecules in the first hydration layer are spatially and temporally correlated. To interpret these collective motions, we apply quantitative measures of dynamic heterogeneity that are standard tools for considering glassy systems. Specifically, we carry out an analysis in terms of mobility fields and distributions of persistence times and exchange times. In so doing, we show that dynamics in these systems is facilitated by transient disorder in frustrated two-dimensional hydrogen bonding networks. The frustration is the result of unfavorable geometry imposed by strong metal-water bonding. The geometry depends upon the structure of the underlying metal surface. Dynamic heterogeneity of water on the Pt 111 surface is therefore qualitatively different than that for water on the Pt 100 surface. In both cases, statistics of this ad-layer dynamic heterogeneity responds asymmetrically to applied voltage.

Characterizing heterogeneous dynamics at hydrated electrode surfaces.

Science.gov (United States)

Willard, Adam P; Limmer, David T; Madden, Paul A; Chandler, David

2013-05-14

In models of Pt 111 and Pt 100 surfaces in water, motions of molecules in the first hydration layer are spatially and temporally correlated. To interpret these collective motions, we apply quantitative measures of dynamic heterogeneity that are standard tools for considering glassy systems. Specifically, we carry out an analysis in terms of mobility fields and distributions of persistence times and exchange times. In so doing, we show that dynamics in these systems is facilitated by transient disorder in frustrated two-dimensional hydrogen bonding networks. The frustration is the result of unfavorable geometry imposed by strong metal-water bonding. The geometry depends upon the structure of the underlying metal surface. Dynamic heterogeneity of water on the Pt 111 surface is therefore qualitatively different than that for water on the Pt 100 surface. In both cases, statistics of this ad-layer dynamic heterogeneity responds asymmetrically to applied voltage.

Estimation of the frequency of occult mutations for an autosomal recessive disease in the presence of genetic heterogeneity: application to genetic hearing loss disorders.

Science.gov (United States)

Kimberling, William J

2005-11-01

The routine testing for pathologic mutation(s) in a patient's DNA has become the foundation of modern molecular genetic diagnosis. It is especially valuable when the phenotype shows genetic heterogeneity, and its importance will grow as treatments become genotype specific. However, the technology of mutation detection is imperfect and mutations are often missed. This can be especially troublesome when dealing with a recessive disorder where the combination of genetic heterogeneity and missed mutation creates an imprecision in the genotypic assessment of individuals who do not appear to have the expected complement of two pathologic mutations. This article describes a statistical approach to the estimation of the likelihood of a genetic diagnosis under these conditions. In addition to providing a means of testing for missed mutations, it also provides a method of estimating and testing for the presence of genetic heterogeneity in the absence of linkage data. Gene frequencies as well as estimates of sensitivity and specificity can be obtained as well. The test is applied to GJB2 recessive nonsyndromic deafness, Usher syndrome types Ib and IIa, and Pendred-enlarged vestibular aqueduct syndrome. Copyright 2005 Wiley-Liss, Inc.

Spatially heterogeneous ages in glassy dynamics

International Nuclear Information System (INIS)

Castillo, Horacio E.; Chamon, Claudio Chamon; Cugliandolo, Leticia F.; Iguain, Jose Luis; Kennett, Malcolm P.

2003-09-01

We construct a framework for the study of fluctuations in the nonequilibrium relaxation of glassy systems with and without quenched disorder. We study two types of two-time local correlators with the aim of characterizing the heterogeneous evolution in these systems: in one case we average the local correlators over histories of the thermal noise, in the other case we simply coarse-grain the local correlators obtained for a given noise realization. We explain why the noise-averaged correlators describe the fingerprint of quenched disorder when it exists, while the coarse-grained correlators are linked to noise-induced mesoscopic fluctuations. We predict constraints on the distribution of the fluctuations of the coarse-grained quantities. In particular, we show that locally defined correlations and responses are connected by a generalized local out-of-equilibrium fluctuation-dissipation relation. We argue that large size heterogeneities in the age of the system survive in the long-time limit. A symmetry of the underlying theory, namely invariance under reparametrizations of the time coordinates, underlies these results. We establish a connection between the probabilities of spatial distributions of local coarse-grained quantities and the theory of dynamic random manifolds. We define, and discuss the behavior of, a two-time dependent correlation length from the spatial decay of the fluctuations in the two-time local functions. We characterize the fluctuations in the system in terms of their fractal properties. For concreteness, we present numerical tests performed on disordered spin models in finite and infinite dimensions. Finally, we explain how these ideas can be applied to the analysis of the dynamics of other glassy systems that can be either spin models without disorder or atomic and molecular glassy systems. (author)

Clinical and Biochemical Pitfalls in the Diagnosis of Peroxisomal Disorders

NARCIS (Netherlands)

Klouwer, Femke C. C.; Huffnagel, Irene C.; Ferdinandusse, Sacha; Waterham, Hans R.; Wanders, Ronald J. A.; Engelen, Marc; Poll-The, Bwee Tien

2016-01-01

Peroxisomal disorders are a heterogeneous group of genetic metabolic disorders, caused by a defect in peroxisome biogenesis or a deficiency of a single peroxisomal enzyme. The peroxisomal disorders include the Zellweger spectrum disorders, the rhizomelic chondrodysplasia punctata spectrum disorders,

Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic challenge.

Science.gov (United States)

Lynch, Henry T; Lanspa, Stephen; Shaw, Trudy; Casey, Murray Joseph; Rendell, Marc; Stacey, Mark; Townley, Theresa; Snyder, Carrie; Hitchins, Megan; Bailey-Wilson, Joan

2018-07-01

Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer. It is caused by germline mutations in the mismatch repair genes. Both its phenotype and genotype show marked heterogeneity. This review gives a historical overview of the syndrome, its heterogeneity, its genomic landscape, and its implications for complex diagnosis, genetic counseling and putative implications for immunotherapy.

Genotype-Phenotype Correlation of Maternally Inherited Disorders due to Mutations in Mitochondrial DNA

Directory of Open Access Journals (Sweden)

Peterus Thajeb

2006-09-01

Full Text Available Mitochondrial disorders are heterogeneous systemic ailments that are most often caused by maternal inheritance of a variety of mutations of the mitochondrial (mt DNA. Paternal inheritance and somatic mutation are rare. The disorders are well recognized not only for the genotypic heterogeneity, but also the phenotypic variation among the affected members of a single family. The genotype-phenotype correlation of the diversity of the syndromic and non-syndromic features of mitochondrial disorders are discussed. Some aspects of the molecular mechanisms of this heterogeneity, and the histopathologic findings are highlighted.

Abdominal multi-organ CT segmentation using organ correlation graph and prediction-based shape and location priors.

Science.gov (United States)

Okada, Toshiyuki; Linguraru, Marius George; Hori, Masatoshi; Summers, Ronald M; Tomiyama, Noriyuki; Sato, Yoshinobu

2013-01-01

The paper addresses the automated segmentation of multiple organs in upper abdominal CT data. We propose a framework of multi-organ segmentation which is adaptable to any imaging conditions without using intensity information in manually traced training data. The features of the framework are as follows: (1) the organ correlation graph (OCG) is introduced, which encodes the spatial correlations among organs inherent in human anatomy; (2) the patient-specific organ shape and location priors obtained using OCG enable the estimation of intensity priors from only target data and optionally a number of untraced CT data of the same imaging condition as the target data. The proposed methods were evaluated through segmentation of eight abdominal organs (liver, spleen, left and right kidney, pancreas, gallbladder, aorta, and inferior vena cava) from 86 CT data obtained by four imaging conditions at two hospitals. The performance was comparable to the state-of-the-art method using intensity priors constructed from manually traced data.

Review: The nucleation of disorder

International Nuclear Information System (INIS)

Cahn, R.W.; Johnson, W.L.

1986-01-01

Four types of phase transformation that involve the conversion of crystalline phases into more disordered forms are reviewed: melting, disordering of superlattices, amorphization by diffusion between crystalline phases, and irradation amorphization. In the review emphasis is placed on evidence for the heterogeneous nucleation of the product phases; in this connection, the role of surfaces, antiphase domain boundaries, dislocations, vacancies, and grain boundaries is specifically discussed. All of these features have been either observed, or hypothesized, to play a role as heterogeneous nucleation sites in one or more of the four transformations. An attempt is made to draw parallels between nucleation mechanisms in the various processes

Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS Guidelines.

Science.gov (United States)

Parker, Anne; Bowles, Kristin; Bradley, J Andrew; Emery, Vincent; Featherstone, Carrie; Gupte, Girish; Marcus, Robert; Parameshwar, Jayan; Ramsay, Alan; Newstead, Charles

2010-06-01

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Transplantation Society (BTS) has reviewed the available literature and made recommendations for the diagnosis and management of post-transplant lymphoproliferative disorder in adult recipients of solid organ transplants. This review details the therapeutic options recommended including reduction in immunosuppression (RIS), transplant organ resection, radiotherapy and chemotherapy. Effective therapy should be instituted before progressive disease results in declining performance status and multi-organ dysfunction. The goal of treatment should be a durable complete remission with retention of transplanted organ function with minimal toxicity.

Quantifying heterogeneity attributable to polythetic diagnostic criteria: theoretical framework and empirical application.

Science.gov (United States)

Olbert, Charles M; Gala, Gary J; Tupler, Larry A

2014-05-01

Heterogeneity within psychiatric disorders is both theoretically and practically problematic: For many disorders, it is possible for 2 individuals to share very few or even no symptoms in common yet share the same diagnosis. Polythetic diagnostic criteria have long been recognized to contribute to this heterogeneity, yet no unified theoretical understanding of the coherence of symptom criteria sets currently exists. A general framework for analyzing the logical and mathematical structure, coherence, and diversity of Diagnostic and Statistical Manual diagnostic categories (DSM-5 and DSM-IV-TR) is proposed, drawing from combinatorial mathematics, set theory, and information theory. Theoretical application of this framework to 18 diagnostic categories indicates that in most categories, 2 individuals with the same diagnosis may share no symptoms in common, and that any 2 theoretically possible symptom combinations will share on average less than half their symptoms. Application of this framework to 2 large empirical datasets indicates that patients who meet symptom criteria for major depressive disorder and posttraumatic stress disorder tend to share approximately three-fifths of symptoms in common. For both disorders in each of the datasets, pairs of individuals who shared no common symptoms were observed. Any 2 individuals with either diagnosis were unlikely to exhibit identical symptomatology. The theoretical and empirical results stemming from this approach have substantive implications for etiological research into, and measurement of, psychiatric disorders.

Heterogeneity in 10-Year Course Trajectories of Moderate to Severe Major Depressive Disorder: A Danish National Register-Based Study.

Science.gov (United States)

Musliner, Katherine L; Munk-Olsen, Trine; Laursen, Thomas M; Eaton, William W; Zandi, Peter P; Mortensen, Preben B

2016-04-01

Evidence suggests that long-term trajectories of major depressive disorder (MDD) are heterogeneous. The Danish Psychiatric Central Research Register (DPCRR) provides a rare opportunity to examine patterns and correlates of long-term trajectories in a large sample of patients with moderate to severe MDD. To characterize patterns and correlates of 10-year course trajectories of MDD in the DPCRR. A cohort containing 11 640 individuals born in Denmark in 1955 or later with their first recorded MDD diagnosis in the DPCRR between 1995 and 2002 was established. Patients were followed for 10 years from the date of their initial MDD diagnosis. Data were obtained from Danish civil and psychiatric national registers in June 2013 and were analyzed from April 4, 2014, to December 17, 2015. Correlates of trajectory class membership were sex, characteristics of the first recorded MDD episode (ie, age, severity, inpatient treatment, and record of suicide attempt or self-harm), and psychiatric diagnoses in parents (ie, depression, bipolar disorder, schizophrenia-spectrum disorders, substance abuse, and anxiety or somatoform disorders). The outcome variable was past-year contact at a psychiatric hospital with a main diagnosis of MDD during each of the 10 years following the initial MDD diagnosis. Trajectories were modeled using latent class growth analysis. The sample included 11 640 individuals (7493 [64.4%] women) aged 18 to 48 years (mean [SD], 31.4 [7.3]) at their first recorded MDD diagnosis. Four trajectory classes were identified: brief contact (77.0%) (characterized by low probability of contact after 2 years); prolonged initial contact (12.8%) (characterized by high decreasing probability of contact during the first 5 years); later reentry (7.1%) (characterized by moderate probability of contact during the second 5 years); and persistent contact (3.1%) (characterized by high or moderate probability of contact throughout). Female sex (odds ratio [OR] range, 1

Ambient air pollution and pregnancy-induced hypertensive disorders

DEFF Research Database (Denmark)

Pedersen, Marie; Stayner, Leslie; Slama, Rémy

2014-01-01

to ambient air pollution and pregnancy-induced hypertensive disorders including gestational hypertension and preeclampsia. We searched electronic databases for English language studies reporting associations between ambient air pollution and pregnancy-induced hypertensive disorders published between December.......5), carbon monoxide (CO), ozone (O3), proximity to major roads, and traffic density met our inclusion criteria. Most studies reported that air pollution increased risk for pregnancy-induced hypertensive disorders. There was significant heterogeneity in meta-analysis, which included 16 studies reporting...... on gestational hypertension and preeclampsia as separate or combined outcomes; there was less heterogeneity in findings of the 10 studies reporting solely on preeclampsia. Meta-analyses showed increased risks of hypertensive disorders in pregnancy for all pollutants except CO. Random-effect meta...

Autism Spectrum Disorders Associated with Chromosomal Abnormalities

Science.gov (United States)

Lo-Castro, Adriana; Benvenuto, Arianna; Galasso, Cinzia; Porfirio, Cristina; Curatolo, Paolo

2010-01-01

Autism spectrum disorders (ASDs) constitute a class of severe neurodevelopmental conditions with complex multifactorial and heterogeneous etiology. Despite high estimates of heritability, genetic causes of ASDs remain elusive, due to a high degree of genetic and phenotypic heterogeneity. So far, several "monogenic" forms of autism have been…

Attention network functioning in children with anxiety disorders, attention-deficit/hyperactivity disorder and non-clinical anxiety.

Science.gov (United States)

Mogg, K; Salum, G A; Bradley, B P; Gadelha, A; Pan, P; Alvarenga, P; Rohde, L A; Pine, D S; Manfro, G G

2015-01-01

Research with adults suggests that anxiety is associated with poor control of executive attention. However, in children, it is unclear (a) whether anxiety disorders and non-clinical anxiety are associated with deficits in executive attention, (b) whether such deficits are specific to anxiety versus other psychiatric disorders, and (c) whether there is heterogeneity among anxiety disorders (in particular, specific phobia versus other anxiety disorders). We examined executive attention in 860 children classified into three groups: anxiety disorders (n = 67), attention-deficit/hyperactivity disorder (ADHD; n = 67) and no psychiatric disorder (n = 726). Anxiety disorders were subdivided into: anxiety disorders excluding specific phobia (n = 43) and specific phobia (n = 21). The Attention Network Task was used to assess executive attention, alerting and orienting. Findings indicated heterogeneity among anxiety disorders, as children with anxiety disorders (excluding specific phobia) showed impaired executive attention, compared with disorder-free children, whereas children with specific phobia showed no executive attention deficit. Among disorder-free children, executive attention was less efficient in those with high, relative to low, levels of anxiety. There were no anxiety-related deficits in orienting or alerting. Children with ADHD not only had poorer executive attention than disorder-free children, but also higher orienting scores, less accurate responses and more variable response times. Impaired executive attention in children (reflected by difficulty inhibiting processing of task-irrelevant information) was not fully explained by general psychopathology, but instead showed specific associations with anxiety disorders (other than specific phobia) and ADHD, as well as with high levels of anxiety symptoms in disorder-free children.

Multiple Spatial Coherence Resonances and Spatial Patterns in a Noise-Driven Heterogeneous Neuronal Network

International Nuclear Information System (INIS)

Li Yu-Ye; Ding Xue-Li

2014-01-01

Heterogeneity of the neurons and noise are inevitable in the real neuronal network. In this paper, Gaussian white noise induced spatial patterns including spiral waves and multiple spatial coherence resonances are studied in a network composed of Morris—Lecar neurons with heterogeneity characterized by parameter diversity. The relationship between the resonances and the transitions between ordered spiral waves and disordered spatial patterns are achieved. When parameter diversity is introduced, the maxima of multiple resonances increases first, and then decreases as diversity strength increases, which implies that the coherence degrees induced by noise are enhanced at an intermediate diversity strength. The synchronization degree of spatial patterns including ordered spiral waves and disordered patterns is identified to be a very low level. The results suggest that the nervous system can profit from both heterogeneity and noise, and the multiple spatial coherence resonances are achieved via the emergency of spiral waves instead of synchronization patterns. (interdisciplinary physics and related areas of science and technology)

Multiple Spatial Coherence Resonances and Spatial Patterns in a Noise-Driven Heterogeneous Neuronal Network

Science.gov (United States)

Li, Yu-Ye; Ding, Xue-Li

2014-12-01

Heterogeneity of the neurons and noise are inevitable in the real neuronal network. In this paper, Gaussian white noise induced spatial patterns including spiral waves and multiple spatial coherence resonances are studied in a network composed of Morris—Lecar neurons with heterogeneity characterized by parameter diversity. The relationship between the resonances and the transitions between ordered spiral waves and disordered spatial patterns are achieved. When parameter diversity is introduced, the maxima of multiple resonances increases first, and then decreases as diversity strength increases, which implies that the coherence degrees induced by noise are enhanced at an intermediate diversity strength. The synchronization degree of spatial patterns including ordered spiral waves and disordered patterns is identified to be a very low level. The results suggest that the nervous system can profit from both heterogeneity and noise, and the multiple spatial coherence resonances are achieved via the emergency of spiral waves instead of synchronization patterns.

BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

Directory of Open Access Journals (Sweden)

Sara V. Bates

2013-10-01

Full Text Available Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH, positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH.

Reward and aversion in a heterogeneous midbrain dopamine system.

Science.gov (United States)

Lammel, Stephan; Lim, Byung Kook; Malenka, Robert C

2014-01-01

The ventral tegmental area (VTA) is a heterogeneous brain structure that serves a central role in motivation and reward processing. Abnormalities in the function of VTA dopamine (DA) neurons and the targets they influence are implicated in several prominent neuropsychiatric disorders including addiction and depression. Recent studies suggest that the midbrain DA system is composed of anatomically and functionally heterogeneous DA subpopulations with different axonal projections. These findings may explain a number of previously confusing observations that suggested a role for DA in processing both rewarding as well as aversive events. Here we will focus on recent advances in understanding the neural circuits mediating reward and aversion in the VTA and how stress as well as drugs of abuse, in particular cocaine, alter circuit function within a heterogeneous midbrain DA system. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump.

Science.gov (United States)

Umakanthan, Ramanan; Dubose, Robert; Byrne, John G; Ahmad, Rashid M

2010-10-01

The management of acute myocardial infarction with resultant acute ischemic mitral regurgitation and acute multi-organ failure can prove to be a very challenging scenario. The presence of concomitant vascular disease can only serve to further compromise the complexity of the situation. We demonstrate a new indication for the transthoracic intra-aortic balloon pump as a preoperative means of unloading the heart and improving clinical outcome in such high-risk patients with severe vascular disease. We present the case of a 75-year-old man with a history of severe vascular disease who was transferred emergently to Vanderbilt University Medical Center with an acute inferolateral wall myocardial infarction resulting in severe acute ischemic mitral regurgitation and acute multi-organ failure. He presented with shock liver (serum glutamic-oxaloacetic transaminase [SGOT] of 958), renal failure (creatinine of 3.0), and respiratory failure with a pH of 7.18. Emergent cardiac catheterization revealed 100% occlusion of the left circumflex artery as well as severe ileofemoral disease. The advanced nature of his ileofemoral disease was such that the arterial access catheter occluded the right femoral artery. The duration of time that the catheter was in the artery led to transient limb ischemia with an elevation of his creatine phosphokinase (CPK) to 10,809. Balloon angioplasty followed by stent placement was successfully performed, which restored flow to the coronary vessel. Given the grave nature of the patient's condition, we were very concerned that immediate operative intervention for his condition would entail prohibitively high risk. In fact, the Society of Thoracic Surgeons predicted risk adjusted mortality was calculated to be 56%. In order to minimize patient mortality and morbidity, it was critical to help restore perfusion and organ recovery. Therefore, we decided that the chances for this patient's survival would improve if his condition could be optimized by

Nanoscale heterogeneity at the aqueous electrolyte-electrode interface

Science.gov (United States)

Limmer, David T.; Willard, Adam P.

2015-01-01

Using molecular dynamics simulations, we reveal emergent properties of hydrated electrode interfaces that while molecular in origin are integral to the behavior of the system across long times scales and large length scales. Specifically, we describe the impact of a disordered and slowly evolving adsorbed layer of water on the molecular structure and dynamics of the electrolyte solution adjacent to it. Generically, we find that densities and mobilities of both water and dissolved ions are spatially heterogeneous in the plane parallel to the electrode over nanosecond timescales. These and other recent results are analyzed in the context of available experimental literature from surface science and electrochemistry. We speculate on the implications of this emerging microscopic picture on the catalytic proficiency of hydrated electrodes, offering a new direction for study in heterogeneous catalysis at the nanoscale.

Conduction and Narrow Escape in Dense, Disordered, Particulate-based Heterogeneous Materials

Science.gov (United States)

Lechman, Jeremy

For optimal and reliable performance, many technological devices rely on complex, disordered heterogeneous or composite materials and their associated manufacturing processes. Examples include many powder and particulate-based materials found in phyrotechnic devices for car airbags, electrodes in energy storage devices, and various advanced composite materials. Due to their technological importance and complex structure, these materials have been the subject of much research in a number of fields. Moreover, the advent of new manufacturing techniques based on powder bed and particulate process routes, the potential of functional nano-structured materials, and the additional recognition of persistent shortcomings in predicting reliable performance of high consequence applications; leading to ballooning costs of fielding and maintaining advanced technologies, should motivate renewed efforts in understanding, predicting and controlling these materials' fabrication and behavior. Our particular effort seeks to understand the link between the top-down control presented in specific non-equilibrium processes routes (i.e., manufacturing processes) and the variability and uncertainty of the end product performance. Our ultimate aim is to quantify the variability inherent in these constrained dynamical or random processes and to use it to optimize and predict resulting material properties/performance and to inform component design with precise margins. In fact, this raises a set of deep and broad-ranging issues that have been recognized and as touching the core of a major research challenge at Sandia National Laboratories. In this talk, we will give an overview of recent efforts to address aspects of this vision. In particular the case of conductive properties of packed particulate materials will be highlighted. Combining a number of existing approaches we will discuss new insights and potential directions for further development toward the stated goal. Sandia National

Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders

Science.gov (United States)

Polla, Daniel L.; Cardoso, Maria T. O.; Silva, Mayara C. B.; Cardoso, Isabela C. C.; Medina, Cristina T. N.; Araujo, Rosenelle; Fernandes, Camila C.; Reis, Alessandra M. M.; de Andrade, Rosangela V.; Pereira, Rinaldo W.; Pogue, Robert

2015-01-01

Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known. PMID:26380986

Geological entropy and solute transport in heterogeneous porous media

Science.gov (United States)

Bianchi, Marco; Pedretti, Daniele

2017-06-01

We propose a novel approach to link solute transport behavior to the physical heterogeneity of the aquifer, which we fully characterize with two measurable parameters: the variance of the log K values (σY2), and a new indicator (HR) that integrates multiple properties of the K field into a global measure of spatial disorder or geological entropy. From the results of a detailed numerical experiment considering solute transport in K fields representing realistic distributions of hydrofacies in alluvial aquifers, we identify empirical relationship between the two parameters and the first three central moments of the distributions of arrival times of solute particles at a selected control plane. The analysis of experimental data indicates that the mean and the variance of the solutes arrival times tend to increase with spatial disorder (i.e., HR increasing), while highly skewed distributions are observed in more orderly structures (i.e., HR decreasing) or at higher σY2. We found that simple closed-form empirical expressions of the bivariate dependency of skewness on HR and σY2 can be used to predict the emergence of non-Fickian transport in K fields considering a range of structures and heterogeneity levels, some of which based on documented real aquifers. The accuracy of these predictions and in general the results from this study indicate that a description of the global variability and structure of the K field in terms of variance and geological entropy offers a valid and broadly applicable approach for the interpretation and prediction of transport in heterogeneous porous media.

The serotonin transporter in psychiatric disorders

DEFF Research Database (Denmark)

Spies, Marie; Knudsen, Karen Birgitte Moos; Lanzenberger, Rupert

2015-01-01

Over the past 20 years, psychotropics affecting the serotonergic system have been used extensively in the treatment of psychiatric disorders. Molecular imaging, in particular PET, has allowed for elucidation of the essential contribution of the serotonin transporter to the pathophysiology...... of various psychiatric disorders and their treatment. We review studies that use PET to measure cerebral serotonin transporter activity in psychiatric disorders, focusing on major depressive disorder and antidepressant treatment. We also discuss opportunities and limitations in the application...... of this neuroimaging method in clinical practice. Although results from individual studies diverge, meta-analysis indicates a trend towards reduced serotonin transporter availability in patients with major depressive disorder. Inconsistencies in results might suggest symptom heterogeneity in major depressive disorder...

A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region.

Science.gov (United States)

Liu, Xiaohua; Kelsoe, John R; Greenwood, Tiffany A

2016-01-01

Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10(-8) for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10(-6) for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10(-7) and 4.3×10(-6), respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness. Copyright © 2015 Elsevier B.V. All rights reserved.

The heterogeneous gas with singular interaction: generalized circular law and heterogeneous renormalized energy

International Nuclear Information System (INIS)

Molino, Luis Carlos García del; Pakdaman, Khashayar; Touboul, Jonathan

2015-01-01

We introduce and analyze d-dimensional Coulomb gases with random charge distribution and general external confining potential. We show that these gases satisfy a large-deviation principle. The analysis of the minima of the rate function (which is the leading term of the energy) reveals that, at equilibrium, the particle distribution is a generalized circular law (i.e. with spherical support but not necessarily uniform distribution). In the classical electrostatic external potential, there are infinitely many minimizers of the rate function. The most likely macroscopic configuration is a disordered distribution in which particles are uniformly distributed (for d = 2, the circular law), and charges are independent of the positions of the particles. General charge-dependent confining potentials unfold this degenerate situation: in contrast, the particle density is not uniform, and particles spontaneously organize according to their charge. In this picture the classical electrostatic potential appears as a transition at which order is lost. Sub-leading terms of the energy are derived: we show that these are related to an operator, generalizing the Coulomb renormalized energy, which incorporates the heterogeneous nature of the charges. This heterogeneous renormalized energy informs us about the microscopic arrangements of the particles, which are non-standard, strongly dependent on the charges, and include progressive and irregular lattices. (paper)

MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis

Directory of Open Access Journals (Sweden)

Yunyan Zhang

2014-01-01

Conclusions: Tissue heterogeneity may be a potential measure of functional outcome in ON patients and advanced analysis of the texture in standard MRI could provide insights into mechanisms of injury and recovery in patients with similar disorders.

Bare lymphocyte syndrome: imaging findings in an adult

International Nuclear Information System (INIS)

Bernaerts, A.; Vandevenne, J.E.; De Schepper, A.M.; Lambert, J.; De Clerck, L.S.

2001-01-01

Bare lymphocyte syndrome (BLS) is a rare primary immune disorder characterized by defective expression of human leukocyte antigen (HLA) on lymphocytes, often resulting in extensive and recurrent multi-organ infections. We describe a previously undiagnosed case of an adult woman who presented with radiological findings of severe bronchiectases, near-total granulomatous destruction of facial bones, and osteomyelitis. Diagnosis of BLS should be considered when evaluating children with unexplained bronchiectases or adults with long history of chronic multi-organ infections. (orig.)

Neuropsychological Functioning in Childhood-Onset Psychosis and Attention-Deficit/Hyperactivity Disorder

Science.gov (United States)

Brodsky, Kimberly; Willcutt, Erik G.; Davalos, Deana B.; Ross, Randal G.

2014-01-01

Background: Attention-deficit/hyperactivity disorder (ADHD) and childhood-onset psychosis (COP) are chronic, heterogeneous disorders with symptoms that frequently co-occur, but the etiology of their comorbidity is unknown. Studies of each disorder indicate that both ADHD and COP are associated with a range of neuropsychological weaknesses, but few…

Esophageal motility disorders

International Nuclear Information System (INIS)

Hannig, C.; Rummeny, E.; Wuttge-Hannig, A.

2007-01-01

For the better understanding of esophageal motility, the muscle texture and the distribution of skeletal and smooth muscle fibers in the esophagus are of crucial importance. Esophageal physiology will be shortly mentioned as far as necessary for a comprehensive understanding of peristaltic disturbances. Besides the pure depiction of morphologic criteria, a complete esophageal study has to include an analysis of the motility. New diagnostic tools with reduced radiation for dynamic imaging (digital fluoroscopy, videofluoroscopy) at 4-30 frames/s are available. Radiomanometry is a combination of a functional pressure measurement and a simultaneous dynamic morphologic analysis. Esophageal motility disorders are subdivided by radiologic and manometric criteria into primary, secondary, and nonclassifiable forms. Primary motility disorders of the esophagus are achalasia, diffuse esophageal spasm, nutcracker esophagus, and the hypertonic lower esophageal sphincter. The secondary motility disorders include pseudoachalasia, reflux-associated motility disorders, functionally caused impactions, Boerhaave's syndrome, Chagas' disease, scleroderma, and presbyesophagus. The nonclassificable motility disorders (NEMD) are a very heterogeneous collective. (orig.) [de

Clinical Heterogeneity in Patients with the Hypermobility Type of Ehlers-Danlos Syndrome

Science.gov (United States)

De Wandele, Inge; Rombaut, Lies; Malfait, Fransiska; De Backer, Tine; De Paepe, Anne; Calders, Patrick

2013-01-01

EDS-HT is a connective tissue disorder characterized by large inter-individual differences in the clinical presentation, complicating diagnosis and treatment. We aim to describe the clinical heterogeneity and to investigate whether differences in the symptom profile are also reflected as disparity in functional impairment and pain experience. In…

Beyond Symptom Counts for Diagnosing Oppositional Defiant Disorder and Conduct Disorder?

Science.gov (United States)

Lindhiem, Oliver; Bennett, Charles B; Hipwell, Alison E; Pardini, Dustin A

2015-10-01

Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD) are among the most commonly diagnosed childhood behavioral health disorders. Although there is substantial evidence of heterogeneity of symptom presentations, DSM diagnoses of CD and ODD are formally diagnosed on the basis of symptom counts without regard to individual symptom patterns. We used unidimensional item response theory (IRT) two-parameter logistic (2PL) models to examine item parameters for the individual symptoms of CD and ODD using data on 6,491 adolescents (ages 13-17) from the National Comorbidity Study: Adolescent Supplement (NCS-A). For each disorder, the symptoms differed in terms of severity and discrimination parameters. As a result, some adolescents who were above DSM diagnostic thresholds for disruptive behavior disorders exhibited lower levels of the underlying construct than others below the thresholds, based on their unique symptom profile. In terms of incremental benefit, our results suggested an advantage of latent trait scores for CD but not ODD.

Alpha-linolenic acid-enriched diacylglycerol oil does not promote tumor development in tongue and gastrointestinal tract tissues in a medium-term multi-organ carcinogenesis bioassay using male F344 rat.

Science.gov (United States)

Honda, Hiroshi; Kawamoto, Taisuke; Doi, Yuko; Matsumura, Shoji; Ito, Yuichi; Imai, Norio; Ikeda, Naohiro; Mera, Yukinori; Morita, Osamu

2017-08-01

Alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil is an edible oil enriched with DAG (>80%) and ALA (>50%). The present study investigated whether ALA-DAG oil promotes tumorigenesis in the tongue and gastrointestinal tract, using a rat medium-term multi-organ carcinogenesis bioassay model. Rats were treated with five genotoxic carcinogens to induce multi-organ tumorigenesis until week 4, and from 1 week after withdrawal, fed a semi-synthetic diet (AIN-93G) containing ALA-DAG oil at concentrations of 0, 13,750, 27,500, and 55,000 ppm. Rats fed AIN-93G containing 55,000 ppm ALA-triacylglycerol or a standard basal diet served as reference and negative control groups, respectively. Animals were euthanized at week 30. ALA-DAG oil was shown to have no effects on survival, general condition, body weight, food consumption, or organ weight. More discolored spots were observed in the stomachs of the 13,750- and 55,000-ppm ALA-DAG groups than in those of the control groups; however, there were no differences in the frequency of histopathological findings across groups. There were no meaningful increases in the incidence of pre-neoplastic and neoplastic lesions in the tongue and gastrointestinal tract among the groups. We therefore conclude that ALA-DAG oil does not promote tumor development in the digestive system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large epidemic thresholds emerge in heterogeneous networks of heterogeneous nodes

Science.gov (United States)

Yang, Hui; Tang, Ming; Gross, Thilo

2015-08-01

One of the famous results of network science states that networks with heterogeneous connectivity are more susceptible to epidemic spreading than their more homogeneous counterparts. In particular, in networks of identical nodes it has been shown that network heterogeneity, i.e. a broad degree distribution, can lower the epidemic threshold at which epidemics can invade the system. Network heterogeneity can thus allow diseases with lower transmission probabilities to persist and spread. However, it has been pointed out that networks in which the properties of nodes are intrinsically heterogeneous can be very resilient to disease spreading. Heterogeneity in structure can enhance or diminish the resilience of networks with heterogeneous nodes, depending on the correlations between the topological and intrinsic properties. Here, we consider a plausible scenario where people have intrinsic differences in susceptibility and adapt their social network structure to the presence of the disease. We show that the resilience of networks with heterogeneous connectivity can surpass those of networks with homogeneous connectivity. For epidemiology, this implies that network heterogeneity should not be studied in isolation, it is instead the heterogeneity of infection risk that determines the likelihood of outbreaks.

Large epidemic thresholds emerge in heterogeneous networks of heterogeneous nodes.

Science.gov (United States)

Yang, Hui; Tang, Ming; Gross, Thilo

2015-08-21

One of the famous results of network science states that networks with heterogeneous connectivity are more susceptible to epidemic spreading than their more homogeneous counterparts. In particular, in networks of identical nodes it has been shown that network heterogeneity, i.e. a broad degree distribution, can lower the epidemic threshold at which epidemics can invade the system. Network heterogeneity can thus allow diseases with lower transmission probabilities to persist and spread. However, it has been pointed out that networks in which the properties of nodes are intrinsically heterogeneous can be very resilient to disease spreading. Heterogeneity in structure can enhance or diminish the resilience of networks with heterogeneous nodes, depending on the correlations between the topological and intrinsic properties. Here, we consider a plausible scenario where people have intrinsic differences in susceptibility and adapt their social network structure to the presence of the disease. We show that the resilience of networks with heterogeneous connectivity can surpass those of networks with homogeneous connectivity. For epidemiology, this implies that network heterogeneity should not be studied in isolation, it is instead the heterogeneity of infection risk that determines the likelihood of outbreaks.

Multiorgan Failure and Refractory Lactic Acidosis due to Pasteurella multocida Septicemia in a Patient with No Animal Exposure

Directory of Open Access Journals (Sweden)

Damaris Pena

2018-01-01

Full Text Available Introduction. Pasteurella multocida is a gram-negative coccobacillus pathogenic to animals. It can cause infection in humans by a bite, scratch, or lick from a cat or dog. P. multocida can cause a variety of infections in humans, including cellulitis, osteomyelitis, endocarditis, peritonitis, and septic shock. Case Presentation. A 56-year-old male presented to our hospital with a 2-day history of fever, abdominal pain, nausea, and vomiting. He denied exposure to cats, dogs or other pets. He had severe respiratory distress requiring ventilator support, profound septic shock requiring multiple vasopressors, severe lactic acidosis, and renal failure requiring emergent hemodialysis. Blood cultures confirmed the presence of P. multocida. The patient subsequently died of cardiopulmonary arrest due to multiorgan failure with refractory shock. Conclusion. P. multocida septicemia can lead to septic shock. Early identification of this organism may decrease mortality. Although our patient had no known cat or dog exposure, physicians should enquire about a history of animal exposure when a patient presents with an infection with no obvious cause.

Health status, renal function, and quality of life after multiorgan failure and acute kidney injury requiring renal replacement therapy

Directory of Open Access Journals (Sweden)

Faulhaber-Walter R

2016-05-01

short-term prospective studies show, and morbidity is significant. Kidney recovery as well as general health remains incomplete. Reduction of QoL is minor, and social rehabilitation is very good. Affectivity is heterogeneous, but most patients experience emotional well-being. In summary, AKI in critically ill patients leads to incomplete rehabilitation but acceptable QoL after 5 years. Keywords: acute kidney injury, renal replacement therapy, QoL, HANDOUT, multiorgan failure, long-term follow-up

Disease: H00417 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available nherited disorder characterized by multiorgan dysfunction. AS shares several features with the common metabolic syndrome, namely obes...ity, hyperinsulinemia, and hypertriglyceridemia. A wide range of clinical variabili

Subcortical brain alterations in major depressive disorder : findings from the ENIGMA Major Depressive Disorder working group

NARCIS (Netherlands)

Schmaal, L.; Veltman, D. J.; van Erp, T. G. M.; Saemann, P. G.; Frodl, T.; Jahanshad, N.; Loehrer, E.; Tiemeier, H.; Hofman, A.; Niessen, W. J.; Vernooij, M. W.; Ikram, M. A.; Wittfeld, K.; Grabe, H. J.; Block, A.; Hegenscheid, K.; Voelzke, H.; Hoehn, D.; Czisch, M.; Lagopoulos, J.; Hatton, S. N.; Hickie, I. B.; Goya-Maldonado, R.; Kraemer, B.; Gruber, O.; Couvy-Duchesne, B.; Renteria, M. E.; Strike, L. T.; Mills, N. T.; de Zubicaray, G. I.; McMahon, K. L.; Medland, S. E.; Martin, N. G.; Gillespie, N. A.; Wright, M. J.; Hall, G.B.; MacQueen, G. M.; Frey, E. M.; Carballedo, A.; van Velzen, L. S.; van Tol, M. J.; van der Wee, N. J.; Veer, I. M.; Walter, H.; Schnell, K.; Schramm, E.; Normann, C.; Schoepf, D.; Konrad, C.; Penninx, B. W. J. H.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical

Sjogren syndrome complicated by mucosa-associated lymphoid tissue lymphoma and lymphocytic interstitial pneumonia

Directory of Open Access Journals (Sweden)

Fatma eAhmed

2015-08-01

Full Text Available Sjogren Syndrome (SS is an autoimmune disease with exocrine glands dysfunction and multiorgan involvement. It is associated with increased risk of lymphoproliferative disorders, especially B-cell marginal zone lymphoma. While the role of F-18 Flurodoxyglucose position emission tomography/CT (F-18 FDG PET/CT for evaluation of lymphoma has been established, its use in patients with a chronic history of SS to evaluate for possible lymphoproliferative disorders or multiorgan involvement is limited. We present a case of chronic SS in which F-18 FDG PET/CT demonstrated FDG avid intraparotid and cervical lymph nodes pathologically proven to be Mucosa-associated lymphoid tissue (MALT lymphoma. In addition, the patient had bibasilar cystic changes consistent with lymphocytic interstitial pneumonia (LIP.

Heterogeneity in development of adolescent anxiety disorder symptoms in an 8-year longitudinal community study

NARCIS (Netherlands)

Nelemans, S.A.; Hale, W.W.; Branje, S.J.T.; Raaijmakers, Q.A.W.; Frijns, T.; van Lier, P.A.C.; Meeus, W.H.J.

2014-01-01

In this study, we prospectively examined developmental trajectories of five anxiety disorder symptom dimensions (generalized anxiety disorder, panic disorder, school anxiety, separation anxiety disorder, and social anxiety disorder) from early to late adolescence in a community sample of 239

Respiratory disorders in patients with polymyositis/dermatomyositis

Directory of Open Access Journals (Sweden)

Olga Alekseyevna Antelava

2014-01-01

Full Text Available Idiopathic inflammatory myopathies (IIM are rare disorders characterized by inflammatory lesions in skeletal muscles. These diseases include polymyositis (PM, dermatomyositis (DM, and inclusion body myositis, which exhibit clinicoimmunological heterogeneity and give different response to therapy. The most frequent manifestation in PM/DM patients is respiratory system dysfunction. The developing respiratory disorders are varied and may outpace the presentation of muscle pathology.

Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

DEFF Research Database (Denmark)

Nielsen, Mette Gilling

Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...

[About the heterogeneity in adolescents with gender identity disorder: differential importance of psychiatric comorbidity and considerations of individual psychodynamics].

Science.gov (United States)

Korte, Alexander; Beier, Klaus M; Vukorepa, Julia; Mersmann, Maik; Albiez, Verena

2014-01-01

Gender identity disorder (GID), gender dysphoria (GD) respectively, is considered a multifactorial disease whose etiology is subject to complex bio-psycho-social conditions, each with different weighting. As a result, therapists, who treat children and adolescents with GID/GD, have to deal with a very heterogeneous group with individually varying causes, differing psychopathology and varying disease progression. In addition to general psychiatric aspects of development, particularly psychiatric comorbidity, but also the different individual psychodynamics--i. e. the specific constellation of conflicts and possible ego deficits and structural deficits in the learning history of the person are of differential importance. In regard to the indication for gender reassignment measures this sometimes is relevant for the decision. The difficulties arising for decision making and the usefulness of a systematic evaluation of case reports as a basis for further optimization of the treatment recommendations are illustrated by two case reports. In the course of this, also the disadvantages and potential dangers of too early diagnostic definition and introduction of gender somato-medical and legal measures are shown exemplarily.

Rare cause of post-squalene disorder of cholesterol biosynthesis ...

African Journals Online (AJOL)

Errors of cholesterol biosynthesis represent a heterogeneous group of metabolic disorders. The aim of the authors of this article is to present a case of a patient with typical symptoms of a rare post-squalene disorder of cholesterol biosynthesis, its diagnostics and progress in neonatal period. The differential diagnosis of a ...

Gene-set analysis shows association between FMRP targets and autism spectrum disorder

NARCIS (Netherlands)

Jansen, Arija; Dieleman, Gwen C; Smit, August B; Verhage, Matthijs; Verhulst, Frank C; Polderman, Tinca J C; Posthuma, Danielle

Autism spectrum disorder (ASD) is a heterogeneous group of disorders characterized by problems with social interaction, communication, and repetitive and restricted behavior. Despite its high heritability and the substantial progress made in elucidating genetic associations, the corresponding

The prune belly anomaly: heterogeneity and superficial X-linkage mimicry.

Science.gov (United States)

Riccardi, V M; Grum, C M

1977-01-01

The genetic, clinical, and necropsy findings of 2 brothers with the prune belly anomaly are presented and the literature reviewed. The combined data emphasise the clinical and genetic heterogeneity of the disorder and show that in at least some instances a heritable component may be the primary insult. The most likely heritable explanation involves a two-step autosomal dominant mutation with sex-limited expression that partially mimics X-linkage. PMID:144797

Attention Deficit Hyperactivity Disorder

Science.gov (United States)

Matthews, Marguerite; Nigg, Joel T.

2014-01-01

Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder’s pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID:24214656

Diagnosis and heterogeneity of MS in MRI

International Nuclear Information System (INIS)

Holst, B.; Fiehler, J.; Schippling, S.

2008-01-01

An efficient therapy of MS requires a quick and reliable diagnosis of the disease. MRI is the most leading paraclinical examination for MS diagnosis. Even though there is no pathognomic finding in MRI, there are MS characteristics with respect to morphology and localization. To exclude other neurological disorders and distinguish between different characteristics within MS, the use of contrast agent is advantageous. Postulated MRI criteria have been increasingly adjusted to the clinical routine and have become clearer, more sensitive, and more specific. Different imaging criteria will be introduced. In addition to the McDonald criteria of 2001 and 2005, new criteria will be presented in which the use of contrast agent is replaced by a second MRI and the dissemination in time and space is simplified. Different pathomechanisms which help to separate MS patients into subgroups are postulated. The diverse pathomechanisms also enable the development of new pharmaceuticals to manipulate the immunologic course in different stages. For varying therapy approaches, it is increasingly important to differentiate the heterogeneous appearance forms into subtypes. The two visible main components of the disorder in MRI are inflammation and neurodegeneration and are responsible for different clinical courses. Both are interdependent and independent of each other. We introduce a stratification which uses both components as a function of their different outcomes to compose subgroups. The previous challenge with respect to MRI was to support the diagnosis of MS via MRI criteria. A future problem will be the heterogeneity and classification of subgroups. This article gives an overview of both problems. (orig.)

Heterogeneity of subclinical autistic traits among parents of children with autism spectrum disorder: Identifying the broader autism phenotype with a data-driven method.

Science.gov (United States)

Bora, Emre; Aydın, Aydan; Saraç, Tuğba; Kadak, Muhammed Tayyib; Köse, Sezen

2017-02-01

Clinical diagnosis of autism spectrum disorder (ASD) can be conceptualized as the extreme end of the distribution of subclinical autistic traits related to genetic susceptibility factors (broad autism phenotype (BAP)) in the general population. Subclinical autistic traits are significantly more common among unaffected first-degree relatives of probands with autism. However, there is a significant heterogeneity of autistic traits in family members of individuals with ASD and severity of autistic traits are not significantly different from controls in the majority of these relatives. The current study investigated the heterogeneity of autistic traits using latent class analysis (LCA) of the Autism Spectrum Quotient (AQ) ratings of 673 parents of children with ASD and 147 parents of typically developing children. Two distinct subgroups, including a "low-scoring" and a "high-scorer (BAP)" groups, were found. In comparison to control parents, a significantly larger proportion (21.1% vs. 7.5%) of parents of ASD were members of BAP group. Communication subscale made a distinctive contribution to the separation of high and low-scoring groups (d = 2.77). Further studies investigating neurobiological and genetic biomarkers and stability of these two subgroups over time are important for understanding the nature of autistic traits in the general population. Autism Res 2017, 10: 321-326. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia.

Science.gov (United States)

Landau, Dan A; Clement, Kendell; Ziller, Michael J; Boyle, Patrick; Fan, Jean; Gu, Hongcang; Stevenson, Kristen; Sougnez, Carrie; Wang, Lili; Li, Shuqiang; Kotliar, Dylan; Zhang, Wandi; Ghandi, Mahmoud; Garraway, Levi; Fernandes, Stacey M; Livak, Kenneth J; Gabriel, Stacey; Gnirke, Andreas; Lander, Eric S; Brown, Jennifer R; Neuberg, Donna; Kharchenko, Peter V; Hacohen, Nir; Getz, Gad; Meissner, Alexander; Wu, Catherine J

2014-12-08

Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLLs). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories. Copyright © 2014 Elsevier Inc. All rights reserved.

Typology of Internet gaming disorder and its clinical implications.

Science.gov (United States)

Lee, Seung-Yup; Lee, Hae Kook; Choo, Hyekyung

2017-07-01

Various perspectives exist regarding Internet gaming disorder. While the concept of behavioral addiction is gaining recognition, some view the phenomenon as merely excessive indulgence in online pastimes. Still, in recent years, complaints from patients or their family members about problems related to Internet use, particularly Internet gaming, have become more common. However, the clinical picture of Internet gaming disorder could be obscured by its heterogeneous manifestations with other intertwined factors, such as psychiatric comorbidities, neurodevelopmental factors, sociocultural factors, and game-related factors, which may influence the pathogenesis as well as the clinical course. To mitigate such problems, clinicians should be able to consider diverse aspects related to Internet gaming disorder. Classifying such a heterogeneous problem into subtypes that share a similar etiology or phenomenology may provide additional clues in the diagnostic process and allow us to designate available clinical resources for particularly vulnerable factors. In this review paper, we suggest a typology of 'impulsive/aggressive,' 'emotionally vulnerable,' 'socially conditioned,' and 'not otherwise specified' as subtypes of the heterogeneous phenomena of pathological Internet gaming. The implications of these subtypes for assessment and treatment planning will also be highlighted. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Intervention for Children with Severe Speech Disorder: A Comparison of Two Approaches

Science.gov (United States)

Crosbie, Sharon; Holm, Alison; Dodd, Barbara

2005-01-01

Background: Children with speech disorder are a heterogeneous group (e.g. in terms of severity, types of errors and underlying causal factors). Much research has ignored this heterogeneity, giving rise to contradictory intervention study findings. This situation provides clinical motivation to identify the deficits in the speech-processing chain…

Complex single gene disorders and epilepsy.

LENUS (Irish Health Repository)

Merwick, Aine

2012-09-01

Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation.

[Motility disorders of the esophagus].

Science.gov (United States)

Bruder, E; Rougemont, A-L; Furlano, R I; Schneider, J F; Mayr, J; Haecker, F-M; Beier, K; Schneider, J; Weber, P; Berberich, T; Cathomas, G; Meier-Ruge, W A

2013-03-01

Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

Local-Global Processing in Obsessive-Compulsive Disorder and Comorbid Tourette's Syndrome

Science.gov (United States)

Rankins, D.; Bradshaw, J. L.; Georgiou-Karistianis, N.

2005-01-01

Neuropsychological and neuroimaging studies implicate attentional difficulties in obsessive-compulsive disorder (OCD), but results are inconsistent due possibly to sample heterogeneity and lack of control of comorbid disorders, such as Tourette's syndrome (TS). Nevertheless, it has been suggested that OCD symptomatology may be a result of…

Heterogeneity of Mental Health Service Utilization and High Mental Health Service Use Among Women Eight Years After Initiating Substance Use Disorder Treatment.

Science.gov (United States)

Evans, Elizabeth; Padwa, Howard; Li, Libo; Lin, Veronique; Hser, Yih-Ing

2015-12-01

The aim of this study was to determine mental health service utilization patterns among women treated for substance use disorders (SUD) and identify factors associated with patterns of high mental health service use. Data were provided by 4447 women treated for SUD in California during 2000-2002 for whom mental health services utilization records were acquired. A latent class model was fitted to women's high use of services (>6 services/year over 8 years). Multinomial logistic regression was used to identify predisposing, enabling, and need factors associated with utilization patterns. In 8 years after initiating SUD treatment, 50% of women utilized mental health services. High use probability was consistently low for most women (76.9%); for others, however, it decreased immediately following SUD treatment and then increased over time (8.7%), increased immediately following SUD treatment and then decreased (9.3%), or remained consistently high (5.1%). Consistently high services use was negatively associated with marriage (OR 0.60, pwomen with co-occurring mental health disorders at SUD treatment entry did not receive any mental health treatment in the subsequent 8 years. Mental health services utilization patterns among women treated for SUD are heterogeneous and dynamic. Understanding factors related to women's utilization patterns may aid efforts to optimize care and ensure appropriate use of mental health services. Copyright © 2015 Elsevier Inc. All rights reserved.

Caspase-8 Deficiency Presenting as Late-Onset Multi-Organ Lymphocytic Infiltration with Granulomas in two Adult Siblings.

Science.gov (United States)

Niemela, Julie; Kuehn, Hye Sun; Kelly, Corin; Zhang, Mingchang; Davies, Joie; Melendez, Jose; Dreiling, Jennifer; Kleiner, David; Calvo, Katherine; Oliveira, João B; Rosenzweig, Sergio D

2015-05-01

Caspase-8 deficiency (CED) was originally described in 2002 in two pediatric patients presenting with clinical manifestations resembling autoimmune lymphoproliferative syndrome (ALPS) accompanied by infections, and T, B and NK cell defects. Since then, no new CED patients were published. Here we report two adult siblings (Pt1 and Pt2) presenting in their late thirties with pulmonary hypertension leading to lung transplant (Pt1), and a complex neurological disease leading to multiple cranial nerves palsies (Pt2) as their main manifestations. A thorough clinical and immunological evaluation was performed at the Primary Immunodeficiency Clinic at NIH, followed by whole exome sequencing. The patients had multiorgan lymphocytic infiltration and granulomas, as well as clinical signs of immune deficiency/ immune dysregulation. Both siblings carried homozygous mutations in CASP8, c.1096C > T, p.248R > W. This was the same mutation described on the previously published CED patients, to whom these new patients were likely distantly related. We report two new CED patients presenting during adulthood with life-threatening end-organ lymphocyte infiltrates affecting the lungs, liver, spleen, bone marrow and central nervous system. This phenotype broadens the clinical spectrum of manifestations associated with this disease and warrants the search of CASP8 mutations in other cohorts of patients.

Language growth in children with heterogeneous language disorders: a population study.

Science.gov (United States)

Norbury, Courtenay Frazier; Vamvakas, George; Gooch, Debbie; Baird, Gillian; Charman, Tony; Simonoff, Emily; Pickles, Andrew

2017-10-01

Language development has been characterised by significant individual stability from school entry. However, the extent to which trajectories of language growth vary in children with language disorder as a function of co-occurring developmental challenges is a question of theoretical import, with implications for service provision. SCALES employed a population-based survey design with sample weighting procedures to estimate growth in core language skills over the first three years of school. A stratified sample (n = 529) received comprehensive assessment of language, nonverbal IQ, and social, emotional and behavioural difficulties at 5-6 years of age and 95% of the sample (n = 499) were assessed again at ages 7-8. Language growth was measured using both raw and standard scores in children with typical development, children with language disorder of unknown origin, and children with language disorders associated with a known clinical condition and/or intellectual disability. Overall, language was stable at the individual level (estimated ICC = 0.95) over the first three years of school. Linear mixed effects models highlighted steady growth in language raw scores across all three groups, including those with multiple developmental challenges. There was little evidence, however, that children with language disorders were narrowing the gap with peers (z-scores). Adjusted models indicated that while nonverbal ability, socioeconomic status and social, emotional and behavioural deficits predicted initial language score (intercept), none predicted language growth (slope). These findings corroborate previous studies suggesting stable language trajectories after ages 5-6 years, but add considerably to previous work by demonstrating similar developmental patterns in children with additional nonverbal cognitive deficits, social, emotional, and behavioural challenges, social disadvantage or clinical diagnoses. © 2017 The Authors. Journal of Child Psychology and

Locally disordered methylation forms the basis of intra-tumor methylome variation in chronic lymphocytic leukemia

Science.gov (United States)

Landau, Dan A.; Clement, Kendell; Ziller, Michael J.; Boyle, Patrick; Fan, Jean; Gu, Hongcang; Stevenson, Kristen; Sougnez, Carrie; Wang, Lili; Li, Shuqiang; Kotliar, Dylan; Zhang, Wandi; Ghandi, Mahmoud; Garraway, Levi; Fernandes, Stacey M.; Livak, Kenneth J.; Gabriel, Stacey; Gnirke, Andreas; Lander, Eric S.; Brown, Jennifer R.; Neuberg, Donna; Kharchenko, Peter V.; Hacohen, Nir; Getz, Gad; Meissner, Alexander; Wu, Catherine J.

2014-01-01

SUMMARY Intra-tumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLL). Compared to 26 normal B cell samples, CLLs consistently displayed higher intra-sample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories. PMID:25490447

Systematic review of the prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies

Directory of Open Access Journals (Sweden)

José Caetano Dell'Aglio Jr.

2013-01-01

Full Text Available This paper describes the findings of a systematic literature review aimed at providing an overview of the lifetime prevalence of bipolar disorder and bipolar spectrum disorders in population-based studies. Databases MEDLINE, ProQuest, Psychnet, and Web of Science were browsed for papers published in English between 1999 and May 2012 using the following search string: bipolar disorders OR bipolar spectrum disorders AND prevalence OR cross-sectional OR epidemiology AND population-based OR non-clinical OR community based. The search yielded a total of 434 papers, but only those published in peer-reviewed journals and with samples aged ≥ 18 years were included, resulting in a final sample of 18 papers. Results revealed rather heterogeneous findings concerning the prevalence of bipolar disorders and bipolar spectrum disorders. Lifetime prevalence of bipolar disorder ranged from 0.1 to 7.5%, whereas lifetime prevalence of bipolar spectrum disorders ranged from 2.4 to 15.1%. Differences in the rates of bipolar disorder and bipolar spectrum disorders may be related to the consideration of subthreshold criteria upon diagnosis. Differences in the prevalence of different subtypes of the disorder are discussed in light of diagnostic criteria and instruments applied.

Empirical support for a reclassification of eating disorders NOS.

Science.gov (United States)

Helverskov, J L; Lyng, B; Clausen, L; Mors, O; Frydenberg, M; Thomsen, P H; Rokkedal, K

2011-01-01

To explore the empirical support for a reclassification of the eating disorders NOS (EDNOS) category. In a cross-sectional design eight specific subgroups of EDNOS were compared to anorexia nervosa (AN) and bulimia nervosa (BN) on interview-based data and questionnaire measures. The sample consisted of 965 patients in the age 13-54 years admitted to treatment for an eating disorder. According to the DSM-IV 176(18%) presented with AN, 290(30%) with BN and 499(52%) with EDNOS. Of all EDNOS cases 34% could be reclassified as AN or BN. Three specific subgroups emerged as separate diagnostic entities. A heterogeneous subgroup of 122 patients (13% of all) was proposed as 'true' EDNOS. Implications of the results on the DSM-V are discussed. The results support a broader definition of AN and BN and suggest subgroups of EDNOS as separate diagnostic entities. This results in a substantial reduction of the heterogeneous EDNOS group. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.

Neuroimaging Endophenotypes in Autism Spectrum Disorder

Science.gov (United States)

Mahajan, Rajneesh; Mostofsky, Stewart H.

2015-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response and lead to the development of new therapies. PMID:26234701

Scattering theory and effective medium approximations to heterogeneous materials

International Nuclear Information System (INIS)

Gubernatis, J.E.

1977-01-01

The formal analogy existing between problems studied in the microscopic theory of disordered alloys and problems concerned with the effective (macroscopic) behavior of heterogeneous materials is discussed. Attention is focused on (1) analogous approximations (effective medium approximations) developed for the microscopic problems by scattering theory concepts and techniques, but for the macroscopic problems principally by intuitive means, (2) the link, provided by scattering theory, of the intuitively developed approximations to a well-defined perturbative analysis, (3) the possible presence of conditionally convergent integrals in effective medium approximations

Collective Motion in Behaviorally Heterogeneous Systems

Science.gov (United States)

Copenhagen, Katherine

Collective motion is a widespread phenomenon in nature where individuals actively propel themselves, gather together and move as a group. Some examples of collective motion are bird flocks, fish schools, bacteria swarms, cell clusters, and crowds of people. Many models seek to understand the effects of activity in collective systems including things such as environmental disorder, density, and interaction details primarily at infinite size limits and with uniform populations. In this dissertation I investigate the effects of finite sizes and behavioral heterogeneity as it exists in nature. Behavioral heterogeneity can originate from several different sources. Mixed populations of individuals can have inherently different behaviors such as mutant bacteria, injured fish, or agents that prefer individualistic behavior over coordinated motion. Alternatively, agents may modify their own behavior based on some local environmental dependency, such as local substrate, or density. In cases such as mutant cheaters in bacteria or malfunctioning drones in swarms, mixed populations of behaviorally heterogeneous agents can be modelled as arising in the form of aligning and non-aligning agents. When this kind of heterogeneity is introduced, there is a critical carrying capacity of non-aligners above which the system is unable to form a cohesive ordered group. However, if the cohesion of the group is relaxed to allow for fracture, the system will actively sort out non-aligning agents the system will exist at a critical non-aligner fraction. A similar heterogeneity could result in a mixture of high and low noise individuals. In this case there is also a critical carry capacity beyond which the system is unable to reach an ordered state, however the nature of this transition depends on the model details. Agents which are part of an ordered collective may vary their behavior as the group changes environments such as a flock of birds flying into a cloud. Using a unique model of a

Cognitive Clusters in Specific Learning Disorder

Science.gov (United States)

Poletti, Michele; Carretta, Elisa; Bonvicini, Laura; Giorgi-Rossi, Paolo

2018-01-01

The heterogeneity among children with learning disabilities still represents a barrier and a challenge in their conceptualization. Although a dimensional approach has been gaining support, the categorical approach is still the most adopted, as in the recent fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders." The…

Organizing heterogeneous samples using community detection of GIMME-derived resting state functional networks.

Directory of Open Access Journals (Sweden)

Kathleen M Gates

Full Text Available Clinical investigations of many neuropsychiatric disorders rely on the assumption that diagnostic categories and typical control samples each have within-group homogeneity. However, research using human neuroimaging has revealed that much heterogeneity exists across individuals in both clinical and control samples. This reality necessitates that researchers identify and organize the potentially varied patterns of brain physiology. We introduce an analytical approach for arriving at subgroups of individuals based entirely on their brain physiology. The method begins with Group Iterative Multiple Model Estimation (GIMME to assess individual directed functional connectivity maps. GIMME is one of the only methods to date that can recover both the direction and presence of directed functional connectivity maps in heterogeneous data, making it an ideal place to start since it addresses the problem of heterogeneity. Individuals are then grouped based on similarities in their connectivity patterns using a modularity approach for community detection. Monte Carlo simulations demonstrate that using GIMME in combination with the modularity algorithm works exceptionally well--on average over 97% of simulated individuals are placed in the accurate subgroup with no prior information on functional architecture or group identity. Having demonstrated reliability, we examine resting-state data of fronto-parietal regions drawn from a sample (N = 80 of typically developing and attention-deficit/hyperactivity disorder (ADHD -diagnosed children. Here, we find 5 subgroups. Two subgroups were predominantly comprised of ADHD, suggesting that more than one biological marker exists that can be used to identify children with ADHD based from their brain physiology. Empirical evidence presented here supports notions that heterogeneity exists in brain physiology within ADHD and control samples. This type of information gained from the approach presented here can assist in

Diagnostic Biomarkers for Posttraumatic Stress Disorder (PTSD): Promising Horizons from Translational Neuroscience Research

OpenAIRE

Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

2015-01-01

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently re-classified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. T...

Neuroanatomical heterogeneity of essential tremor according to propranolol response.

Directory of Open Access Journals (Sweden)

Seok Jong Chung

Full Text Available BACKGROUND: Recent studies have suggested that essential tremor (ET is a more complex and heterogeneous clinical entity than initially thought. In the present study, we assessed the pattern of cortical thickness and diffusion tensor white matter (WM changes in patients with ET according to the response to propranolol to explore the pathogenesis underlying the clinical heterogeneity of ET. METHODS: A total of 32 patients with drug naive ET were recruited prospectively from the Movement Disorders outpatient clinic. The patients were divided into a propranolol-responder group (n = 18 and a non-responder group (n = 14. We analyzed the pattern of cortical thickness and diffusion tensor WM changes between these two groups and performed correlation analysis between imaging and clinical parameters. RESULTS: There were no significant differences in demographic characteristics, general cognition, or results of detailed neuropsychological tests between the groups. The non-responder group showed more severe cortical atrophy in the left orbitofrontal cortex and right temporal cortex relative to responders. However, the responders exhibited significantly lower fractional anisotropy values in the bilateral frontal, corpus callosal, and right parietotemporal WM compared with the non-responder group. There were no significant clusters where the cortical thickness or WM alterations were significantly correlated with initial tremor severity or disease duration. CONCLUSIONS: The present data suggest that patients with ET have heterogeneous cortical thinning and WM alteration with respect to responsiveness to propranolol, suggesting that propranolol responsiveness may be a predictive factor to determine ET subtypes in terms of neuroanatomical heterogeneity.

Effects of X-irradiation on N-methyl-N-nitrosourea-induced multi-organ carcinogenesis in rats

International Nuclear Information System (INIS)

Morishita, Yukiko; Tanaka, Takuji; Mori, Hideki; Sasaki, Shunsaku.

1993-01-01

The effects of X-irradiation on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single intraperitoneal injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, group 3 and group 4 were X-irradiated at dose of 3 Gy. Group 5 (24 males, 24 females) received X-irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1-5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/kg MNU and X-irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, p<0.05; large intestine: 8%, p<0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X-irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, p<0.05). These results indicated that X-irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats. (author)

Effects of X-irradiation on N-methyl-N-nitrosourea-induced multi-organ carcinogenesis in rats

Energy Technology Data Exchange (ETDEWEB)

Morishita, Yukiko; Tanaka, Takuji; Mori, Hideki (Gifu Univ. (Japan). Faculty of Medicine); Sasaki, Shunsaku

1993-01-01

The effects of X-irradiation on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single intraperitoneal injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, group 3 and group 4 were X-irradiated at dose of 3 Gy. Group 5 (24 males, 24 females) received X-irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1-5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/kg MNU and X-irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, p<0.05; large intestine: 8%, p<0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X-irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, p<0.05). These results indicated that X-irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats. (author).

Heterogeneous network architectures

DEFF Research Database (Denmark)

Christiansen, Henrik Lehrmann

2006-01-01

is flexibility. This thesis investigates such heterogeneous network architectures and how to make them flexible. A survey of algorithms for network design is presented, and it is described how using heuristics can increase the speed. A hierarchical, MPLS based network architecture is described......Future networks will be heterogeneous! Due to the sheer size of networks (e.g., the Internet) upgrades cannot be instantaneous and thus heterogeneity appears. This means that instead of trying to find the olution, networks hould be designed as being heterogeneous. One of the key equirements here...... and it is discussed that it is advantageous to heterogeneous networks and illustrated by a number of examples. Modeling and simulation is a well-known way of doing performance evaluation. An approach to event-driven simulation of communication networks is presented and mixed complexity modeling, which can simplify...

Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

Directory of Open Access Journals (Sweden)

Guangyu Zhao

Full Text Available The Middle East Respiratory Syndrome Coronavirus (MERS-CoV causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4, the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

Clinical and Biochemical Pitfalls in the Diagnosis of Peroxisomal Disorders.

Science.gov (United States)

Klouwer, Femke C C; Huffnagel, Irene C; Ferdinandusse, Sacha; Waterham, Hans R; Wanders, Ronald J A; Engelen, Marc; Poll-The, Bwee Tien

2016-08-01

Peroxisomal disorders are a heterogeneous group of genetic metabolic disorders, caused by a defect in peroxisome biogenesis or a deficiency of a single peroxisomal enzyme. The peroxisomal disorders include the Zellweger spectrum disorders, the rhizomelic chondrodysplasia punctata spectrum disorders, X-linked adrenoleukodystrophy, and multiple single enzyme deficiencies. There are several core phenotypes caused by peroxisomal dysfunction that clinicians can recognize. The diagnosis is suggested by biochemical testing in blood and urine and confirmed by functional assays in cultured skin fibroblasts, followed by mutation analysis. This review describes the phenotype of the main peroxisomal disorders and possible pitfalls in (laboratory) diagnosis to aid clinicians in the recognition of this group of diseases. Georg Thieme Verlag KG Stuttgart · New York.

Escitalopram in the treatment of social anxiety disorder: analysis of efficacy for different clinical subgroups and symptom dimensions

DEFF Research Database (Denmark)

Stein, Dan J; Kasper, Siegfried; Andersen, Elisabeth Anne Wreford

2004-01-01

Escitalopram has demonstrated efficacy for the acute treatment of social anxiety disorder (SAD) in two placebo-controlled trials and for long-term treatment in a relapse-prevention study. Social anxiety disorder is a heterogeneous disorder. This study questions whether this new selective serotonin...

Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism

Directory of Open Access Journals (Sweden)

Nadia eUcciferri

2014-12-01

Full Text Available Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step towards building an integrated picture of systemic metabolism and signalling in physiological or pathological conditions. However the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here we analyse the physiologic relationship between cells, cell metabolism and exchange in the human body using allometric rules, downscaling them to an organ-on-a plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (Cell Number Scaling Model, CNSM, and Metabolic and Surface Scaling model, MSSM are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions which can be extrapolated to the in vivo

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

International Nuclear Information System (INIS)

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

Energy Technology Data Exchange (ETDEWEB)

Ucciferri, Nadia [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Sbrana, Tommaso [Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Ahluwalia, Arti, E-mail: arti.ahluwalia@unipi.it [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy)

2014-12-17

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

Science.gov (United States)

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

[Waardenburg syndrome. A heterogenic disorder with variable penetrance].

Science.gov (United States)

Apaydin, F; Bereketoglu, M; Turan, O; Hribar, K; Maassen, M M; Günhan, O; Zenner, H-P; Pfister, M

2004-06-01

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

Antisocial personality disorder: a current review.

Science.gov (United States)

Glenn, Andrea L; Johnson, Alexandria K; Raine, Adrian

2013-12-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM 5) classification of antisocial personality disorder (ASPD) describes individuals who engage in repetitive irresponsible, delinquent, and criminal behavior. The diagnosis is highly controversial, with many researchers and clinicians arguing that the category is too heterogeneous, overinclusive, and demonstrates considerable overlap with other disorders. This review focuses on recent studies that have improved our understanding of the characteristics of individuals who fit the ASPD definition by exploring how subtypes differ and how comorbid conditions influence the presentation of ASPD. In addition, we discuss research on the etiology of ASPD that has identified genetic and environmental factors that may contribute to the development and persistence of antisocial behavior, and brain imaging research that has improved our understanding of the relationships between ASPD and other psychopathology. Finally, we discuss promising preliminary research on treatment for this disorder.

Dynamic heterogeneity in life histories

DEFF Research Database (Denmark)

Tuljapurkar, Shripad; Steiner, Uli; Orzack, Steven Hecht

2009-01-01

or no fixed heterogeneity influences this trait. We propose that dynamic heterogeneity provides a 'neutral' model for assessing the possible role of unobserved 'quality' differences between individuals. We discuss fitness for dynamic life histories, and the implications of dynamic heterogeneity...... generate dynamic heterogeneity: life-history differences produced by stochastic stratum dynamics. We characterize dynamic heterogeneity in a range of species across taxa by properties of the Markov chain: the entropy, which describes the extent of heterogeneity, and the subdominant eigenvalue, which...... distributions of lifetime reproductive success. Dynamic heterogeneity contrasts with fixed heterogeneity: unobserved differences that generate variation between life histories. We show by an example that observed distributions of lifetime reproductive success are often consistent with the claim that little...

Dielectric spectroscopy studies of low-disorder and low-dimensional materials

OpenAIRE

Tripathi, Pragya

2016-01-01

In this thesis we employ dielectric spectroscopy (in different implementations) to study the dielectric properties of different materials ranging from completely disordered supercooled liquids to low-disorder solids with only ratcheting reorientational motions, to low-dimensional systems such as thin films or needle-like crystals. The probed material properties include the electrical conductivity, the space-charge processes due to sample heterogeneities, molecular dynamics, hydrogen-bond dyna...

New insights on developmental dyslexia subtypes: heterogeneity of mixed reading profiles.

Directory of Open Access Journals (Sweden)

Rachel Zoubrinetzky

Full Text Available We examined whether classifications based on reading performance are relevant to identify cognitively homogeneous subgroups of dyslexic children. Each of the 71 dyslexic participants was selected to have a mixed reading profile, i.e. poor irregular word and pseudo-word reading performance (accuracy and speed. Despite their homogeneous reading profile, the participants were found to split into four distinct cognitive subgroups, characterized by a single phonological disorder, a single visual attention span disorder, a double deficit or none of these disorders. The two subgroups characterized by single and contrasted cognitive disorders were found to exhibit a very similar reading pattern but more contrasted spelling performance (quantitative analysis. A qualitative analysis of the error types produced in reading and spelling provided some cues about the participants' underlying cognitive deficit. The overall findings disqualify subtyping based on reading profiles as a classification method to identify cognitively homogeneous subgroups of dyslexic children. They rather show an opaque relationship between the cognitive underpinnings of developmental dyslexia and their behavioral manifestations in reading and spelling. Future neuroimaging and genetic studies should take this issue into account since synthesizing over cognitively heterogeneous children would entail potential pitfalls.

New Insights on Developmental Dyslexia Subtypes: Heterogeneity of Mixed Reading Profiles

Science.gov (United States)

Zoubrinetzky, Rachel; Bielle, Frédérique; Valdois, Sylviane

2014-01-01

We examined whether classifications based on reading performance are relevant to identify cognitively homogeneous subgroups of dyslexic children. Each of the 71 dyslexic participants was selected to have a mixed reading profile, i.e. poor irregular word and pseudo-word reading performance (accuracy and speed). Despite their homogeneous reading profile, the participants were found to split into four distinct cognitive subgroups, characterized by a single phonological disorder, a single visual attention span disorder, a double deficit or none of these disorders. The two subgroups characterized by single and contrasted cognitive disorders were found to exhibit a very similar reading pattern but more contrasted spelling performance (quantitative analysis). A qualitative analysis of the error types produced in reading and spelling provided some cues about the participants' underlying cognitive deficit. The overall findings disqualify subtyping based on reading profiles as a classification method to identify cognitively homogeneous subgroups of dyslexic children. They rather show an opaque relationship between the cognitive underpinnings of developmental dyslexia and their behavioral manifestations in reading and spelling. Future neuroimaging and genetic studies should take this issue into account since synthesizing over cognitively heterogeneous children would entail potential pitfalls. PMID:24918441

Thoracic cavity segmentation algorithm using multiorgan extraction and surface fitting in volumetric CT

Energy Technology Data Exchange (ETDEWEB)

Bae, JangPyo [Interdisciplinary Program, Bioengineering Major, Graduate School, Seoul National University, Seoul 110-744, South Korea and Department of Radiology, University of Ulsan College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Kim, Namkug, E-mail: namkugkim@gmail.com; Lee, Sang Min; Seo, Joon Beom [Department of Radiology, University of Ulsan College of Medicine, 388-1 Pungnap2-dong, Songpa-gu, Seoul 138-736 (Korea, Republic of); Kim, Hee Chan [Department of Biomedical Engineering, College of Medicine and Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-744 (Korea, Republic of)

2014-04-15

Purpose: To develop and validate a semiautomatic segmentation method for thoracic cavity volumetry and mediastinum fat quantification of patients with chronic obstructive pulmonary disease. Methods: The thoracic cavity region was separated by segmenting multiorgans, namely, the rib, lung, heart, and diaphragm. To encompass various lung disease-induced variations, the inner thoracic wall and diaphragm were modeled by using a three-dimensional surface-fitting method. To improve the accuracy of the diaphragm surface model, the heart and its surrounding tissue were segmented by a two-stage level set method using a shape prior. To assess the accuracy of the proposed algorithm, the algorithm results of 50 patients were compared to the manual segmentation results of two experts with more than 5 years of experience (these manual results were confirmed by an expert thoracic radiologist). The proposed method was also compared to three state-of-the-art segmentation methods. The metrics used to evaluate segmentation accuracy were volumetric overlap ratio (VOR), false positive ratio on VOR (FPRV), false negative ratio on VOR (FNRV), average symmetric absolute surface distance (ASASD), average symmetric squared surface distance (ASSSD), and maximum symmetric surface distance (MSSD). Results: In terms of thoracic cavity volumetry, the mean ± SD VOR, FPRV, and FNRV of the proposed method were (98.17 ± 0.84)%, (0.49 ± 0.23)%, and (1.34 ± 0.83)%, respectively. The ASASD, ASSSD, and MSSD for the thoracic wall were 0.28 ± 0.12, 1.28 ± 0.53, and 23.91 ± 7.64 mm, respectively. The ASASD, ASSSD, and MSSD for the diaphragm surface were 1.73 ± 0.91, 3.92 ± 1.68, and 27.80 ± 10.63 mm, respectively. The proposed method performed significantly better than the other three methods in terms of VOR, ASASD, and ASSSD. Conclusions: The proposed semiautomatic thoracic cavity segmentation method, which extracts multiple organs (namely, the rib, thoracic wall, diaphragm, and heart

Bipolar Disorder and Cancer

Directory of Open Access Journals (Sweden)

Sermin Kesebir

2012-06-01

Full Text Available Prevalence studies and studies on causation relations have shown that the relation between psychiatric disorders and chronic physical diseases is neglected. For heterogeneous diseases an increasing number of susceptibility variants are being defined. Alzheimer disease, bipolar disorder, breast and prostate cancer, coronary artery disease, Chron's disease, systemic lupus eritematosus, type 1 and type 2 diabetes mellitus are mentioned together with epigenetic concept. In acrocentric zone of chromosome 13, breast cancer, retinoblastoma, chronic Iymphocytic leukemia genes with B cells, dopamin loci of bipolar disorder are found together. Among bipolar and healthy individuals, an increase risk of breast cancer in female cases has been resported. On the other hand, psychosocial factors that affect stress and response to stress itself may be important variables in prognosis and progression of different cancer types. During the course of many cancer types –especially brain tumors- and during treatment of chemotherapeutic agents, bipolar symptomatology may appear. In this article, it is reviewed with relevant literature that whether an etiological relation between bipolar disorder and cancer exist and how both diseases affect each other's course and treatment.

Self-disorders and the Schizophrenia Spectrum

DEFF Research Database (Denmark)

Nordgaard, Julie; Parnas, Josef

2014-01-01

INTRODUCTION: Self-disorders (SD) have been described as a core feature of schizophrenia both in classical and recent psychopathological literature. However, the specificity of SD for the schizophrenia spectrum disorders has never been demonstrated in a diagnostically heterogeneous sample, nor has...... the concurrent validity of SD been examined. AIM: (1) To examine the specificity of Examination of Anomalous Self-Experiences (EASE) measured SD to the schizophrenia spectrum disorder in first contact inpatients, (2) to explore the internal consistency and factorial structure of the EASE, (3) to assess...... the concurrent validity of SD by exploring correlations between SD and the canonical psychopathological dimensions of schizophrenia, (4) to explore relations of SD to intelligence, sociodemographic, and extrinsic illness characteristics. METHODS: A total of 100 consecutive first admission patients underwent...

Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure

NARCIS (Netherlands)

Langereis, Eveline J.; Borgo, Andrea; Crushell, Ellen; Harmatz, Paul R.; van Hasselt, Peter M.; Jones, Simon A.; Kelly, Paula M.; Lampe, Christina; van der Lee, Johanna H.; Odent, Thierry; Sakkers, Ralph; Scarpa, Maurizio; Schafroth, Matthias U.; Struijs, Peter A.; Valayannopoulos, Vassili; White, Klane K.; Wijburg, Frits A.

2013-01-01

Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder characterized by progressive multi-organ disease. The standard of care for patients with the severe phenotype (Hurler syndrome, MPS I-H) is early hematopoietic stem cell transplantation (HSCT). However, skeletal disease, including

Löffler's endomyocarditis in the idiopathic hypereosinophilic syndrome

NARCIS (Netherlands)

Corssmit, E. P.; Trip, M. D.; Durrer, J. D.

1999-01-01

The idiopathic hypereosinophilic syndrome (HES) is a leukoproliferative disorder characterized by sustained eosinophilia (> 1.5 x 10(9)/l) and (multi-)organ dysfunction caused by infiltration of eosinophils. Especially the heart is frequently affected. In this report, we describe 2 patients with HES

Scrub typhus complicated by acute respiratory distress syndrome and multiorgan failure; an unrecognized alarming entity in central India: A report of two cases

Directory of Open Access Journals (Sweden)

Amrish Saxena

2014-01-01

Full Text Available Scrub typhus is an acute infectious illness, distributed throughout the Asia Pacific rim. In India, it has been reported from northern, eastern, and southern India. However, cases of scrub typhus have not been well-documented from Vidarbha, an eastern region of Maharashtra state in central India. We report two cases of complicated scrub typhus from Vidarbha region. These cases admitted in unconscious state with 8-10 days history of fever, body ache, cough, and progressive breathlessness. The diagnosis in both cases was based on presence of eschar, a positive Weil-Felix test, and a positive rapid diagnostic test (immunochromatographic assay. Both cases were complicated by acute respiratory distress syndrome (ARDS and multiorgan failure. Both of them presented in their 2 nd week of illness and died during the hospital course in spite of intensive supportive care. The main cause of mortality was delayed referral leading to delay in diagnosis and treatment.

Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder.

Science.gov (United States)

Beesdo, Katja; Pine, Daniel S; Lieb, Roselind; Wittchen, Hans-Ulrich

2010-01-01

Controversy surrounds the diagnostic categorization of generalized anxiety disorder (GAD). To examine the incidence, comorbidity, and risk patterns for anxiety and depressive disorders and to test whether developmental features of GAD more strongly support a view of this condition as a depressive as opposed to an anxiety disorder. Face-to-face, 10-year prospective longitudinal and family study with as many as 4 assessment waves. The DSM-IV Munich Composite International Diagnostic Interview was administered by clinically trained interviewers. Munich, Germany. A community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34 years at last follow-up. Cumulative incidence of GAD, other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic disorder), and depressive disorders (major depressive disorder, and dysthymia). Longitudinal associations between GAD and depressive disorders are not stronger than those between GAD and anxiety disorders or between other anxiety and depressive disorders. Survival analyses reveal that the factors associated with GAD overlap more strongly with those specific to anxiety disorders than those specific to depressive disorders. In addition, GAD differs from anxiety and depressive disorders with regard to family climate and personality profiles. Anxiety and depressive disorders appear to differ with regard to risk constellations and temporal longitudinal patterns, and GAD is a heterogeneous disorder that is, overall, more closely related to other anxiety disorders than to depressive disorders. More work is needed to elucidate the potentially unique aspects of pathways and mechanisms involved in the etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by cross-sectional features and diagnostic comorbidity patterns, minimizes the importance of longitudinal data on risk factors and symptom trajectories.

The neurobiology of oppositional defiant disorder and conduct disorder: altered functioning in three mental domains.

Science.gov (United States)

Matthys, Walter; Vanderschuren, Louk J M J; Schutter, Dennis J L G

2013-02-01

This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

Intraoperative Adrenal Insufficiency in a Patient with Prader-Willi Syndrome

OpenAIRE

Barbara, David W.; Hannon, James D.; Hartman, William R.

2012-01-01

Prader-Willi syndrome (PW) is a rare genetic disorder with multi-organ system involvement. These patients present many perioperative challenges including sleep-related breathing disorders, morbid obesity, thick salivary secretions, mental retardation, and difficult intravenous access. PW has been suggested to be associated with central adrenal insufficiency. We report a novel case of persistent severe hypotension from previously undiagnosed and asymptomatic adrenal insufficiency in a pediatri...

Examining the Stability of "DSM-IV" and Empirically Derived Eating Disorder Classification: Implications for "DSM-5"

Science.gov (United States)

Peterson, Carol B.; Crow, Scott J.; Swanson, Sonja A.; Crosby, Ross D.; Wonderlich, Stephen A.; Mitchell, James E.; Agras, W. Stewart; Halmi, Katherine A.

2011-01-01

Objective: The purpose of this investigation was to derive an empirical classification of eating disorder symptoms in a heterogeneous eating disorder sample using latent class analysis (LCA) and to examine the longitudinal stability of these latent classes (LCs) and the stability of DSM-IV eating disorder (ED) diagnoses. Method: A total of 429…

Interaction Heterogeneity can Favorably Impact Colloidal Crystal Nucleation

Science.gov (United States)

Jenkins, Ian C.; Crocker, John C.; Sinno, Talid

2017-10-01

Colloidal particles with short-ranged attractions, e.g., micron-scale spheres functionalized with single-stranded DNA oligomers, are susceptible to becoming trapped in disordered configurations even when a crystalline arrangement is the ground state. Moreover, for reasons that are not well understood, seemingly minor variations in the particle formulation can lead to dramatic changes in the crystallization outcome. We demonstrate, using a combination of equilibrium and nonequilibrium computer simulations, that interaction heterogeneity—variations in the energetic interactions among different particle pairs in the population—may favorably impact crystal nucleation. Specifically, interaction heterogeneity is found to lower the free energy barrier to nucleation via the formation of clusters comprised preferentially of strong-binding particle pairs. Moreover, gelation is inhibited by "spreading out over time" the nucleation process, resulting in a reduced density of stable nuclei, allowing each to grow unhindered and larger. Our results suggest a simple and robust approach for enhancing colloidal crystallization near the "sticky sphere" limit, and support the notion that differing extents of interaction heterogeneity arising from various particle functionalization protocols may contribute to the otherwise unexplained variations in crystallization outcomes reported in the literature.

Heterogeneous cellular networks

CERN Document Server

Hu, Rose Qingyang

2013-01-01

A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

Neurofeedback Treatment and Posttraumatic Stress Disorder: Effectiveness of Neurofeedback on Posttraumatic Stress Disorder and the Optimal Choice of Protocol.

Science.gov (United States)

Reiter, Karen; Andersen, Søren Bo; Carlsson, Jessica

2016-02-01

Neurofeedback is an alternative, noninvasive approach used in the treatment of a wide range of neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Many different neurofeedback protocols and methods exist. Likewise, PTSD is a heterogeneous disorder. To review the evidence on effectiveness and preferred protocol when using neurofeedback treatment on PTSD, a systematic search of PubMed, PsychInfo, Embase, and Cochrane databases was undertaken. Five studies were included in this review. Neurofeedback had a statistically significant effect in three studies. Neurobiological changes were reported in three studies. Interpretation of results is, however, limited by differences between the studies and several issues regarding design. The optimistic results presented here qualify neurofeedback as probably efficacious for PTSD treatment.

Obsessive-compulsive disorder comorbidity: clinical assessment and therapeutic implications

Directory of Open Access Journals (Sweden)

Stefano ePallanti

2011-12-01

Full Text Available Obsessive-compulsive disorder (OCD is a neuropsychiatric disorder affecting approximately 1-3% of the population. OCD is probably an etiologically heterogeneous condition. Individuals with OCD frequently have additional psychiatric disorders concomitantly or at some time during their lifetime. Recently, some authors proposed an OCD sub-classification based on co-morbidity. An important issue in assessing comorbidity is the fact that the non-response to treatment often involves the presence of comorbid conditions. Non-responsive patients are more likely to meet criteria for comorbid axis I or axis II disorders and the presence of a specific comorbid condition could be a distinguishing feature in OCD, with influence on the treatment adequacy and outcome.

The Neuroanatomy of Autism Spectrum Disorder: An Overview of Structural Neuroimaging Findings and Their Translatability to the Clinical Setting

Science.gov (United States)

Ecker, Christine

2017-01-01

Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult…

Predictive Validity of a Continuous Alternative to Nominal Subtypes of Attention-Deficit/Hyperactivity Disorder for "DSM-V"

Science.gov (United States)

Lahey, Benjamin B.; Willcutt, Erik G.

2010-01-01

Three subtypes of attention-deficit/hyperactivity disorder (ADHD) based on numbers of symptoms of inattention (I) and hyperactivity-impulsivity (HI) were defined in the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.) to reduce heterogeneity of the disorder, but the subtypes proved to be highly unstable over time. A continuous…

Broad Categories for the Diagnosis of Eating Disorders (BCD-ED): An Alternative System for Classification

OpenAIRE

Walsh, B. Timothy; Sysko, Robyn

2009-01-01

Eating Disorder Not Otherwise Specified (EDNOS), a residual category in DSM-IV, is the most commonly used eating disorder diagnosis in clinical settings. However, the features of individuals with EDNOS are heterogeneous and difficult to characterize. A diagnostic scheme, termed Broad Categories for the Diagnosis of Eating Disorders (BCD-ED), is proposed to diminish use of the EDNOS category markedly while preserving the existing eating disorder categories. The BCD-ED scheme consists of three ...

[Clinical and neurophysiological heterogeneity of attention deficit hyperactivity disorder].

Science.gov (United States)

Chutko, L S; Yakovenko, E A; Surushkina, S Yu; Anisimova, T I; Kropotov, Yu D

To determine clinical/neurophysiological characteristics of different forms of attention deficit hyperactivity disorder (ADHD) and the efficacy of treatment with cerebrolysin. Sixty children, aged 9 to 12 years, with ADHD were examined using clinical and electroencephalographic methods. Idiopathic and residual-organic forms were compared. The study shows significantly higher levels of impulsivity and hyperactivity in children with residual-organic form of the disease. There were significant differences in the amplitude component of engaging in action (P3 Go) and the amplitude of the action suppression component (P3 NOGO) in patients with different forms of ADHD. The high clinical efficacy (improvement in 70.0% of patients with idiopathic form of ADHD and 86.7% of patients with residual-organic form of the disease) was found.

The evolving diagnostic and genetic landscapes of autism spectrum disorder

Directory of Open Access Journals (Sweden)

Mark Nicholas Ziats

2016-04-01

Full Text Available The autism spectrum disorders (ASD are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

The Evolving Diagnostic and Genetic Landscapes of Autism Spectrum Disorder.

Science.gov (United States)

Ziats, Mark N; Rennert, Owen M

2016-01-01

The autism spectrum disorders (ASD) are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

Role of Disorder in Enhancing Lithium-Ion Battery Performance

DEFF Research Database (Denmark)

Yue, Yuanzheng; He, W.

and type of disorder, material performances can be significantly enhanced. Disorder can be tuned by doping, calcination, redox reaction, composition tuning, and so on. Recently we have fabricated a cathode material for lithium ion battery by introducing heterostructure and disorder into the material...... material exhibits the extremely high reversible lithium ion capacity and extraordinary rate capability with high cycling stability at high discharge current. In this presentation we demonstrate that the disorder plays a decisive role in achieving those exceptional electrochemical performances. We describe...... how the disorder affects the migration of both lithium ions and electrons. It is found that both the modified glassy surface and the heterogeneous superlattice structure greatly contribute to the extremely high discharge/charge rates owing to the enhanced storage capacity of lithium ions and ultrafast...

Psychometric Characteristics of a Measure of Emotional Dispositions Developed to Test a Developmental Propensity Model of Conduct Disorder

Science.gov (United States)

Lahey, Benjamin B.; Applegate, Brooks; Chronis, Andrea M.; Jones, Heather A.; Williams, Stephanie Hall; Loney, Jan; Waldman, Irwin D.

2008-01-01

Lahey and Waldman proposed a developmental propensity model in which three dimensions of children's emotional dispositions are hypothesized to transact with the environment to influence risk for conduct disorder, heterogeneity in conduct disorder, and comorbidity with other disorders. To prepare for future tests of this model, a new measure of…

DNA methylation in a Scottish family multiply affected by bipolar disorder and major depressive disorder.

Science.gov (United States)

Walker, Rosie May; Christoforou, Andrea Nikie; McCartney, Daniel L; Morris, Stewart W; Kennedy, Nicholas A; Morten, Peter; Anderson, Susan Maguire; Torrance, Helen Scott; Macdonald, Alix; Sussmann, Jessika Elizabeth; Whalley, Heather Clare; Blackwood, Douglas H R; McIntosh, Andrew Mark; Porteous, David John; Evans, Kathryn Louise

2016-01-01

Bipolar disorder (BD) is a severe, familial psychiatric condition. Progress in understanding the aetiology of BD has been hampered by substantial phenotypic and genetic heterogeneity. We sought to mitigate these confounders by studying a multi-generational family multiply affected by BD and major depressive disorder (MDD), who carry an illness-linked haplotype on chromosome 4p. Within a family, aetiological heterogeneity is likely to be reduced, thus conferring greater power to detect illness-related changes. As accumulating evidence suggests that altered DNA methylation confers risk for BD and MDD, we compared genome-wide methylation between (i) affected carriers of the linked haplotype (ALH) and married-in controls (MIs), (ii) well unaffected haplotype carriers (ULH) and MI, (iii) ALH and ULH and (iv) all haplotype carriers (LH) and MI. Nominally significant differences in DNA methylation were observed in all comparisons, with differences withstanding correction for multiple testing when the ALH or LH group was compared to the MIs. In both comparisons, we observed increased methylation at a locus in FANCI, which was accompanied by increased FANCI expression in the ALH group. FANCI is part of the Fanconi anaemia complementation (FANC) gene family, which are mutated in Fanconi anaemia and participate in DNA repair. Interestingly, several FANC genes have been implicated in psychiatric disorders. Regional analyses of methylation differences identified loci implicated in psychiatric illness by genome-wide association studies, including CACNB2 and the major histocompatibility complex. Gene ontology analysis revealed enrichment for methylation differences in neurologically relevant genes. Our results highlight altered DNA methylation as a potential mechanism by which the linked haplotype might confer risk for mood disorders. Differences in the phenotypic outcome of haplotype carriers might, in part, arise from additional changes in DNA methylation that converge on

Attentional Profiles and White Matter Correlates in Attention-Deficit/Hyperactivity Disorder Predominantly Inattentive Type

OpenAIRE

Rossi, Adriana Suzart Ungaretti; de Moura, Luciana Monteiro; de Mello, Claudia Berlim; de Souza, Altay Alves Lino; Muszkat, Mauro; Bueno, Orlando Francisco Amodeo

2015-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a widely studied neurodevelopmental disorder. It is a highly heterogeneous condition, encompassing different types of expression. The predominantly inattentive type is the most prevalent and the most stable over the lifetime, yet it is the least-studied presentation. To increase understanding of its cognitive profile, 29 children with Attention-deficit/hyperactivity disorder of predominantly inattentive type (ADHD-I) and 29 matched controls, ...

Paranoid Schizophrenia versus Schizoaffective Disorder: Neuropsychological Aspects.

Science.gov (United States)

Leposavić, Ljubica; Leposavić, Ivana; Šaula-Marojević, Bijana; Gavrilović, Predrag

2015-01-01

Neuropsychological aspects of paranoid schizophrenia have still not been examined enough.These disorders are usually not studied separately, but are included in the studies about schizophrenic patients with positive symptoms. Despite the fact that schizophrenia represents a heterogeneous group of mental disorders, usually it is not separated from schizoaffective disorder in neuropsychological researches. The essence of this research is to evaluate cognitive functioning of patients with paranoid schizophrenia and schizoaffective disorder by applying neuropsychological tests. The research included 91 subjects, right handed, from 30 to 53 years old, who were classified into three groups: inpatients with paranoid schizophrenia in remission (n=31), inpatients with schizoaffective disorder in remission (n=30) and healthy subjects (n=30). Both groups of patients showed poorer achievements than healthy subjects in most of the applied tests. Patients with schizoaffective disorder showed global loss of intellectual efficiency, executive dysfunction and compromised visual-construction organization. Patients with paranoid schizophrenia expressed partial loss of intellectual efficiency with verbal IQ and executive functions preserved. In the remission phase, patients with paranoid schizophrenia expressed cognitive disorders in moderate degree, but when it comes to patients with schizoaffective disorder, more massive cognitive, deficits were registered.

Joint analysis of psychiatric disorders increases accuracy of risk prediction for schizophrenia, bipolar disorder, and major depressive disorder

DEFF Research Database (Denmark)

Maier, Robert; Moser, Gerhard; Chen, Guo-Bo

2015-01-01

Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk...... number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low...

Screening for copy number alterations in loci associated with autism spectrum disorders by two-color multiplex ligation-dependent probe amplification

DEFF Research Database (Denmark)

Bremer, Anna; Giacobini, Maibritt; Nordenskjöld, Magnus

2010-01-01

The autism spectrum disorder (ASD) is a heterogenous condition characterized by impaired socialization and communication in association with stereotypic behaviors. ASD is highly heritable and heterogeneous with a complex genetic etiology. Recurrent submicroscopic deletions or duplications have been...

Heterogeneous shear elasticity of glasses: The origin of the boson peak

KAUST Repository

Marruzzo, Alessia

2013-03-08

The local elasticity of glasses is known to be inhomogeneous on a microscopic scale compared to that of crystalline materials. Their vibrational spectrum strongly deviates from that expected from Debye\\'s elasticity theory: The density of states deviates from Debye\\'s law, the sound velocity shows a negative dispersion in the boson-peak frequency regime and there is a strong increase of the sound attenuation near the boson-peak frequency. By comparing a mean-field theory of shear-elastic heterogeneity with a large-scale simulation of a soft-sphere glass we demonstrate that the observed anomalies in glasses are caused by elastic heterogeneity. By observing that the macroscopic bulk modulus is frequency independent we show that the boson-peak-related vibrational anomalies are predominantly due to the spatially fluctuating microscopic shear stresses. It is demonstrated that the boson-peak arises from the steep increase of the sound attenuation at a frequency which marks the transition from wave-like excitations to disorder-dominated ones.

Heterogeneous shear elasticity of glasses: The origin of the boson peak

KAUST Repository

Marruzzo, Alessia; Schirmacher, Walter; Fratalocchi, Andrea; Ruocco, Giancarlo

2013-01-01

The local elasticity of glasses is known to be inhomogeneous on a microscopic scale compared to that of crystalline materials. Their vibrational spectrum strongly deviates from that expected from Debye's elasticity theory: The density of states deviates from Debye's law, the sound velocity shows a negative dispersion in the boson-peak frequency regime and there is a strong increase of the sound attenuation near the boson-peak frequency. By comparing a mean-field theory of shear-elastic heterogeneity with a large-scale simulation of a soft-sphere glass we demonstrate that the observed anomalies in glasses are caused by elastic heterogeneity. By observing that the macroscopic bulk modulus is frequency independent we show that the boson-peak-related vibrational anomalies are predominantly due to the spatially fluctuating microscopic shear stresses. It is demonstrated that the boson-peak arises from the steep increase of the sound attenuation at a frequency which marks the transition from wave-like excitations to disorder-dominated ones.

Short overview on metabolomic approach and redox changes in psychiatric disorders

Directory of Open Access Journals (Sweden)

Gordana Nedic Erjavec

2018-04-01

Full Text Available Schizophrenia, depression and posttraumatic stress disorder (PTSD are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment. Metabolomics is a discipline that combines different strategies with the aim to extract, detect, identify and quantify all metabolites that are present in a biological sample and might provide mechanistic insights into the etiology of various psychiatric disorders. Therefore, oxidative stress research combined with metabolomics might offer a novel approach in dissecting psychiatric disorders, since these data-driven but not necessarily hypothesis-driven methods might identify new targets, molecules and pathways responsible for development of schizophrenia, depression or PTSD. Findings from the oxidative research in psychiatry together with metabolomics data might facilitate development of specific and validated prognostic, therapeutic and clinical biomarkers. These methods might reveal bio-signatures of individual patients, leading to individualized treatment approach. In reviewing findings related to oxidative stress and metabolomics in selected psychiatric disorders, we have highlighted how these novel approaches might make a unique contribution to deeper understanding of psychopathological alterations underlying schizophrenia, depression and PTSD. Keywords: Schizophrenia, Depression, Posttraumatic stress disorder, Oxidative stress, Lipid peroxidation, Metabolomics, Biomarkers

Abdominal multi-organ segmentation from CT images using conditional shape-location and unsupervised intensity priors.

Science.gov (United States)

Okada, Toshiyuki; Linguraru, Marius George; Hori, Masatoshi; Summers, Ronald M; Tomiyama, Noriyuki; Sato, Yoshinobu

2015-12-01

This paper addresses the automated segmentation of multiple organs in upper abdominal computed tomography (CT) data. The aim of our study is to develop methods to effectively construct the conditional priors and use their prediction power for more accurate segmentation as well as easy adaptation to various imaging conditions in CT images, as observed in clinical practice. We propose a general framework of multi-organ segmentation which effectively incorporates interrelations among multiple organs and easily adapts to various imaging conditions without the need for supervised intensity information. The features of the framework are as follows: (1) A method for modeling conditional shape and location (shape-location) priors, which we call prediction-based priors, is developed to derive accurate priors specific to each subject, which enables the estimation of intensity priors without the need for supervised intensity information. (2) Organ correlation graph is introduced, which defines how the conditional priors are constructed and segmentation processes of multiple organs are executed. In our framework, predictor organs, whose segmentation is sufficiently accurate by using conventional single-organ segmentation methods, are pre-segmented, and the remaining organs are hierarchically segmented using conditional shape-location priors. The proposed framework was evaluated through the segmentation of eight abdominal organs (liver, spleen, left and right kidneys, pancreas, gallbladder, aorta, and inferior vena cava) from 134 CT data from 86 patients obtained under six imaging conditions at two hospitals. The experimental results show the effectiveness of the proposed prediction-based priors and the applicability to various imaging conditions without the need for supervised intensity information. Average Dice coefficients for the liver, spleen, and kidneys were more than 92%, and were around 73% and 67% for the pancreas and gallbladder, respectively. Copyright © 2015

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

OpenAIRE

Stephanie Zettner; Sandeep G. Mistry

2014-01-01

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospital...

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

NARCIS (Netherlands)

Lowe, N.; Kirley, A.; Hawi, Z.; Sham, P.; Wickham, H.; Kratochvil, C.J.; Smith, S.D.; Lee, S.Y.; Levy, F.; Kent, L.; Middle, F.; Rohde, L.A.; Roman, T.; Tahir, E.; Yazgan, Y.; Asherson, P.; Mill, J.; Thapar, A.; Payton, A.; Todd, R.D.; Stephens, T.; Ebstein, R.P.; Manor, I.; Barr, C.L.; Wigg, K.G.; Sinke, R.J.; Buitelaar, J.K.; Smalley, S.L.; Nelson, S.F.; Biederman, J.; Faraone, S.V.; Gill, M.

2004-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the

Diagnostic Biomarkers for Posttraumatic Stress Disorder: Promising Horizons from Translational Neuroscience Research.

Science.gov (United States)

Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

2015-09-01

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently reclassified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition, the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the etiology and maintenance of PTSD. Translational research spanning the past few decades has revealed several potential avenues for the identification of diagnostic biomarkers for PTSD. These include, but are not limited to, monoaminergic transmitter systems, the hypothalamic-pituitary-adrenal axis, metabolic hormonal pathways, inflammatory mechanisms, psychophysiological reactivity, and neural circuits. The current review provides an update to the literature with regard to the most promising putative PTSD biomarkers, with specific emphasis on the interaction between neurobiological influences on disease risk and symptom progression. Such biomarkers will most likely be identified by multi-dimensional models derived from comprehensive descriptions of molecular, neurobiological, behavioral, and clinical phenotypes. Copyright © 2015 Society of Biological Psychiatry. All rights reserved.

Psychoneuroimmunological disorders and temporomandibular joint pain: A review

Directory of Open Access Journals (Sweden)

Ranjani Shetty

2014-01-01

Full Text Available Psychoneuroimmunology characterizes a disease entity that combines psychological components, central nervous system regulation, and immunology, to explain the etiological complexity of a disease. Temporomandibular disorders (TMDs include a heterogeneous group of painful conditions that involve the temporomandibular joint (TMJ, muscles of mastication, and the adjacent anatomic structures. This review focuses on the psychoneuroimmunological diseases and disorders that mimic the symptoms of TMDs. The differentiation of these disorders is of great significance to the oral physician - differentiating and diagnosing the cause of TMJ pain and treating it effectively to benefit the patient.The literature for this review was taken from Medline/PubMed, other indexed journals, standard text books, and online material.

Tic disorders: administrative prevalence and co-occurrence with attention-deficit/hyperactivity disorder in a German community sample.

Science.gov (United States)

Schlander, M; Schwarz, O; Rothenberger, A; Roessner, V

2011-09-01

Coexistence of tics and attention-deficit/hyperactivity disorder (ADHD) has important clinical and scientific implications. Existing data on the co-occurrence of tic disorders, Tourette Syndrome (TS), and ADHD are largely derived from small-scale studies in selected samples and therefore heterogeneous. The Nordbaden project captures the complete outpatient claims data of more than 2.2 million persons, representing 82% of the regional population in 2003. Based upon the number of diagnosed cases of tic disorders, TS, and ADHD, we determined 12-months administrative prevalence rates as well as rates of co-occurrence. Both tic disorders and ADHD were diagnosed most often in the age group 7-12 years (any tic disorder: 0.8%; ADHD: 5.0%). With increasing age, the administrative prevalence difference in favor of males disappeared, with tic disorders being somewhat more frequently reported in females than males in the age groups above 30 years. The highest rate of ADHD co-occurring with tic disorders was found in adolescents (age 13-18 years, 15.1%). Tic disorders were observed in 2.3% of patients with ADHD. Administrative prevalence rates of tic disorders and TS were substantially lower compared to rates found in community-based epidemiological studies, suggesting that a large number of cases remain undetected and untreated under present conditions of routine outpatient care. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Schizoaffective disorder--an ongoing challenge for psychiatric nosology.

Science.gov (United States)

Jäger, M; Haack, S; Becker, T; Frasch, K

2011-04-01

Schizoaffective disorder is a common diagnosis in mental health services. The present article aims to provide an overview of diagnostic reliability, symptomatology, outcome, neurobiology and treatment of schizoaffective disorder. Literature was identified by searches in "Medline" and "Cochrane Library". The diagnosis of schizoaffective disorder has a low reliability. There are marked differences between the current diagnostic systems. With respect to psychopathological symptoms, no clear boundaries were found between schizophrenia, schizoaffective disorder and affective disorders. Common neurobiological factors were found across the traditional diagnostic categories. Schizoaffective disorder according to ICD-10 criteria, but not to DSM-IV criteria, shows a more favorable outcome than schizophrenia. With regard to treatment, only a small and heterogeneous database exists. Due to the low reliability and questionable validity there is a substantial need for revision and unification of the current diagnostic concepts of schizoaffective disorder. If future diagnostic systems return to Kraepelin's dichotomous classification of non-organic psychosis or adopt a dimensional diagnostic approach, schizoaffective disorder will disappear from the psychiatric nomenclature. A nosological model with multiple diagnostic entities, however, would be compatible with retaining the diagnostic category of schizoaffective disorder. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Stability and change in the clinical course of schizoaffective disorder.

Science.gov (United States)

Durla, Anca; Lenciu, M; Bredicean, C; Papava, I; Cristanovici, M

2013-01-01

Schizoaffective disorder currently raises several questions, one of them being related to the stability of the clinical diagnosis over time. The aim of this study is to identify the clinical and evolutional particularities in the longitudinal course of schizoaffective disorder. 44 subjects with a current diagnosis of schizoaffective disorder have been assessed prospectively. Following parameters were analyzed: socio-demographic (age at onset, gender, educational, professional and marital status at onset) and clinical (total duration of evolution, diagnosis at onset, duration of the evolution until the switch to the schizoaffective disorder diagnosis). Socio-demographic parameters are similar to those in literature and the clinical assessment revealed that schizoaffective disorder is present as a diagnosis along with the longitudinal course of other types of psychosis. Schizoaffective disorder appears as a heterogeneous pathology in terms of the longitudinal course.

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

Science.gov (United States)

Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

Avoidant/Restrictive Food Intake Disorder (ARFID).

Science.gov (United States)

Zimmerman, Jacqueline; Fisher, Martin

2017-04-01

Avoidant/restrictive food intake disorder (ARFID) is an entirely new diagnosis in the DSM-5. ARFID replaces "feeding disorder of infancy or early childhood," which was a diagnosis in the DSM-IV restricted to children 6 years of age or younger; ARFID has no such age limitations and it is distinct from anorexia nervosa and bulimia nervosa in that there is no body image disturbance. ARFID involves a complex and heterogenous etiology, which is reviewed herein. What is known to date regarding the characteristics and medical and psychiatric comorbidities of this patient population are described and compared to other eating disorders. Evaluation and management strategies are also discussed. No data yet exist regarding ARFID׳s prognosis and prevention; however, recommendations to guide parents in establishing appropriate infant and child feeding practices are provided. Copyright © 2017 Mosby, Inc. All rights reserved.

Relationship of functional gastrointestinal disorders and psychiatric disorders: Implications for treatment

Science.gov (United States)

North, Carol S; Hong, Barry A; Alpers, David H

2007-01-01

This article revisits the links between psychopathology and functional gastrointestinal disorders such as irritable bowel syndrome (IBS), discusses the rational use of antidepressants as well as non-pharmacological approaches to the management of IBS, and suggests guidelines for the treatment of IBS based on an interdisciplinary perspective from the present state of knowledge. Relevant published literature on psychiatric disorders, especially somatization disorder, in the context of IBS, and literature providing direction for management is reviewed, and new directions are provided from findings in the literature. IBS is a heterogeneous syndrome with various potential mechanisms responsible for its clinical presentations. IBS is typically complicated with psychiatric issues, unexplained symptoms, and functional syndromes in other organ systems. Most IBS patients have multiple complaints without demonstrated cause, and that these symptoms can involve systems other than the intestine, e.g. bones and joints (fibromyalgia, temporomandibular joint syndrome), heart (non-cardiac chest pain), vascular (post-menopausal syndrome), and brain (anxiety, depression). Most IBS patients do not have psychiatric illness per se, but a range of psychoform (psychological complaints in the absence of psychiatric disorder) symptoms that accompany their somatoform (physical symptoms in the absence of medical disorder) complaints. It is not correct to label IBS patients as psychiatric patients (except those more difficult patients with true somatization disorder). One mode of treatment is unlikely to be universally effective or to resolve most symptoms. The techniques of psychotherapy or cognitive-behavioral therapy can allow IBS patients to cope more readily with their illness. Specific episodes of depressive or anxiety disorders can be managed as appropriate for those conditions. Medications designed to improve anxiety or depression are not uniformly useful for psychiatric complaints in

Relationship of functional gastrointestinal disorders and psychiatric disorders: Implications for treatment

Institute of Scientific and Technical Information of China (English)

Carol S North; Barry A Hong; David H Alpers

2007-01-01

This article revisits the links between psychopathology and functional gastrointestinal disorders such as irritable bowel syndrome (IBS), discusses the rational use of antidepressants as well as non-pharmacological approaches to the management of IBS, and suggests guidelines for the treatment of IBS based on an interdisciplinary perspective from the present state of knowledge. Relevant published literature on psychiatric disorders, especially somatization disorder, in the context of IBS, and literature providing direction for management is reviewed, and new directions are provided from findings in the literature. IBS is a heterogeneous syndrome with various potential mechanisms responsible for its clinical presentations. IBS is typically complicated with psychiatric issues, unexplained symptoms, and functional syndromes in other organ systems. Most IBS patients have multiple complaints without demonstrated cause, and that these symptoms can involve systems other than the intestine, e.g. Bones and joints (fibromyalgia, temporomandibular joint syndrome), heart (non-cardiac chest pain), vascular (post-menopausal syndrome), and brain (anxiety, depression). Most IBS patients do not have psychiatric illness per se, but a range of psychoform (psychological complaints in the absence of psychiatric disorder) symptoms that accompany their somatoform (physical symptoms in the absence of medical disorder) complaints. It is not correct to label IBS patients as psychiatric patients (except those more difficult patients with true somatization disorder).One mode of treatment is unlikely to be universally effective or to resolve most symptoms. The techniques of psychotherapy or cognitive-behavioral therapy can allow IBS patients to cope more readily with their illness.Specific episodes of depressive or anxiety disorders can be managed as appropriate for those conditions.Medications designed to improve anxiety or depression are not uniformly useful for psychiatric complaints in IBS

A practical guide for the diagnosis of primary enteric nervous system disorders

DEFF Research Database (Denmark)

Schäppi, M G; Staiano, A; Milla, P J

2013-01-01

OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques...

Fatal hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine

DEFF Research Database (Denmark)

Madsen, Kristian Roerbaek

2014-01-01

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure wi...... and possibly plasmapheresis in case of extreme hypertriglyceridaemia....

Brucellosis With Multi-Organ Involvement in a Patient With History of Composite Aortic Graft and Hepatitis B.

Science.gov (United States)

Dehghan Manshadi, Seyed Ali; Rezahosseini, Omid; Abdi Liaei, Zahra

2016-11-01

The brucellosis with multi-organ involvement in a patient with a history of the composite aortic graft (Bentall procedure) and Hepatitis B infection is rare. A 35-year-old man presented to us with fever and loss of consciousness. Four years ago, he was IDU and underwent cardiac surgery because of endocarditis. Recently lumbar spondylodiscitis was diagnosed. The Wright (1/320) and Coombs Wright tests (1/640) were positive. After CNS imaging, lumbar puncture was done. The CSF pleocytosis was lymphocyte dominant. In cardiac echocardiography, large vegetation on prosthetic aortic valve leaflets was seen. The brain MRI was reported abnormal. Treatment of brucellosis started with Ceftriaxone, Doxycycline, Rifampin and Gentamycin. After 4 days, he became oriented, and fever was disappeared then we continued the treatment for 16 days. The patient discharged and followed by daily phone calls. As symptoms of abdominal pain and jaundice were presented on the fifth day, he re-admitted. The patient expired because of hepatorenal and cardiac insufficiency. Drug side effects, activation of Hepatitis B and embolism of cardiac vegetation to other organs were suspected causes of death. We do not suggest medical therapy without cardiac surgery in such cases. When combination therapy is necessary for brucellosis in an HBsAg-positive patient, hepatitis virus activity should be assess by HBV-DNA PCR and the dose of drugs with known hepatotoxic effects such as rifampin and co-trimoxazole should be adjust. Combination therapy with quinolones instead of hepatoxic drugs is one of our suggustions.

The varied clinical presentations of major depressive disorder.

Science.gov (United States)

Rush, A John

2007-01-01

DSM-IV major depressive disorder (MDD) is a clinical syndrome notable for heterogeneity of its clinical presentation, genetics, neurobiology, clinical course, and treatment responsiveness. In an attempt to make sense of this heterogeneity, clinicians and researchers have proposed a number of MDD "subtypes" based on differences in characteristic symptoms (e.g., atypical, melancholic, psychotic), onset (e.g., early vs. late, post-partum, seasonal), course of illness (e.g., single vs. recurrent, chronic, double), and severity. This article provides a brief review of the status of several of the most common subtypes in terms of their clinical features, biological correlates, course of illness, and treatment implications.

Epigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia.

Science.gov (United States)

Moos, Walter H; Maneta, Eleni; Pinkert, Carl A; Irwin, Michael H; Hoffman, Michelle E; Faller, Douglas V; Steliou, Kosta

2016-03-01

Neuropsychiatric disorders are a heterogeneous group of conditions that often share underlying mitochondrial dysfunction and biological pathways implicated in their pathogenesis, progression, and treatment. To date, these disorders have proven notoriously resistant to molecular-targeted therapies, and clinical options are relegated to interventional types, which do not address the core symptoms of the disease. In this review, we discuss emerging epigenetic-driven approaches using novel acylcarnitine esters (carnitinoids) that act on master regulators of antioxidant and cytoprotective genes and mitophagic pathways. These carnitinoids are actively transported, mitochondria-localizing, biomimetic coenzyme A surrogates of short-chain fatty acids, which inhibit histone deacetylase and may reinvigorate synaptic plasticity and protect against neuronal damage. We outline these neuroprotective effects in the context of treatment of neuropsychiatric disorders such as autism spectrum disorder and schizophrenia. © 2016 Wiley Periodicals, Inc.

Genetic heterogeneity of retinitis pigmentosa

OpenAIRE

Hartono, Hartono

2015-01-01

Genetic heterogeneity is a phenomenon in which a genetic disease can be transmitted by several modes of inheritance. The understanding of genetic heterogeneity is important in giving genetic counselling.The presence of genetic heterogeneity can be explained by the existence of:1.different mutant alleles at a single locus, and2.mutant alleles at different loci affecting the same enzyme or protein, or affecting different enzymes or proteins.To have an overall understanding of genetic heterogene...

Paranoid schizophrenia versus schizoaffective disorder: Neuropsychological aspects

Directory of Open Access Journals (Sweden)

Leposavić Ljubica

2015-01-01

Full Text Available Introduction. Neuropsychological aspects of paranoid schizophrenia have still not been examined enough. These disorders are usually not studied separately, but are included in the studies about schizophrenic patients with positive symptoms. Despite the fact that schizophrenia represents a heterogeneous group of mental disorders, usually it is not separated from schizoaffective disorder in neuropsychological researches. Objective. The essence of this research is to evaluate cognitive functioning of patients with paranoid schizophrenia and schizoaffective disorder by applying neuropsychological tests. Methods. The research included 91 subjects, right handed, from 30 to 53 years old, who were classified into three groups: inpatients with paranoid schizophrenia in remission (n=31, inpatients with schizoaffective disorder in remission (n=30 and healthy subjects (n=30. Results. Both groups of patients showed poorer achievements than healthy subjects in most of the applied tests. Patients with schizoaffective disorder showed global loss of intellectual efficiency, executive dysfunction and compromised visual-construction organization. Patients with paranoid schizophrenia expressed partial loss of intellectual efficiency with verbal IQ and executive functions preserved. Conclusion. In the remission phase, patients with paranoid schizophrenia expressed cognitive disorders in moderate degree, but when it comes to patients with schizoaffective disorder, more massive cognitive deficits were registered.

Diagnostic Biomarkers for Posttraumatic Stress Disorder (PTSD): Promising Horizons from Translational Neuroscience Research

Science.gov (United States)

Michopoulos, Vasiliki; Norrholm, Seth Davin; Jovanovic, Tanja

2015-01-01

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). Although its diagnostic features have been recently re-classified with the emergence of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), the disorder remains characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the etiology and maintenance of PTSD. Translational research spanning the past few decades has revealed several potential avenues for the identification of diagnostic biomarkers for PTSD. These include, but are not limited to, monoaminergic transmitter systems, the hypothalamic-pituitary-adrenal (HPA) axis, metabolic hormonal pathways, inflammatory mechanisms, psychophysiological reactivity, and neural circuits. The current review provides an update to the literature with regard to the most promising putative PTSD biomarkers with specific emphasis on the interaction between neurobiological influences on disease risk and symptom progression. Such biomarkers will most likely be identified by multi-dimensional models derived from comprehensive descriptions of molecular, neurobiological, behavioral, and clinical phenotypes. PMID:25727177

Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

International Nuclear Information System (INIS)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik; Kim, Eung Yeop; Lee, Young-Mock; Lee, Joon Soo; Kim, Heung Dong

2008-01-01

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

Energy Technology Data Exchange (ETDEWEB)

Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

2008-08-15

Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

Esophageal motility disorders; Motilitaetsstoerungen des Oesophagus

Energy Technology Data Exchange (ETDEWEB)

Hannig, C.; Rummeny, E. [Klinikum rechts der Isar der Technischen Universitaet Muenchen, Institut fuer Roentgendiagnostik, Muenchen (Germany); Wuttge-Hannig, A. [Gemeinschaftspraxis fuer Radiologie, Nuklearmedizin und Strahlentherapie, Muenchen (Germany)

2007-02-15

For the better understanding of esophageal motility, the muscle texture and the distribution of skeletal and smooth muscle fibers in the esophagus are of crucial importance. Esophageal physiology will be shortly mentioned as far as necessary for a comprehensive understanding of peristaltic disturbances. Besides the pure depiction of morphologic criteria, a complete esophageal study has to include an analysis of the motility. New diagnostic tools with reduced radiation for dynamic imaging (digital fluoroscopy, videofluoroscopy) at 4-30 frames/s are available. Radiomanometry is a combination of a functional pressure measurement and a simultaneous dynamic morphologic analysis. Esophageal motility disorders are subdivided by radiologic and manometric criteria into primary, secondary, and nonclassifiable forms. Primary motility disorders of the esophagus are achalasia, diffuse esophageal spasm, nutcracker esophagus, and the hypertonic lower esophageal sphincter. The secondary motility disorders include pseudoachalasia, reflux-associated motility disorders, functionally caused impactions, Boerhaave's syndrome, Chagas' disease, scleroderma, and presbyesophagus. The nonclassificable motility disorders (NEMD) are a very heterogeneous collective. (orig.) [German] Zum Verstaendnis der Motilitaet des Oesophagus sind muskulaere Architektur und Verteilung der quergestreiften und glatten Muskelfasern von Bedeutung. Die Physiologie des Oesophagus wird in soweit kurz dargestellt, als sie fuer das Verstaendnis von peristaltischen Stoerungen notwendig ist. Neben der Erfassung rein morphologischer Kriterien ist bei der Untersuchung der Speiseroehre eine diagnostische Bewertung der Motilitaet erforderlich. Es stehen uns heute strahlungsarme dynamische Aufzeichnungsverfahren (digitale dynamische Aufzeichnung, Videofluoroskopie) mit Bildsequenzen von 4-30 Bildern/s zur Verfuegung. Die Kombination einer funktionellen Methode zur Darstellung der Morphologie und der

Analysis of shared heritability in common disorders of the brain.

Science.gov (United States)

Anttila, Verneri; Bulik-Sullivan, Brendan; Finucane, Hilary K; Walters, Raymond K; Bras, Jose; Duncan, Laramie; Escott-Price, Valentina; Falcone, Guido J; Gormley, Padhraig; Malik, Rainer; Patsopoulos, Nikolaos A; Ripke, Stephan; Wei, Zhi; Yu, Dongmei; Lee, Phil H; Turley, Patrick; Grenier-Boley, Benjamin; Chouraki, Vincent; Kamatani, Yoichiro; Berr, Claudine; Letenneur, Luc; Hannequin, Didier; Amouyel, Philippe; Boland, Anne; Deleuze, Jean-François; Duron, Emmanuelle; Vardarajan, Badri N; Reitz, Christiane; Goate, Alison M; Huentelman, Matthew J; Kamboh, M Ilyas; Larson, Eric B; Rogaeva, Ekaterina; St George-Hyslop, Peter; Hakonarson, Hakon; Kukull, Walter A; Farrer, Lindsay A; Barnes, Lisa L; Beach, Thomas G; Demirci, F Yesim; Head, Elizabeth; Hulette, Christine M; Jicha, Gregory A; Kauwe, John S K; Kaye, Jeffrey A; Leverenz, James B; Levey, Allan I; Lieberman, Andrew P; Pankratz, Vernon S; Poon, Wayne W; Quinn, Joseph F; Saykin, Andrew J; Schneider, Lon S; Smith, Amanda G; Sonnen, Joshua A; Stern, Robert A; Van Deerlin, Vivianna M; Van Eldik, Linda J; Harold, Denise; Russo, Giancarlo; Rubinsztein, David C; Bayer, Anthony; Tsolaki, Magda; Proitsi, Petra; Fox, Nick C; Hampel, Harald; Owen, Michael J; Mead, Simon; Passmore, Peter; Morgan, Kevin; Nöthen, Markus M; Rossor, Martin; Lupton, Michelle K; Hoffmann, Per; Kornhuber, Johannes; Lawlor, Brian; McQuillin, Andrew; Al-Chalabi, Ammar; Bis, Joshua C; Ruiz, Agustin; Boada, Mercè; Seshadri, Sudha; Beiser, Alexa; Rice, Kenneth; van der Lee, Sven J; De Jager, Philip L; Geschwind, Daniel H; Riemenschneider, Matthias; Riedel-Heller, Steffi; Rotter, Jerome I; Ransmayr, Gerhard; Hyman, Bradley T; Cruchaga, Carlos; Alegret, Montserrat; Winsvold, Bendik; Palta, Priit; Farh, Kai-How; Cuenca-Leon, Ester; Furlotte, Nicholas; Kurth, Tobias; Ligthart, Lannie; Terwindt, Gisela M; Freilinger, Tobias; Ran, Caroline; Gordon, Scott D; Borck, Guntram; Adams, Hieab H H; Lehtimäki, Terho; Wedenoja, Juho; Buring, Julie E; Schürks, Markus; Hrafnsdottir, Maria; Hottenga, Jouke-Jan; Penninx, Brenda; Artto, Ville; Kaunisto, Mari; Vepsäläinen, Salli; Martin, Nicholas G; Montgomery, Grant W; Kurki, Mitja I; Hämäläinen, Eija; Huang, Hailiang; Huang, Jie; Sandor, Cynthia; Webber, Caleb; Muller-Myhsok, Bertram; Schreiber, Stefan; Salomaa, Veikko; Loehrer, Elizabeth; Göbel, Hartmut; Macaya, Alfons; Pozo-Rosich, Patricia; Hansen, Thomas; Werge, Thomas; Kaprio, Jaakko; Metspalu, Andres; Kubisch, Christian; Ferrari, Michel D; Belin, Andrea C; van den Maagdenberg, Arn M J M; Zwart, John-Anker; Boomsma, Dorret; Eriksson, Nicholas; Olesen, Jes; Chasman, Daniel I; Nyholt, Dale R; Avbersek, Andreja; Baum, Larry; Berkovic, Samuel; Bradfield, Jonathan; Buono, Russell; Catarino, Claudia B; Cossette, Patrick; De Jonghe, Peter; Depondt, Chantal; Dlugos, Dennis; Ferraro, Thomas N; French, Jacqueline; Hjalgrim, Helle; Jamnadas-Khoda, Jennifer; Kälviäinen, Reetta; Kunz, Wolfram S; Lerche, Holger; Leu, Costin; Lindhout, Dick; Lo, Warren; Lowenstein, Daniel; McCormack, Mark; Møller, Rikke S; Molloy, Anne; Ng, Ping-Wing; Oliver, Karen; Privitera, Michael; Radtke, Rodney; Ruppert, Ann-Kathrin; Sander, Thomas; Schachter, Steven; Schankin, Christoph; Scheffer, Ingrid; Schoch, Susanne; Sisodiya, Sanjay M; Smith, Philip; Sperling, Michael; Striano, Pasquale; Surges, Rainer; Thomas, G Neil; Visscher, Frank; Whelan, Christopher D; Zara, Federico; Heinzen, Erin L; Marson, Anthony; Becker, Felicitas; Stroink, Hans; Zimprich, Fritz; Gasser, Thomas; Gibbs, Raphael; Heutink, Peter; Martinez, Maria; Morris, Huw R; Sharma, Manu; Ryten, Mina; Mok, Kin Y; Pulit, Sara; Bevan, Steve; Holliday, Elizabeth; Attia, John; Battey, Thomas; Boncoraglio, Giorgio; Thijs, Vincent; Chen, Wei-Min; Mitchell, Braxton; Rothwell, Peter; Sharma, Pankaj; Sudlow, Cathie; Vicente, Astrid; Markus, Hugh; Kourkoulis, Christina; Pera, Joana; Raffeld, Miriam; Silliman, Scott; Boraska Perica, Vesna; Thornton, Laura M; Huckins, Laura M; William Rayner, N; Lewis, Cathryn M; Gratacos, Monica; Rybakowski, Filip; Keski-Rahkonen, Anna; Raevuori, Anu; Hudson, James I; Reichborn-Kjennerud, Ted; Monteleone, Palmiero; Karwautz, Andreas; Mannik, Katrin; Baker, Jessica H; O'Toole, Julie K; Trace, Sara E; Davis, Oliver S P; Helder, Sietske G; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Danner, Unna N; van Elburg, Annemarie A; Clementi, Maurizio; Forzan, Monica; Docampo, Elisa; Lissowska, Jolanta; Hauser, Joanna; Tortorella, Alfonso; Maj, Mario; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Papezova, Hana; Yilmaz, Zeynep; Wagner, Gudrun; Cohen-Woods, Sarah; Herms, Stefan; Julià, Antonio; Rabionet, Raquel; Dick, Danielle M; Ripatti, Samuli; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri J; Steen, Vidar M; Pinto, Dalila; Scherer, Stephen W; Aschauer, Harald; Schosser, Alexandra; Alfredsson, Lars; Padyukov, Leonid; Halmi, Katherine A; Mitchell, James; Strober, Michael; Bergen, Andrew W; Kaye, Walter; Szatkiewicz, Jin Peng; Cormand, Bru; Ramos-Quiroga, Josep Antoni; Sánchez-Mora, Cristina; Ribasés, Marta; Casas, Miguel; Hervas, Amaia; Arranz, Maria Jesús; Haavik, Jan; Zayats, Tetyana; Johansson, Stefan; Williams, Nigel; Dempfle, Astrid; Rothenberger, Aribert; Kuntsi, Jonna; Oades, Robert D; Banaschewski, Tobias; Franke, Barbara; Buitelaar, Jan K; Arias Vasquez, Alejandro; Doyle, Alysa E; Reif, Andreas; Lesch, Klaus-Peter; Freitag, Christine; Rivero, Olga; Palmason, Haukur; Romanos, Marcel; Langley, Kate; Rietschel, Marcella; Witt, Stephanie H; Dalsgaard, Soeren; Børglum, Anders D; Waldman, Irwin; Wilmot, Beth; Molly, Nikolas; Bau, Claiton H D; Crosbie, Jennifer; Schachar, Russell; Loo, Sandra K; McGough, James J; Grevet, Eugenio H; Medland, Sarah E; Robinson, Elise; Weiss, Lauren A; Bacchelli, Elena; Bailey, Anthony; Bal, Vanessa; Battaglia, Agatino; Betancur, Catalina; Bolton, Patrick; Cantor, Rita; Celestino-Soper, Patrícia; Dawson, Geraldine; De Rubeis, Silvia; Duque, Frederico; Green, Andrew; Klauck, Sabine M; Leboyer, Marion; Levitt, Pat; Maestrini, Elena; Mane, Shrikant; De-Luca, Daniel Moreno-; Parr, Jeremy; Regan, Regina; Reichenberg, Abraham; Sandin, Sven; Vorstman, Jacob; Wassink, Thomas; Wijsman, Ellen; Cook, Edwin; Santangelo, Susan; Delorme, Richard; Rogé, Bernadette; Magalhaes, Tiago; Arking, Dan; Schulze, Thomas G; Thompson, Robert C; Strohmaier, Jana; Matthews, Keith; Melle, Ingrid; Morris, Derek; Blackwood, Douglas; McIntosh, Andrew; Bergen, Sarah E; Schalling, Martin; Jamain, Stéphane; Maaser, Anna; Fischer, Sascha B; Reinbold, Céline S; Fullerton, Janice M; Guzman-Parra, José; Mayoral, Fermin; Schofield, Peter R; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska; Schumacher, Johannes; Bauer, Michael; Mitchell, Philip B; Gershon, Elliot S; Rice, John; Potash, James B; Zandi, Peter P; Craddock, Nick; Ferrier, I Nicol; Alda, Martin; Rouleau, Guy A; Turecki, Gustavo; Ophoff, Roel; Pato, Carlos; Anjorin, Adebayo; Stahl, Eli; Leber, Markus; Czerski, Piotr M; Cruceanu, Cristiana; Jones, Ian R; Posthuma, Danielle; Andlauer, Till F M; Forstner, Andreas J; Streit, Fabian; Baune, Bernhard T; Air, Tracy; Sinnamon, Grant; Wray, Naomi R; MacIntyre, Donald J; Porteous, David; Homuth, Georg; Rivera, Margarita; Grove, Jakob; Middeldorp, Christel M; Hickie, Ian; Pergadia, Michele; Mehta, Divya; Smit, Johannes H; Jansen, Rick; de Geus, Eco; Dunn, Erin; Li, Qingqin S; Nauck, Matthias; Schoevers, Robert A; Beekman, Aartjan Tf; Knowles, James A; Viktorin, Alexander; Arnold, Paul; Barr, Cathy L; Bedoya-Berrio, Gabriel; Bienvenu, O Joseph; Brentani, Helena; Burton, Christie; Camarena, Beatriz; Cappi, Carolina; Cath, Danielle; Cavallini, Maria; Cusi, Daniele; Darrow, Sabrina; Denys, Damiaan; Derks, Eske M; Dietrich, Andrea; Fernandez, Thomas; Figee, Martijn; Freimer, Nelson; Gerber, Gloria; Grados, Marco; Greenberg, Erica; Hanna, Gregory L; Hartmann, Andreas; Hirschtritt, Matthew E; Hoekstra, Pieter J; Huang, Alden; Huyser, Chaim; Illmann, Cornelia; Jenike, Michael; Kuperman, Samuel; Leventhal, Bennett; Lochner, Christine; Lyon, Gholson J; Macciardi, Fabio; Madruga-Garrido, Marcos; Malaty, Irene A; Maras, Athanasios; McGrath, Lauren; Miguel, Eurípedes C; Mir, Pablo; Nestadt, Gerald; Nicolini, Humberto; Okun, Michael S; Pakstis, Andrew; Paschou, Peristera; Piacentini, John; Pittenger, Christopher; Plessen, Kerstin; Ramensky, Vasily; Ramos, Eliana M; Reus, Victor; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Roessner, Veit; Rosário, Maria; Samuels, Jack F; Sandor, Paul; Stein, Dan J; Tsetsos, Fotis; Van Nieuwerburgh, Filip; Weatherall, Sarah; Wendland, Jens R; Wolanczyk, Tomasz; Worbe, Yulia; Zai, Gwyneth; Goes, Fernando S; McLaughlin, Nicole; Nestadt, Paul S; Grabe, Hans-Jorgen; Depienne, Christel; Konkashbaev, Anuar; Lanzagorta, Nuria; Valencia-Duarte, Ana; Bramon, Elvira; Buccola, Nancy; Cahn, Wiepke; Cairns, Murray; Chong, Siow A; Cohen, David; Crespo-Facorro, Benedicto; Crowley, James; Davidson, Michael; DeLisi, Lynn; Dinan, Timothy; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Haan, Lieuwe; Hougaard, David; Karachanak-Yankova, Sena; Khrunin, Andrey; Klovins, Janis; Kučinskas, Vaidutis; Lee Chee Keong, Jimmy; Limborska, Svetlana; Loughland, Carmel; Lönnqvist, Jouko; Maher, Brion; Mattheisen, Manuel; McDonald, Colm; Murphy, Kieran C; Nenadic, Igor; van Os, Jim; Pantelis, Christos; Pato, Michele; Petryshen, Tracey; Quested, Digby; Roussos, Panos; Sanders, Alan R; Schall, Ulrich; Schwab, Sibylle G; Sim, Kang; So, Hon-Cheong; Stögmann, Elisabeth; Subramaniam, Mythily; Toncheva, Draga; Waddington, John; Walters, James; Weiser, Mark; Cheng, Wei; Cloninger, Robert; Curtis, David; Gejman, Pablo V; Henskens, Frans; Mattingsdal, Morten; Oh, Sang-Yun; Scott, Rodney; Webb, Bradley; Breen, Gerome; Churchhouse, Claire; Bulik, Cynthia M; Daly, Mark; Dichgans, Martin; Faraone, Stephen V; Guerreiro, Rita; Holmans, Peter; Kendler, Kenneth S; Koeleman, Bobby; Mathews, Carol A; Price, Alkes; Scharf, Jeremiah; Sklar, Pamela; Williams, Julie; Wood, Nicholas W; Cotsapas, Chris; Palotie, Aarno; Smoller, Jordan W; Sullivan, Patrick; Rosand, Jonathan; Corvin, Aiden; Neale, Benjamin M

2018-06-22

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

Directory of Open Access Journals (Sweden)

Tallulah Andrews

2015-03-01

Full Text Available Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51% groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Gene networks underlying convergent and pleiotropic phenotypes in a large and systematically-phenotyped cohort with heterogeneous developmental disorders.

Science.gov (United States)

Andrews, Tallulah; Meader, Stephen; Vulto-van Silfhout, Anneke; Taylor, Avigail; Steinberg, Julia; Hehir-Kwa, Jayne; Pfundt, Rolph; de Leeuw, Nicole; de Vries, Bert B A; Webber, Caleb

2015-03-01

Readily-accessible and standardised capture of genotypic variation has revolutionised our understanding of the genetic contribution to disease. Unfortunately, the corresponding systematic capture of patient phenotypic variation needed to fully interpret the impact of genetic variation has lagged far behind. Exploiting deep and systematic phenotyping of a cohort of 197 patients presenting with heterogeneous developmental disorders and whose genomes harbour de novo CNVs, we systematically applied a range of commonly-used functional genomics approaches to identify the underlying molecular perturbations and their phenotypic impact. Grouping patients into 408 non-exclusive patient-phenotype groups, we identified a functional association amongst the genes disrupted in 209 (51%) groups. We find evidence for a significant number of molecular interactions amongst the association-contributing genes, including a single highly-interconnected network disrupted in 20% of patients with intellectual disability, and show using microcephaly how these molecular networks can be used as baits to identify additional members whose genes are variant in other patients with the same phenotype. Exploiting the systematic phenotyping of this cohort, we observe phenotypic concordance amongst patients whose variant genes contribute to the same functional association but note that (i) this relationship shows significant variation across the different approaches used to infer a commonly perturbed molecular pathway, and (ii) that the phenotypic similarities detected amongst patients who share the same inferred pathway perturbation result from these patients sharing many distinct phenotypes, rather than sharing a more specific phenotype, inferring that these pathways are best characterized by their pleiotropic effects.

Heterogeneous reactors

International Nuclear Information System (INIS)

Moura Neto, C. de; Nair, R.P.K.

1979-08-01

The microscopic study of a cell is meant for the determination of the infinite multiplication factor of the cell, which is given by the four factor formula: K(infinite) = n(epsilon)pf. The analysis of an homogeneous reactor is similar to that of an heterogeneous reactor, but each factor of the four factor formula can not be calculated by the formulas developed in the case of an homogeneous reactor. A great number of methods was developed for the calculation of heterogeneous reactors and some of them are discussed. (Author) [pt

Heterogeneous gas core reactor

International Nuclear Information System (INIS)

Han, K.I.

1977-01-01

Preliminary investigations of a heterogeneous gas core reactor (HGCR) concept suggest that this potential power reactor offers distinct advantages over other existing or conceptual reactor power plants. One of the most favorable features of the HGCR is the flexibility of the power producing system which allows it to be efficiently designed to conform to a desired optimum condition without major conceptual changes. The arrangement of bundles of moderator/coolant channels in a fissionable gas or mixture of gases makes a truly heterogeneous nuclear reactor core. It is this full heterogeneity for a gas-fueled reactor core which accounts for the novelty of the heterogeneous gas core reactor concept and leads to noted significant advantages over previous gas core systems with respect to neutron and fuel economy, power density, and heat transfer characteristics. The purpose of this work is to provide an insight into the design, operating characteristics, and safety of a heterogeneous gas core reactor system. The studies consist mainly of neutronic, energetic and kinetic analyses of the power producing and conversion systems as a preliminary assessment of the heterogeneous gas core reactor concept and basic design. The results of the conducted research indicate a high potential for the heterogeneous gas core reactor system as an electrical power generating unit (either large or small), with an overall efficiency as high as 40 to 45%. The HGCR system is found to be stable and safe, under the conditions imposed upon the analyses conducted in this work, due to the inherent safety of ann expanding gaseous fuel and the intrinsic feedback effects of the gas and water coolant

Stress Transmission and Failure in Disordered Porous Media

Science.gov (United States)

Laubie, Hadrien; Radjai, Farhang; Pellenq, Roland; Ulm, Franz-Josef

2017-08-01

By means of extensive lattice-element simulations, we investigate stress transmission and its relation with failure properties in increasingly disordered porous systems. We observe a non-Gaussian broadening of stress probability density functions under tensile loading with increasing porosity and disorder, revealing a gradual transition from a state governed by single-pore stress concentration to a state controlled by multipore interactions and metric disorder. This effect is captured by the excess kurtosis of stress distributions and shown to be nicely correlated with the second moment of local porosity fluctuations, which appears thus as a (dis)order parameter for the system. By generating statistical ensembles of porous textures with varying porosity and disorder, we derive a general expression for the fracture stress as a decreasing function of porosity and disorder. Focusing on critical sites where the local stress is above the global fracture threshold, we also analyze the transition to failure in terms of a coarse-graining length. These findings provide a general framework which can also be more generally applied to multiphase and structural heterogeneous materials.

Test-retest reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression--a systematic review and meta-analysis.

Science.gov (United States)

Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher

2015-11-01

Schizoaffective disorder is a frequent diagnosis, and its reliability is subject to ongoing discussion. We compared the diagnostic reliability of schizoaffective disorder with its main differential diagnoses. We systematically searched Medline, Embase, and PsycInfo for all studies on the test-retest reliability of the diagnosis of schizoaffective disorder as compared with schizophrenia, bipolar disorder, and unipolar depression. We used meta-analytic methods to describe and compare Cohen's kappa as well as positive and negative agreement. In addition, multiple pre-specified and post hoc subgroup and sensitivity analyses were carried out. Out of 4,415 studies screened, 49 studies were included. Test-retest reliability of schizoaffective disorder was consistently lower than that of schizophrenia (in 39 out of 42 studies), bipolar disorder (27/33), and unipolar depression (29/35). The mean difference in kappa between schizoaffective disorder and the other diagnoses was approximately 0.2, and mean Cohen's kappa for schizoaffective disorder was 0.50 (95% confidence interval: 0.40-0.59). While findings were unequivocal and homogeneous for schizoaffective disorder's diagnostic reliability relative to its three main differential diagnoses (dichotomous: smaller versus larger), heterogeneity was substantial for continuous measures, even after subgroup and sensitivity analyses. In clinical practice and research, schizoaffective disorder's comparatively low diagnostic reliability should lead to increased efforts to correctly diagnose the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Heterogeneity in pineapple fruit quality results from plant heterogeneity at flower induction.

Science.gov (United States)

Fassinou Hotegni, V Nicodème; Lommen, Willemien J M; Agbossou, Euloge K; Struik, Paul C

2014-01-01

Heterogeneity in fruit quality constitutes a major constraint in agri-food chains. In this paper the sources of the heterogeneity in pineapple in the field were studied in four experiments in commercial pineapple fields. The aims were to determine (a) whether differences in pineapple fruit quality among individual fruits are associated with differences in vigor of the individual plants within the crop at the time of artificial flower induction; and (b) whether the side shoots produced by the plant during the generative phase account for the fruit quality heterogeneity. Two pineapple cultivars were considered: cv. Sugarloaf and cv. Smooth Cayenne. Plant vigor at the time of artificial flower induction was measured by three variates: the number of functional leaves, the D-leaf length and their cross product. Fruit quality attributes measured at harvest time included external attributes (weight and height of fruit, infructescence and crown) and internal quality attributes [total soluble solids (TSS), pH, translucent flesh]. Results showed that the heterogeneity in fruit weight was a consequence of the heterogeneity in vigor of the plants at the moment of flower induction; that effect was mainly on the infructescence weight and less or not on the crown weight. The associations between plant vigor variates at flower induction and the internal quality attributes of the fruit were poor and/or not consistent across experiments. The weight of the slips (side shoots) explained part of the heterogeneity in fruit weight, infructescence weight and fruit height in cv. Sugarloaf. Possibilities for reducing the variation in fruit quality by precise cultural practices are discussed.

Heterogeneity in pineapple fruit quality results from plant heterogeneity at flower induction

Directory of Open Access Journals (Sweden)

V. Nicodeme eFassinou Hotegni

2014-12-01

Full Text Available Heterogeneity in fruit quality constitutes a major constraint in agri-food chains. In this paper the sources of the heterogeneity in pineapple in the field were studied in four experiments in commercial pineapple fields. The aims were to determine (a whether differences in pineapple fruit quality among individual fruits are associated with differences in vigor of the individual plants within the crop at the time of artificial flower induction; and (b whether the side shoots produced by the plant during the generative phase account for the fruit quality heterogeneity. Two pineapple cultivars were considered: cv. Sugarloaf and cv. Smooth Cayenne. Plant vigor at the time of artificial flower induction was measured by three variates: the number of functional leaves, the D-leaf length and their cross product. Fruit quality attributes measured at harvest time included external attributes (weight and height of fruit, infructescence and crown and internal quality attributes (total soluble solids, pH, translucent flesh. Results showed that the heterogeneity in fruit weight was a consequence of the heterogeneity in vigor of the plants at the moment of flower induction; that effect was mainly on the infructescence weight and less or not on the crown weight. The association between plant vigor variates at flower induction and the internal quality attributes of the fruit were poor and/or not consistent across experiments. The weight of the slips (side shoots, explained part of the heterogeneity in fruit weight, infructescence weight and fruit height in cv. Sugarloaf. Possibilities for reducing the variation in fruit quality by precise cultural practices are discussed.

Classification of cognitive performance in bipolar disorder.

Science.gov (United States)

Sparding, Timea; Silander, Katja; Pålsson, Erik; Östlind, Josefin; Ekman, Carl Johan; Sellgren, Carl M; Joas, Erik; Hansen, Stefan; Landén, Mikael

2017-09-01

To understand the etiology of cognitive impairment associated with bipolar disorder, we need to clarify potential heterogeneity in cognitive functioning. To this end, we used multivariate techniques to study if the correlation structure of cognitive abilities differs between persons with bipolar disorder and controls. Clinically stable patients with bipolar disorder (type I: n = 64; type II: n = 44) and healthy controls (n = 86) were assessed with a wide range of cognitive tests measuring executive function, speed, memory, and verbal skills. Data were analysed with multivariate techniques. A distinct subgroup (∼30%) could be identified that performed significantly poorer on tests concerning memory function. This cognitive phenotype subgroup did not differ from the majority of bipolar disorder patients with respect to other demographic or clinical characteristics. Whereas the majority of patients performed similar to controls, a subgroup of patients with bipolar disorder differed substantially from healthy controls in the correlation pattern of low-level cognitive abilities. This suggests that cognitive impairment is not a general trait in bipolar disorder but characteristic of a cognitive subgroup. This has important clinical implications for cognitive rehabilitation and remediation.

The genetic validation of heterogeneity in schizophrenia.

Science.gov (United States)

Tsutsumi, Atsushi; Glatt, Stephen J; Kanazawa, Tetsufumi; Kawashige, Seiya; Uenishi, Hiroyuki; Hokyo, Akira; Kaneko, Takao; Moritani, Makiko; Kikuyama, Hiroki; Koh, Jun; Matsumura, Hitoshi; Yoneda, Hiroshi

2011-10-07

Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.

Immune-based strategies for mood disorders: facts and challenges.

Science.gov (United States)

Colpo, Gabriela D; Leboyer, Marion; Dantzer, Robert; Trivedi, Mahdukar H; Teixeira, Antonio L

2018-02-01

Inflammation seems to play a role in the pathophysiology of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). In the last years several studies have shown increased levels of inflammatory and/or immune markers in patients with mood disorders. Accordingly, the immune system has become a target of interest for the development of biomarkers and therapeutics for mood disorders. Areas covered: Here, we review the evidence showing low-grade inflammation in mood disorders and the studies evaluating immune-based strategies for the treatment of these conditions. Expert commentary: Clinical trials with non-steroidal anti-inflammatory drugs, polyunsaturated acids, N-acetylcysteine, anti-cytokines, physical activity and probiotics have provided promising results in terms of antidepressant efficacy in patients with MDD and BD. Regarding stem cells, only studies with animal models have been performed so far with interesting pre-clinical results. Due to the preliminary nature of the results, most of the clinical studies need to be replicated and/or confirmed in larger clinical settings, embracing the highly heterogeneous pathophysiology of mood disorders.

Heterogeneity in pineapple fruit quality results from plant heterogeneity at flower induction

NARCIS (Netherlands)

Fassinou Hotegni, V.N.; Lommen, W.J.M.; Agbossou, E.K.; Struik, P.C.

2014-01-01

Heterogeneity in fruit quality constitutes a major constraint in agri-food chains. In this paper the sources of the heterogeneity in pineapple in the field were studied in four experiments in commercial pineapple fields. The aims were to determine (a) whether differences in pineapple fruit quality

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.

LENUS (Irish Health Repository)

Toal, F

2010-07-01

Autistic spectrum disorder (ASD) is characterized by stereotyped\\/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype.

Biophysical dynamics in disorderly environments.

Science.gov (United States)

Nelson, David R

2012-01-01

Three areas where time-independent disorder plays a key role in biological dynamics far from equilibrium are reviewed. We first discuss the anomalous localization dynamics that arises when a single species spreads in space and time via diffusion and fluid advection in the presence of frozen heterogeneities in the growth rate. Next we treat the unzipping of double-stranded DNA as a function of force and temperature, a challenge that must be surmounted every time a cell divides. Heterogeneity in the DNA sequence dominates the physics of single-molecule force-extension curves for a broad range of forces upon approaching a sharp unzipping transition. The dynamics of the unzipping fork exhibits anomalous drift and diffusion in a similar range above this transition, with energy barriers that scale as the square root of the genome size. Finally, we describe how activated peptidoglycan strand extension sites, called dislocations in materials science, can mediate the growth of bacterial cell walls. Enzymatically driven circumferential motions of a few dozen of these defects are sufficient to describe the exponential elongation rates observed in experiments on Escherichia coli in a nutrient-rich environment. However, long-range elastic forces transmitted by the peptidoglycan meshwork cause the moving dislocations to interact not only with each other, but also with a disorderly array of frozen, inactivated strand ends.

Patterns and Predictors of Tic Suppressibility in Youth With Tic Disorders.

Science.gov (United States)

Conelea, Christine A; Wellen, Brianna; Woods, Douglas W; Greene, Deanna J; Black, Kevin J; Specht, Matthew; Himle, Michael B; Lee, Han-Joo; Capriotti, Matthew

2018-01-01

Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of reward-enhanced tic suppression in youth with tic disorders using a large, pooled dataset. Individual-level data from nine studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics. A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, tic and premonitory urge severity, and self-rated tic suppressibility. The mechanisms underlying the observed heterogeneity in reward-enhanced tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

Cigarette smoking, nicotine dependence and anxiety disorders: a systematic review of population-based, epidemiological studies

Directory of Open Access Journals (Sweden)

Moylan Steven

2012-10-01

Full Text Available Abstract Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective, the population assessed (random sample versus clinical population and diagnostic instrument utilized. Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM or International Classification of Diseases (ICD for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders. Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder, although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified. Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as

Heterogeneity effects in neutron transport computations

International Nuclear Information System (INIS)

Gelbard, E.M.

1975-01-01

A nuclear reactor is, generally, an intricate heterogeneous structure whose adjacent components may differ radically in their neutronic properties. The heterogeneities in the structure of the reactor complicate the work of the reactor analyst and tend to degrade the efficiency of the numerical methods used in reactor computations. Two types of heterogeneity effects are considered. First, certain singularities in the solution of the neutron transport equation, induced by heterogeneities, are briefly described. Second, the effect of heterogeneities on neutron leakage rates, and consequently on effective diffusion coefficients, are discussed. (5 figures) (U.S.)

The effect of police on crime, disorder and victim precaution

NARCIS (Netherlands)

Vollaard, B.A.; Koning, P.W.C.

2009-01-01

Using individual data from a large-scale Dutch crime victimization survey, we are able to expand the analysis of the effect of police on crime to crimes types that do not easily find their way into police statistics, and to public disorder and victim precaution. To address heterogeneity and

Functional evaluations of genes disrupted in patients with Tourette’s Disorder

Directory of Open Access Journals (Sweden)

Nawei eSun

2016-02-01

Full Text Available Tourette Disorder (TD is a highly heritable neurodevelopmental disorder with complex genetic architecture and unclear neuropathology. Disruptions of particular genes have been identified in subsets of TD patients. However, none of the findings has been replicated, probably due to the complex and heterogeneous genetic architecture of TD that involves both common and rare variants. To understand the etiology of TD, functional analyses are required to characterize the molecular and cellular consequences caused by mutations in candidate genes. Such molecular and cellular alterations may converge into common biological pathways underlying the heterogeneous genetic etiology of TD patients. Herein, we review specific genes implicated in TD etiology, discuss the functions of these genes in the mammalian central nervous system and the corresponding behavioral anomalies exhibited in animal models and, importantly, review functional analyses that can be performed to evaluate the role(s that the genetic disruptions might play in TD. Specifically, the functional assays include novel cell culture systems, genome editing techniques, bioinformatics approaches, transcriptomic analyses and genetically modified animal models applied or developed to study genes associated with TD or with other neurodevelopmental and neuropsychiatric disorders. By describing methods used to study diseases with genetic architecture similar to TD, we hope to develop a systematic framework for investigating the etiology of TD and related disorders.

Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure.

Science.gov (United States)

Richardson, Paul G; Riches, Marcie L; Kernan, Nancy A; Brochstein, Joel A; Mineishi, Shin; Termuhlen, Amanda M; Arai, Sally; Grupp, Stephan A; Guinan, Eva C; Martin, Paul L; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D'Agostino, Ralph B; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L; Soiffer, Robert J

2016-03-31

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #. © 2016 by The American Society of Hematology.

Characterizing heterogeneous cellular responses to perturbations.

Science.gov (United States)

Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

2008-12-09

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

Metacognitive therapy versus disorder-specific CBT for comorbid anxiety disorders: A randomized controlled trial.

Science.gov (United States)

Johnson, Sverre Urnes; Hoffart, Asle; Nordahl, Hans M; Wampold, Bruce E

2017-08-01

Few studies have compared the effects of Metacognitive therapy (MCT) and Cognitive behavioral therapy (CBT) for comorbid anxiety disorders. In the current study we compared CBT and MCT for heterogeneous anxiety disorders in a residential setting. Ninety patients with a primary diagnosis of Post Traumatic Stress Disorder, Social Phobia or Panic disorder, with and without Agoraphobia, were randomized to either CBT or MCT. Patients were assessed at pre-treatment, post-treatment and one-year follow-up. Primary outcome measures were Beck Anxiety Inventory and ADIS IV and secondary outcome measures were SCID II, Beck Depression Inventory, Penn State Worry Questionnaire, The Symptom Checklist-90 and the Inventory of Interpersonal Problems-64. Treatment fidelity was satisfactory and therapist credibility was equal in both treatments. There was a significant difference in the level of anxiety favouring MCT at post-treatment (d=0.7), but there were no differences at one-year follow-up, mainly due to a further improvement in the CBT group during the follow-up period. Both treatments were efficacious. No differences in effect on comorbid diagnoses and symptoms were found, but MCT produced larger change in personality problems. MCT seems to have a more rapid effect on anxiety symptoms, but there were no significant differences in the long term for patients with comorbid anxiety disorders. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Randomized Clinical Trial of Cognitive Behavioral Therapy (CBT) versus Acceptance and Commitment Therapy (ACT) for Mixed Anxiety Disorders

Science.gov (United States)

Arch, Joanna J.; Eifert, Georg H.; Davies, Carolyn; Vilardaga, Jennifer C. Plumb; Rose, Raphael D.; Craske, Michelle G.

2012-01-01

Objective: Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method: One hundred twenty-eight individuals (52% female, mean age = 38, 33%…

HETEROGENEOUS INTEGRATION TECHNOLOGY

Science.gov (United States)

2017-08-24

AFRL-RY-WP-TR-2017-0168 HETEROGENEOUS INTEGRATION TECHNOLOGY Dr. Burhan Bayraktaroglu Devices for Sensing Branch Aerospace Components & Subsystems...Final September 1, 2016 – May 1, 2017 4. TITLE AND SUBTITLE HETEROGENEOUS INTEGRATION TECHNOLOGY 5a. CONTRACT NUMBER In-house 5b. GRANT NUMBER N/A...provide a structure for this review. The history and the current status of integration technologies in each category are examined and product examples are

Combinations of SNPs Related to Signal Transduction in Bipolar Disorder

DEFF Research Database (Denmark)

Koefoed, Pernille; Andreassen, Ole A; Bennike, Bente

2011-01-01

of complex diseases, it may be useful to look at combinations of genotypes. Genes related to signal transmission, e.g., ion channel genes, may be of interest in this respect in the context of bipolar disorder. In the present study, we analysed 803 SNPs in 55 genes related to aspects of signal transmission...... and calculated all combinations of three genotypes from the 3×803 SNP genotypes for 1355 controls and 607 patients with bipolar disorder. Four clusters of patient-specific combinations were identified. Permutation tests indicated that some of these combinations might be related to bipolar disorder. The WTCCC...... in the clusters in the two datasets. The present analyses of the combinations of SNP genotypes support a role for both genetic heterogeneity and interactions in the genetic architecture of bipolar disorder....

in Heterogeneous Media

Directory of Open Access Journals (Sweden)

Saeed Balouchi

2013-01-01

Full Text Available Fractured reservoirs contain about 85 and 90 percent of oil and gas resources respectively in Iran. A comprehensive study and investigation of fractures as the main factor affecting fluid flow or perhaps barrier seems necessary for reservoir development studies. High degrees of heterogeneity and sparseness of data have incapacitated conventional deterministic methods in fracture network modeling. Recently, simulated annealing (SA has been applied to generate stochastic realizations of spatially correlated fracture networks by assuming that the elastic energy of fractures follows Boltzmann distribution. Although SA honors local variability, the objective function of geometrical fracture modeling is defined for homogeneous conditions. In this study, after the introduction of SA and the derivation of the energy function, a novel technique is presented to adjust the model with highly heterogeneous data for a fractured field from the southwest of Iran. To this end, the regular object-based model is combined with a grid-based technique to cover the heterogeneity of reservoir properties. The original SA algorithm is also modified by being constrained in different directions and weighting the energy function to make it appropriate for heterogeneous conditions. The simulation results of the presented approach are in good agreement with the observed field data.

Cognitive hypnotherapy for major depressive disorder.

Science.gov (United States)

Alladin, Assen

2012-04-01

Since the publication of the special issue on cognitive hypnotherapy in the Journal of Cognitive Psychotherapy: An International Quarterly (1994), there have been major developments in the application of hypnosis to the treatment of depression. However, there is no "one-size-fits-all" treatment for depressive disorders as the conditions represent a complex set of heterogeneous symptoms, involving multiple etiologies. It is thus important for therapists to promote a multimodal approach to treating depressive disorders. This article describes cognitive hypnotherapy (CH), an evidence-based multimodal psychological treatment that can be applied to a wide range of depressed patients. CH combines hypnosis with cognitive behavior therapy as the latter provides the best integrative lodestone for assimilating empirically supported treatment techniques derived from various psychotherapies.

Optimal Control of Heterogeneous Systems with Endogenous Domain of Heterogeneity

International Nuclear Information System (INIS)

Belyakov, Anton O.; Tsachev, Tsvetomir; Veliov, Vladimir M.

2011-01-01

The paper deals with optimal control of heterogeneous systems, that is, families of controlled ODEs parameterized by a parameter running over a domain called domain of heterogeneity. The main novelty in the paper is that the domain of heterogeneity is endogenous: it may depend on the control and on the state of the system. This extension is crucial for several economic applications and turns out to rise interesting mathematical problems. A necessary optimality condition is derived, where one of the adjoint variables satisfies a differential inclusion (instead of equation) and the maximization of the Hamiltonian takes the form of “min-max”. As a consequence, a Pontryagin-type maximum principle is obtained under certain regularity conditions for the optimal control. A formula for the derivative of the objective function with respect to the control from L ∞ is presented together with a sufficient condition for its existence. A stylized economic example is investigated analytically and numerically.

Bird diversity and environmental heterogeneity in North America: A test of the area-heterogeneity trade-off

Science.gov (United States)

Rachel Chocron; Curtis H. Flather; Ronen Kadmon

2015-01-01

Aim: Deterministic niche theory predicts that increasing environmental heterogeneity increases species richness. In contrast, a recent stochastic model suggests that heterogeneity has a unimodal effect on species richness since high levels of heterogeneity reduce the effective area available per species, thereby increasing the likelihood of stochastic...

Customization in prescribing for bipolar disorder.

Science.gov (United States)

Hodgkin, Dominic; Volpe-Vartanian, Joanna; Merrick, Elizabeth L; Horgan, Constance M; Nierenberg, Andrew A; Frank, Richard G; Lee, Sue

2012-06-01

For many disorders, patient heterogeneity requires physicians to customize their treatment to each patient's needs. We test for the existence of customization in physicians' prescribing for bipolar disorder, using data from a naturalistic clinical effectiveness trial of bipolar disorder treatment (STEP-BD), which did not constrain physician prescribing. Multinomial logit is used to model the physician's choice among five combinations of drug classes. We find that our observed measure of the patient's clinical status played only a limited role in the choice among drug class combinations, even for conditions such as mania that are expected to affect class choice. However, treatment of a patient with given characteristics differed widely depending on which physician was seen. The explanatory power of the model was low. There was variation within each physician's prescribing, but the results do not suggest a high degree of customization in physicians' prescribing, based on our measure of clinical status. Copyright © 2011 John Wiley & Sons, Ltd.

Noonan syndrome and clinically related disorders

Science.gov (United States)

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 Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

DEFF Research Database (Denmark)

Martin, Joanna; Walters, Raymond K; Demontis, Ditte

2017-01-01

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk...... disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological...... using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum...

A Review of the Role of Female Gender in Autism Spectrum Disorders

Science.gov (United States)

Kirkovski, Melissa; Enticott, Peter G.; Fitzgerald, Paul B.

2013-01-01

This paper reviews the literature exploring gender differences associated with the clinical presentation of autism spectrum disorders (ASD). The potentially mediating effect of comorbid psychopathology, biological and neurodevelopmental implications on these gender differences is also discussed. A vastly heterogeneous condition, while females on…

Quantifying spatial heterogeneity from images

International Nuclear Information System (INIS)

Pomerantz, Andrew E; Song Yiqiao

2008-01-01

Visualization techniques are extremely useful for characterizing natural materials with complex spatial structure. Although many powerful imaging modalities exist, simple display of the images often does not convey the underlying spatial structure. Instead, quantitative image analysis can extract the most important features of the imaged object in a manner that is easier to comprehend and to compare from sample to sample. This paper describes the formulation of the heterogeneity spectrum to show the extent of spatial heterogeneity as a function of length scale for all length scales to which a particular measurement is sensitive. This technique is especially relevant for describing materials that simultaneously present spatial heterogeneity at multiple length scales. In this paper, the heterogeneity spectrum is applied for the first time to images from optical microscopy. The spectrum is measured for thin section images of complex carbonate rock cores showing heterogeneity at several length scales in the range 10-10 000 μm.

Next-generation sequencing in schizophrenia and other neuropsychiatric disorders.

Science.gov (United States)

Schreiber, Matthew; Dorschner, Michael; Tsuang, Debby

2013-10-01

Schizophrenia is a debilitating lifelong illness that lacks a cure and poses a worldwide public health burden. The disease is characterized by a heterogeneous clinical and genetic presentation that complicates research efforts to identify causative genetic variations. This review examines the potential of current findings in schizophrenia and in other related neuropsychiatric disorders for application in next-generation technologies, particularly whole-exome sequencing (WES) and whole-genome sequencing (WGS). These approaches may lead to the discovery of underlying genetic factors for schizophrenia and may thereby identify and target novel therapeutic targets for this devastating disorder. © 2013 Wiley Periodicals, Inc.

Meta-analysis: aerobic exercise for the treatment of anxiety disorders.

Science.gov (United States)

Bartley, Christine A; Hay, Madeleine; Bloch, Michael H

2013-08-01

This meta-analysis investigates the efficacy of exercise as a treatment for DSM-IV diagnosed anxiety disorders. We searched PubMED and PsycINFO for randomized, controlled trials comparing the anxiolytic effects of aerobic exercise to other treatment conditions for DSM-IV defined anxiety disorders. Seven trials were included in the final analysis, totaling 407 subjects. The control conditions included non-aerobic exercise, waitlist/placebo, cognitive-behavioral therapy, psychoeducation and meditation. A fixed-effects model was used to calculate the standardized mean difference of change in anxiety rating scale scores of aerobic exercise compared to control conditions. Subgroup analyses were performed to examine the effects of (1) comparison condition; (2) whether comparison condition controlled for time spent exercising and (3) diagnostic indication. Aerobic exercise demonstrated no significant effect for the treatment of anxiety disorders (SMD=0.02 (95%CI: -0.20-0.24), z = 0.2, p = 0.85). There was significant heterogeneity between trials (χ(2) test for heterogeneity = 22.7, df = 6, p = 0.001). The reported effect size of aerobic exercise was highly influenced by the type of control condition. Trials utilizing waitlist/placebo controls and trials that did not control for exercise time reported large effects of aerobic exercise while other trials report no effect of aerobic exercise. Current evidence does not support the use of aerobic exercise as an effective treatment for anxiety disorders as compared to the control conditions. This remains true when controlling for length of exercise sessions and type of anxiety disorder. Future studies evaluating the efficacy of aerobic exercise should employ larger sample sizes and utilize comparison interventions that control for exercise time. Copyright © 2013. Published by Elsevier Inc.

Interconnecting heterogeneous database management systems

Science.gov (United States)

Gligor, V. D.; Luckenbaugh, G. L.

1984-01-01

It is pointed out that there is still a great need for the development of improved communication between remote, heterogeneous database management systems (DBMS). Problems regarding the effective communication between distributed DBMSs are primarily related to significant differences between local data managers, local data models and representations, and local transaction managers. A system of interconnected DBMSs which exhibit such differences is called a network of distributed, heterogeneous DBMSs. In order to achieve effective interconnection of remote, heterogeneous DBMSs, the users must have uniform, integrated access to the different DBMs. The present investigation is mainly concerned with an analysis of the existing approaches to interconnecting heterogeneous DBMSs, taking into account four experimental DBMS projects.

Estrogen deficiency heterogeneously affects tissue specific stem cells in mice

Science.gov (United States)

Kitajima, Yuriko; Doi, Hanako; Ono, Yusuke; Urata, Yoshishige; Goto, Shinji; Kitajima, Michio; Miura, Kiyonori; Li, Tao-Sheng; Masuzaki, Hideaki

2015-01-01

Postmenopausal disorders are frequently observed in various organs, but their relationship with estrogen deficiency and mechanisms remain unclear. As tissue-specific stem cells have been found to express estrogen receptors, we examined the hypothesis that estrogen deficiency impairs stem cells, which consequently contributes to postmenopausal disorders. Six-week-old C57BL/6 female mice were ovariectomized, following which they received 17β-estradiol replacement or vehicle (control). Sham-operated mice were used as healthy controls. All mice were killed for evaluation 2 months after treatments. Compared with the healthy control, ovariectomy significantly decreased uterine weight, which was partially recovered by 17β-estradiol replacement. Ovariectomy significantly increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, but impaired their capacity to grow mixed cell-type colonies in vitro. Estrogen replacement further increased the numbers of c-kit-positive hematopoietic stem/progenitor cells in bone marrow, without significantly affecting colony growth in vitro. The number of CD105-positive mesenchymal stem cells in bone marrow also significantly decreased after ovariectomy, but completely recovered following estrogen replacement. Otherwise, neither ovariectomy nor estrogen replacement changed the number of Pax7-positive satellite cells, which are a skeletal muscle-type stem cell. Estrogen deficiency heterogeneously affected tissue-specific stem cells, suggesting a likely and direct relationship with postmenopausal disorders. PMID:26245252

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

NARCIS (Netherlands)

Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Wical, Beverly; Finetti, Claudio; Brückner, Reinhard; Pietz, Joachim; Golla, Günther; Jillella, Dinesh; Linnet, Karen M; Charles, Perrine; Moog, Ute; Õiglane-Shlik, Eve; Mantovani, John F; Park, Kristen; Deprez, Marie; Lederer, Damien; Mary, Sandrine; Scalais, Emmanuel; Selim, Laila; Van Coster, Rudy; Lagae, Lieven; Nikanorova, Marina; Hjalgrim, Helle; Korenke, G Christoph; Trivisano, Marina; Specchio, Nicola; Ceulemans, Berten; Dorn, Thomas; Helbig, Katherine L; Hardies, Katia; Stamberger, Hannah; de Jonghe, Peter; Weckhuysen, Sarah; Lemke, Johannes R; Krägeloh-Mann, Ingeborg; Helbig, Ingo; Kluger, Gerhard; Lerche, Holger; Møller, Rikke S

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with

Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder.

Science.gov (United States)

Heitmann, Carina Yvonne; Feldker, Katharina; Neumeister, Paula; Zepp, Britta Maria; Peterburs, Jutta; Zwitserlood, Pienie; Straube, Thomas

2016-04-01

Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies. © 2016 Wiley Periodicals, Inc.

DOE Energy Frontiers Research Center for Heterogeneous Functional Materials; the “HeteroFoaM Center”

Energy Technology Data Exchange (ETDEWEB)

Reifsnider, Kenneth Leonard [Univ. of South Carolina, Columbia, SC (United States)

2016-11-03

Synopsis of five year accomplishments: Devices that convert and store energy are generally made from heterogeneous constituent materials that act and interact to selectively conduct, transport, and separate mass, heat, and charge. Controlling these actions and interactions enables the technical breakthroughs that have made fuel cells, batteries, and solid state membranes, for example, essential parts of our society. In the biological sense, these materials are ‘vascular’ rather than primitive ‘cellular’ materials, in which the arrangements and configurations of the constituents (including their void phases) play essential and definitive roles in their functional capabilities. In 2009 a group of investigators, with lifetime investments of effort in the understanding of heterogeneous materials, recognized that the design of such material systems is not an optimization problem as such. Local interactions of the constituents create “emergent” properties and responses that are not part of the formal set of constituent characteristics, in much the same sense that society and culture is created by the group interactions of the people involved. The design of emergent properties is an open question in all formal science, but for energy materials the lack of this foundation science relegates development tasks to Edisonian trial and error, with anecdotal success and frequent costly failures. That group defined, for the first time, multi-scale heterogeneous functional materials with functional disordered and void phase regions as “HeteroFoaM,” and formed the first multidisciplinary research team to define and codify the foundation science of that material class. The primary goal of the HeteroFoaM Center was, and is, to create and establish the multi-scale fundamental knowledge and related methodology required for the rational and systematic multiphysics design of heterogeneous functional materials and their interfaces and surfaces for applications in energy

Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

Science.gov (United States)

Hildebrandt, Tom; Epstein, Elizabeth E.; Sysko, Robyn; Bux, Donald A.

2017-01-01

Background The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. Method We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. Results Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. Conclusions The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs. PMID:28247423

Learning and Consolidation of New Spoken Words in Autism Spectrum Disorder

Science.gov (United States)

Henderson, Lisa; Powell, Anna; Gaskell, M. Gareth; Norbury, Courtenay

2014-01-01

Autism spectrum disorder (ASD) is characterized by rich heterogeneity in vocabulary knowledge and word knowledge that is not well accounted for by current cognitive theories. This study examines whether individual differences in vocabulary knowledge in ASD might be partly explained by a difficulty with consolidating newly learned spoken words…

CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation

NARCIS (Netherlands)

Jansen, Jos C.; Cirak, Sebahattin; van Scherpenzeel, Monique; Timal, Sharita; Reunert, Janine; Rust, Stephan; Pérez, Belén; Vicogne, Dorothée; Krawitz, Peter; Wada, Yoshinao; Ashikov, Angel; Pérez-Cerdá, Celia; Medrano, Celia; Arnoldy, Andrea; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; Quelhas, Dulce; Diogo, Luisa; Rymen, Daisy; Jaeken, Jaak; Guffon, Nathalie; Cheillan, David; van den Heuvel, Lambertus P.; Maeda, Yusuke; Kaiser, Olaf; Schara, Ulrike; Gerner, Patrick; van den Boogert, Marjolein A. W.; Holleboom, Adriaan G.; Nassogne, Marie-Cécile; Sokal, Etienne; Salomon, Jody; van den Bogaart, Geert; Drenth, Joost P. H.; Huynen, Martijn A.; Veltman, Joris A.; Wevers, Ron A.; Morava, Eva; Matthijs, Gert; Foulquier, François; Marquardt, Thorsten; Lefeber, Dirk J.

2016-01-01

Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are

The application of deep brain stimulation in the treatment of psychiatric disorders

NARCIS (Netherlands)

Graat, Ilse; Figee, Martijn; Denys, D.

2017-01-01

Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex

A Network Approach to Environmental Impact in Psychotic Disorder : Brief Theoretical Framework

NARCIS (Netherlands)

Isvoranu, A.M.; Borsboom, D.; van Os, J.; Guloksuz, S.

2016-01-01

The spectrum of psychotic disorder represents a multifactorial and heterogeneous condition and is thought to result from a complex interplay between genetic and environmental factors. In the current paper, we analyze this interplay using network analysis, which has been recently proposed as a novel

Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD

Directory of Open Access Journals (Sweden)

Petermann Franz

2009-09-01

Full Text Available Abstract Background Attention Deficit/Hyperactivity Disorder (ADHD, formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. Method According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Results Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. Conclusion These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

Developmental psychopathology: Attention Deficit Hyperactivity Disorder (ADHD).

Science.gov (United States)

Schmidt, Sören; Petermann, Franz

2009-09-17

Attention Deficit/Hyperactivity Disorder (ADHD), formerly regarded as a typical childhood disorder, is now known as a developmental disorder persisting over the lifespan. Starting in preschool-age, symptoms vary depending on the age group affected. According to the variability of ADHD-symptoms and the heterogeneity of comorbid psychiatric disorders, a broad review of recent studies was performed. These findings were summarized in a developmental psychopathological model, documenting relevant facts on a timeline. Based on a genetic disposition and a neuropsychological deregulation, there is evidence for factors which persist across the lifespan, change age-dependently, or show validity in a specific developmental phase. Qualitative changes can be found for children in preschool-age and adults. These differences have implications for clinical practice as they can be used for prevention, diagnostic proceedings, and therapeutic intervention as well as for planning future studies. The present article is a translated and modified version of the German article "Entwicklungspsychopathologie der ADHS", published in Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 56, 2008, S. 265-274.

Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome.

Science.gov (United States)

Campbell, Malcolm G; Kohane, Isaac S; Kong, Sek Won

2013-09-24

Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Two previously published blood gene expression data sets--the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members)--were analyzed. All individuals of each dataset were projected to biological pathways, and each sample's Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression

Inpatient and outpatient costs in patients with coronary artery disease and mental disorders: a systematic review.

Science.gov (United States)

Baumeister, Harald; Haschke, Anne; Munzinger, Marie; Hutter, Nico; Tully, Phillip J

2015-01-01

To systematically review in- and outpatient costs in patients with coronary artery disease (CAD) and comorbid mental disorders. A comprehensive database search was conducted for studies investigating persons with CAD and comorbid mental disorders (Medline, EMBASE, PsycINFO, Psyndex, EconLit, IBSS). All studies were included which allowed a comparison of in- and outpatient health care costs (assessed either monetarily or in terms of health care utilization) of CAD patients with comorbid mental disorders (mood, anxiety, alcohol, eating, somatoform and personality disorders) and those without. Random effects meta-analyses were conducted and results reported using forest plots. The literature search resulted in 7,275 potentially relevant studies, of which 52 met inclusion criteria. Hospital readmission rates were increased in CAD patients with any mental disorder (pooled standardized mean difference (SMD) = 0.34 [0.17;0.51]). Results for depression, anxiety and posttraumatic stress disorder pointed in the same direction with heterogeneous SMDs on a primary study level ranging from -0.44 to 1.26. Length of hospital stay was not increased in anxiety and any mental disorder, while studies on depression reported heterogeneous SMDs ranging from -0.08 to 0.82. Most studies reported increased overall and outpatient costs for patients with comorbid mental disorders. Results for invasive procedures were non-significant respectively inconclusive. Comorbid mental disorders in CAD patients are associated with an increased healthcare utilization in terms of higher hospital readmission rates and increased overall and outpatient health care costs. From a health care point of view, it is requisite to improve the diagnosis and treatment of comorbid mental disorders in patients with CAD to minimize incremental costs.

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

DEFF Research Database (Denmark)

Wolff, Markus; Johannesen, Katrine M.; Hedrich, Ulrike B. S.

2017-01-01

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infa...

Course and cognitive outcome in major affective disorder

DEFF Research Database (Denmark)

Kessing, Lars Vedel

2015-01-01

analyses conducted without survival models and without paying attention to diagnostic instability or the individual heterogeneity of the course of episodes. Totally, these drawbacks and pitfalls affect the results of previous studies in unpredictable ways and make it hazardous to draw conclusions about...... as an expression of an affective episode. On average, a progressive course with increasing risk of recurrence with every new episode was found for unipolar and bipolar affective disorders. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the risk...... a progressive course of episodes. Initially in the course of affective disorders, socio-demographic variables such as gender, age at onset, and marital status and co-morbidity with alcoholism acted as risk factors for further recurrence. Later, however, particularly variables related to the previous course...

Brain stimulation in posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Vladan Novakovic

2011-10-01

Full Text Available Posttraumatic stress disorder (PTSD is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT and Cranial electrotherapy stimulation (CES have both been in use for decades; transcranial magnetic stimulation (TMS, magnetic seizure therapy (MST, deep brain stimulation (DBS, transcranial Direct Current Stimulation (tDCS, and vagus nerve stimulation (VNS have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES, depression (ECT, CES, rTMS, VNS, DBS, obsessive-compulsive disorder (OCD (DBS, essential tremor, dystonia (DBS, epilepsy (DBS, VNS, Parkinson Disease (DBS, pain (CES, and insomnia (CES. To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

Direct measurement of superdiffusive energy transport in disordered granular chains.

Science.gov (United States)

Kim, Eunho; Martínez, Alejandro J; Phenisee, Sean E; Kevrekidis, P G; Porter, Mason A; Yang, Jinkyu

2018-02-13

Energy transport properties in heterogeneous materials have attracted scientific interest for more than half of a century, and they continue to offer fundamental and rich questions. One of the outstanding challenges is to extend Anderson theory for uncorrelated and fully disordered lattices in condensed-matter systems to physical settings in which additional effects compete with disorder. Here we present the first systematic experimental study of energy transport and localization properties in simultaneously disordered and nonlinear granular crystals. In line with prior theoretical studies, we observe in our experiments that disorder and nonlinearity-which individually favor energy localization-can effectively cancel each other out, resulting in the destruction of wave localization. We also show that the combined effect of disorder and nonlinearity can enable manipulation of energy transport speed in granular crystals. Specifically, we experimentally demonstrate superdiffusive transport. Furthermore, our numerical computations suggest that subdiffusive transport should be attainable by controlling the strength of the system's external precompression force.

Quantifying the propagation of distress and mental disorders in social networks.

Science.gov (United States)

Scatà, Marialisa; Di Stefano, Alessandro; La Corte, Aurelio; Liò, Pietro

2018-03-22

Heterogeneity of human beings leads to think and react differently to social phenomena. Awareness and homophily drive people to weigh interactions in social multiplex networks, influencing a potential contagion effect. To quantify the impact of heterogeneity on spreading dynamics, we propose a model of coevolution of social contagion and awareness, through the introduction of statistical estimators, in a weighted multiplex network. Multiplexity of networked individuals may trigger propagation enough to produce effects among vulnerable subjects experiencing distress, mental disorder, which represent some of the strongest predictors of suicidal behaviours. The exposure to suicide is emotionally harmful, since talking about it may give support or inadvertently promote it. To disclose the complex effect of the overlapping awareness on suicidal ideation spreading among disordered people, we also introduce a data-driven approach by integrating different types of data. Our modelling approach unveils the relationship between distress and mental disorders propagation and suicidal ideation spreading, shedding light on the role of awareness in a social network for suicide prevention. The proposed model is able to quantify the impact of overlapping awareness on suicidal ideation spreading and our findings demonstrate that it plays a dual role on contagion, either reinforcing or delaying the contagion outbreak.

Brief Interventions in the Treatment of Alcohol Use Disorders: Definition and Overview.

Science.gov (United States)

Osburn, Cynthia J.

2001-01-01

Reviews the literature and describes the nature and feasibility of brief interventions in the treatment of alcohol use disorders. Attention is given to the promising results of outcome studies, and recommendations are provided for the implementation of brief interventions with a heterogeneous clientele. (Contains 39 references.) (GCP)

Influence of mental disorders on school dropout in Mexico.

Science.gov (United States)

Borges, Guilherme; Medina Mora-Icaza, María Elena; Benjet, Corina; Lee, Sing; Lane, Michael; Breslau, Joshua

2011-11-01

To study the impact of mental disorders on failure in educational attainment in Mexico. Diagnoses and age of onset for each of 16 DSM-IV disorders were assessed through retrospective self-reports with the Composite International Diagnostic Instrument (CIDI) during fieldwork in 2001-2002. Survival analysis was used to examine associations between early onset DSM-IV/CIDI disorders and subsequent school dropout or failure to reach educational milestones. More than one of two Mexicans did not complete secondary education. More than one-third of those who finished secondary education did not enter college, and one of four students who entered college did not graduate. Impulse control disorders and substance use disorders were associated with higher risk for school dropout, secondary school dropout and to a lesser degree failure to enter college. Anxiety disorders were associated with lower risk for school dropout, especially secondary school dropout and, to a lesser degree, primary school dropout. The heterogeneity of results found in Mexico may be due to the effect of mental disorders being diminished or masked by the much greater effect of economic hardship and low cultural expectations for educational achievement. Future research should inquire deeper into possible reasons for the better performance of students with anxiety disorders in developing countries.

Interrater reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression - A systematic review and meta-analysis.

Science.gov (United States)

Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher

2016-10-01

Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking. Using a highly sensitive literature search in Medline, Embase, and PsycInfo we identified studies measuring the interrater reliability of schizoaffective disorder in comparison to schizophrenia, bipolar disorder, and unipolar disorder. Out of 4126 records screened we included 25 studies reporting on 7912 patients diagnosed by different raters. The interrater reliability of schizoaffective disorder was moderate (meta-analytic estimate of Cohen's kappa 0.57 [95% CI: 0.41-0.73]), and substantially lower than that of its main differential diagnoses (difference in kappa between 0.22 and 0.19). Although there was considerable heterogeneity, analyses revealed that the interrater reliability of schizoaffective disorder was consistently lower in the overwhelming majority of studies. The results remained robust in subgroup and sensitivity analyses (e.g., diagnostic manual used) as well as in meta-regressions (e.g., publication year) and analyses of publication bias. Clinically, the results highlight the particular importance of diagnostic re-evaluation in patients diagnosed with schizoaffective disorder. They also quantify a widely held clinical impression of lower interrater reliability and agree with earlier meta-analysis reporting low test-retest reliability. Copyright © 2016. Published by Elsevier B.V.

Crack phantoms: localized damage correlations and failure in network models of disordered materials

International Nuclear Information System (INIS)

Zaiser, M; Moretti, P; Lennartz-Sassinek, S

2015-01-01

We study the initiation of failure in network models of disordered materials such as random fuse and spring models, which serve as idealized representations of fracture processes in quasi-two-dimensional, disordered material systems. We consider two different geometries, namely rupture of thin sheets and delamination of thin films, and demonstrate that irrespective of geometry and implementation of the disorder (random failure thresholds versus dilution disorder) failure initiation is associated with the emergence of typical localized correlation structures in the damage patterns. These structures (‘crack phantoms’) exhibit well-defined characteristic lengths, which relate to the failure stress by scaling relations that are typical for critical crack nuclei in disorder-free materials. We discuss our findings in view of the fundamental nature of failure processes in materials with random microstructural heterogeneity. (paper)

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia

Directory of Open Access Journals (Sweden)

Stephanie Zettner

2014-11-01

Full Text Available Chronic myelogenous leukemia (CML is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia.

Science.gov (United States)

Zettner, Stephanie; Mistry, Sandeep G

2014-11-01

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.

DSM-IV-TR "pain disorder associated with psychological factors" as a nonhysterical form of somatization.

Science.gov (United States)

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful subscales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of "pain disorder associated with psychological factors" were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization.

Intratumor and Intertumor Heterogeneity in Melanoma

Directory of Open Access Journals (Sweden)

Tomasz M. Grzywa

2017-12-01

Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

[Antiepileptic drugs in the control of the impulses disorders].

Science.gov (United States)

Roncero, C; Rodríguez-Urrutia, A; Grau-López, L; Casas, M

2009-01-01

The disorders classified as control of the impulses; explosive intermittent disorder, pathological gambling, kleptomania, pyromania, pathological gambling, hair pullers, compulsive purchases, skin picking and onychophagia are a heterogeneous set of clinical entities, most of them with little prevalence. Nevertheless, they cause important personal and social dysfunctions and present great comorbidity with other psychiatric disorders. Antipsychotics, antidepressive agents, serotoninergic agonists, naltrexone, beta blockers antiandrogen, lithium and anticonvulsants have been used in their pharmacological treatment. Currently, interest is growing on the use of the antiepileptics because their possible usefulness has been described in these disorders. However, the neurobiological effects are only partially known in some cases. We have reviewed the literature regarding the treatment of these disorders with mood stabilizers, (lithium, carbamazepine, valproate, phenitoin, oxcarbacepin, topiramate, lamotrigin, leviteracetam) and have described those studies on which the current knowledge and evidence are based. The results must be considered as provisional and must be updated in the future, since they are mostly based on case reports, case series or opened clinical trials, their being little knowledge based on double blind clinical trials.

Cannabinoid Receptor Type 2, but Not Type 1, Is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders

Science.gov (United States)

Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Bradstreet, James Jeffrey; Maione, Sabatino; Antonucci, Nicola

2013-01-01

Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering…

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

Science.gov (United States)

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.

Internet gaming disorder in children and adolescents: a systematic review.

Science.gov (United States)

Paulus, Frank W; Ohmann, Susanne; von Gontard, Alexander; Popow, Christian

2018-04-06

Internet gaming disorder (IGD) is a serious disorder leading to and maintaining pertinent personal and social impairment. IGD has to be considered in view of heterogeneous and incomplete concepts. We therefore reviewed the scientific literature on IGD to provide an overview focusing on definitions, symptoms, prevalence, and aetiology. We systematically reviewed the databases ERIC, PsyARTICLES, PsycINFO, PSYNDEX, and PubMed for the period January 1991 to August 2016, and additionally identified secondary references. The proposed definition in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition provides a good starting point for diagnosing IGD but entails some disadvantages. Developing IGD requires several interacting internal factors such as deficient self, mood and reward regulation, problems of decision-making, and external factors such as deficient family background and social skills. In addition, specific game-related factors may promote IGD. Summarizing aetiological knowledge, we suggest an integrated model of IGD elucidating the interplay of internal and external factors. So far, the concept of IGD and the pathways leading to it are not entirely clear. In particular, long-term follow-up studies are missing. IGD should be understood as an endangering disorder with a complex psychosocial background. In representative samples of children and adolescents, on average, 2% are affected by Internet gaming disorder (IGD). The mean prevalences (overall, clinical samples included) reach 5.5%. Definitions are heterogeneous and the relationship with substance-related addictions is inconsistent. Many aetiological factors are related to the development and maintenance of IGD. This review presents an integrated model of IGD, delineating the interplay of these factors. This article's abstract has been translated into Spanish and Portuguese. Follow the links from the abstract to view the translations. © 2018 Mac Keith Press.

Classifying Autism Spectrum Disorders by ADI-R: Subtypes or Severity Gradient?

Science.gov (United States)

Cholemkery, Hannah; Medda, Juliane; Lempp, Thomas; Freitag, Christine M.

2016-01-01

To reduce phenotypic heterogeneity of Autism spectrum disorders (ASD) and add to the current diagnostic discussion this study aimed at identifying clinically meaningful ASD subgroups. Cluster analyses were used to describe empirically derived groups based on the Autism Diagnostic Interview-revised (ADI-R) in a large sample of n = 463 individuals…

Meta-analysis of the association between N-methyl-d-aspartate receptor antibodies and schizophrenia, schizoaffective disorder, bipolar disorder, and major depressive disorder.

Science.gov (United States)

Pearlman, Daniel M; Najjar, Souhel

2014-08-01

N-methyl-d-aspartate receptor (NMDAR) antibodies have been documented in the serum of individuals with primary psychiatric disorders from several independent cohorts, but these findings have not been systematically assessed in aggregate or in relation to methodological covariates. We searched MEDLINE, EMBASE, and PsycINFO for studies in any language that provided data on NMDAR antibody seropositivity or absolute serum titers in schizophrenia or schizoaffective, bipolar, or major depressive disorders. We used a random effects model to pool estimates across studies. Nine studies met the eligibility criteria. Five studies (3387 participants) provided data on NMDAR antibody seropositivity in psychiatric versus control groups based on high-specificity seropositivity thresholds (cell-based assays [CBAs]: 1:320 dilution, 1:200 dilution, visual score>1; enzyme-linked immunosorbent assay [ELISA]: 90(th) percentile of control titers). Meta-analysis showed significantly higher odds of NMDAR antibody seropositivity among those with schizophrenia or schizoaffective, bipolar, or major depressive disorders compared with healthy controls (odds ratio [OR], 3.10; 95% confidence interval [CI], 1.04-9.27; P=.043; I(2)=68%). Four studies (3194 participants) provided outcome data for these groups based on low-specificity seropositivity thresholds (CBAs 1:10 dilution; ELISA: 75(th) percentile of control titers). Meta-analysis showed greater heterogeneity and no significant between-group difference (OR, 2.31; 95% CI, 0.55-9.73; P=.25; I(2)=90%). Seropositive participants in psychiatric groups had various combinations of IgG, IgM, and IgA class antibodies against NR1, NR1/NR2B, and NR2A/NR2B subunits. Subgroup analysis revealed significantly higher odds of seropositivity among all participants based on 1:10 versus 1:320 dilution seropositivity thresholds (OR, 4.56; 95% CI, 2.41-8.62; Pschizoaffective disorder (OR, 1.15; 95% CI, 0.19-7.24; P=.88, I(2)=43%, studies=2, n=1108). Average NR2A

Examining Autism Spectrum Disorders by Biomarkers: Example from the Oxytocin and Serotonin Systems

Science.gov (United States)

Hammock, Elizabeth; Veenstra-VanderWeele, Jeremy; Yan, Zhongyu; Kerr, Travis M.; Morris, Marianna; Anderson, George M.; Carter, C. Sue; Cook, Edwin H.; Jacob, Suma

2012-01-01

Objective: Autism spectrum disorder (ASD) is a heritable but highly heterogeneous neuropsychiatric syndrome, which poses challenges for research relying solely on behavioral symptoms or diagnosis. Examining biomarkers may give us ways to identify individuals who demonstrate specific developmental trajectories and etiological factors related to…

Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder

NARCIS (Netherlands)

Delucchi, K.L.; Katerberg, H.; Stewart, S.E.; Denys, D.A.; Lochner, C.; Stack, D.E.; den Boer, J.A.; van Balkom, A.J.L.M.; Jenike, M.A.; Stein, D.J.; Cath, D.C.; Mathews, C.A.

2011-01-01

Objective: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of

Viscous fingering with permeability heterogeneity

International Nuclear Information System (INIS)

Tan, C.; Homsy, G.M.

1992-01-01

Viscous fingering in miscible displacements in the presence of permeability heterogeneities is studied using two-dimensional simulations. The heterogeneities are modeled as stationary random functions of space with finite correlation scale. Both the variance and scale of the heterogeneities are varied over modest ranges. It is found that the fingered zone grows linearly in time in a fashion analogous to that found in homogeneous media by Tan and Homsy [Phys. Fluids 31, 1330 (1988)], indicating a close coupling between viscous fingering on the one hand and flow through preferentially more permeable paths on the other. The growth rate of the mixing zone increases monotonically with the variance of the heterogeneity, as expected, but shows a maximum as the correlation scale is varied. The latter is explained as a ''resonance'' between the natural scale of fingers in homogeneous media and the correlation scale

Quantification of heterogeneity observed in medical images

International Nuclear Information System (INIS)

Brooks, Frank J; Grigsby, Perry W

2013-01-01

There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities. In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection. We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts. These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity

Quantification of heterogeneity observed in medical images.

Science.gov (United States)

Brooks, Frank J; Grigsby, Perry W

2013-03-02

There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities. In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection. We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts. These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity.

[Neuropsychological profiles associated with the children's oral language disorders].

Science.gov (United States)

Conde-Guzón, P A; Conde-Guzón, M J; Bartolomé-Albistegui, M T; Quirós-Expósito, P

Oral language disorders constitute a group of syndromes with a high prevalence among the childhood population. They form a heterogeneous group that ranges from simple problems in articulating a phoneme (dyslalias) to severe disorders affecting communication, such as children's dysarthrias and aphasias. In this paper our objective is to review the neuropsychological profiles of children who manifest different oral language disorders. Due to the wide range of clinical pictures and causations covered by children's oral language disorders, very few systematic reviews have been conducted to obtain an overall view of the neuropsychological profiles of these children. Although the linguistic signs and symptoms of these disorders are well understood, the associated neuropsychological signs and symptoms have not been studied. In some cases, these neuropsychological signs cause greater learning problems in children than the actual language problems themselves. Childhood language disorders are associated with different neuropsychological problems. The most commonly associated neuropsychological deficits are problems involving memory, attention, executive functions, motor dysfunctions, temporal perception, tactile recognition, body scheme, spatial orientation and difficulties in visual discrimination. Mnemonic disorders (essentially in short-term and working auditory memory) are usually a common denominator in the different clinical pictures that make up language disorders. The mnemonic impairment associated to dyslalias deserves special attention as this disorder is sometimes similar to that seen in language problems deriving from clinical pictures with important neurological alterations.

A consequence of local equilibration and heterogeneity in glassy materials

International Nuclear Information System (INIS)

Berthier, Ludovic

2003-01-01

The existence of a generalized fluctuation-dissipation theorem observed in simulations and experiments performed in various glassy materials is related to the concepts of local equilibration and heterogeneity in space. Assuming the existence of a dynamic coherence length scale up to which the system is locally equilibrated, we extend previous generalizations of the FDT relating static to dynamic quantities to the physically relevant domain where asymptotic limits of large times and sizes are not reached. The formulation relies on a simple scaling argument and thus does not have the character of a theorem. Extensive numerical simulations support this proposition. Our results quite generally apply to systems with slow dynamics, independently of the space dimensionality, the chosen dynamics or the presence of disorder

Endocrine disorders in mitochondrial disease.

Science.gov (United States)

Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

2013-10-15

Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders

Science.gov (United States)

Paleologou, Eleni; Ismayilova, Naila; Kinali, Maria

2017-01-01

Mitochondrial disorders are a clinically heterogeneous group of disorders that are caused by defects in the respiratory chain, the metabolic pathway of the adenosine tri-phosphate (ATP) production system. Epilepsy is a common and important feature of these disorders and its management can be challenging. Epileptic seizures in the context of mitochondrial disease are usually treated with conventional anti-epileptic medication, apart from valproic acid. However, in accordance with the treatment of intractable epilepsy where there are limited treatment options, the ketogenic diet (KD) has been considered as an alternative therapy. The use of the KD and its more palatable formulations has shown promising results. It is especially indicated and effective in the treatment of mitochondrial disorders due to complex I deficiency. Further research into the mechanism of action and the neuroprotective properties of the KD will allow more targeted therapeutic strategies and thus optimize the treatment of both epilepsy in the context of mitochondrial disorders but also in other neurodegenerative disorders. PMID:28587136

Neurophysiological approach to disorders of peripheral nerve

DEFF Research Database (Denmark)

Crone, Clarissa; Krarup, Christian

2013-01-01

Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves......, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological...

Relationship between movement disorders and obsessive-compulsive disorder: beyond the obsessive-compulsive-tic phenotype. A systematic review.

Science.gov (United States)

Fibbe, Lieneke A; Cath, Danielle C; van den Heuvel, Odile A; Veltman, Dick J; Tijssen, Marina A J; van Balkom, Anton J L M

2012-06-01

Obsessive-compulsive disorder (OCD) and symptoms (OC symptoms) are associated with tic disorders and share an aetiological relationship. The extent to which OCD/OC symptoms are correlated with other hyperkinetic movement disorders is unclear. The aim of this review was to investigate this co-occurrence and the extent to which OCD/OC symptoms and hyperkinetic movement disorders share a neurobiological basis. A systematic review was performed, specifically searching for OCD/OC symptom comorbidity in hyperkinetic movement disorders using case control studies, longitudinal studies and family based studies. The literature search was conducted using PubMed and PsycINFO databases. Heterogeneity of measurement instruments to detect OCD diagnosis and OC symptoms decreased comparability between studies. The most convincing evidence for a relationship was found between the choreas (Huntington's disease and Sydenham's chorea) and OCD/OC symptoms. Furthermore, elevated frequencies of OC symptoms were found in small case control series of dystonias. Small family based studies in dystonia subtypes modestly suggest shared familial/genetic relationships between OC symptoms and dystonia. Current data indicate a relationship between OCD/OC symptoms and the choreas. As OCD and the choreas have been associated with dysfunctional frontal-striatal circuits, the observed relationships might converge at the level of dysfunctions of these circuits. However, paucity of longitudinal and family studies hampers strong conclusions on the nature of the relationship. The relationship between OCD and movement disorders needs further elaboration using larger family based longitudinal studies and sound instruments to characterise OC symptomatology. This could lead to better understanding of the shared pathology between OCD and hyperkinetic movement disorders.

Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

International Nuclear Information System (INIS)

Inda, Maria-del-Mar; Bonavia, Rudy; Seoane, Joan

2014-01-01

Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape

Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

Energy Technology Data Exchange (ETDEWEB)

Inda, Maria-del-Mar, E-mail: mminda@vhio.net; Bonavia, Rudy [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Seoane, Joan [Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 119-129 Passeig Vall d’Hebron, Barcelona 08035 (Spain); Catalan Institution of Research and Advanced Studies (ICREA), Barcelona 08035 (Spain)

2014-01-27

Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

Directory of Open Access Journals (Sweden)

Maria-del-Mar Inda

2014-01-01

Full Text Available Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM, the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

Glioblastoma multiforme: a look inside its heterogeneous nature.

Science.gov (United States)

Inda, Maria-Del-Mar; Bonavia, Rudy; Seoane, Joan

2014-01-27

Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.

Prevalence of Voice Disorders in Singers: Systematic Review and Meta-Analysis.

Science.gov (United States)

Pestana, Pedro Melo; Vaz-Freitas, Susana; Manso, Maria Conceição

2017-11-01

The study aimed to review the prevalence of self-reported voice disorders in singers. The study is a systematic review and meta-analysis. A systematic review of five major scientific databases was conducted. An extensive search strategy was used considering the rules of each database. Original articles were included only if they had data related to self-perception of dysphonia in the past. Furthermore, heterogeneity and its relative significance were assessed. There were 2371 articles identified; duplicates were deleted, screenings were conducted, and inclusion and exclusion criteria were applied. The final analysis was conducted on 11 studies. The most implemented instruments for the study were customized questionnaires. The findings about singing styles, voice use, and age were found to be different among subjects. The overall prevalence of self-reported dysphonia in singers was 46.09% (95% confidence interval: 38.16-54.12). The heterogeneity was considerable among the studied samples (I 2  = 90.59%). Four groups were then established-students, teachers, classical, and nonclassical-and compared regarding overall prevalence (21.76% in students, and significantly higher and nondifferent in the other three groups, 55.15%, 40.53%, and 46.96%, respectively) and heterogeneity (low only for the students' studies). Although with low homogeneity, singers present a high prevalence of self-perceived dysphonia over their careers. Singing students were the group with a lower prevalence. On the other hand, traditional and popular music singers, as well as singing teachers, revealed significantly higher prevalence of self-perceived dysphonia. Overall, singers are likely to report voice disorders, no matter their singing style or skills. This highlights the need of a preventive approach to address voice disorders in traditional and untrained singers. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The implications of heterogeneity for repository performance assessments

International Nuclear Information System (INIS)

Jackson, C.P.; Porter, J.D.; Morris, S.T.; Herbert, A.W.

1991-01-01

We outline the current views of the Nirex Disposal Safety Assessment Team on heterogeneity, we describe the pragmatic approach to modelling the consequences of heterogeneity that is being currently used, we present work that is being undertaken in the Nirex Safety Assessment Research Programme to develop improved models and we discuss the implications of heterogeneity for site investigation. We point out the need to develop simple models for use in probabilistic analyses. Heterogeneity leads to dispersion, which is currently modelled using a simple diffusion-like model. We discuss the differences between structured heterogeneity, such as fracture zones, and random heterogeneity. We consider that the geostatistical approach to modelling random heterogeneity is probably that most suitable for the needs of Nirex. More measurements are needed in order to characterize heterogeneous media than to characterize homogeneous media. 18 refs., 4 figs

Engineering Microbial Metabolite Dynamics and Heterogeneity.

Science.gov (United States)

Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

2017-10-01

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intratumor and Intertumor Heterogeneity in Melanoma.

Science.gov (United States)

Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

2017-12-01

Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design Technology for Heterogeneous Embedded Systems

CERN Document Server

O'Connor, Ian; Piguet, Christian

2012-01-01

Designing technology to address the problem of heterogeneous embedded systems, while remaining compatible with standard “More Moore” flows, i.e. capable of handling simultaneously both silicon complexity and system complexity, represents one of the most important challenges facing the semiconductor industry today. While the micro-electronics industry has built its own specific design methods to focus mainly on the management of complexity through the establishment of abstraction levels, the emergence of device heterogeneity requires new approaches enabling the satisfactory design of physically heterogeneous embedded systems for the widespread deployment of such systems. This book, compiled largely from a set of contributions from participants of past editions of the Winter School on Heterogeneous Embedded Systems Design Technology (FETCH), proposes a broad and holistic overview of design techniques used to tackle the various facets of heterogeneity in terms of technology and opportunities at the physical ...

Developmentally Stable Whole-Brain Volume Reductions and Developmentally Sensitive Caudate and Putamen Volume Alterations in Those With Attention-Deficit/Hyperactivity Disorder and Their Unaffected Siblings

NARCIS (Netherlands)

Greven, Corina U.; Bralten, Janita; Mennes, Maarten; O'Dwyer, Laurence; van Hulzen, Kimm J. E.; Rommelse, Nanda; Schweren, Lizanne J. S.; Hoekstra, Pieter J.; Hartman, Catharina A.; Heslenfeld, Dirk; Oosterlaan, Jaap; Faraone, Stephen V.; Franke, Barbara; Zwiers, Marcel P.; Arias-Vasquez, Alejandro; Buitelaar, Jan K.

IMPORTANCE Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder. It has been linked to reductions in total brain volume and subcortical abnormalities. However, owing to heterogeneity within and between studies and limited sample sizes, findings on the

Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing

NARCIS (Netherlands)

Timal, Sharita; Hoischen, Alexander; Lehle, Ludwig; Adamowicz, Maciej; Huijben, Karin; Sykut-Cegielska, Jolanta; Paprocka, Justyna; Jamroz, Ewa; van Spronsen, Francjan J.; Koerner, Christian; Gilissen, Christian; Rodenburg, Richard J.; Eidhof, Ilse; Van den Heuvel, Lambert; Thiel, Christian; Wevers, Ron A.; Morava, Eva; Veltman, Joris; Lefeber, Dirk J.

2012-01-01

Congenital disorders of glycosylation type I (CDG-I) form a growing group of recessive neurometabolic diseases. Identification of disease genes is compromised by the enormous heterogeneity in clinical symptoms and the large number of potential genes involved. Until now, gene identification included

Measuring DSM-5 internet gaming disorder: development and validation of a short psychometric scale

OpenAIRE

Pontes, HM; Griffiths, MD

2015-01-01

Despite the large growth on gaming behaviour research, little has been done to overcome the problem stemming from the heterogeneity of gaming addiction nomenclature and the use of non-standardised measurement tools. Following the recent inclusion of Internet Gaming Disorder [IGD] as a condition worthy of future studies in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM-5], researchers have now an opportunity to reach consensus and unification in the field. ...

A Meta-Analysis of Sensory Modulation Symptoms in Individuals with Autism Spectrum Disorders

Science.gov (United States)

Ben-Sasson, Ayelet; Hen, Liat; Fluss, Ronen; Cermak, Sharon A.; Engel-Yeger, Batya; Gal, Eynat

2009-01-01

Sensory modulation symptoms are common in persons with autism spectrum disorders (ASD); however have a heterogeneous presentation. Results from 14 studies indicated a significant high difference between ASD and typical groups in the presence/frequency of sensory symptoms, with the greatest difference in under-responsivity, followed by…

Latent profile analyses of posttraumatic stress disorder, depression and generalized anxiety disorder symptoms in trauma-exposed soldiers.

Science.gov (United States)

Contractor, Ateka A; Elhai, Jon D; Fine, Thomas H; Tamburrino, Marijo B; Cohen, Gregory; Shirley, Edwin; Chan, Philip K; Liberzon, Israel; Galea, Sandro; Calabrese, Joseph R

2015-09-01

Posttraumatic stress disorder (PTSD) is comorbid with major depressive disorder (MDD; Kessler et al., 1995) and generalized anxiety disorder (GAD; Brown et al., 2001). We aimed to (1) assess discrete patterns of post-trauma PTSD-depression-GAD symptoms using latent profile analyses (LPAs), and (2) assess covariates (gender, income, education, age) in defining the best fitting class solution. The PTSD Checklist (assessing PTSD symptoms), GAD-7 scale (assessing GAD symptoms), and Patient Health Questionnaire-9 (assessing depression) were administered to 1266 trauma-exposed Ohio National Guard soldiers. Results indicated three discrete subgroups based on symptom patterns with mild (class 1), moderate (class 2) and severe (class 3) levels of symptomatology. Classes differed in symptom severity rather than symptom type. Income and education significantly predicted class 1 versus class 3 membership, and class 2 versus class 3. In conclusion, there is heterogeneity regarding severity of PTSD-depression-GAD symptomatology among trauma-exposed soldiers, with income and education predictive of class membership. Copyright © 2015 Elsevier Ltd. All rights reserved.

Opioid peptides and gastrointestinal symptoms in autism spectrum disorders

Directory of Open Access Journals (Sweden)

Cristiane P. Lázaro

2016-01-01

Full Text Available Autism spectrum disorders (ASDs are characterized by deficits in the individual’s ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.

Updates on genome-wide association findings in eating disorders and future application to precision medicine.

Science.gov (United States)

Breithaupt, Lauren; Hubel, Christopher; Bulik, Cynthia M

2018-02-22

Heterogeneity, frequent diagnostic fluctuation across presentations, and global concerns with the absence of effective treatments all encourage science that moves the field toward individualized or precision medicine in eating disorders. We review recent advances in psychiatric genetics focusing on genome-wide association studies (GWAS) in eating disorders and enumerate the prospects and challenges of a genomics-driven approach towards personalized intervention. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder from Traumatic Brain Injury in Focused and Large Community Datasets

OpenAIRE

Amen, Daniel G.; Raji, Cyrus A.; Willeumier, Kristen; Taylor, Derek; Tarzwell, Robert; Newberg, Andrew; Henderson, Theodore A.

2015-01-01

Background Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct. Methods Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large gr...

Organizational heterogeneity of vertebrate genomes.

Science.gov (United States)

Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

2012-01-01

Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

Organizational heterogeneity of vertebrate genomes.

Directory of Open Access Journals (Sweden)

Svetlana Frenkel

Full Text Available Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

Structural brain abnormalities in a single gene disorder associated with epilepsy, language impairment and intellectual disability

Directory of Open Access Journals (Sweden)

Joe Bathelt

2016-01-01

Full Text Available Childhood speech and language deficits are highly prevalent and are a common feature of neurodevelopmental disorders. However, it is difficult to investigate the underlying causal pathways because many diagnostic groups have a heterogeneous aetiology. Studying disorders with a shared genetic cause and shared cognitive deficits can provide crucial insight into the cellular mechanisms and neural systems that give rise to those impairments. The current study investigated structural brain differences of individuals with mutations in ZDHHC9, which is associated with a specific neurodevelopmental phenotype including prominent speech and language impairments and intellectual disability. We used multiple structural neuroimaging methods to characterise neuroanatomy in this group, and observed bilateral reductions in cortical thickness in areas surrounding the temporo-parietal junction, parietal lobule, and inferior frontal lobe, and decreased microstructural integrity of cortical, subcortical-cortical, and interhemispheric white matter projections. These findings are compared to reports for other genetic groups and genetically heterogeneous disorders with a similar presentation. Overlap in the neuroanatomical phenotype suggests a common pathway that particularly affects the development of temporo-parietal and inferior frontal areas, and their connections.

Cultural Issues in Anxiety Disorders: Some Particularities of the Iranian Culture

Directory of Open Access Journals (Sweden)

Azadeh Malekian

2014-01-01

Full Text Available Anxiety disorders occur in all human societies; yet there are cross- cultural variations in the symptomatology, prevalence, the etiologically contributing bio-psycho-social factors and the social responses to the symptoms and their management. Iran has a heterogeneous population with numerous subcultures bounded closely to each other through the common history, language, Old Persian culture and the similarities in their impressing experiences as a nation. In the format of a narrative review article, here we intend to induce a minimal insight into a few areas of particularity of anxiety disorders in Iranian culture. We will focus on the examples of socio-cultural factors affecting the source of distress, help-seeking behaviors, symptom presentation and treatment of these disorders in Iran.

Characterization of heterogeneous SiO2 materials by scanning electron microscope and micro fluorescence XAS techniques

International Nuclear Information System (INIS)

Khouchaf, L.; Boinski, F.; Tuilier, M.H.; Flank, A.M.

2006-01-01

Micro X-ray absorption near edge structure XANES and micro fluorescence experiments have been carried out using X-ray microbeam from synchrotron radiation source with high brightness to investigate the local structural evolutions of heterogeneous and natural SiO 2 submitted to alkali-silica reaction ASR process. Compared to elemental maps obtained by Environmental Scanning Electron Microscope ESEM, micro fluorescence X maps showed the diffusion of potassium cations inside the grains with higher accuracy. Si K-edge spectra show the disorder induced by the dissolution of the grain from the outside to the inside. Potassium K-edge spectra do not show significant changes around K cations. The breaking of Si-O-Si bonds and the disorder of the (SiO 4 ) n network may be affected to potassium cations

The clinical trajectory of emerging bipolar disorder among the high-risk offspring of bipolar parents: current understanding and future considerations.

Science.gov (United States)

Duffy, A; Vandeleur, C; Heffer, N; Preisig, M

2017-11-22

Relatively little is known about the onset of bipolar disorder, yet the early illness course is already associated with significant morbidity and mortality. Therefore, characterizing the bipolar illness trajectory is key to risk prediction and early intervention advancement. In this narrative review, we discuss key findings from prospective longitudinal studies of the high-risk offspring of bipolar parents and related meta-analyses that inform us about the clinical trajectory of emerging bipolar disorder. Challenges such as phenotypic and etiologic heterogeneity and the non-specificity of early symptoms and syndromes are highlighted. Implications of the findings for both research and clinical practice are discussed. Bipolar disorder in young people at familial risk does not typically onset with a hypomanic or manic episode. Rather the first activated episode is often preceded by years of impairing psychopathological states that vary over development and across emerging bipolar subtype. Taking heterogeneity into account and adopting a more comprehensive approach to diagnosis seems necessary to advance earlier identification and our understanding of the onset of bipolar disorder.

Tumor Heterogeneity and Drug Resistance

International Nuclear Information System (INIS)

Kucerova, L.; Skolekova, S.; Kozovska, Z.

2015-01-01

New generation of sequencing methodologies revealed unexpected complexity and genomic alterations linked with the tumor subtypes. This diversity exists across the tumor types, histologic tumor subtypes and subsets of the tumor cells within the same tumor. This phenomenon is termed tumor heterogeneity. Regardless of its origin and mechanisms of development it has a major impact in the clinical setting. Genetic, phenotypic and expression pattern diversity of tumors plays critical role in the selection of suitable treatment and also in the prognosis prediction. Intratumoral heterogeneity plays a key role in the intrinsic and acquired chemoresistance to cytotoxic and targeted therapies. In this review we focus on the mechanisms of intratumoral and inter tumoral heterogeneity and their relationship to the drug resistance. Understanding of the mechanisms and spatiotemporal dynamics of tumor heterogeneity development before and during the therapy is important for the ability to design individual treatment protocols suitable in the given molecular context. (author)

Accelerated long-term forgetting and autobiographical memory disorders in temporal lobe epilepsy: One entity or two?

Science.gov (United States)

Lemesle, B; Planton, M; Pagès, B; Pariente, J

Temporal lobe epilepsy (TLE) is a type of epilepsy that often has a negative impact on patients' memory. Despite the importance of patients' complaints in this regard, the difficulties described by these patients are often not easy to demonstrate through a standard neuropsychological assessment. Accelerated long-term forgetting and autobiographical memory disorders are the two main memory impairments reported in the literature in patients with TLE. However, the methods used by different authors to evaluate long-term memory and autobiographical memory are heterogeneous. This heterogeneity can lead to differences in the observed results as well as how they are interpreted. Yet, despite the methodological differences, objectification of such memory deficits appears to be both specific and robust within this patient population. Analysis of the literature shows that accelerated long-term forgetting and autobiographical memory disorders share the same clinical characteristics. This leads to the assumption that they are, in fact, only one entity and that their evaluation may be done through a single procedure. Our proposal is to place this evaluation within the context of memory consolidation disorders. With such a perspective, evaluation of accelerated forgetting in autobiographical memory should consist of identifying a disorder in the formation and/or recovery of new memory traces. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

Science.gov (United States)

Mete, Ozgur; Duan, Kai

2018-01-01

Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Imaging metabolic heterogeneity in cancer.

Science.gov (United States)

Sengupta, Debanti; Pratx, Guillem

2016-01-06

As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

Epigenetics of Autism Spectrum Disorder.

Science.gov (United States)

Siu, Michelle T; Weksberg, Rosanna

2017-01-01

Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development. In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.

Imaging of collagen deposition disorders using optical coherence tomography

DEFF Research Database (Denmark)

Ring, H C; Mogensen, M; Hussain, A A

2015-01-01

BACKGROUND: Collagen deposition disorders such as hypertrophic scars, keloids and scleroderma can be associated with significant stigma and embarrassment. These disorders often constitute considerable impairment to quality of life, with treatment posing to be a substantial challenge. Optical...... lesion type. Hypertrophic scars displayed an increased vascularity and signal-rich bands correlating to excessive collagen deposition. Keloids depicted a disarray of hyper-reflective areas primarily located in the upper dermis. Additionally, the dermis displayed a heterogeneous morphology without...... indications of any vascular supply or lymphatic network. In contrast to keloids, scleroderma displayed a more cohesive backscattering indicating a difference in density of collagen or other dermal structures. OCT images demonstrated no significant differences between mean density measurements in OCT images...

Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of speech.

Science.gov (United States)

Worthey, Elizabeth A; Raca, Gordana; Laffin, Jennifer J; Wilk, Brandon M; Harris, Jeremy M; Jakielski, Kathy J; Dimmock, David P; Strand, Edythe A; Shriberg, Lawrence D

2013-10-02

Childhood apraxia of speech (CAS) is a rare, severe, persistent pediatric motor speech disorder with associated deficits in sensorimotor, cognitive, language, learning and affective processes. Among other neurogenetic origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely studied, multigenerational London family. We report the first whole-exome sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to 19 years, with well-characterized CAS. As part of a larger study of children and youth with motor speech sound disorders, 32 participants were classified as positive for CAS on the basis of a behavioral classification marker using auditory-perceptual and acoustic methods that quantify the competence, precision and stability of a speaker's speech, prosody and voice. WES of 10 randomly selected participants was completed using the Illumina Genome Analyzer IIx Sequencing System. Image analysis, base calling, demultiplexing, read mapping, and variant calling were performed using Illumina software. Software developed in-house was used for variant annotation, prioritization and interpretation to identify those variants likely to be deleterious to neurodevelopmental substrates of speech-language development. Among potentially deleterious variants, clinically reportable findings of interest occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1, KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically reportable variants in one or two of the six genes, with variants in ATP13A4, KIAA0319 and CNTNAP2 being the most prevalent. Similar to the results reported in emerging WES studies of other complex neurodevelopmental disorders, our findings from this first WES study of CAS are interpreted as support for heterogeneous genetic origins of

Evidence-Based Assessment of Child Obsessive Compulsive Disorder: Recommendations for Clinical Practice and Treatment Research

Science.gov (United States)

Lewin, Adam B.; Piacentini, John

2010-01-01

Obsessive-compulsive disorder (OCD) presents heterogeneously and can be difficult to assess in youth. This review focuses on research-supported assessment approaches for OCD in childhood. Content areas include pre-visit screening, diagnostic establishment, differential diagnosis, assessment of comorbid psychiatric conditions, tracking symptom…

Broad Categories for the Diagnosis of Eating Disorders (BCD-ED): An Alternative System for Classification

Science.gov (United States)

Walsh, B. Timothy; Sysko, Robyn

2009-01-01

Eating Disorder Not Otherwise Specified (EDNOS), a residual category in DSM-IV, is the most commonly used eating disorder diagnosis in clinical settings. However, the features of individuals with EDNOS are heterogeneous and difficult to characterize. A diagnostic scheme, termed Broad Categories for the Diagnosis of Eating Disorders (BCD-ED), is proposed to diminish use of the EDNOS category markedly while preserving the existing eating disorder categories. The BCD-ED scheme consists of three broad categories, in a hierarchical relationship, consisting of: Anorexia Nervosa and Behaviorally Similar disorders, Bulimia Nervosa and Behaviorally Similar Disorders, Binge Eating Disorder and Behaviorally Similar Disorders, and a residual category of EDNOS. The advantages and disadvantages of adopting this scheme for DSM-V are considered, and issues relevant to BCD-ED are discussed. Specifically, we review the proportion of individuals with DSM-IV EDNOS that would be re-classified under the BCD-ED system, support for the hierarchy of the three categories, and the potential risk of “overdiagnosis.” PMID:19650083

Green heterogeneous wireless networks

CERN Document Server

Ismail, Muhammad; Nee, Hans-Peter; Qaraqe, Khalid A; Serpedin, Erchin

2016-01-01

This book focuses on the emerging research topic "green (energy efficient) wireless networks" which has drawn huge attention recently from both academia and industry. This topic is highly motivated due to important environmental, financial, and quality-of-experience (QoE) considerations. Specifically, the high energy consumption of the wireless networks manifests in approximately 2% of all CO2 emissions worldwide. This book presents the authors’ visions and solutions for deployment of energy efficient (green) heterogeneous wireless communication networks. The book consists of three major parts. The first part provides an introduction to the "green networks" concept, the second part targets the green multi-homing resource allocation problem, and the third chapter presents a novel deployment of device-to-device (D2D) communications and its successful integration in Heterogeneous Networks (HetNets). The book is novel in that it specifically targets green networking in a heterogeneous wireless medium, which re...

A genome-wide linkage study of bipolar disorder and co-morbid migraine

DEFF Research Database (Denmark)

Oedegaard, K. J.; Greenwood, T. A.; Lunde, Asger

2010-01-01

Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genomewide linkage studies in BPAD...... that using migraine comorbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with comorbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar...... osome 4 (not co-segregating with BPAD) in a sample of BPAD families with comorbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine....

Subjective Experience, Heterophenomenology, or Neuroimaging? A Perspective on the Meaning and Application of Mental Disorder Terms, in Particular Major Depressive Disorder.

Science.gov (United States)

Schleim, Stephan

2018-01-01

Increasing research efforts try to identify biological markers in order to support or eventually replace current practices of diagnosing mental disorders. Inasmuch as these disorders refer to subjective mental states, such efforts amount to their objectification. This gives rise to conceptual as well as empirical challenges: What kind of things are mental disorders? And how to deal with situations where subjective reports, clinical decisions, and brain scans contradict each other? The present paper starts out with a discussion of recent efforts to objectify beauty. Such attempts to quantify and localize psychological constructs in the brain are compared to earlier examples from the history of psychology. The paper then discusses personal and social implications of the objectification of subjective mental states, including mental disorders. The construct of Major Depressive Disorder, one of the most prevalent mental disorders, is then analyzed in more detail. It turns out that this is a very complex construct probably associated with highly heterogeneous actual instances of the disorder. It is then shown that it is unlikely to replace these symptoms' descriptions with patterns of brain activations, at least in the near future, given these patterns' empirical lack of specificity. The paper then discusses which of the disorder's core symptoms are more or less amenable to behavioral or neuroscientific investigation and analyses whether the heterophenomenological method can solve the problem. The conclusion is that the disorder construct is neither entirely subjective, nor completely objectifiable, and that clinical experts do well by continuing to take a pragmatical stance.

Heterogeneity of emotional and interpersonal difficulties in alcohol-dependence: A cluster analytic approach.

Science.gov (United States)

Maurage, Pierre; Timary, Philippe de; D'Hondt, Fabien

2017-08-01

Emotional and interpersonal impairments have been largely reported in alcohol-dependence, and their role in its development and maintenance is widely established. However, earlier studies have exclusively focused on group comparisons between healthy controls and alcohol-dependent individuals, considering them as a homogeneous population. The variability of socio-emotional profiles in this disorder thus remains totally unexplored. The present study used a cluster analytic approach to explore the heterogeneity of affective and social disorders in alcohol-dependent individuals. 296 recently-detoxified alcohol-dependent patients were first compared with 246 matched healthy controls regarding self-reported emotional (i.e. alexithymia) and social (i.e. interpersonal problems) difficulties. Then, a cluster analysis was performed, focusing on the alcohol-dependent sample, to explore the presence of differential patterns of socio-emotional deficits and their links with demographic, psychopathological and alcohol-related variables. The group comparison between alcohol-dependent individuals and controls clearly confirmed that emotional and interpersonal difficulties constitute a key factor in alcohol-dependence. However, the cluster analysis identified five subgroups of alcohol-dependent individuals, presenting distinct combinations of alexithymia and interpersonal problems ranging from a total absence of reported impairment to generalized socio-emotional difficulties. Alcohol-dependent individuals should no more be considered as constituting a unitary group regarding their affective and interpersonal difficulties, but rather as a population encompassing a wide variety of socio-emotional profiles. Future experimental studies on emotional and social variables should thus go beyond mere group comparisons to explore this heterogeneity, and prevention programs proposing an individualized evaluation and rehabilitation of these deficits should be promoted. Copyright © 2017

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

Science.gov (United States)

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

2012-01-01

This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

Microbial population heterogeneity versus bioreactor heterogeneity: evaluation of Redox Sensor Green as an exogenous metabolic biosensor

DEFF Research Database (Denmark)

Baert, Jonathan; Delepierre, Anissa; Telek, Samuel

2016-01-01

Microbial heterogeneity in metabolic performances has attracted a lot of attention, considering its potential impact on industrial bioprocesses. However, little is known about the impact of extracellular perturbations (i.e. bioreactor heterogeneity) on cell-to-cell variability in metabolic...

An empirical investigation of incompleteness in a large clinical sample of obsessive compulsive disorder.

Science.gov (United States)

Sibrava, Nicholas J; Boisseau, Christina L; Eisen, Jane L; Mancebo, Maria C; Rasmussen, Steven A

2016-08-01

Obsessive Compulsive Disorder (OCD) is a disorder with heterogeneous clinical presentations. To advance our understanding of this heterogeneity we investigated the prevalence and clinical features associated with incompleteness (INC), a putative underlying core feature of OCD. We predicted INC would be prominent in individuals with OCD and associated with greater severity and impairment. We examined the impact of INC in 307 adults with primary OCD. Participants with clinically significant INC (22.8% of the sample) had significantly greater OCD severity, greater rates of comorbidity, poorer ratings of functioning, lower quality of life, and higher rates of unemployment and disability. Participants with clinically significant INC were also more likely to be diagnosed with OCPD and to endorse symmetry/exactness obsessions and ordering/arranging compulsions than those who reported low INC. Our findings provide evidence that INC is associated with greater severity, comorbidity, and impairment, highlighting the need for improved assessment and treatment of INC in OCD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brain Structural Effects of Psychopharmacological Treatment in Bipolar Disorder

Science.gov (United States)

McDonald, Colm

2015-01-01

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimaging studies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies. PMID:26412064

[Neuroimaging data of ADHD, tic-disorder and obsessive-compulsive-disorder in children and adolescents].

Science.gov (United States)

Vloet, Timo D; Neufang, Susanne; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2006-09-01

ADHD, Tic Disorder, Tourette's Syndrome, and Obsessive-Compulsive Disorder are all characterised by an impairment of executive functioning and often occur together. There are thus indications of a similar neurobiological basis. This review presents an overview of neuroimaging studies of these disorders in childhood and adolescence, focusing thereby on magnet resonance imaging data. Studies provide concurring data about structural changes in the basal ganglia and the prefrontal cortex, and abnormal activation in the fronto-striatal circuitry in patients as compared to healthy controls. ADHD and Tourette's Syndrome are both associated with prefrontal aberrations. However, variances in Tourette's Syndrome are less pronounced, which might be due to compensation mechanisms. ADHD children show small, but more global, morphological alterations in the cortex and cerebellum, while Tourette's Syndrome seems to be linked additionally to differences in the occipital cortex. Furthermore, structural and functional data for obsessive-compulsive disorder indicate aberrations in the amygdala and thalamus, and functional changes in the orbito-frontal cortex. By comparison, findings in children with ADHD point towards abnormal activity in the ventral prefrontal cortex. To summarise, the data display an impairment of cortico-striato-thalamic circuits which appears to be associated with dysfunctioning motor inhibition, and impulsive behaviour and objectionable thoughts. Since the majority of the studies reviewed are characterised by small and heterogeneous samples, and since the studies differ in their methods, comparability is limited and general conclusions can not be drawn.

Eating disorder not otherwise specified in adolescents.

Science.gov (United States)

Eddy, Kamryn T; Celio Doyle, Angela; Hoste, Renee Rienecke; Herzog, David B; le Grange, Daniel

2008-02-01

To examine the frequency, type, and clinical severity of eating disorder not otherwise specified (EDNOS) in adolescents seeking treatment through an outpatient eating disorders service. Two hundred eighty-one consecutive referrals to an eating disorders program were assessed using the Eating Disorder Examination (EDE) and self-report measures of depression and self-esteem. The majority of adolescents presented with EDNOS (59.1%; n = 166) relative to anorexia nervosa (AN; 20.3%; n = 57) and bulimia nervosa (BN; 20.6%; n = 58). Most EDNOS youths could be described as subthreshold AN (SAN; 27.7%; n = 46), subthreshold BN (SBN; 19.9%; n = 33), EDNOS purging (27.7%; n = 46), or EDNOS bingeing (6.0%; n = 10); yet 31 (18.7%) could not be categorized as such (EDNOS "other"). Overall differences in eating disorder pathology, depressive symptoms, and self-esteem emerged between the EDNOS types, wherein adolescents with EDNOS bulimic variants (SBN, EDNOS purging, and EDNOS bingeing) had more pathology than youths with SAN or EDNOS "other." There were no differences in these variables between AN and SAN; in contrast, compared with BN, youths with EDNOS bulimic variants reported lower EDE scores and higher self-esteem, although there were no between-group differences in depression. As in adults with eating disorders, EDNOS predominates and is heterogeneous with regard to eating disorder pathology and associated features in an adolescent clinical sample. Lack of differences between AN and SAN suggests that the strict criteria for AN could be relaxed; differences between BN and EDNOS bulimic variants do not support their combination.

Afternoon serum-melatonin in sleep disordered breathing.

Science.gov (United States)

Ulfberg, J; Micic, S; Strøm, J

1998-08-01

To study afternoon serum-melatonin values in patients with sleep disordered breathing. Melatonin has a strong circadian rhythm with high values during the night-time and low values in the afternoon. Sleep disordered breathing may change the circadian rhythm of melatonin which may have diagnostic implications. The Sleep Laboratory, The Department of Internal Medicine, Avesta Hospital, Sweden, and the Department of Anaesthesiology, Glostrup University Hospital, Copenhagen, Denmark. We examined 60 consecutive patients admitted for sleep disordered breathing and 10 healthy non snoring controls. The patients underwent a sleep apnoea screening test having a specificity of 100% for the obstructive sleep apnoea syndrome (OSAS) using a combination of static charge sensitive bed and oximetry. Obstructive sleep apnoea syndrome was found in 49 patients, eight patients had borderline sleep disordered breathing (BSDB) and three patients were excluded due to interfering disease. Patients and controls had an afternoon determination of serum-melatonin. The Epworth Sleepiness Scale was used to score day-time sleepiness. In comparison with normal controls patients suffering from OSAS had significantly higher serum-melatonin levels in the afternoon. However, as a diagnostic test for OSAS in patients with sleep disordered breathing serum-melatonin showed a low sensitivity but a high specificity. The results indicate that breathing disorders during sleep in general affect pineal function. Sleep disordered breathing seems to disturb pineal function. Determination of afternoon serum-melatonin alone or together with a scoring of daytime sleepiness does not identify OSAS-patients in a heterogeneous population of patients complaining of heavy snoring and excessive daytime sleepiness.

Tourette's syndrome and associated disorders: a systematic review

Directory of Open Access Journals (Sweden)

Bárbara R. Ferreira

2014-09-01

Full Text Available Objective: To compile data on Tourette's syndrome (TS, tics and associated disorders.Methods: A systematic review of the literature was conducted using the 5S levels of organization of healthcare research evidence (systems, summaries, synopses, syntheses, studies, based on the model described by Haynes. The search keywords were Tourette, tics and comorbidity, which were cross-referenced. Studies provided by publishers and articles being processed on July 31, 2013, were also included.Results: Of all studies retrieved during the search, 64 were selected because they analyzed the epidemiology, clinical features and etiopathogenesis of TS and its comorbidities. TS is classified as a hyperkinetic movement disorder, and at least 90% of the patients have neuropsychiatric comorbidities, of which attention deficit hyperactivity and obsessive-compulsive disorders are the most common. The syndrome is clinically heterogeneous and has been associated with a dysfunction of cortico-striatal-thalamic-cortical circuits involving various neurotransmitters. Although its genetic etiology has been widely studied, other factors may be important to understand this syndrome and its associated disorders.Conclusions: TS is a neurodevelopmental disorder that results from the impact of stress factors on a vulnerable biological substrate during the critical periods of neurodevelopment. The study of TS and its comorbidities may contribute, at different levels, to the understanding of several neuropsychiatric disorders of clinical and therapeutic relevance.

In-situ characterization of heterogeneous catalysts

CERN Document Server

Rodriguez, Jose A; Chupas, Peter J

2013-01-01

Helps researchers develop new catalysts for sustainable fuel and chemical production Reviewing the latest developments in the field, this book explores the in-situ characterization of heterogeneous catalysts, enabling readers to take full advantage of the sophisticated techniques used to study heterogeneous catalysts and reaction mechanisms. In using these techniques, readers can learn to improve the selectivity and the performance of catalysts and how to prepare catalysts as efficiently as possible, with minimum waste. In-situ Characterization of Heterogeneous Catalysts feat

Heterogeneous Beliefs, Public Information, and Option Markets

DEFF Research Database (Denmark)

Qin, Zhenjiang

In an incomplete market setting with heterogeneous prior beliefs, I show that public information and strike price of option have substantial infl‡uence on asset pricing in option markets, by investigating an absolute option pricing model with negative exponential utility investors and normally...... distributed dividend. I demonstrate that heterogeneous prior variances give rise to the economic value of option markets. Investors speculate in option market and public information improves allocational efficiency of markets only when there is heterogeneity in prior variance. Heterogeneity in mean is neither...... a necessary nor sufficient condition for generating speculations in option markets. With heterogeneous beliefs, options are non-redundant assets which can facilitate side-betting and enable investors to take advantage of the disagreements and the differences in con…dence. This fact leads to a higher growth...

How to measure genetic heterogeneity

International Nuclear Information System (INIS)

Yamada, Ryo

2009-01-01

Genetic information of organisms is coded as a string of four letters, A, T, G and C, a sequence in macromolecules called deoxyribonucleic acid (DNA). DNA sequence offers blueprint of organisms and its heterogeneity determines identity and variation of species. The quantitation of this genetic heterogeneity is fundamental to understand biology. We compared previously-reported three measures, covariance matrix expression of list of loci (pair-wise r 2 ), the most popular index in genetics, and its multi-dimensional form, Ψ, and entropy-based index, ε. Thereafter we proposed two methods so that we could handle the diplotypic heterogeneity and quantitate the conditions where the number of DNA sequence samples is much smaller than the number of possible variants.

DSM-IV-TR “pain disorder associated with psychological factors” as a nonhysterical form of somatization

Science.gov (United States)

Aragona, Massimiliano; Tarsitani, Lorenzo; De Nitto, Serena; Inghilleri, Maurizio

2008-01-01

BACKGROUND: Elevated Minnesota Multiphasic Personality Inventory (MMPI) scores on the hysteria (Hy) scale are reported in several forms of pain. Previous results were possibly biased by diagnostic heterogeneity (psychogenic, somatic and mixed pain syndromes included in the same index sample) or Hy heterogeneity (failure to differentiate Hy scores into clinically meaningful sub-scales, such as admission of symptoms [Ad] and denial of symptoms [Dn]). METHODS: To overcome this drawback, 48 patients diagnosed as having a Diagnostic and Statistical Manual of Mental Disorders, 4th edn, Text Revision (DSM-IV-TR) diagnosis of “pain disorder associated with psychological factors” were compared with 48 patients experiencing somatic pain excluding psychological factors, and 42 somatic controls without pain. RESULTS: MMPI Hy and hypochondriasis (Hs) scores were significantly higher in the pain disorder group than in control groups, who scored similarly. MMPI correction (K) scores and Dn scores were similar in the three groups, whereas Ad was significantly higher in the pain disorder group and lower and similar in the two control groups, respectively. In the pain disorder group, Ad and Dn were negatively correlated, whereas in control groups they were unrelated. CONCLUSIONS: These findings suggest that whereas a pattern of high Hs and Hy scores together with a normal K score might characterize patients with a pain disorder associated with psychological factors, elevated Hy scores per se do not indicate hysterical traits. In the pain disorder group, elevated Hy scores reflected the Ad subscale alone, indicating a strikingly high frequency of distressing somatic symptoms. They tend not to repress or deny the emotional malaise linked to symptoms, as the hysterical construct expects. The pain disorder designation should be considered a nonhysterical form of somatization. PMID:18301811

The Role of Epigenetic Change in Autism Spectrum Disorders.

Science.gov (United States)

Loke, Yuk Jing; Hannan, Anthony John; Craig, Jeffrey Mark

2015-01-01

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders characterized by problems with social communication, social interaction, and repetitive or restricted behaviors. ASD are comorbid with other disorders including attention deficit hyperactivity disorder, epilepsy, Rett syndrome, and Fragile X syndrome. Neither the genetic nor the environmental components have been characterized well enough to aid diagnosis or treatment of non-syndromic ASD. However, genome-wide association studies have amassed evidence suggesting involvement of hundreds of genes and a variety of associated genetic pathways. Recently, investigators have turned to epigenetics, a prime mediator of environmental effects on genomes and phenotype, to characterize changes in ASD that constitute a molecular level on top of DNA sequence. Though in their infancy, such studies have the potential to increase our understanding of the etiology of ASD and may assist in the development of biomarkers for its prediction, diagnosis, prognosis, and eventually in its prevention and intervention. This review focuses on the first few epigenome-wide association studies of ASD and discusses future directions.

The role of epigenetic change in autism spectrum disorders

Directory of Open Access Journals (Sweden)

Yuk Jin eLoke

2015-05-01

Full Text Available Autism spectrum disorders (ASD are a heterogeneous group of neurodevelopmental disorders characterised by problems with social communication, social interaction and repetitive or restricted behaviours. ASD is comorbid with other disorders including attention deficit hyperactivity disorder, epilepsy, Rett syndrome and Fragile X syndrome. Neither the genetic nor the environmental components have been characterised well enough to aid diagnosis or treatment of non-syndromic ASD. However, genome-wide association studies have amassed evidence suggesting involvement of hundreds of genes and a variety of associated genetic pathways. Recently, investigators have turned to epigenetics, a prime mediator of environmental effects on genomes and phenotype, to characterise changes in ASD that constitute a molecular level on top of DNA sequence. Though in their infancy, such studies have the potential to increase our understanding of the aetiology of ASD and may assist in the development of biomarkers for its prediction, diagnosis, prognosis and eventually in its prevention and intervention. This review focuses on the first few epigenome-wide association studies of ASD and discusses future directions.

Elevation discrepancies between MMPI-2 clinical and MMPI-2-RF restructured clinical (RC) scales in people with seizure disorders.

Science.gov (United States)

Bowden, Stephen C; White, Jessica R; Simpson, Leonie; Ben-Porath, Yossef S

2014-05-01

People with seizure disorders experience elevated rates of psychopathology, often undiagnosed and untreated. Accurate diagnosis of psychopathology remains an important goal of quality health care for people with seizure disorders. One of the most widely used dimensional measures of psychopathology is the Minnesota Multiphasic Personality Inventory-Second Edition (MMPI-2). Research in heterogeneous mental health samples suggests that the 2008 revision of this measure, the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF), offers better construct fidelity and more cost-effective administration. This study seeks to extend research on MMPI-2-RF scale elevations to a sample of people with seizure disorders. In a consecutive, heterogeneous sample of people with seizure disorders, MMPI-2 and MMPI-2-RF scores were compared in terms of categorical classification agreement (clinically elevated versus not clinically elevated). Scores were also compared in terms of variance attributable to diagnosis-specific items, general demoralization, subtle items, social desirability, and demographic factors. Scores on MMPI-2 and MMPI-2-RF provided a statistically significant level of agreement between corresponding clinical diagnostic scales ranging from 68% to 84%. Most classification disagreement was attributable to MMPI-2 clinical scale elevations when MMPI-2-RF scales were not elevated. Regression analysis supported the interpretation that general demoralization, subtle items, social desirability, and demographic factors led to MMPI-2 clinical scale elevations. The results provide evidence that in the context of strong psychopathology classification agreement, the MMPI-2-RF restructured clinical scales provide better construct fidelity compared with the more trait heterogeneous MMPI-2 clinical scales. These results should encourage clinicians to use the MMPI-2 Restructured Form (MMPI-2-RF) for improved psychopathology assessment compared with

Strong disorder RG approach of random systems

International Nuclear Information System (INIS)

Igloi, Ferenc; Monthus, Cecile

2005-01-01

There is a large variety of quantum and classical systems in which the quenched disorder plays a dominant ro-circumflex le over quantum, thermal, or stochastic fluctuations: these systems display strong spatial heterogeneities, and many averaged observables are actually governed by rare regions. A unifying approach to treat the dynamical and/or static singularities of these systems has emerged recently, following the pioneering RG idea by Ma and Dasgupta and the detailed analysis by Fisher who showed that the Ma-Dasgupta RG rules yield asymptotic exact results if the broadness of the disorder grows indefinitely at large scales. Here we report these new developments by starting with an introduction of the main ingredients of the strong disorder RG method. We describe the basic properties of infinite disorder fixed points, which are realized at critical points, and of strong disorder fixed points, which control the singular behaviors in the Griffiths-phases. We then review in detail applications of the RG method to various disordered models, either (i) quantum models, such as random spin chains, ladders and higher dimensional spin systems, or (ii) classical models, such as diffusion in a random potential, equilibrium at low temperature and coarsening dynamics of classical random spin chains, trap models, delocalization transition of a random polymer from an interface, driven lattice gases and reaction diffusion models in the presence of quenched disorder. For several one-dimensional systems, the Ma-Dasgupta RG rules yields very detailed analytical results, whereas for other, mainly higher dimensional problems, the RG rules have to be implemented numerically. If available, the strong disorder RG results are compared with another, exact or numerical calculations

Characterization of heterogeneous SiO{sub 2} materials by scanning electron microscope and micro fluorescence XAS techniques

Energy Technology Data Exchange (ETDEWEB)

Khouchaf, L. [Centre de Recherche de l' Ecole des Mines deDouai, 941, rue Charles Bourseul, BP. 10838, 59508 Douai (France)]. E-mail: khouchaf@ensm-douai.fr; Boinski, F. [Centre de Recherche de l' Ecole des Mines deDouai, 941, rue Charles Bourseul, BP. 10838, 59508 Douai (France); Tuilier, M.H. [GMP Equipe de recherche: MMPF, Universite de Haute-Alsace, 61 rue Albert Camus, F-68093, Mulhouse Cedex (France); Flank, A.M. [SOLEIL and Swiss Light Source SLS CH-5232 Villigen PSI (Switzerland)

2006-11-15

Micro X-ray absorption near edge structure XANES and micro fluorescence experiments have been carried out using X-ray microbeam from synchrotron radiation source with high brightness to investigate the local structural evolutions of heterogeneous and natural SiO{sub 2} submitted to alkali-silica reaction ASR process. Compared to elemental maps obtained by Environmental Scanning Electron Microscope ESEM, micro fluorescence X maps showed the diffusion of potassium cations inside the grains with higher accuracy. Si K-edge spectra show the disorder induced by the dissolution of the grain from the outside to the inside. Potassium K-edge spectra do not show significant changes around K cations. The breaking of Si-O-Si bonds and the disorder of the (SiO{sub 4}) {sub n} network may be affected to potassium cations.

[Rethink the panic disorder].

Science.gov (United States)

Amami, O; Aloulou, J; Siala, M; Aribi, L

2010-04-01

. This frequent comorbidity could be also due to the community of certain symptoms of each disorder. These observations increase the validity of the anxiety generalized disorder as an autonomous morbid entity, rather than corresponding to a residual syndrome of the panic disorder, and could be an argument of an implicit return to the Freudian concept of the anxiety neurosis. The frequent comorbidity of panic disorder and personality disorders suggests the existence of a link. The pathological personality can be a factor of vulnerability in the panic disorder, as it can be a consequence of the panic disorder through the personality changing related on the evolution of the disorder and its complications. The relationship between panic disorder and depression has been interpreted in various ways, with mainly three assumptions: the unit position, which considers anxiety and depression as concerning a common diathesis; the dualistic position, which suggests that anxiety and depression are heterogeneous diagnostic categories and the anxio-depressive position that considers anxiety and depression combined as a syndrome differing from the pure anxiety and pure depression. The genetic studies, as well as the family studies, clearly show that the two entities are undissociated. Likewise, the therapeutic action of serotoninergic antidepressants in the two types of disorders reinforces the idea of a common biological vulnerability between anxiety and depression. Several studies have shown a significant association between panic disorder and suicide. However, the suicidal conducts are multiple and proceed by complex interactions between factors of features and states. Accordingly, panic disorder can be considered as a factor of state associated with the suicidal risk. 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

A systematic review of personality disorder, race and ethnicity: prevalence, aetiology and treatment

Directory of Open Access Journals (Sweden)

Lee Tennyson

2010-05-01

Full Text Available Abstract Background Although psychoses and ethnicity are well researched, the importance of culture, race and ethnicity has been overlooked in Personality Disorders (PD research. This study aimed to review the published literature on ethnic variations of prevalence, aetiology and treatment of PD. Method A systematic review of studies of PD and race, culture and ethnicity including a narrative synthesis of observational data and meta-analyses of prevalence data with tests for heterogeneity. Results There were few studies with original data on personality disorder and ethnicity. Studies varied in their classification of ethnic group, and few studies defined a specific type of personality disorder. Overall, meta-analyses revealed significant differences in prevalence between black and white groups (OR 0.476, CIs 0.248 - 0.915, p = 0.026 but no differences between Asian or Hispanic groups compared with white groups. Meta-regression analyses found that heterogeneity was explained by some study characteristics: a lower prevalence of PD was reported among black compared with white patients in UK studies, studies using case-note diagnoses rather than structured diagnostic interviews, studies of borderline PD compared with the other PD, studies in secure and inpatient compared with community settings, and among subjects with co-morbid disorders compared to the rest. The evidence base on aetiology and treatment was small. Conclusion There is some evidence of ethnic variations in prevalence of personality disorder but methodological characteristics are likely to account for some of the variation. The findings may indicate neglect of PD diagnosis among ethnic groups, or a true lower prevalence amongst black patients. Further studies are required using more precise cultural and ethnic groups.

A systematic review of personality disorder, race and ethnicity: prevalence, aetiology and treatment.

Science.gov (United States)

McGilloway, Angela; Hall, Ruth E; Lee, Tennyson; Bhui, Kamaldeep S

2010-05-11

Although psychoses and ethnicity are well researched, the importance of culture, race and ethnicity has been overlooked in Personality Disorders (PD) research. This study aimed to review the published literature on ethnic variations of prevalence, aetiology and treatment of PD. A systematic review of studies of PD and race, culture and ethnicity including a narrative synthesis of observational data and meta-analyses of prevalence data with tests for heterogeneity. There were few studies with original data on personality disorder and ethnicity. Studies varied in their classification of ethnic group, and few studies defined a specific type of personality disorder. Overall, meta-analyses revealed significant differences in prevalence between black and white groups (OR 0.476, CIs 0.248 - 0.915, p = 0.026) but no differences between Asian or Hispanic groups compared with white groups. Meta-regression analyses found that heterogeneity was explained by some study characteristics: a lower prevalence of PD was reported among black compared with white patients in UK studies, studies using case-note diagnoses rather than structured diagnostic interviews, studies of borderline PD compared with the other PD, studies in secure and inpatient compared with community settings, and among subjects with co-morbid disorders compared to the rest. The evidence base on aetiology and treatment was small. There is some evidence of ethnic variations in prevalence of personality disorder but methodological characteristics are likely to account for some of the variation. The findings may indicate neglect of PD diagnosis among ethnic groups, or a true lower prevalence amongst black patients. Further studies are required using more precise cultural and ethnic groups.

Reactive and Proactive Interference Control in Adults with Autism Spectrum Disorder across the Lifespan

Science.gov (United States)

Lever, Anne G.; Ridderinkhof, K. Richard; Marsman, Maarten; Geurts, Hilde M.

2017-01-01

As a large heterogeneity is observed across studies on interference control in autism spectrum disorder (ASD), research may benefit from the use of a cognitive framework that models specific processes underlying reactive and proactive control of interference. Reactive control refers to the expression and suppression of responses and proactive…

Adsorption of gases on heterogeneous surfaces

CERN Document Server

Rudzinski, W

1991-01-01

All real solid surfaces are heterogeneous to a greater or lesser extent and this book provides a broad yet detailed survey of the present state of gas adsorption. Coverage is comprehensive and extends from basic principles to computer simulation of adsorption. Underlying concepts are clarified and the strengths and weaknesses of the various methods described are discussed.Key Features* Adsorption isotherm equations for various types of heterogeneous solid surfaces* Methods of determining the nature of surface heterogeneity and porosity from experimental data* Studies of pha

Heterogeneous Causal Effects and Sample Selection Bias

DEFF Research Database (Denmark)

Breen, Richard; Choi, Seongsoo; Holm, Anders

2015-01-01

The role of education in the process of socioeconomic attainment is a topic of long standing interest to sociologists and economists. Recently there has been growing interest not only in estimating the average causal effect of education on outcomes such as earnings, but also in estimating how...... causal effects might vary over individuals or groups. In this paper we point out one of the under-appreciated hazards of seeking to estimate heterogeneous causal effects: conventional selection bias (that is, selection on baseline differences) can easily be mistaken for heterogeneity of causal effects....... This might lead us to find heterogeneous effects when the true effect is homogenous, or to wrongly estimate not only the magnitude but also the sign of heterogeneous effects. We apply a test for the robustness of heterogeneous causal effects in the face of varying degrees and patterns of selection bias...

Alstr?m Syndrome: Genetics and Clinical Overview

OpenAIRE

Marshall, Jan D; Maffei, Pietro; Collin, Gayle B; Naggert, J?rgen K

2011-01-01

Alstr?m syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinic...

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits.

Science.gov (United States)

Corominas, M; Ramos-Quiroga, J A; Ferrer, M; Sáez-Francàs, N; Palomar, G; Bosch, R; Casas, M

2012-06-01

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.

Probing Mantle Heterogeneity Across Spatial Scales

Science.gov (United States)

Hariharan, A.; Moulik, P.; Lekic, V.

2017-12-01

Inferences of mantle heterogeneity in terms of temperature, composition, grain size, melt and crystal structure may vary across local, regional and global scales. Probing these scale-dependent effects require quantitative comparisons and reconciliation of tomographic models that vary in their regional scope, parameterization, regularization and observational constraints. While a range of techniques like radial correlation functions and spherical harmonic analyses have revealed global features like the dominance of long-wavelength variations in mantle heterogeneity, they have limited applicability for specific regions of interest like subduction zones and continental cratons. Moreover, issues like discrepant 1-D reference Earth models and related baseline corrections have impeded the reconciliation of heterogeneity between various regional and global models. We implement a new wavelet-based approach that allows for structure to be filtered simultaneously in both the spectral and spatial domain, allowing us to characterize heterogeneity on a range of scales and in different geographical regions. Our algorithm extends a recent method that expanded lateral variations into the wavelet domain constructed on a cubed sphere. The isolation of reference velocities in the wavelet scaling function facilitates comparisons between models constructed with arbitrary 1-D reference Earth models. The wavelet transformation allows us to quantify the scale-dependent consistency between tomographic models in a region of interest and investigate the fits to data afforded by heterogeneity at various dominant wavelengths. We find substantial and spatially varying differences in the spectrum of heterogeneity between two representative global Vp models constructed using different data and methodologies. Applying the orthonormality of the wavelet expansion, we isolate detailed variations in velocity from models and evaluate additional fits to data afforded by adding such complexities to long

Structural disorder in metallic glass-forming liquids.

Science.gov (United States)

Pan, Shao-Peng; Feng, Shi-Dong; Wang, Li-Min; Qiao, Jun-Wei; Niu, Xiao-Feng; Dong, Bang-Shao; Wang, Wei-Min; Qin, Jing-Yu

2016-06-09

We investigated structural disorder by a new structural parameter, quasi-nearest atom (QNA), in atomistic configurations of eight metallic glass-forming systems generated through molecular dynamics simulations at various temperatures. Structural analysis reveals that the scaled distribution of the number of QNA appears to be an universal property of metallic liquids and the spatial distribution of the number of QNA displays to be clearly heterogeneous. Furthermore, the new parameter can be directly correlated with potential energy and structural relaxation at the atomic level. Some straightforward relationships between QNA and other properties (per-atom potential energy and α-relaxation time) are introduced to reflect structure-property relationship in metallic liquids. We believe that the new structural parameter can well reflect structure disorder in metallic liquids and play an important role in understanding various properties in metallic liquids.

Patient-reported outcomes in borderline personality disorder

Science.gov (United States)

Hasler, Gregor; Hopwood, Christopher J.; Jacob, Gitta A.; Brändle, Laura S.; Schulte-Vels, Thomas

2014-01-01

Patient-reported outcome (PRO) refers to measures that emphasize the subjective view of patients about their health-related conditions and behaviors. Typically, PROs include self-report questionnaires and clinical interviews. Defining PROs for borderline personality disorder (BPD) is particularly challenging given the disorder's high symptomatic heterogeneity, high comorbidity with other psychiatric conditions, highly fluctuating symptoms, weak correlations between symptoms and functional outcomes, and lack of valid and reliable experimental measures to complement self-report data. Here, we provide an overview of currently used BPD outcome measures and discuss them from clinical, psychometric, experimental, and patient perspectives. In addition, we review the most promising leads to improve BPD PROs, including the DSM-5 Section III, the Recovery Approach, Ecological Momentary Assessments, and novel experimental measures of social functioning that are associated with functional and social outcomes. PMID:25152662

Implications of Heterogeneity in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Sanjay de Mel

2014-01-01

Full Text Available Multiple myeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated.

Selective Oxidations using Nanostructured Heterogeneous Catalysts

DEFF Research Database (Denmark)

Mielby, Jerrik Jørgen

and because they produce H2O as the only by-product. Chapter 1 gives a short introduction to basic concepts in heterogeneous catalysis and green chemistry. Furthermore, the chapter gives an overview of the most important strategies to synthesise functional nanostructured materials and highlights how detailed......The aim of this thesis is to investigate and develop new efficient methods to oxidise alcohols and amines using heterogeneous catalysts and either O2 or H2O2 as oxidants. From an economic and environmental point of view, these oxidants are ideal, because they are cheap and readily available...... understanding of size, shape and structure can help in the development of new and more efficient heterogeneous catalysts. The chapter is not intended to give a complete survey, but rather to introduce some of the recent developments in the synthesis of nanostructured heterogeneous catalysts. Finally...

Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

Directory of Open Access Journals (Sweden)

Albert H Gough

Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

A heterogeneous graph-based recommendation simulator

Energy Technology Data Exchange (ETDEWEB)

Yeonchan, Ahn [Seoul National University; Sungchan, Park [Seoul National University; Lee, Matt Sangkeun [ORNL; Sang-goo, Lee [Seoul National University

2013-01-01

Heterogeneous graph-based recommendation frameworks have flexibility in that they can incorporate various recommendation algorithms and various kinds of information to produce better results. In this demonstration, we present a heterogeneous graph-based recommendation simulator which enables participants to experience the flexibility of a heterogeneous graph-based recommendation method. With our system, participants can simulate various recommendation semantics by expressing the semantics via meaningful paths like User Movie User Movie. The simulator then returns the recommendation results on the fly based on the user-customized semantics using a fast Monte Carlo algorithm.

Interest rate rules with heterogeneous expectations

NARCIS (Netherlands)

Anufriev, M.; Assenza, T.; Hommes, C.; Massaro, D.

2011-01-01

The recent macroeconomic literature stresses the importance of managing heterogeneous expectations in the formulation of monetary policy. We use a simple frictionless DSGE model to investigate inflation dynamics under alternative interest rate rules when agents have heterogeneous expectations and

Unobserved heterogeneity in the power law nonhomogeneous Poisson process

International Nuclear Information System (INIS)

Asfaw, Zeytu Gashaw; Lindqvist, Bo Henry

2015-01-01

A study of possible consequences of heterogeneity in the failure intensity of repairable systems is presented. The basic model studied is the nonhomogeneous Poisson process with power law intensity function. When several similar systems are under observation, the assumption that the corresponding processes are independent and identically distributed is often questionable. In practice there may be an unobserved heterogeneity among the systems. The heterogeneity is modeled by introduction of unobserved gamma distributed frailties. The relevant likelihood function is derived, and maximum likelihood estimation is illustrated. In a simulation study we then compare results when using a power law model without taking into account heterogeneity, with the corresponding results obtained when the heterogeneity is accounted for. A motivating data example is also given. - Highlights: • Consequences of overlooking heterogeneity in similar repairable systems are studied. • Likelihood functions are established for power law NHPP w/ and w/o heterogeneity. • ML estimators for parameters of power law NHPP with heterogeneity are derived. • A simulation study shows the effects of heterogeneity and its ignorance in models

Obsessive–compulsive disorder: subclassification based on co-morbidity

Science.gov (United States)

Nestadt, G.; Di, C. Z.; Riddle, M. A.; Grados, M. A.; Greenberg, B. D.; Fyer, A. J.; McCracken, J. T.; Rauch, S. L.; Murphy, D. L.; Rasmussen, S. A.; Cullen, B.; Pinto, A.; Knowles, J. A.; Piacentini, J.; Pauls, D. L.; Bienvenu, O. J.; Wang, Y.; Liang, K. Y.; Samuels, J. F.; Roche, K. Bandeen

2011-01-01

Background Obsessive–compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Method Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Results Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive–compulsive personality disorder (OCPD) features, high scores on the ‘taboo’ factor of OCD symptoms, and low conscientiousness. Conclusions OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors. PMID:19046474

Eosinophilic myositis: an updated review.

Science.gov (United States)

Selva-O'Callaghan, A; Trallero-Araguás, E; Grau, J M

2014-01-01

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis.

Science.gov (United States)

Greenbaum, Alissa; Yadak, Nour; Perez, Steven; Rajput, Ashwani

2017-06-08

IgG 4 -related disease (IgG 4 -RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG 4 and tissue IgG 4 levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid treatment. The low incidence and the heterogeneous nature of the disease has made consensus on diagnostic criteria for IgG 4 -RD difficult. Whether sclerosing mesenteritis (SM) is considered a manifestation of IgG 4 -RD is strongly debated. We present the case of a patient with a history of rheumatoid arthritis who presented with a calcified abdominal mass. She was found to have an isolated, pedunculated mesenteric mass positive for IgG 4 and concurrently elevated serum IgG 4 levels. Clinical features did not classify her disease as either SM or IgG 4 -RD as currently described in consensus statements. Concurrent diagnoses of IgG 4 -RD, SM and other autoimmune disorders, as well as postoperative recommendations for resected isolated IgG 4 -positive masses, are discussed. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Heterogeneous Embedded Real-Time Systems Environment

Science.gov (United States)

2003-12-01

AFRL-IF-RS-TR-2003-290 Final Technical Report December 2003 HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT Integrated...HETEROGENEOUS EMBEDDED REAL - TIME SYSTEMS ENVIRONMENT 6. AUTHOR(S) Cosmo Castellano and James Graham 5. FUNDING NUMBERS C - F30602-97-C-0259

The failure rate dynamics in heterogeneous populations

International Nuclear Information System (INIS)

Cha, Ji Hwan; Finkelstein, Maxim

2013-01-01

Most populations encountered in real world are heterogeneous. In reliability applications, the mixture (observed) failure rate, obviously, can be considered as a measure of ‘average’ quality in these populations. However, in addition to this average measure, some variability characteristics for failure rates can be very helpful in describing the time-dependent changes in quality of heterogeneous populations. In this paper, we discuss variance and the coefficient of variation of the corresponding random failure rate as variability measures for items in heterogeneous populations. Furthermore, there is often a risk that items of poor quality are selected for important missions. Therefore, along with the ‘average quality’ of a population, more ‘conservative’ quality measures should be also defined and studied. For this purpose, we propose the percentile and the tail-mixture of the failure rates as the corresponding conservative measures. Some illustrative examples are given. -- Highlights: ► This paper provides the insight on the variability measures in heterogeneous populations. ► The conservative quality measures in heterogeneous populations are defined. ► The utility of these measures is illustrated by meaningful examples. ► This paper provides a better understanding of the dynamics in heterogeneous populations

Isotopes in heterogeneous catalysis

CERN Document Server

Hargreaves, Justin SJ

2006-01-01

The purpose of this book is to review the current, state-of-the-art application of isotopic methods to the field of heterogeneous catalysis. Isotopic studies are arguably the ultimate technique in in situ methods for heterogeneous catalysis. In this review volume, chapters have been contributed by experts in the field and the coverage includes both the application of specific isotopes - Deuterium, Tritium, Carbon-14, Sulfur-35 and Oxygen-18 - as well as isotopic techniques - determination of surface mobility, steady state transient isotope kinetic analysis, and positron emission profiling.

Cancer heterogeneity and imaging.

Science.gov (United States)

O'Connor, James P B

2017-04-01

There is interest in identifying and quantifying tumor heterogeneity at the genomic, tissue pathology and clinical imaging scales, as this may help better understand tumor biology and may yield useful biomarkers for guiding therapy-based decision making. This review focuses on the role and value of using x-ray, CT, MRI and PET based imaging methods that identify, measure and map tumor heterogeneity. In particular we highlight the potential value of these techniques and the key challenges required to validate and qualify these biomarkers for clinical use. Copyright © 2016. Published by Elsevier Ltd.

The prevalence of mental disorders among the homeless in western countries: systematic review and meta-regression analysis.

Directory of Open Access Journals (Sweden)

Seena Fazel

2008-12-01

Full Text Available BACKGROUND: There are well over a million homeless people in Western Europe and North America, but reliable estimates of the prevalence of major mental disorders among this population are lacking. We undertook a systematic review of surveys of such disorders in homeless people. METHODS AND FINDINGS: We searched for surveys of the prevalence of psychotic illness, major depression, alcohol and drug dependence, and personality disorder that were based on interviews of samples of unselected homeless people. We searched bibliographic indexes, scanned reference lists, and corresponded with authors. We explored potential sources of any observed heterogeneity in the estimates by meta-regression analysis, including geographical region, sample size, and diagnostic method. Twenty-nine eligible surveys provided estimates obtained from 5,684 homeless individuals from seven countries. Substantial heterogeneity was observed in prevalence estimates for mental disorders among the studies (all Cochran's chi(2 significant at p 85%. The most common mental disorders were alcohol dependence, which ranged from 8.1% to 58.5%, and drug dependence, which ranged from 4.5% to 54.2%. For psychotic illness, the prevalence ranged from 2.8% to 42.3%, with similar findings for major depression. The prevalence of alcohol dependence was found to have increased over recent decades. CONCLUSIONS: Homeless people in Western countries are substantially more likely to have alcohol and drug dependence than the age-matched general population in those countries, and the prevalences of psychotic illnesses and personality disorders are higher. Models of psychiatric and social care that can best meet these mental health needs requires further investigation.

The Prevalence of Mental Disorders among the Homeless in Western Countries: Systematic Review and Meta-Regression Analysis

Science.gov (United States)

Fazel, Seena; Khosla, Vivek; Doll, Helen; Geddes, John

2008-01-01

Background There are well over a million homeless people in Western Europe and North America, but reliable estimates of the prevalence of major mental disorders among this population are lacking. We undertook a systematic review of surveys of such disorders in homeless people. Methods and Findings We searched for surveys of the prevalence of psychotic illness, major depression, alcohol and drug dependence, and personality disorder that were based on interviews of samples of unselected homeless people. We searched bibliographic indexes, scanned reference lists, and corresponded with authors. We explored potential sources of any observed heterogeneity in the estimates by meta-regression analysis, including geographical region, sample size, and diagnostic method. Twenty-nine eligible surveys provided estimates obtained from 5,684 homeless individuals from seven countries. Substantial heterogeneity was observed in prevalence estimates for mental disorders among the studies (all Cochran's χ2 significant at p 85%). The most common mental disorders were alcohol dependence, which ranged from 8.1% to 58.5%, and drug dependence, which ranged from 4.5% to 54.2%. For psychotic illness, the prevalence ranged from 2.8% to 42.3%, with similar findings for major depression. The prevalence of alcohol dependence was found to have increased over recent decades. Conclusions Homeless people in Western countries are substantially more likely to have alcohol and drug dependence than the age-matched general population in those countries, and the prevalences of psychotic illnesses and personality disorders are higher. Models of psychiatric and social care that can best meet these mental health needs requires further investigation. PMID:19053169

DOES THE CONSTRUCT OF INTERNET ADDICTION REFLECT A SINGLE ENTITY OR A SPECTRUM OF DISORDERS?

Directory of Open Access Journals (Sweden)

Joël Billieux

2017-02-01

Full Text Available Objective: This article aimed to examine the issue of whether the construct of Internet addiction represents a single entity or a spectrum of disorders. Method: A literature review was performed and a conceptual synthesis was proposed. Results: Most research supports the notion that Internet addiction is a spectrum of Internet-related disorders, which pertain to addictive online behaviours, such as gaming and sexual activities. Although there are certain similarities between these behaviours, they are often associated with different socio-demographic and psychological variables (e.g., motivations and psychopathological symptoms, suggesting entities that are related, but still distinct. As constructs, addictive online activities are generally less heterogeneous than addictive use of the Internet, i.e., Internet addiction. Conclusions: The umbrella term “Internet addiction” is inadequate because it overlooks important differences between various addictive online activities. However, it may be unrealistic to expect a demise of the term before determining more clearly the acceptable level of internal heterogeneity of the psychopathological constructs.

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

Directory of Open Access Journals (Sweden)

Ozgur Mete

2018-03-01

Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Guanidinoacetate methyltransferase (GAMT) deficiency: late onset of movement disorder and preserved expressive language.

Science.gov (United States)

O'Rourke, Declan J; Ryan, Stephanie; Salomons, Gajja; Jakobs, Cornelis; Monavari, Ahmad; King, Mary D

2009-05-01

Guanidinoacetate methyltransferase (GAMT) deficiency is a disorder of creatine biosynthesis, characterized by early-onset learning disability and epilepsy in most affected children. Severe expressive language delay is a constant feature even in the mildest clinical phenotypes.We report the clinical, biochemical, imaging, and treatment data of two female siblings (18y and 13y) with an unusual phenotype of GAMT deficiency. The oldest sibling had subacute onset of a movement disorder at age 17 years, later than has been previously reported. The younger sibling had better language skills than previously described in this disorder. After treatment with creatine, arginine restriction and ornithine-supplemented diet, seizure severity and movement disorder were reduced but cognition did not improve. This report confirms that GAMT deficiency, a heterogeneous, potentially treatable disorder, detected by increased levels of guanidinoacetate in body fluids (e.g. plasma or urine) or by an abnormal creatine peak on magnetic resonance spectroscopy, should be considered in patients of any age with unexplained, apparently static learning disability and epilepsy.

Investigation on generalized Variational Nodal Methods for heterogeneous nodes

International Nuclear Information System (INIS)

Wang, Yongping; Wu, Hongchun; Li, Yunzhao; Cao, Liangzhi; Shen, Wei

2017-01-01

Highlights: • We developed two heterogeneous nodal methods based on the Variational Nodal Method. • Four problems were solved to evaluate the two heterogeneous nodal methods. • The function expansion method is good at treating continuous-changing heterogeneity. • The finite sub-element method is good at treating discontinuous-changing heterogeneity. - Abstract: The Variational Nodal Method (VNM) is generalized for heterogeneous nodes and applied to four kinds of problems including Molten Salt Reactor (MSR) core problem with continuous cross section profile, Pressurized Water Reactor (PWR) control rod cusping effect problem, PWR whole-core pin-by-pin problem, and heterogeneous PWR core problem without fuel-coolant homogenization in each pin cell. Two approaches have been investigated for the treatment of the nodal heterogeneity in this paper. To concentrate on spatial heterogeneity, diffusion approximation was adopted for the angular variable in neutron transport equation. To provide demonstrative numerical results, the codes in this paper were developed in slab geometry. The first method, named as function expansion (FE) method, expands nodal flux by orthogonal polynomials and the nodal cross sections are also expressed as spatial depended functions. The second path, named as finite sub-element (FS) method, takes advantage of the finite-element method by dividing each node into numbers of homogeneous sub-elements and expanding nodal flux into the combination of linear sub-element trial functions. Numerical tests have been carried out to evaluate the ability of the two nodal (coarse-mesh) heterogeneous VNMs by comparing with the fine-mesh homogeneous VNM. It has been demonstrated that both heterogeneous approaches can handle heterogeneous nodes. The FE method is good at continuous-changing heterogeneity as in the MSR core problem, while the FS method is good at discontinuous-changing heterogeneity such as the PWR pin-by-pin problem and heterogeneous PWR core

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure : a literature review

NARCIS (Netherlands)

Joosten, H.; Strunk, A. L. M.; Meijer, S.; Boers, J. E.; Aries, M.J.H.; Abbes, A. P.; Engel, H.; Beukhof, J. R.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these

Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation.

Science.gov (United States)

Brasic, J R; Barnett, J Y; Kaplan, D; Sheitman, B B; Aisemberg, P; Lafargue, R T; Kowalik, S; Clark, A; Tsaltas, M O; Young, J G

1994-07-01

In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.

Spatially correlated heterogeneous aspirations to enhance network reciprocity

Science.gov (United States)

Tanimoto, Jun; Nakata, Makoto; Hagishima, Aya; Ikegaya, Naoki

2012-02-01

Perc & Wang demonstrated that aspiring to be the fittest under conditions of pairwise strategy updating enhances network reciprocity in structured populations playing 2×2 Prisoner's Dilemma games (Z. Wang, M. Perc, Aspiring to the fittest and promoted of cooperation in the Prisoner's Dilemma game, Physical Review E 82 (2010) 021115; M. Perc, Z. Wang, Heterogeneous aspiration promotes cooperation in the Prisoner's Dilemma game, PLOS one 5 (12) (2010) e15117). Through numerical simulations, this paper shows that network reciprocity is even greater if heterogeneous aspirations are imposed. We also suggest why heterogeneous aspiration fosters network reciprocity. It distributes strategy updating speed among agents in a manner that fortifies the initially allocated cooperators' clusters against invasion. This finding prompted us to further enhance the usual heterogeneous aspiration cases for heterogeneous network topologies. We find that a negative correlation between degree and aspiration level does extend cooperation among heterogeneously structured agents.

Heterogeneous computing with OpenCL

CERN Document Server

2013-01-01

Heterogeneous Computing with OpenCL teaches OpenCL and parallel programming for complex systems that may include a variety of device architectures: multi-core CPUs, GPUs, and fully-integrated Accelerated Processing Units (APUs) such as AMD Fusion technology. Designed to work on multiple platforms and with wide industry support, OpenCL will help you more effectively program for a heterogeneous future. Written by leaders in the parallel computing and OpenCL communities, this book will give you hands-on OpenCL experience to address a range of fundamental parallel algorithms. The authors explore memory spaces, optimization techniques, graphics interoperability, extensions, and debugging and profiling. Intended to support a parallel programming course, Heterogeneous Computing with OpenCL includes detailed examples throughout, plus additional online exercises and other supporting materials.

Heterogeneity in Preferences and Productivity

DEFF Research Database (Denmark)

Gørtz, Mette

This paper discusses the determinants of the retirement decision and the implications of retirement on economic well-being. The main contribution of the paper is to formulate the role of individual heterogeneity explicitly. We argue that individual heterogeneity in 1) productivity of market work...... choices of expenditure, household production and leisure for people in and around retirement. The unobserved individual heterogeneity factor is isolated by comparing cross-sectional evidence and panel data estimates of the effects of retirement on consumption and time allocation. Based on cross......-section data, we can identify a difference in consumption due to retirement status, but when the panel nature of the data is exploited, the effect of retirement on consumption is small and insignificant. Moreover, the analyses point at a large positive effect of retirement on household production. Our results...

Neural mechanisms of impaired fear inhibition in posttraumatic stress disorder

Directory of Open Access Journals (Sweden)

Tanja eJovanovic

2011-07-01

Full Text Available Posttraumatic stress disorder (PTSD can develop in some individuals who are exposed to an event that causes extreme fear, horror, or helplessness (APA, 1994. PTSD is a complex and heterogeneous disorder, which is often co-morbid with depression, substance abuse, and anxiety disorders such as panic or social phobia. Given this complexity, progress in the field can be greatly enhanced by focusing on phenotypes that are more proximal to the neurobiology of the disorder. Such neurobiological intermediate phenotypes can provide investigative tools to increase our understanding of the roots of the disorder and develop better prevention or intervention programs. In the present paper, we argue that the inhibition of fear responses is an intermediate phenotype that is related to both the neurocircuitry associated with the disorder, and is linked to its clinical symptoms. An advantage of focusing on fear inhibition is that the neurobiology of fear has been well investigated in animal models providing the necessary groundwork in understanding alterations. Furthermore, because many paradigms can be tested across species, fear inhibition is an ideal translational tool. Here we review both the behavioral tests and measures of fear inhibition and the related neurocircuitry in neuroimaging studies with both healthy and clinical samples.

Conversion disorder: current problems and potential solutions for DSM-5.

Science.gov (United States)

Stone, Jon; LaFrance, W Curt; Brown, Richard; Spiegel, David; Levenson, James L; Sharpe, Michael

2011-12-01

Conversion disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) describes neurological symptoms, including weakness, numbness and events resembling epilepsy or syncope, which can be positively identified as not being due to recognised neurological disease. This review combines perspectives from psychiatry, psychology and neurology to identify and discuss key problems with the current diagnostic DSM-IV criteria for conversion disorder and to make the following proposals for DSM-5: (a) abandoning the label "conversion disorder" and replacing it with an alternative term that is both theoretically neutral and potentially more acceptable to patients and practitioners; (b) relegating the requirements for "association of psychological factors" and the "exclusion of feigning" to the accompanying text; (c) adding a criterion requiring clinical findings of internal inconsistency or incongruity with recognised neurological or medical disease and altering the current 'disease exclusion' criteria to one in which the symptom must not be 'better explained' by a disease if present, (d) adding a 'cognitive symptoms' subtype. We also discuss whether conversion symptoms are better classified with other somatic symptom disorders or with dissociative disorders and how we might address the potential heterogeneity of conversion symptoms in classification. 2011 Elsevier Inc. All rights reserved.

Monetary policy, banking and heterogeneous agents

NARCIS (Netherlands)

Wolski, M.

2012-01-01

The influence of heterogeneous expectations on monetary policy performance has gained a lot of attention in the recent years. It proved to be an important factor that, under some circumstances, may even destabilize the economy (Massaro, 2012). This paper investigates the phenomenon of heterogeneous

Heterogeneity in preferences and behavior in threshold models

Directory of Open Access Journals (Sweden)

Philip R Neary

2017-12-01

Full Text Available A coordination game is repeatedly played on a graph by players (vertices who have heterogeneous cardinal preferences and whose strategy choice is governed by the individualistic asynchronous logit dynamic. The idea of potential driven autonomy of sets of players is used to derive results on the possibility of heterogeneous preferences leading to heterogeneous behavior. In particular, a class of graphs is identified such that for large enough graphs in this class, diversity in ordinal preferences will nearly always lead to heterogeneity in behavior, regardless of the cardinal strength of the preferences. These results have implications for network design problems, such as when a social planner wishes to induce homogeneous/heterogeneous behavior in a population.

Sampling strategies to capture single-cell heterogeneity

OpenAIRE

Satwik Rajaram; Louise E. Heinrich; John D. Gordan; Jayant Avva; Kathy M. Bonness; Agnieszka K. Witkiewicz; James S. Malter; Chloe E. Atreya; Robert S. Warren; Lani F. Wu; Steven J. Altschuler

2017-01-01

Advances in single-cell technologies have highlighted the prevalence and biological significance of cellular heterogeneity. A critical question is how to design experiments that faithfully capture the true range of heterogeneity from samples of cellular populations. Here, we develop a data-driven approach, illustrated in the context of image data, that estimates the sampling depth required for prospective investigations of single-cell heterogeneity from an existing collection of samples. ...

Genetic variants influencing phenotypic variance heterogeneity.

Science.gov (United States)

Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

2018-03-01

Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

Individual heterogeneity generating explosive system network dynamics.

Science.gov (United States)

Manrique, Pedro D; Johnson, Neil F

2018-03-01

Individual heterogeneity is a key characteristic of many real-world systems, from organisms to humans. However, its role in determining the system's collective dynamics is not well understood. Here we study how individual heterogeneity impacts the system network dynamics by comparing linking mechanisms that favor similar or dissimilar individuals. We find that this heterogeneity-based evolution drives an unconventional form of explosive network behavior, and it dictates how a polarized population moves toward consensus. Our model shows good agreement with data from both biological and social science domains. We conclude that individual heterogeneity likely plays a key role in the collective development of real-world networks and communities, and it cannot be ignored.

Individual heterogeneity generating explosive system network dynamics

Science.gov (United States)

Manrique, Pedro D.; Johnson, Neil F.

2018-03-01

Individual heterogeneity is a key characteristic of many real-world systems, from organisms to humans. However, its role in determining the system's collective dynamics is not well understood. Here we study how individual heterogeneity impacts the system network dynamics by comparing linking mechanisms that favor similar or dissimilar individuals. We find that this heterogeneity-based evolution drives an unconventional form of explosive network behavior, and it dictates how a polarized population moves toward consensus. Our model shows good agreement with data from both biological and social science domains. We conclude that individual heterogeneity likely plays a key role in the collective development of real-world networks and communities, and it cannot be ignored.

Exploring heterogeneous market hypothesis using realized volatility

Science.gov (United States)

Chin, Wen Cheong; Isa, Zaidi; Mohd Nor, Abu Hassan Shaari

2013-04-01

This study investigates the heterogeneous market hypothesis using high frequency data. The cascaded heterogeneous trading activities with different time durations are modelled by the heterogeneous autoregressive framework. The empirical study indicated the presence of long memory behaviour and predictability elements in the financial time series which supported heterogeneous market hypothesis. Besides the common sum-of-square intraday realized volatility, we also advocated two power variation realized volatilities in forecast evaluation and risk measurement in order to overcome the possible abrupt jumps during the credit crisis. Finally, the empirical results are used in determining the market risk using the value-at-risk approach. The findings of this study have implications for informationally market efficiency analysis, portfolio strategies and risk managements.

The heterogeneity of craniofacial morphology in Prader-Willi patients.

Science.gov (United States)

Belengeanu, D; Bratu, Cristina; Stoian, Monica; Motoc, A; Ormerod, Eli; Podariu, Angela Codruţa; Farcaş, Simona; Andreescu, Nicoleta

2012-01-01

Prader-Willi syndrome is a complex genetic disorder with narrow spectrum of facial phenotypic signs, which make the clinical diagnosis difficult in some cases. There are several reports describing the craniofacial appearance of Prader-Willi patients, but there are only a few cephalometric studies for these patients. In this study were included 18 patients with Prader-Willi syndrome and a control group of 18 subjects of both sexes selected based on specific criteria. The cephalometric radiographs of the patients were taken using the standardized technique with centric teeth in occlusion and lips in relaxed position. Angular, horizontal and linear measurements were analyzed for the study group and for the control group. We established that in Prader-Willi patients, there is a decrease of the majority of parameters but the degree of this reduction varies widely between patients and clinically typical facies not always have smaller measurements which can be found in an unusual facies. Facial dysmorphism in Prader-Willi patients varies a group ranging from miss proportions that do not alter the facial architecture as regard of facial typology, skeletal class and pattern of development to a severe disturbance of those. There is a degree of clinical heterogeneity between subjects with Prader-Willi syndrome on clinical evaluation and cephalometric study confirms the heterogeneity for this patients. Because the identification of smaller dimensions for majority of parameters in children and adults, the possibility of developmental delay or growth retardation delay can be excluded. These findings are important for the orthodontist for optimum timing of orthodontic management of patients with Prader-Willi syndrome.

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

Science.gov (United States)

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

An overview of posttraumatic stress disorder genetic studies by analyzing and integrating genetic data into genetic database PTSDgene

NARCIS (Netherlands)

Zhang, Kunlin; Qu, Susu; Chang, Suhua; Li, Gen; Cao, Chengqi; Fang, Kechi; Olff, Miranda; Wang, Li; Wang, Jing

2017-01-01

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric syndrome with complex etiology. Studies aiming to explore genetic susceptibility and environmental triggers of PTSD have been increasing. However, the results are limited and highly heterogeneous. To understand the genetic study

Green's Function and Stress Fields in Stochastic Heterogeneous Continua

Science.gov (United States)

Negi, Vineet

Many engineering materials used today are heterogenous in composition e.g. Composites - Polymer Matrix Composites, Metal Matrix Composites. Even, conventional engineering materials - metals, plastics, alloys etc. - may develop heterogeneities, like inclusions and residual stresses, during the manufacturing process. Moreover, these materials may also have intrinsic heterogeneities at a nanoscale in the form of grain boundaries in metals, crystallinity in amorphous polymers etc. While, the homogenized constitutive models for these materials may be satisfactory at a macroscale, recent studies of phenomena like fatigue failure, void nucleation, size-dependent brittle-ductile transition in polymeric nanofibers reveal a major play of micro/nanoscale physics in these phenomena. At this scale, heterogeneities in a material may no longer be ignored. Thus, this demands a study into the effects of various material heterogeneities. In this work, spatial heterogeneities in two material properties - elastic modulus and yield stress - have been investigated separately. The heterogeneity in the elastic modulus is studied in the context of Green's function. The Stochastic Finite Element method is adopted to get the mean statistics of the Green's function defined on a stochastic heterogeneous 2D infinite space. A study of the elastic-plastic transition in a domain having stochastic heterogenous yield stress was done using Mont-Carlo methods. The statistics for various stress and strain fields during the transition were obtained. Further, the effects of size of the domain and the strain-hardening rate on the stress fields during the heterogeneous elastic-plastic transition were investigated. Finally, a case is made for the role of the heterogenous elastic-plastic transition in damage nucleation and growth.

Imaging of Hereditary Hemorrhagic Telangiectasia

International Nuclear Information System (INIS)

Carette, Marie-France; Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine

2009-01-01

This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

[Internet-based resilience training and prevention of mental disorders].

Science.gov (United States)

Lehr, D; Kunzler, A; Helmreich, I; Behrendt, D; Chmitorz, A; Lieb, K

2018-05-30

Resilience is associated with a positive and resource-oriented perspective. Therefore, it seems especially attractive for health promotion and prevention. In recent years, interventions to foster resilience have been increasingly developed, which train resilience factors and are mainly conducted in a face to face group format. The question is raised what potential internet-based interventions (i-interventions) that train resilience factors have for health promotion and prevention. Based on a narrative overview, the possibilities for i‑interventions that train resilience factors for health promotion and prevention are investigated and the state of research is described. The effects of the i‑interventions presented here, which aim at fostering resilience, on measures of mental health and well-being are heterogeneous and vary between low to high effects. Stronger evidence for the efficacy of these measures exists for more general i‑interventions that also train resilience factors but are conceptualized for the prevention of specific disorders, such as depression or for stress reduction. Given the heterogeneous nature of intervention contents, theoretical foundations and therapeutic methods used, the heterogeneity of the evidence is discussed. In addition, perspectives for the further development of resource-oriented resilience interventions are outlined.

Mechanochemical formation of heterogeneous diamond structures during rapid uniaxial compression in graphite

Science.gov (United States)

Kroonblawd, Matthew P.; Goldman, Nir

2018-05-01

We predict mechanochemical formation of heterogeneous diamond structures from rapid uniaxial compression in graphite using quantum molecular dynamics simulations. Ensembles of simulations reveal the formation of different diamondlike products starting from thermal graphite crystal configurations. We identify distinct classes of final products with characteristic probabilities of formation, stress states, and electrical properties and show through simulations of rapid quenching that these products are nominally stable and can be recovered at room temperature and pressure. Some of the diamond products exhibit significant disorder and partial closure of the energy gap between the highest-occupied and lowest-unoccupied molecular orbitals (i.e., the HOMO-LUMO gap). Seeding atomic vacancies in graphite significantly biases toward forming products with small HOMO-LUMO gap. We show that a strong correlation between the HOMO-LUMO gap and disorder in tetrahedral bonding configurations informs which kinds of structural defects are associated with gap closure. The rapid diffusionless transformation of graphite is found to lock vacancy defects into the final diamond structure, resulting in configurations that prevent s p3 bonding and lead to localized HOMO and LUMO states with a small gap.

Heterogeneous inflation expectations, learning, and market outcomes

OpenAIRE

Madeira, Carlos; Zafar, Basit

2012-01-01

Using the panel component of the Michigan Survey of Consumers, we show that individuals, in particular women and ethnic minorities, are highly heterogeneous in their expectations of inflation. We estimate a model of inflation expectations based on learning from experience that also allows for heterogeneity in both private information and updating. Our model vastly outperforms existing models of inflation expectations in explaining the heterogeneity in the data. We find that women, ethnic mino...

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

Science.gov (United States)

Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Gluten-related disorders: certainties, questions and doubts.

Science.gov (United States)

Valenti, Simona; Corica, Domenico; Ricciardi, Luisa; Romano, Claudio

2017-11-01

In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12-25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. KEY MESSAGE Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.

Molecular ingredients of heterogeneous catalysis

International Nuclear Information System (INIS)

Somorjai, G.A.

1982-06-01

The purpose of this paper is to present a review and status report to those in theoretical chemistry of the rapidly developing surface science of heterogeneous catalysis. The art of catalysis is developing into science. This profound change provides one with opportunities not only to understand the molecular ingredients of important catalytic systems but also to develop new and improved catalyst. The participation of theorists to find answers to important questions is sorely needed for the sound development of the field. It is the authors hope that some of the outstanding problems of heterogeneous catalysis that are identified in this paper will be investigated. For this purpose the paper is divided into several sections. The brief Introduction to the methodology and recent results of the surface science of heterogeneous catalysis is followed by a review of the concepts of heterogeneous catalysis. Then, the experimental results that identified the three molecular ingredients of catalysis, structure, carbonaceous deposit and the oxidation state of surface atoms are described. Each section is closed with a summary and a list of problems that require theoretical and experimental scrutiny. Finally attempts to build new catalyst systems and the theoretical and experimental problems that appeared in the course of this research are described

Molecular ingredients of heterogeneous catalysis

Energy Technology Data Exchange (ETDEWEB)

Somorjai, G.A.

1982-06-01

The purpose of this paper is to present a review and status report to those in theoretical chemistry of the rapidly developing surface science of heterogeneous catalysis. The art of catalysis is developing into science. This profound change provides one with opportunities not only to understand the molecular ingredients of important catalytic systems but also to develop new and improved catalyst. The participation of theorists to find answers to important questions is sorely needed for the sound development of the field. It is the authors hope that some of the outstanding problems of heterogeneous catalysis that are identified in this paper will be investigated. For this purpose the paper is divided into several sections. The brief Introduction to the methodology and recent results of the surface science of heterogeneous catalysis is followed by a review of the concepts of heterogeneous catalysis. Then, the experimental results that identified the three molecular ingredients of catalysis, structure, carbonaceous deposit and the oxidation state of surface atoms are described. Each section is closed with a summary and a list of problems that require theoretical and experimental scrutiny. Finally attempts to build new catalyst systems and the theoretical and experimental problems that appeared in the course of this research are described.

Chloride Transport in Heterogeneous Formation

Science.gov (United States)

Mukherjee, A.; Holt, R. M.

2017-12-01

The chloride mass balance (CMB) is a commonly-used method for estimating groundwater recharge. Observations of the vertical distribution of pore-water chloride are related to the groundwater infiltration rates (i.e. recharge rates). In CMB method, the chloride distribution is attributed mainly to the assumption of one dimensional piston flow. In many places, however, the vertical distribution of chloride will be influenced by heterogeneity, leading to horizontal movement of infiltrating waters. The impact of heterogeneity will be particularly important when recharge is locally focused. When recharge is focused in an area, horizontal movement of chloride-bearing waters, coupled with upward movement driven by evapotranspiration, may lead to chloride bulges that could be misinterpreted if the CMB method is used to estimate recharge. We numerically simulate chloride transport and evaluate the validity of the CMB method in highly heterogeneous systems. This simulation is conducted for the unsaturated zone of Ogallala, Antlers, and Gatuna (OAG) formations in Andrews County, Texas. A two dimensional finite element model will show the movement of chloride through heterogeneous systems. We expect to see chloride bulges not only close to the surface but also at depths characterized by horizontal or upward movement. A comparative study of focused recharge estimates in this study with available recharge data will be presented.

Diverse Profiles of Anxiety Related Disorders in Fragile X, Cornelia de Lange and Rubinstein-Taybi Syndromes

Science.gov (United States)

Crawford, Hayley; Waite, Jane; Oliver, Chris

2017-01-01

Anxiety disorders are heightened in specific genetic syndromes in comparison to intellectual disability of heterogeneous aetiology. In this study, we described and contrasted anxiety symptomatology in fragile X (FXS), Cornelia de Lange (CdLS) and Rubinstein-Taybi syndromes (RTS), and compared the symptomatology to normative data for…

Late onset bipolar disorder and frontotemporal dementia with mutation in progranulin gene: a case report.

Science.gov (United States)

Rubino, Elisa; Vacca, Alessandro; Gallone, Salvatore; Govone, Flora; Zucca, Milena; Gai, Annalisa; Ferrero, Patrizia; Fenoglio, Pierpaola; Giordana, Maria Teresa; Rainero, Innocenzo

2017-11-01

Bipolar disorder is a chronic psychiatric illness characterised by fluctuation in mood state, with a relapsing and remitting course. Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous syndrome, with the most frequent phenotype being behavioural variant frontotemporal dementia (bvFTD). Here, we report the case of an Italian male presenting with late-onset bipolar disorder that developed into bvFTD over time, carrying a mutation in the GRN gene. Interestingly, the patient carried the c.1639 C > T variant in the GRN gene, resulting in a R547C substitution. Our case report further corroborates the notion that, in addition to FTD, progranulin may be involved in the neurobiology of bipolar disorder type 1, and suggests to screen patients with late-onset bipolar disorder for GRN mutations.

Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences.

Directory of Open Access Journals (Sweden)

Kohei Fujikura

Full Text Available Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI. I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA. The population exome-based epidemiology of SCA [African (allele frequency (AF = 0.0454, N = 2447, Asian (AF = 0, N = 286, European (AF = 0.000214, N = 4677, and Hispanic (AF = 0.0111, N = 362] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05. I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders.

Relationship of Tree Stand Heterogeneity and Forest Naturalness

Directory of Open Access Journals (Sweden)

BARTHA, Dénes

2006-01-01

Full Text Available The aim of our study was to investigate if compositional (tree species richness andstructural (vertical structure, age-structure, patterns of canopy closure heterogeneity of the canopylayer is related to individual naturalness criteria and to overall forest naturalness at the stand scale. Thenaturalness values of the assessed criteria (tree species composition, tree stand structure, speciescomposition and structure of shrub layer and forest floor vegetation, dead wood, effects of game, sitecharacteristics showed similar behaviour when groups of stands with different heterogeneity werecompared, regardless of the studied aspect of canopy heterogeneity. The greatest difference was foundfor criteria describing the canopy layer. Composition and structure of canopy layer, dead wood andtotal naturalness of the stand differed significantly among the stand groups showing consistentlyhigher values from homogeneous to the most heterogeneous group. Naturalness of the compositionand structure of the shrub layer is slightly but significantly higher in stands with heterogeneous canopylayer. Regarding other criteria, significant differences were found only between the homogeneous andthe most heterogeneous groups, while groups with intermediate level of heterogeneity did not differsignificantly from one extreme. However, the criterion describing effects of game got lowernaturalness values in more heterogeneous stands. Naturalness of site characteristics did not differsignificantly among the groups except for when stands were grouped based on pattern of canopyclosure. From the practical viewpoint it is shown that purposeful forestry operations affecting thecanopy layer cause changes in compositional and structural characteristics of other layers as well as inoverall stand scale forest naturalness.

Targeting population heterogeneity for optimal cell factories

DEFF Research Database (Denmark)

Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

Spatial heterogeneity in liquid–liquid phase transition

International Nuclear Information System (INIS)

Duan Yun-Rui; Li Tao; Wu Wei-Kang; Li Jie; Zhou Xu-Yan; Liu Si-Da; Li Hui

2017-01-01

Molecular dynamics simulations are performed to investigate the liquid–liquid phase transition (LLPT) and the spatial heterogeneity in Al–Pb monotectic alloys. The results reveal that homogeneous liquid Al–Pb alloy undergoes an LLPT, separating into Al-rich and Pb-rich domains, which is quite different from the isocompositional liquid water with a transition between low-density liquid (LDL) and high-density liquid (HDL). With spatial heterogeneity becoming large, LLPT takes place correspondingly. The relationship between the cooling rate, relaxation temperature and percentage of Al and the spatial heterogeneity is also reported. This study may throw light on the relationship between the structure heterogeneity and LLPT, which provides novel strategies to control the microstructures in the fabrication of the material with high performance. (paper)

Trade, Industry Structure and Different Sources of Firm-heterogeneity

DEFF Research Database (Denmark)

Schröder, Philipp J.H.; Jørgensen, Jan Guldager

Recently the workhorse model of intra-industry trade has been augmented with heterogeneous cost structures at the firm level. In principle there exist various sources of heterogeneity, yet the literature appears -- for convenience or other reasons -- to settle on marginal cost heterogeneity...... as the preferred modelling device. The present paper develops a unified model framework allowing a systematic comparison of marginal and fixed cost heterogeneity. We find that both types of heterogeneity are in fact able to capture the central stylized facts of international trade. For example can either source...

When words fail us: insights into language processing from developmental and acquired disorders.

Science.gov (United States)

Bishop, Dorothy V M; Nation, Kate; Patterson, Karalyn

2014-01-01

Acquired disorders of language represent loss of previously acquired skills, usually with relatively specific impairments. In children with developmental disorders of language, we may also see selective impairment in some skills; but in this case, the acquisition of language or literacy is affected from the outset. Because systems for processing spoken and written language change as they develop, we should beware of drawing too close a parallel between developmental and acquired disorders. Nevertheless, comparisons between the two may yield new insights. A key feature of connectionist models simulating acquired disorders is the interaction of components of language processing with each other and with other cognitive domains. This kind of model might help make sense of patterns of comorbidity in developmental disorders. Meanwhile, the study of developmental disorders emphasizes learning and change in underlying representations, allowing us to study how heterogeneity in cognitive profile may relate not just to neurobiology but also to experience. Children with persistent language difficulties pose challenges both to our efforts at intervention and to theories of learning of written and spoken language. Future attention to learning in individuals with developmental and acquired disorders could be of both theoretical and applied value.

Heterogeneous Compression of Large Collections of Evolutionary Trees.

Science.gov (United States)

Matthews, Suzanne J

2015-01-01

Compressing heterogeneous collections of trees is an open problem in computational phylogenetics. In a heterogeneous tree collection, each tree can contain a unique set of taxa. An ideal compression method would allow for the efficient archival of large tree collections and enable scientists to identify common evolutionary relationships over disparate analyses. In this paper, we extend TreeZip to compress heterogeneous collections of trees. TreeZip is the most efficient algorithm for compressing homogeneous tree collections. To the best of our knowledge, no other domain-based compression algorithm exists for large heterogeneous tree collections or enable their rapid analysis. Our experimental results indicate that TreeZip averages 89.03 percent (72.69 percent) space savings on unweighted (weighted) collections of trees when the level of heterogeneity in a collection is moderate. The organization of the TRZ file allows for efficient computations over heterogeneous data. For example, consensus trees can be computed in mere seconds. Lastly, combining the TreeZip compressed (TRZ) file with general-purpose compression yields average space savings of 97.34 percent (81.43 percent) on unweighted (weighted) collections of trees. Our results lead us to believe that TreeZip will prove invaluable in the efficient archival of tree collections, and enables scientists to develop novel methods for relating heterogeneous collections of trees.

Detection of structural heterogeneity of glass melts

DEFF Research Database (Denmark)

Yue, Yuanzheng

2004-01-01

The structural heterogeneity of both supercooled liquid and molten states of silicate has been studied using calorimetric method. The objects of this study are basaltic glasses and liquids. Two experimental approaches are taken to detect the structural heterogeneity of the liquids. One is the hyp......The structural heterogeneity of both supercooled liquid and molten states of silicate has been studied using calorimetric method. The objects of this study are basaltic glasses and liquids. Two experimental approaches are taken to detect the structural heterogeneity of the liquids. One...... is the hyperquench-anneal-calorimetric scan approach, by which the structural information of a basaltic supercooled liquid and three binary silicate liquids is acquired. Another is the calorimetrically repeated up- and downscanning approach, by which the structural heterogeneity, the intermediate range order...... is discussed. The ordered structure of glass melts above the liquidus temperature is indirectly characterized by use of X-ray diffraction method. The new approaches are of importance for monitoring the glass melting and forming process and for improving the physical properties of glasses and glass fibers....

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Meer, Dennis; Hartman, Catharina A.; Richards, Jennifer; Bralten, Janita B.; Franke, Barbara; Oosterlaan, Jaap; Heslenfeld, Dirk J.; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.

2014-01-01

IntroductionThe role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

Meer, D. van der; Hartman, C.A.; Richards, J.; Bralten, J.B.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.; Faraone, S.V.; Buitelaar, J.K.; Hoekstra, P.J.

2014-01-01

INTRODUCTION: The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Meer, D.; Hartman, C.A.; Richards, J.; Bralten, J.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.

2015-01-01

Introduction The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder

NARCIS (Netherlands)

van der Meer, D.; Hartman, C.A.; Richards, J.; Bralten, J.; Franke, B.; Oosterlaan, J.; Heslenfeld, D.J.; Faraone, S.V.; Buitelaar, J.K.; Hoekstra, P.J.

2014-01-01

Introduction The role of the serotonin transporter gene polymorphism 5-HTTLPR in attention-deficit/hyperactivity disorder (ADHD) is unclear. Heterogeneity of findings may be explained by gene-environment interactions (GxE), as it has been suggested that S-allele carriers are more reactive to

Trajectories of Return to Work Among People on Sick Leave with Mood or Anxiety Disorders

DEFF Research Database (Denmark)

Hellström, Lone; Madsen, Trine; Nordentoft, Merete

2017-01-01

Purpose The return to work (RTW) of people with mood and anxiety disorders is a heterogeneous process. We aimed to identify prototypical trajectories of RTW over a two-year period in people on sick leave with mood and anxiety disorders, and investigate if socio-demographic or clinical factors...... years, using data from a nationwide Danish register (DREAM). Latent growth mixture modelling analysis was carried out to identify trajectories of RTW and logistic regression analyses were used to estimate predictors for trajectory membership. Results Four trajectory classes of RTW were identified; non...

Acculturative Heterogeneity among Asian/Pacific Islanders in the United States: Associations with DSM Mental and Substance Use Disorders

Science.gov (United States)

Salas-Wright, Christopher P.; Lee, Sharon; Vaughn, Michael G.; Jang, Yuri; Sanglang, Cindy C.

2014-01-01

Extant studies on the links between acculturation and mental and substance use disorders among Asian/Pacific Islanders have been based on the assumption that acculturation is a homogeneous construct. However, emerging evidence suggests that the various components of acculturation do not manifest independently, but rather cluster in ways that reflect distinct profiles. We employ data on Asian/Pacific Islanders from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 968). Latent profile analysis is used to identify acculturation subgroups on the basis of indicator variables related to cultural identification, language ability and preference, and social engagement. Subsequently, the distribution of outcome variables in the domains of DSM disorders (lifetime history of clinical, personality, and substance use disorders) is examined across latent subgroups. We identified a five class solution: Class 1: “Separated” (12.91%), Class 2: “Partial Bilingual/Bicultural” (30.06%), Class 3: “English Dominant/Asian Oriented” (12.29%), Class 4:”Full Bilingual/Bicultural” (19.42%) and Class 5: “Assimilated” (25.31%). The highest rates of clinical disorders were observed among members of the two classes characterized by a strong preference for the use of the English language (Classes 3 and 5). The highest prevalence of nicotine (12%) and illicit drug use (15%) disorders was observed among members of the “Assimilated” class. Consistent with prior research, findings suggest that risk of morbidity is greater among more acculturated individuals; however, findings also suggest that an important level of nuance can be observed with respect to acculturative subtypes identified on the basis of cultural identification, language ability and preference, and social engagement. PMID:26167805

Acculturative heterogeneity among Asian/Pacific Islanders in the United States: Associations with DSM mental and substance use disorders.

Science.gov (United States)

Salas-Wright, Christopher P; Lee, Sharon; Vaughn, Michael G; Jang, Yuri; Sanglang, Cindy C

2015-07-01

Extant studies on the links between acculturation and mental and substance use disorders among Asian/Pacific Islanders have been based on the assumption that acculturation is a homogeneous construct. However, emerging evidence suggests that the various components of acculturation do not manifest independently, but rather cluster in ways that reflect distinct profiles. We employ data on Asian/Pacific Islanders from the National Epidemiologic Survey on Alcohol and Related Conditions (n = 968). Latent profile analysis is used to identify acculturation subgroups on the basis of indicator variables related to cultural identification, language ability and preference, and social engagement. Subsequently, the distribution of outcome variables in the domains of DSM disorders (lifetime history of clinical, personality, and substance use disorders) is examined across latent subgroups. We identified a 5-class solution: Class 1: Separated (12.91%), Class 2: Partial Bilingual/Bicultural (30.06%), Class 3: English Dominant/Asian Oriented (12.29%), Class 4: Full Bilingual/Bicultural (19.42%) and Class 5: Assimilated (25.31%). The highest rates of clinical disorders were observed among members of the 2 classes characterized by a strong preference for the use of the English language (Classes 3 and 5). The highest prevalence of nicotine (12%) and illicit drug use (15%) disorders was observed among members of the Assimilated class. Consistent with prior research, findings suggest that risk of morbidity is greater among more acculturated individuals; however, findings also suggest that an important level of nuance can be observed with respect to acculturative subtypes identified on the basis of cultural identification, language ability and preference, and social engagement. (c) 2015 APA, all rights reserved).

Does heterogeneity of pimonidazole labelling correspond to the heterogeneity of radiation-response of FaDu human squamous cell carcinoma?

International Nuclear Information System (INIS)

Yaromina, Ala; Hoelscher, Tobias; Eicheler, Wolfgang; Rosner, Andrea; Krause, Mechthild; Hessel, Franziska; Petersen, Cordula; Thames, Howard D.; Baumann, Michael; Zips, Daniel

2005-01-01

Background and purpose: Pimonidazole is a marker for hypoxic cells which are radioresistant and thereby important for the outcome of radiotherapy. The present study evaluates heterogeneity in pimonidazole binding within and between tumours and relates the results to the heterogeneity of radiation response in the same tumour cell line. Materials and methods: FaDu, a poorly differentiated human squamous cell carcinoma line, was transplanted subcutaneously into the right hind-leg of NMRI nude mice. Tumours were irradiated with graded single doses either under ambient or clamped blood flow conditions and local tumour control was evaluated after 120 days. Complete dose-response curves for local tumour control were generated and the slope, a measure of heterogeneity of radiation response, was determined. In parallel, 12 unirradiated tumours were examined histologically. Seven serial 10 μm cross-sections per tumour were evaluated using fluorescence microscopy and computerised image analysis to determine the pimonidazole hypoxic fraction (pHF). Heterogeneity in pHF was quantified by its coefficient of variation (CV). Poisson-based model calculations considering the intertumoural heterogeneity of pHF were performed and the slopes of the predicted and the observed dose-response curves were compared. Results: The mean pHF was 11% [CV 50%] when one central section per tumour was evaluated. Measurements of multiple sections per tumour resulted in a mean pHF of 12% [CV 46%] (P=0.7). Intertumoural heterogeneity in pHF was more pronounced than heterogeneity in individual tumours by a factor of 2. Model calculations based on the variability in pHF resulted in similar slopes of the dose-response curve for local tumour control in comparison with the observed slope when the heterogeneity in an unknown and arbitrarily chosen additional radiobiologically relevant parameter, in this example clonogen density, was taken into account. Conclusions: While the average pimonidazole hypoxic

Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11.

Science.gov (United States)

Andrews, G; Pine, D S; Hobbs, M J; Anderson, T M; Sunderland, M

2009-12-01

DSM-IV and ICD-10 are atheoretical and largely descriptive. Although this achieves good reliability, the validity of diagnoses can be increased by an understanding of risk factors and other clinical features. In an effort to group mental disorders on this basis, five clusters have been proposed. We now consider the second cluster, namely neurodevelopmental disorders. We reviewed the literature in relation to 11 validating criteria proposed by a DSM-V Task Force Study Group. This cluster reflects disorders of neurodevelopment rather than a 'childhood' disorders cluster. It comprises disorders subcategorized in DSM-IV and ICD-10 as Mental Retardation; Learning, Motor, and Communication Disorders; and Pervasive Developmental Disorders. Although these disorders seem to be heterogeneous, they share similarities on some risk and clinical factors. There is evidence of a neurodevelopmental genetic phenotype, the disorders have an early emerging and continuing course, and all have salient cognitive symptoms. Within-cluster co-morbidity also supports grouping these disorders together. Other childhood disorders currently listed in DSM-IV share similarities with the Externalizing and Emotional clusters. These include Conduct Disorder, Attention Deficit Hyperactivity Disorder and Separation Anxiety Disorder. The Tic, Eating/Feeding and Elimination disorders, and Selective Mutisms were allocated to the 'Not Yet Assigned' group. Neurodevelopmental disorders meet some of the salient criteria proposed by the American Psychiatric Association (APA) to suggest a classification cluster.

Like father, like son: periventricular nodular heterotopia and nonverbal learning disorder.

Science.gov (United States)

McCann, Marcia V; Pongonis, Stephen J; Golomb, Meredith R; Edwards-Brown, Mary; Christensen, Celanie K; Sokol, Deborah K

2008-08-01

Periventricular nodular heterotopia is a common malformation of cortical development in which the migration of developing neurons destined for the cerebral cortex is abbreviated. Bilateral periventricular nodular heterotopia is most commonly an X-linked disorder that involves mutations in the filamin A (FLNA) gene, but an autosomal recessive form and sporadic forms have been identified. To our knowledge, autosomal dominant transmission of isolated periventricular nodular heterotopia has not been reported. Periventricular nodular heterotopia has a heterogeneous phenotype, associated commonly with seizure disorder, and more recently with reading deficits and visual-spatial deficits in some patients. We present a father and son with bilateral periventricular nodular heterotopia and similar visual-spatial learning deficits, consistent with nonverbal learning disability.

Ergodicity breaking and ageing of underdamped Brownian dynamics with quenched disorder

Science.gov (United States)

Guo, Wei; Li, Yong; Song, Wen-Hua; Du, Lu-Chun

2018-03-01

The dynamics of an underdamped Brownian particle moving in one-dimensional quenched disorder under the action of an external force is investigated. Within the tailored parameter regime, the transiently anomalous diffusion and ergodicity breaking, spanning several orders of magnitude in time, have been obtained. The ageing nature of the system weakens as the dissipation of the system increases for other given parameters. Its origin is ascribed to the highly local heterogeneity of the disorder. Two kinds of approximations (in the stationary state), respectively, for large bias and large damping are derived. These results may be helpful in further understanding the nontrivial response of nonlinear dynamics, and also have potential applications to experiments and activities of biological processes.

Pituitary gland in Bipolar Disorder and Major Depression: Evidence from structural MRI studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summarise relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

Science.gov (United States)

Delvecchio, G; Altamura, A C; Soares, J C; Brambilla, P

2017-08-15

The function of the hypothalamo-pituitary-adrenal axis (HPA) has been widely investigated in mood disorders based on its role in regulating stress response. Particularly, Magnetic Resonance Imaging (MRI) reports have explored pituitary gland (PG) in both bipolar disorder (BD) and major depressive disorder (MDD). In this context, the present review summarizes the results from MRI studies with the final aim of commenting on the presence of common or distinct PG structural alterations between these two disabling illnesses. A bibliographic search on PUBMED of all MRI studies exploring PG volumes in BD and MDD as well as first-degree relatives (RELs) from 2000 up to October 2016 was performed. Following the screening process of the available literature it can be said that a) PG enlargement has been found in both BD and MDD, therefore potentially representing a common neurobiological marker characterizing mood disorders, and b) PG volumes are moderated by age and sex in both illnesses, although the direction and the extent of this moderation are still not fully clear. Few MRI studies with heterogeneous results. These hypotheses must be taken with caution especially because the heterogeneity of the results of the studies reviewed does not allow for a definite answer about the role of PG in affective disorders. Therefore, larger longitudinal studies investigating PG volumes in BD and MDD patients at the early phases of the illness, by considering females and males separately, are needed to further corroborate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Heterogeneous sharpness for cross-spectral face recognition

Science.gov (United States)

Cao, Zhicheng; Schmid, Natalia A.

2017-05-01

Matching images acquired in different electromagnetic bands remains a challenging problem. An example of this type of comparison is matching active or passive infrared (IR) against a gallery of visible face images, known as cross-spectral face recognition. Among many unsolved issues is the one of quality disparity of the heterogeneous images. Images acquired in different spectral bands are of unequal image quality due to distinct imaging mechanism, standoff distances, or imaging environment, etc. To reduce the effect of quality disparity on the recognition performance, one can manipulate images to either improve the quality of poor-quality images or to degrade the high-quality images to the level of the quality of their heterogeneous counterparts. To estimate the level of discrepancy in quality of two heterogeneous images a quality metric such as image sharpness is needed. It provides a guidance in how much quality improvement or degradation is appropriate. In this work we consider sharpness as a relative measure of heterogeneous image quality. We propose a generalized definition of sharpness by first achieving image quality parity and then finding and building a relationship between the image quality of two heterogeneous images. Therefore, the new sharpness metric is named heterogeneous sharpness. Image quality parity is achieved by experimentally finding the optimal cross-spectral face recognition performance where quality of the heterogeneous images is varied using a Gaussian smoothing function with different standard deviation. This relationship is established using two models; one of them involves a regression model and the other involves a neural network. To train, test and validate the model, we use composite operators developed in our lab to extract features from heterogeneous face images and use the sharpness metric to evaluate the face image quality within each band. Images from three different spectral bands visible light, near infrared, and short

Global gene expression profiling of individual human oocytes and embryos demonstrates heterogeneity in early development.

Directory of Open Access Journals (Sweden)

Lisa Shaw

Full Text Available Early development in humans is characterised by low and variable embryonic viability, reflected in low fecundity and high rates of miscarriage, relative to other mammals. Data from assisted reproduction programmes provides additional evidence that this is largely mediated at the level of embryonic competence and is highly heterogeneous among embryos. Understanding the basis of this heterogeneity has important implications in a number of areas including: the regulation of early human development, disorders of pregnancy, assisted reproduction programmes, the long term health of children which may be programmed in early development, and the molecular basis of pluripotency in human stem cell populations. We have therefore investigated global gene expression profiles using polyAPCR amplification and microarray technology applied to individual human oocytes and 4-cell and blastocyst stage embryos. In order to explore the basis of any variability in detail, each developmental stage is replicated in triplicate. Our data show that although transcript profiles are highly stage-specific, within each stage they are relatively variable. We describe expression of a number of gene families and pathways including apoptosis, cell cycle and amino acid metabolism, which are variably expressed and may be reflective of embryonic developmental competence. Overall, our data suggest that heterogeneity in human embryo developmental competence is reflected in global transcript profiles, and that the vast majority of existing human embryo gene expression data based on pooled oocytes and embryos need to be reinterpreted.

Impact of Gender, Age at Onset, and Lifetime Tic Disorders on the Clinical Presentation and Comorbidity Pattern of Obsessive-Compulsive Disorder in Children and Adolescents.

Science.gov (United States)

Tanidir, Canan; Adaletli, Hilal; Gunes, Hatice; Kilicoglu, Ali Guven; Mutlu, Caner; Bahali, Mustafa Kayhan; Aytemiz, Tugce; Uneri, Ozden Sukran

2015-06-01

Obsessive-compulsive disorder (OCD) is a heterogeneous disorder; therefore, there is a need for identifying more homogeneous subtypes. This study aimed to examine the clinical characteristics and comorbidity pattern of a large sample of pediatric OCD subjects, and to examine the impact of gender, age at onset, and lifetime tic disorders on the clinical presentation and comorbidity pattern. A total of 110 children and adolescents diagnosed with OCD were assessed using the Kiddle Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL) for psychiatric comorbidity, and a clinical data form was filled out. The cutoff for differentiating prepubertal from adolescent onset was 11 years of age. A total of 83.6% of the subjects had at least one comorbid psychiatric disorder. Oppositional defiant disorder and contamination/somatic obsessions were significantly higher in males (p=0.036 and p=0.03, respectively) than in females. Depressive disorders and religious obsessions were significantly higher in the adolescent-onset group (p=0.02, p=0.05, respectively) whereas disruptive behavior disorders were higher in the prepubertal-onset group (p=0.037). Disruptive behavior disorders were significantly more frequent in the tic (+) group than in tic (-) group (p=0.021). There were differences in the comorbidity pattern and clinical expression between genders and between prepubertal and adolescent-onset cases. Findings of this study supported the introduction of tic-related OCD as a specifier in Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), and the necessity of a detailed assessment of other psychiatric disorders in youth with OCD.

Interleukin-10 and posttransplant lymphoproliferative disorder after kidney transplantation

DEFF Research Database (Denmark)

Birkeland, S.A.; Bendtzen, K.; Moller, B.

1999-01-01

Background. Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation, which comprises a morphologically and clinically heterogeneous spectrum of B-lymphocyte diseases. Risk factors include primary or reactivated Epstein-Barr virus (EBV) infection...... to the development of PTLD in three kidney transplanted patients. The study now includes nine patients that could be followed before and/or after the occurrence of lymphoma, Methods. Nine patients with lymphomas (eight PTLDs and one Hodgkin's disease) were diagnosed among 268 consecutive renal transplantations (1990...

Relationship between symptom dimensions and brain morphology in obsessive-compulsive disorder.

Science.gov (United States)

Hirose, Motohisa; Hirano, Yoshiyuki; Nemoto, Kiyotaka; Sutoh, Chihiro; Asano, Kenichi; Miyata, Haruko; Matsumoto, Junko; Nakazato, Michiko; Matsumoto, Koji; Masuda, Yoshitada; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

2017-10-01

Obsessive-compulsive disorder (OCD) is known as a clinically heterogeneous disorder characterized by symptom dimensions. Although substantial numbers of neuroimaging studies have demonstrated the presence of brain abnormalities in OCD, their results are controversial. The clinical heterogeneity of OCD could be one of the reasons for this. It has been hypothesized that certain brain regions contributed to the respective obsessive-compulsive dimensions. In this study, we investigated the relationship between symptom dimensions of OCD and brain morphology using voxel-based morphometry to discover the specific regions showing alterations in the respective dimensions of obsessive-compulsive symptoms. The severities of symptom dimensions in thirty-three patients with OCD were assessed using Obsessive-Compulsive Inventory-Revised (OCI-R). Along with numerous MRI studies pointing out brain abnormalities in autistic spectrum disorder (ASD) patients, a previous study reported a positive correlation between ASD traits and regional gray matter volume in the left dorsolateral prefrontal cortex and amygdala in OCD patients. We investigated the correlation between gray and white matter volumes at the whole brain level and each symptom dimension score, treating all remaining dimension scores, age, gender, and ASD traits as confounding covariates. Our results revealed a significant negative correlation between washing symptom dimension score and gray matter volume in the right thalamus and a significant negative correlation between hoarding symptom dimension score and white matter volume in the left angular gyrus. Although our result was preliminary, our findings indicated that there were specific brain regions in gray and white matter that contributed to symptom dimensions in OCD patients.

Epidemic Spreading with Heterogeneous Awareness on Human Networks

Directory of Open Access Journals (Sweden)

Yanling Lu

2017-01-01

Full Text Available The spontaneous awareness behavioral responses of individuals have a significant impact on epidemic spreading. In this paper, a modified Susceptible-Alert-Infected-Susceptible (SAIS epidemic model with heterogeneous awareness is presented to study epidemic spreading in human networks and the impact of heterogeneous awareness on epidemic dynamics. In this model, when susceptible individuals receive awareness information about the presence of epidemic from their infected neighbor nodes, they will become alert individuals with heterogeneous awareness rate. Theoretical analysis and numerical simulations show that heterogeneous awareness can enhance the epidemic threshold with certain conditions and reduce the scale of virus outbreaks compared with no awareness. What is more, for the same awareness parameter, it also shows that heterogeneous awareness can slow effectively the spreading size and does not delay the arrival time of epidemic spreading peak compared with homogeneous awareness.

The effect of soil heterogeneity on ATES performance

Science.gov (United States)

Sommer, W.; Rijnaarts, H.; Grotenhuis, T.; van Gaans, P.

2012-04-01

Due to an increasing demand for sustainable energy, application of Aquifer Thermal Energy Storage (ATES) is growing rapidly. Large-scale application of ATES is limited by the space that is available in the subsurface. Especially in urban areas, suboptimal performance is expected due to thermal interference between individual wells of a single system, or interference with other ATES systems or groundwater abstractions. To avoid thermal interference there are guidelines on well spacing. However, these guidelines, and also design calculations, are based on the assumption of a homogeneous subsurface, while studies report a standard deviation in logpermeability of 1 to 2 for unconsolidated aquifers (Gelhar, 1993). Such heterogeneity may create preferential pathways, reducing ATES performance due to increased advective heat loss or interference between ATES wells. The role of hydraulic heterogeneity of the subsurface related to ATES performance has received little attention in literature. Previous research shows that even small amounts of heterogeneity can result in considerable uncertainty in the distribution of thermal energy in the subsurface and an increased radius of influence (Ferguson, 2007). This is supported by subsurface temperature measurements around ATES wells, which suggest heterogeneity gives rise to preferential pathways and short-circuiting between ATES wells (Bridger and Allen, 2010). Using 3-dimensional stochastic heat transport modeling, we quantified the influence of heterogeneity on the performance of a doublet well energy storage system. The following key parameters are varied to study their influence on thermal recovery and thermal balance: 1) regional flow velocity, 2) distance between wells and 3) characteristics of the heterogeneity. Results show that heterogeneity at the scale of a doublet ATES system introduces an uncertainty up to 18% in expected thermal recovery. The uncertainty increases with decreasing distance between ATES wells. The

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, JEJ; Hovenga, S; Vellenga, E; Bos, NA

Multiple Myeloma ( MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome.

Who says this is a modern disorder? The early history of attention deficit hyperactivity disorder

Science.gov (United States)

Martinez-Badía, Jose; Martinez-Raga, Jose

2015-01-01

Attention-deficit hyperactivity disorder (ADHD) is a complex, heterogeneous and multifactorial neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and impulsivity. Although the first clinical description of a constellation of symptoms highly resembling to what currently could be diagnosed as ADHD is generally attributed to George F Still in 1902, there are scattered but significant published historical medical, scientific and non-scientific reports, much prior to Still’s lectures, of what is currently conceptualized as ADHD. The present report aimed at exploring the early history of ADHD, prior to the 20th century in the medical literature and in other historical sources, to provide clinicians, researchers and other professionals with a better understanding of the roots and current conceptualization of this disorder. It is possible to find clues and highly suggestive descriptions of individuals presenting symptoms resembling what is currently defined as ADHD in the literature, in paintings or in the Bible. However, the earliest medical reports of individuals with abnormal degrees of inattention, distractibility and overactivity date from the last quarter of the 18th century, included in two of the first textbooks specifically on the subject of mental diseases, published by the German Melchior Adam Weikard and the Scottish Sir Alexander Crichton. During the 19th century some eminent physicians from Germany, France or Great Britain, such as Charles West, Thomas C Albutt, Thomas S Clouston, William W, Ireland, John Haslam, Heinrich Neumann, or Désiré-Magloire Bourneville, among others provided clinical depictions of patients that most likely presently would be diagnosed as having ADHD. Whilst some of the children described by Still and his predecessors may have suffered from a variety of neurological and psychiatric disorders, many of these patients showed clear symptoms of ADHD and may present with comorbid disorders, as

Clinical neurogenetics: neuropathic lysosomal storage disorders.

Science.gov (United States)

Pastores, Gregory M; Maegawa, Gustavo H B

2013-11-01

The lysosomal storage disorders are a clinically heterogeneous group of inborn errors of metabolism, associated with the accumulation of incompletely degraded macromolecules within several cellular sites. Affected individuals present with a broad range of clinical problems, including hepatosplenomegaly and skeletal dysplasia. Onset of symptoms may range from birth to adulthood. Most are associated with neurologic features. Later-onset forms are often misdiagnosed as symptoms, which might include psychiatric manifestations, are slowly progressive, and may precede other neurologic or systemic features. Symptomatic care, which remains the mainstay for most subtypes, can lead to significant improvement in quality of life. Copyright © 2013 Elsevier Inc. All rights reserved.

Composition heterogeneity analysis for DUPIC fuel(I) - Statistical analysis

Energy Technology Data Exchange (ETDEWEB)

Choi, Hang Bok [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-08-01

The fuel composition heterogeneity effect on reactor performance parameters was assessed by refueling simulations for three DUPIC fuel options of fuel composition heterogeneity control: the fissile content adjustment, the reactivity control by slightly enriched and depleted uranium, and the reactivity control by natural uranium. For each DUPIC fuel option, the simulations were performed using 30 heterogeneous fuel types which were determined by the agglomerative hierarchical clustering method. The heterogeneity effect was considered during the refueling simulation by randomly selecting fuel types for the refueling operation. The refueling simulations of the heterogeneous core have shown that the key performance parameters such as the maximum channel power (MCP), maximum bundle power (MBP), and channel power peaking factor (CPPF) are close to those of the core that has single fuel type. For the three DUPIC fuel options, the uncertainties of MCP, MBP, and CPPF due to the fuel composition heterogeneity are less than 0.6, 1.5 and 0.8%, respectively, including the uncertainty of the group-average fuel property. This study has shown that the three DUPIC fuel options reduces the composition heterogeneity effectively and the zone power control system has a sufficient margin to adjust the perturbations cased by the fuel composition heterogeneity. 15 refs., 28 figs.,10 tabs. (Author)

Modeling heterogeneous unsaturated porous media flow at Yucca Mountain

International Nuclear Information System (INIS)

Robey, T.H.

1994-01-01

Geologic systems are inherently heterogeneous and this heterogeneity can have a significant impact on unsaturated flow through porous media. Most previous efforts to model groundwater flow through Yucca Mountain have used stratigraphic units with homogeneous properties. However, modeling heterogeneous porous and fractured tuff in a more realistic manner requires numerical methods for generating heterogeneous simulations of the media, scaling of material properties from core scale to computational scale, and flow modeling that allows channeling. The Yucca Mountain test case of the INTRAVAL project is used to test the numerical approaches. Geostatistics is used to generate more realistic representations of the stratigraphic units and heterogeneity within units is generated using sampling from property distributions. Scaling problems are reduced using an adaptive grid that minimizes heterogeneity within each flow element. A flow code based on the dual mixed-finite-element method that allows for heterogeneity and channeling is employed. In the Yucca Mountain test case, the simulated volumetric water contents matched the measured values at drill hole USW UZ-16 except in the nonwelded portion of Prow Pass

Overview of medium heterogeneity and transport processes

International Nuclear Information System (INIS)

Tsang, Y.; Tsang, C.F.

1993-11-01

Medium heterogeneity can have significant impact on the behavior of solute transport. Tracer breakthrough curves from transport in a heterogeneous medium are distinctly different from that in a homogeneous porous medium. Usually the shape of the breakthrough curves are highly non-symmetrical with a fast rise at early times and very long tail at late times, and often, they consist of multiple peaks. Moreover, unlike transport in a homogeneous medium where the same transport parameters describe the entire medium, transport through heterogeneous media gives rise to breakthrough curves which have strong spatial dependence. These inherent characteristics of transport in heterogeneous medium present special challenge to the performance assessment of a potential high level nuclear waste repository with respect to the possible release of radio nuclides to the accessible environment. Since an inherently desirable site characteristic for a waste repository is that flow and transport should be slow, then transport measurements in site characterization efforts will necessarily be spatially small and temporally short compare to the scales which are of relevance to performance assessment predictions. In this paper we discuss the role of medium heterogeneity in site characterization and performance assessment. Our discussion will be based on a specific example of a 3D heterogeneous stochastic model of a site generally similar to, the Aespoe Island, the site of the Hard Rock Laboratory in Southern Sweden. For our study, alternative 3D stochastic fields of hydraulic conductivities conditioned on ''point'' measurements shall be generated. Results of stochastic flow and transport simulations would be used to address the issues of (1) the relationship of tracer breakthrough with the structure of heterogeneity, and (2) the inference from small scale testing results to large scale and long term predictions

Heterogeneity in the multiple myeloma tumor clone

NARCIS (Netherlands)

Guikema, Jeroen E. J.; Hovenga, Sjoerd; Vellenga, Edo; Bos, Nicolaas A.

2004-01-01

Multiple Myeloma (MM) is a plasma cell malignancy which is characterized by a very heterogeneous disease outcome. Heterogeneity in plasma cell characteristics, including morphology, maturation status, immunophenotype and genetic abnormalities partly account for the variable disease outcome. Although

Heterogeneous treatment in the variational nodal method

International Nuclear Information System (INIS)

Fanning, T.H.

1995-01-01

The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations

Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy--Creatine prophylaxis and the need for multi-organ protection.

Science.gov (United States)

Ellery, Stacey J; Dickinson, Hayley; McKenzie, Matthew; Walker, David W

2016-05-01

Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Schizoaffective disorder: a review of current research themes and pharmacological management.

Science.gov (United States)

Kantrowitz, Joshua T; Citrome, Leslie

2011-04-01

Despite a clear recognition of the existence of patients with co-morbid psychotic and mood symptoms, many studies conclude that schizoaffective disorder as a distinct diagnosis does not exist. Regardless of one's opinion on schizoaffective disorder, psychiatrists remain dependent on phenomenological descriptions for diagnosing psychiatric disorders, and these phenomenological criteria are also used for clinical trial entry. On the other hand, many psychiatrists prescribe for specific target symptoms and do not always rigidly follow diagnostic systems and, moreover, there have been very few trials that have specifically studied schizoaffective disorder. Despite recent intriguing work in epidemiology, genetics, neurocognition and electrophysiology, the diagnosis of schizoaffective disorder remains controversial. Taken together, these studies suggest that even if schizoaffective disorder exists as a separate diagnosis, it may not be useful clinically due to considerable variation in the general use of this term. It is possible that diagnostic criteria in the future will include genetic, imaging and electrophysiological components, and that this will allow for better differentiation of disease states among the heterogeneous pool of patients currently believed to have schizophrenia, schizoaffective disorder or bipolar disorder. Although it is likely that most, if not all, antipsychotics are effective for schizoaffective disorder, given recent regulatory approval of a specific antipsychotic agent for the acute treatment of schizoaffective disorder, greater attention is now being focused on the entity of schizoaffective disorder and potential treatment decisions. However, based on the limited extant evidence, it is not yet possible to make definitive treatment recommendations for schizoaffective disorder. Additional clinical trials that include other antipsychotics, mood stabilizers and antidepressants are desirable and necessary before clear and comprehensive evidence

TMEM199 Deficiency Is a Disorder of Golgi Homeostasis Characterized by Elevated Aminotransferases, Alkaline Phosphatase, and Cholesterol and Abnormal Glycosylation

NARCIS (Netherlands)

Jansen, Jos C.; Timal, Sharita; van Scherpenzeel, Monique; Michelakakis, Helen; Vicogne, Dorothée; Ashikov, Angel; Moraitou, Marina; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; van den Boogert, Marjolein A. W.; Porta, Francesco; Calvo, Pier Luigi; Mavrikou, Mersyni; Cenacchi, Giovanna; van den Bogaart, Geert; Salomon, Jody; Holleboom, Adriaan G.; Rodenburg, Richard J.; Drenth, Joost P. H.; Huynen, Martijn A.; Wevers, Ron A.; Morava, Eva; Foulquier, François; Veltman, Joris A.; Lefeber, Dirk J.

2016-01-01

Congenital disorders of glycosylation (CDGs) form a genetically and clinically heterogeneous group of diseases with aberrant protein glycosylation as a hallmark. A subgroup of CDGs can be attributed to disturbed Golgi homeostasis. However, identification of pathogenic variants is seriously

Integrating mean and variance heterogeneities to identify differentially expressed genes.

Science.gov (United States)

Ouyang, Weiwei; An, Qiang; Zhao, Jinying; Qin, Huaizhen

2016-12-06

In functional genomics studies, tests on mean heterogeneity have been widely employed to identify differentially expressed genes with distinct mean expression levels under different experimental conditions. Variance heterogeneity (aka, the difference between condition-specific variances) of gene expression levels is simply neglected or calibrated for as an impediment. The mean heterogeneity in the expression level of a gene reflects one aspect of its distribution alteration; and variance heterogeneity induced by condition change may reflect another aspect. Change in condition may alter both mean and some higher-order characteristics of the distributions of expression levels of susceptible genes. In this report, we put forth a conception of mean-variance differentially expressed (MVDE) genes, whose expression means and variances are sensitive to the change in experimental condition. We mathematically proved the null independence of existent mean heterogeneity tests and variance heterogeneity tests. Based on the independence, we proposed an integrative mean-variance test (IMVT) to combine gene-wise mean heterogeneity and variance heterogeneity induced by condition change. The IMVT outperformed its competitors under comprehensive simulations of normality and Laplace settings. For moderate samples, the IMVT well controlled type I error rates, and so did existent mean heterogeneity test (i.e., the Welch t test (WT), the moderated Welch t test (MWT)) and the procedure of separate tests on mean and variance heterogeneities (SMVT), but the likelihood ratio test (LRT) severely inflated type I error rates. In presence of variance heterogeneity, the IMVT appeared noticeably more powerful than all the valid mean heterogeneity tests. Application to the gene profiles of peripheral circulating B raised solid evidence of informative variance heterogeneity. After adjusting for background data structure, the IMVT replicated previous discoveries and identified novel experiment

Heterogeneous Gossip

Science.gov (United States)

Frey, Davide; Guerraoui, Rachid; Kermarrec, Anne-Marie; Koldehofe, Boris; Mogensen, Martin; Monod, Maxime; Quéma, Vivien

Gossip-based information dissemination protocols are considered easy to deploy, scalable and resilient to network dynamics. Load-balancing is inherent in these protocols as the dissemination work is evenly spread among all nodes. Yet, large-scale distributed systems are usually heterogeneous with respect to network capabilities such as bandwidth. In practice, a blind load-balancing strategy might significantly hamper the performance of the gossip dissemination.

[Neurotransmission in developmental disorders].

Science.gov (United States)

Takeuchi, Yoshihiro

2008-11-01

Attention deficit/hyperactivity disorder (AD/HD) is a heterogeneous developmental disorder with an etiology that is not fully understood. AD/HD has been considered to occur due to a disturbance in cathecholaminergic neurotransmission, with particular emphasis on dopamine. The neurotransmission of dopamine in subcortical regions such as the basal ganglia and limbic areas is synaptic; on the other hand, dopamine neurotransmission in the frontal cortex is quite different, because there are very few dopamine transporters (DAT) in the frontal cortex that allow dopamine to diffuse away from the dopamine synapse ("volume transmission"). It is now clear that noradrenergic neurons play a key regulatory role in dopaminergic function in the frontal cortex. Furthermore, serotonergic neurons exert an inhibitory effect on midbrain dopamine cell bodies, and they have an influence on dopamine release in terminal regions. There is accumulating neurobiological evidence pointing toward a role of the serotonin system in AD/HD. The etiology of autism spectrum disorders (ASD) is still unclear, but information from genetics, neuropathology, brain imaging, and basic neuroscience has provided insights into the understanding of this developmental disorder. In addition to abnormal circuitry in specific limbic and neocortical areas of the cerebral cortex, impairments in brainstem, cerebellar, thalamic, and basal ganglia connections have been reported. Numerous studies have pointed to abnormalities in serotonin and glutamate neurotransmission. Three important aspects involved in the pathophysiology of ASD have been proposed. The first is cell migration, the second is unbalanced excitatory-inhibitory networks, and the third is synapse formation and pruning, the key factors being reelin, neurexin, and neuroligin. Serotonin is considered to play an important role in all of these aspects of the pathophysiology of ASD. Finally, I would like to emphasize that it is crucial in the field of child

Heterogeneity in Social Dilemmas: The Case of Social Support

NARCIS (Netherlands)

Vogt, S.B.

2007-01-01

“Heterogeneous Social Dilemmas: The Case of Social Support” studies the level of social support between heterogeneous actors. We consider heterogeneity with respect to several individual properties: the likelihood of needing support, the costs of providing support, and the benefits from receiving

[A multidiscipline clinical and biological approach to the study of psychotic types of autistic spectrum disorders in children].

Science.gov (United States)

Simashkova, N V; Iakupova, L P; Kliushnik, T P; Koval'-Zaĭtsev, A A

2013-01-01

The current problem of heterogeneity of psychotic types of autistic spectrum disorders (ASD) is reviewed. The authors present results of a multidiscipline psychopathological, pathopsychological, neurophysiological and immunological examination of 87 patients, aged from 3 to 14 years, with psychotic types of ASD: childhood psychosis (CP) and atypical childhood psychosis (ACP). Significant differences in clinical presentations of CP and ACP that were correlated with pathopsychological, neurophysiological and immunological disorders were found. These findings support different nosological entities of these types of ASD.

A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder.

Science.gov (United States)

Schaffer, Ayal; Isometsä, Erkki T; Azorin, Jean-Michel; Cassidy, Frederick; Goldstein, Tina; Rihmer, Zoltán; Sinyor, Mark; Tondo, Leonardo; Moreno, Doris H; Turecki, Gustavo; Reis, Catherine; Kessing, Lars Vedel; Ha, Kyooseob; Weizman, Abraham; Beautrais, Annette; Chou, Yuan-Hwa; Diazgranados, Nancy; Levitt, Anthony J; Zarate, Carlos A; Yatham, Lakshmi

2015-11-01

Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords 'bipolar disorder' and 'suicide attempts or suicide'. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Heterogeneous chromium catalysts

NARCIS (Netherlands)

2005-01-01

The present invention relates to a heterogeneous chromium catalyst system for the polymerisation of ethylene and/or alpha olefins prepared by the steps of: (a) providing a silica-containing support, (b) treating the silica-containing support with a chromium compound to form a chromium-based

A Rorschach investigation of Autism Spectrum Disorders in Adulthood:

Directory of Open Access Journals (Sweden)

Manuela Crucitti

2015-12-01

Full Text Available Autism is a pervasive developmental disorder characterized by deficits in the areas of communication, socialization and behavior. Current diagnostic criteria have been modified in a restrictive sense, thus the possibility that individuals with milder impairments may not reach the diagnostic threshold is concrete. Furthermore, heterogeneity in phenotypic expression and the high rate of comorbidity with other psychiatric disorders would make even more difficult the diagnostic classification in individuals with autism spectrum disorder (ASD. The present study was a Rorschach investigation aimed to identify specific psychopathological elements to properly orient the diagnosis of ASD in adulthood. Results have shown that the examined subjects were characterized by pragmatism, documented by the presence of details and little details, falls in formal thinking, thought inflexibility, lack of answers with human content, and the prevalence of particular phenomena (denial, perseveration. Data obtained in the study showed a specific pattern of psychopathological signs in adults with ASD, thus suggesting the importance of projective methods for a better understanding of the clinical features of avoidance behaviors and relationships.

Purchasing Power Parity and Heterogeneous Mean Reversion

NARCIS (Netherlands)

C.G. Koedijk (Kees); B. Tims (Ben); M.A. van Dijk (Mathijs)

2005-01-01

textabstractThis paper analyzes the properties of multivariate tests of purchasing power parity (PPP) that fail to take heterogeneity in the speed of mean reversion across real exchange rates into account. We compare the performance of homogeneous and heterogeneous unit root testing methodologies.

Investigating the effect of heterogeneity on infill wells

Directory of Open Access Journals (Sweden)

Mahmood Bagheri

2015-12-01

Full Text Available Abstract In recent years, improving oil recovery (IOR has become an important subject for the petroleum industry. One IOR method is infill drilling, which improves hydrocarbon recovery from virgin zones of the reservoir. Determining the appropriate location for the infill wells is very challenging and greatly depends on different factors such as the reservoir heterogeneity. This study aims to investigate the effect of reservoir heterogeneity on the location of infill well. In order to characterize the effect of heterogeneity on infill well locations, some geostatistical methods, e.g., sequential gaussian simulation, have been applied to generate various heterogeneity models. In particular, different correlation ranges (R were used to observe the effect of heterogeneity. Results revealed that an increase in correlation ranges will lead to (1 a higher field oil production total, and (2 a faster expansion of the drainage radius which consequently reduced the need for infill wells. The results of this study will help engineers to appropriately design infill drilling schemes.

Integration of heterogeneous features for remote sensing scene classification

Science.gov (United States)

Wang, Xin; Xiong, Xingnan; Ning, Chen; Shi, Aiye; Lv, Guofang

2018-01-01

Scene classification is one of the most important issues in remote sensing (RS) image processing. We find that features from different channels (shape, spectral, texture, etc.), levels (low-level and middle-level), or perspectives (local and global) could provide various properties for RS images, and then propose a heterogeneous feature framework to extract and integrate heterogeneous features with different types for RS scene classification. The proposed method is composed of three modules (1) heterogeneous features extraction, where three heterogeneous feature types, called DS-SURF-LLC, mean-Std-LLC, and MS-CLBP, are calculated, (2) heterogeneous features fusion, where the multiple kernel learning (MKL) is utilized to integrate the heterogeneous features, and (3) an MKL support vector machine classifier for RS scene classification. The proposed method is extensively evaluated on three challenging benchmark datasets (a 6-class dataset, a 12-class dataset, and a 21-class dataset), and the experimental results show that the proposed method leads to good classification performance. It produces good informative features to describe the RS image scenes. Moreover, the integration of heterogeneous features outperforms some state-of-the-art features on RS scene classification tasks.

The Effect of Cooperative Teaching on the Development of Reading Skills among Students with Reading Disorders

Science.gov (United States)

Ghanaat Pisheh, Etrat Alzahra; Sadeghpour, Narges; Nejatyjahromy, Yaser; Mir Nasab, Mir Mahmoud

2017-01-01

Cooperative teaching is the result of efforts made by two educators for teaching a heterogeneous group of students, especially one including those with specific needs, due to reading disorders for instance. The present study serves as an experimental investigation focusing on the effect of cooperative teaching on the development of reading skills…

Acute leukaemoid reaction following cardiac surgery

Directory of Open Access Journals (Sweden)

Webb Stephen T

2007-01-01

Full Text Available Abstract Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

Surface current double-heterogeneous multilayer multicell methodology

International Nuclear Information System (INIS)

Stepanek, J.; Segev, M.

1991-01-01

A surface current methodology is developed to respond to the need for treating the various levels of material heterogeneity in a double-heterogeneous multilayer multicell in processing neutron multigroup cross sections in the resonance as well as thermal energy range. First, the basic surface cosine current transport equations to calculate the energy-dependent neutron flux spatial distribution in the multilayered multicell are formulated. Slab, spherical and cylindrical geometries, as well as square and hexagonal lattices and pebble-bed configurations with white or reflective cell boundary conditions, are considered. Second, starting from the surface cosine-current formulation, a two-zone three-layer multicell formalism for reduction of heterogeneous flux expressions to equivalent homogeneous flux expression for table method was developed. This formalism allows an infinite, as well as a limited, number of second-heterogeneity cells within a partial first-heterogeneity cell layer to be considered. Also, the number of the first-and second-heterogeneity cell types is quite general. The 'outer' (right side) as well as 'inner' (left side) Dancoff probabilities can be calculated for any particular layer. An accurate, efficient, and compact interpolation procedure is developed to calculate the basic collision probabilities. These are transmission and escape probabilities for shells in slab, cylindrical, and spherical geometries, as well as Dancoff probabilities for cylinders in square and hexagonal lattices. The use of the interpolation procedure is exemplified in a multilayer multicell approximation for the Dancoff probability, enabling a routine evaluation of the equivalence-based shielded resonance integral in highly complex lattices of slab, cylindrical, or spherical cells. (author) 1 fig., 2 tabs., 10 refs

A 1998 Workshop on Heterogeneous Computing

Science.gov (United States)

1998-09-18

Programming Heterogenous Computing Systems? Panel Chair: GulA. Agha, University of Illinois, Urbana -Champaign, IL, USA Modular Heterogeneous System...electrical engineering from the University of Illinois, Urbana -Champaign, in 1975. She worked at the I.B.M. T.J. Watson Research Center with the...Distributed System Environment". I Encuentro de Computaciön. Taller de Sistemas Distribuidos y Paralelos. Memorias . Queretaro, Qro. Mexico. September 1997

Spatial Heterogeneity of the Forest Canopy Scales with the Heterogeneity of an Understory Shrub Based on Fractal Analysis

Directory of Open Access Journals (Sweden)

Catherine K. Denny

2017-04-01

Full Text Available Spatial heterogeneity of vegetation is an important landscape characteristic, but is difficult to assess due to scale-dependence. Here we examine how spatial patterns in the forest canopy affect those of understory plants, using the shrub Canada buffaloberry (Shepherdia canadensis (L. Nutt. as a focal species. Evergreen and deciduous forest canopy and buffaloberry shrub presence were measured with line-intercept sampling along ten 2-km transects in the Rocky Mountain foothills of west-central Alberta, Canada. Relationships between overstory canopy and understory buffaloberry presence were assessed for scales ranging from 2 m to 502 m. Fractal dimensions of both canopy and buffaloberry were estimated and then related using box-counting methods to evaluate spatial heterogeneity based on patch distribution and abundance. Effects of canopy presence on buffaloberry were scale-dependent, with shrub presence negatively related to evergreen canopy cover and positively related to deciduous cover. The effect of evergreen canopy was significant at a local scale between 2 m and 42 m, while that of deciduous canopy was significant at a meso-scale between 150 m and 358 m. Fractal analysis indicated that buffaloberry heterogeneity positively scaled with evergreen canopy heterogeneity, but was unrelated to that of deciduous canopy. This study demonstrates that evergreen canopy cover is a determinant of buffaloberry heterogeneity, highlighting the importance of spatial scale and canopy composition in understanding canopy-understory relationships.

Job Heterogeneity and Coordination Frictions

DEFF Research Database (Denmark)

Kennes, John; le Maire, Daniel

We develop a new directed search model of a frictional labor market with a continuum of heterogenous workers and firms. We estimate two versions of the model - auction and price posting - using Danish data on wages and productivities. Assuming heterogenous workers with no comparative advantage, we...... the job ladder, how the identification of assortative matching is fundamentally different in directed and undirected search models, how our theory accounts for business cycle facts related to inter-temporal changes in job offer distributions, and how our model could also be used to identify...

Identifying Latent Trajectories of Personality Disorder Symptom Change: Growth Mixture Modeling in the Longitudinal Study of Personality Disorders

Science.gov (United States)

Hallquist, Michael N.; Lenzenweger, Mark F.

2013-01-01

Although previous reports have documented mean-level declines in personality disorder (PD) symptoms over time, little is known about whether personality pathology sometimes emerges among nonsymptomatic adults, or whether rates of change differ qualitatively among symptomatic persons. Our study sought to characterize heterogeneity in the longitudinal course of PD symptoms with the goal of testing for and describing latent trajectories. Participants were 250 young adults selected into two groups using a PD screening measure: those who met diagnostic criteria for a DSM-III-R PD (PPD, n = 129), and those with few PD symptoms (NoPD, n = 121). PD symptoms were assessed three times over a four-year study using semistructured interviews. Total PD symptom counts and symptoms of each DSM-III-R PD were analyzed using growth mixture modeling. In the NoPD group, latent trajectories were characterized by stable, minor symptoms; the rapid or gradual remission of subclinical symptoms; or the emergence of symptoms of Avoidant, Obsessive-Compulsive, or Paranoid PD. In the PPD group, three latent trajectories were evident: rapid symptom remission, slow symptom decline, or a relative absence of symptoms. Rapid remission of PD symptoms was associated with fewer comorbid disorders, lower negative emotionality, and greater positive emotionality and constraint, whereas emergent personality dysfunction was associated with comorbid PD symptoms and lower positive emotionality. In most cases, symptom change for one PD was associated with concomitant changes in other PDs, depressive symptoms, and anxiety. These results indicate that the longitudinal course of PD symptoms is heterogeneous, with distinct trajectories evident for both symptomatic and nonsymptomatic individuals. The prognosis of PD symptoms may be informed by an assessment of personality and comorbid psychopathology. PMID:23231459

Towards an Organizational Economics of Heterogeneous Capabilities

DEFF Research Database (Denmark)

Foss, Nicolai Juul

The notion of “capability” has long been influential in management research as an approach to address firm-level heterogeneity and heterogeneity in competitive outcomes. I discuss how recent advances in economics may allow for a more rigorous understanding and measurement of capability that take...

Understanding the Executive Functioning Heterogeneity in Schizophrenia

Science.gov (United States)

Raffard, Stephane; Bayard, Sophie

2012-01-01

Schizophrenia is characterized by heterogeneous brain abnormalities involving cerebral regions implied in the executive functioning. The dysexecutive syndrome is one of the most prominent and functionally cognitive features of schizophrenia. Nevertheless, it is not clear to what extend executive deficits are heterogeneous in schizophrenia…

Heterogeneity and Networks

OpenAIRE

Goyal, S.

2018-01-01

This chapter shows that networks can have large and differentiated effects on behavior and then argues that social and economic pressures facilitate the formation of heterogenous networks. Thus networks can play an important role in understanding the wide diversity in human behaviour and in economic outcomes.

First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

Energy Technology Data Exchange (ETDEWEB)

Nappi, Carmela; Altiero, Michele; Imbriaco, Massimo; Giudice, Caterina Anna; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Nicolai, Emanuele; Aiello, Marco; Diomiaiuti, Claudio Tommaso [IRCCS SDN, Naples (Italy); Pisani, Antonio [University Federico II, Department of Public Health, Naples (Italy)

2015-03-26

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients. Thirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of {sup 18}F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart. Six patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01). PET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted. (orig.)

First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

International Nuclear Information System (INIS)

Nappi, Carmela; Altiero, Michele; Imbriaco, Massimo; Giudice, Caterina Anna; Spinelli, Letizia; Cuocolo, Alberto; Nicolai, Emanuele; Aiello, Marco; Diomiaiuti, Claudio Tommaso; Pisani, Antonio

2015-01-01

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients. Thirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of 18 F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart. Six patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01). PET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted. (orig.)

Virtual reality for obsessive-compulsive disorder: past and the future.

Science.gov (United States)

Kim, Kwanguk; Kim, Chan-Hyung; Kim, So-Yeon; Roh, Daeyoung; Kim, Sun I

2009-09-01

The use of computers, especially for virtual reality (VR), to understand, assess, and treat various mental health problems has been developed for the last decade, including application for phobia, post-traumatic stress disorder, attention deficits, and schizophrenia. However, the number of VR tools addressing obsessive-compulsive disorder (OCD) is still lacking due to the heterogeneous symptoms of OCD and poor understanding of the relationship between VR and OCD. This article reviews the empirical literatures for VR tools in the future, which involve applications for both clinical work and experimental research in this area, including examining symptoms using VR according to OCD patients' individual symptoms, extending OCD research in the VR setting to also study behavioral and physiological correlations of the symptoms, and expanding the use of VR for OCD to cognitive-behavioral intervention.