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Sample records for comprehensive disease specific

  1. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Seonmi Park

    2017-04-01

    Full Text Available Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes, and fetal hemoglobin (HbF levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes and fetal hemoglobin (HbF levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

  2. A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Park, Seonmi; Gianotti-Sommer, Andreia; Molina-Estevez, Francisco Javier; Vanuytsel, Kim; Skvir, Nick; Leung, Amy; Rozelle, Sarah S; Shaikho, Elmutaz Mohammed; Weir, Isabelle; Jiang, Zhihua; Luo, Hong-Yuan; Chui, David H K; Figueiredo, Maria Stella; Alsultan, Abdulraham; Al-Ali, Amein; Sebastiani, Paola; Steinberg, Martin H; Mostoslavsky, Gustavo; Murphy, George J

    2017-04-11

    Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive diagnostic and organ-specific criteria.

    Science.gov (United States)

    Umehara, Hisanori; Okazaki, Kazuichi; Nakamura, Takuji; Satoh-Nakamura, Tomomi; Nakajima, Akio; Kawano, Mitsuhiro; Mimori, Tsuneyo; Chiba, Tsutomu

    2017-05-01

    IgG4-related disease (IgG4-RD) is a fascinating clinical entity proposed by Japanese investigators, and includes a wide variety of diseases, formerly diagnosed as Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis, retroperitoneal fibrosis, etc. Although all clinicians in every field of medicine may encounter this new disease, a unifying diagnostic criterion has not been established. In 2011, the Japanese IgG4 team, organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan, published comprehensive diagnostic criteria for IgG4-RD. Several problems with these criteria have arisen in clinical practice, however, including the difficulty obtaining biopsy samples from some patients, and the sensitivity and the specificity of techniques used to measure serum IgG4 concentrations. Although serum IgG4 concentration is an important clinical marker for IgG4-RD, its diagnostic utility in differentiating IgG4-RD from other diseases, called IgG4-RD mimickers, remains unclear. This review describes the current optimal approach for the diagnosis of IgG4-RD, based on both comprehensive and organ-specific diagnostic criteria, in patients with diseases such as IgG4-related pancreatitis (AIP), sclerosing cholangitis, and renal, lung and orbital diseases.

  4. Disease-Specific Care: Spine Surgery Program Development.

    Science.gov (United States)

    Koerner, Katie; Franker, Lauren; Douglas, Barbara; Medero, Edgardo; Bromeland, Jennifer

    2017-10-01

    Minimal literature exists describing the process for development of a Joint Commission comprehensive spine surgery program within a community hospital health system. Components of a comprehensive program include structured communication across care settings, preoperative education, quality outcomes tracking, and patient follow-up. Organizations obtaining disease-specific certification must have clear knowledge of the planning, time, and overall commitment, essential to developing a successful program. Health systems benefit from disease-specific certification because of their commitment to a higher standard of service. Certification standards establish a framework for organizational structure and management and provide institutions a competitive edge in the marketplace. A framework for the development of a spine surgery program is described to help guide organizations seeking disease-specific certification. In developing a comprehensive program, it is critical to define the program's mission and vision, identify key stakeholders, implement clinical practice guidelines, and evaluate program outcomes.

  5. Reading comprehension in Parkinson's disease.

    Science.gov (United States)

    Murray, Laura L; Rutledge, Stefanie

    2014-05-01

    Although individuals with Parkinson's disease (PD) self-report reading problems and experience difficulties in cognitive-linguistic functions that support discourse-level reading, prior research has primarily focused on sentence-level processing and auditory comprehension. Accordingly, the authors investigated the presence and nature of reading comprehension in PD, hypothesizing that (a) individuals with PD would display impaired accuracy and/or speed on reading comprehension tests and (b) reading performances would be correlated with cognitive test results. Eleven adults with PD and 9 age- and education-matched control participants completed tests that evaluated reading comprehension; general language and cognitive abilities; and aspects of attention, memory, and executive functioning. The PD group obtained significantly lower scores on several, but not all, reading comprehension, language, and cognitive measures. Memory, language, and disease severity were significantly correlated with reading comprehension for the PD group. Individuals in the early stages of PD without dementia or broad cognitive deficits can display reading comprehension difficulties, particularly for high- versus basic-level reading tasks. These reading difficulties are most closely related to memory, high-level language, and PD symptom severity status. The findings warrant additional research to delineate further the types and nature of reading comprehension impairments experienced by individuals with PD.

  6. Comprehension in grammatical sentences at the level of specificity and schematicity in Alzheimer’s disease: an analysis psycholinguistics and cognitive

    Directory of Open Access Journals (Sweden)

    Berla Moreira de Moraes

    2016-10-01

    Full Text Available The present research aimed at identifying if there is any compromisse regarding the comprehension in grammatical sentences at the level of specificity, through the self-paced reading technique, produced by people suffering from Alzheimer. With the objective of reaching our goals and finding answers to our hypotheses, one experiment was carried out to analyse: the time of reaction while reading the sentence, the time of reaction for reading the comprehension questions and choosing the best answer, and the score of right answers given by Young adults (YA and healthy old (HO taken as groups of control and the old with likely Alzheimer (OLA as case group, considering sentences: at the level of schematicity and specificity. 10 YA, 10 HO and 10 OLA took part in the experiments, totalling thirty participants. Results show that, when compared to the old without cognitive decline, people suffering from Alzheimer presente inferior performance in comprehending conventional imagery when it comes to the rate of right answers and the time of response. As the result of the experiment, in relation to the level of specificity, people with Alzheimer need more time to read and give answers before schematic sentences, in which is also noticed the highest rate of wrong anwers. The hypothesis that the comprehension of conventional imagery in gramatical sentences at the level of specificity, is affected since the early stages of the Alzheimer disease was confirmed. We believe that this is influenced by the progressive cognitive decline of the working memory, by the speed of processing, by the decision making and also by the spacial and temporal orientation.

  7. Hand Specific Representations in Language Comprehension

    Directory of Open Access Journals (Sweden)

    Claire eMoody-Triantis

    2014-06-01

    Full Text Available Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand is recruited in language comprehension and action execution. An fMRI study tested right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences - a dominant hand effect -. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  8. Hand specific representations in language comprehension.

    Science.gov (United States)

    Moody-Triantis, Claire; Humphreys, Gina F; Gennari, Silvia P

    2014-01-01

    Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand) is recruited in language comprehension and action execution. An fMRI study tested self-reported right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences-a dominant hand effect. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a) language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b) language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

  9. Proverb and idiom comprehension in Alzheimer disease.

    Science.gov (United States)

    Kempler, D; Van Lancker, D; Read, S

    1988-01-01

    Twenty-nine patients diagnosed with Probable Alzheimer Disease were administered tests of word, familiar phrases (idioms and proverbs), and novel phrase comprehension. From the early stage of the disease, patients performed worse at understanding familiar phrases than single words or novel phrases. The results uphold common observations that AD patients have difficulty interpreting abstract meanings. Cognitive variables responsible for poor idiom/proverb comprehension and the clinical implications of this new protocol are discussed.

  10. Investigating Patterns of Errors for Specific Comprehension and Fluency Difficulties

    Science.gov (United States)

    Koriakin, Taylor A.; Kaufman, Alan S.

    2017-01-01

    Although word reading has traditionally been viewed as a foundational skill for development of reading fluency and comprehension, some children demonstrate "specific" reading comprehension problems, in the context of intact word reading. The purpose of this study was to identify specific patterns of errors associated with reading…

  11. Overlapping genetic and child-specific nonshared environmental influences on listening comprehension, reading motivation, and reading comprehension.

    Science.gov (United States)

    Schenker, Victoria J; Petrill, Stephen A

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Overlapping Genetic and Child-Specific Nonshared Environmental Influences on Listening Comprehension, Reading Motivation, and Reading Comprehension

    Science.gov (United States)

    Schenker, Victoria J.; Petrill, Stephen A.

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. PMID:26321677

  13. A Comprehensive Review of Celiac Disease/Gluten-Sensitive Enteropathies.

    Science.gov (United States)

    McAllister, Brian P; Williams, Emmanuelle; Clarke, Kofi

    2018-06-02

    Celiac disease is a complex immune-mediated gluten-sensitive enteropathy with protean clinical manifestations. It is manifest in genetically predisposed individuals who ingest gluten in varying amounts. In broad terms, it is thought to affect 1% of the population in the USA. More specifically, the prevalence increases drastically from 1:133 in patients not-at-risk, to 1:56 in symptomatic patients, to 1:39 in patients with a second-degree relative with the diagnosis, and to 1:22 in patients with a first-degree relative with the diagnosis. It may be associated with several immune-mediated phenomena, autoimmune diseases, and complicated by vitamin and other trace element deficiencies, bone disease, and malignancy. Our understanding of celiac disease has evolved rapidly over the past two decades. This has led to several lines of enquiry on the condition and potential treatment options. More recently, several entities including gluten intolerance, non-celiac gluten sensitivity, and seronegative celiac disease have been described. These conditions are distinct from allergies or intolerance to wheat or wheat products. There are challenges in defining some of these entities since a large number of patients self-report these conditions. The absence of confirmatory diagnostic tests poses an added dilemma in distinguishing these entities. The differences in spectrum of symptoms and highlights of the variability between the pediatric and adult populations have been studied in some detail. The role of screening for celiac disease is examined in both the general population and "at risk" populations. Diagnostic strategies including the best available serologic testing, utility of HLA haplotypes DQ2 and DQ8 which are seen in over 90% of patients with celiac disease as compared with approximately 40% of the general population, and endoscopic evaluation are also reviewed. Comprehensive nutritional management after diagnosis is key to sustained health in patients with celiac disease

  14. Determination and Application of Comprehensive Specific Frictional Resistance in Heating Engineering

    Directory of Open Access Journals (Sweden)

    Yanan Tian

    2018-01-01

    Full Text Available In this study, we analyze the deficiencies of specific frictional resistance in heating engineering. Based on economic specific frictional resistance, we put forward the concept of comprehensive specific frictional resistance, which considers the multiple factors of technology, economy, regulation modes, pipe segment differences, and medium pressure. Then, we establish a mathematical model of a heating network across its lifespan in order to develop a method for determining the comprehensive specific frictional resistance. Relevant conclusions can be drawn from the results. As an application, we have planned the heating engineering for Yangyuan County in China, which demonstrates the feasibility and superiority of the method.

  15. A comprehensive questionnaire for the assessment of health-related quality of life in coeliac disease (CDQL).

    Science.gov (United States)

    Skjerning, Halfdan; Hourihane, Jonathan; Husby, Steffen; DunnGalvin, Audrey

    2017-10-01

    Coeliac disease (CD) is a chronic immune-mediated disease in genetically susceptible individuals, induced by ingested gluten. The treatment for CD is a lifelong gluten-free diet (GFD). The GFD involves restrictions in diet that may impact on a person's Health-Related Quality of Life (HRQoL). The aim of the present study was to develop the Coeliac Disease Quality of Life questionnaire (CDQL): a comprehensive CD-specific HRQoL measure that can be completed by children, adolescents, and adults or by proxy. The questionnaire was developed in three phases. In phase 1, focus group methods and qualitative analysis of verbatim transcripts generated CD-specific items for a prototype instrument to sensitively captured patient concerns. In phase 2, CD patients completed the prototype CDQL. The questionnaire was refined through analysis of data and cognitive interviewing. In phase 3, the final version of the CDQL was answered by Danish respondents. The psychometric properties of the CDQL were assessed, and the HRQoL data were analyzed. The CDQL was completed by 422 respondents. The CDQL has 12 patient background items, 2 generic HRQoL items, and 30 CD-specific HRQoL item. The CD-specific HRQoL items were distributed on eight scales with acceptable to excellent reliability. Comprehensiveness and understandability was shown by feedback from cognitive interviewing from children, adolescents, and adults. Content validity was ensured by involving patients and clinicians in the development of the questionnaire. Sensitivity of the questionnaire was demonstrated in differences found between children, adolescents, and adult's perception of their HRQoL in relation to having CD. The CDQL comprehensively measures HRQoL in CD, and is psychometrically robust. The questionnaire may prove useful in tracking HRQoL in CD across age groups.

  16. Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

    Science.gov (United States)

    Bose, Sumit; Ganesan, Chitra; Pant, Manish; Lai, Catherine; Tabbara, Imad A

    2013-02-01

    Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

  17. Aetiology-Specific Estimates of the Global and Regional Incidence and Mortality of Diarrhoeal Diseases Commonly Transmitted through Food

    DEFF Research Database (Denmark)

    Pires, Sara Monteiro; Fischer-Walker, Christa L; Lanata, Claudio F

    2015-01-01

    Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the gl...

  18. The Impact of Chronic Skin Disease on Daily Life (ISDL): a generic and dermatology-specific health instrument.

    NARCIS (Netherlands)

    Evers, A.W.M.; Duller, P.; Kerkhof, P.C.M. van de; Valk, P.G.M. van der; Jong, E.M.G.J. de; Gerritsen, M.J.P.; Otero, E.; Verhoeven, E.W.M.; Verhaak, C.M.; Kraaimaat, F.W.

    2008-01-01

    BACKGROUND: In dermatological research and clinical practice, there is a need for comprehensive self-report instruments that assess a broad spectrum of health implications of chronic skin diseases, including generic and skin-specific aspects of disease-related quality of life. The advantages of

  19. Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind.

    Science.gov (United States)

    Shany-Ur, Tal; Poorzand, Pardis; Grossman, Scott N; Growdon, Matthew E; Jang, Jung Y; Ketelle, Robin S; Miller, Bruce L; Rankin, Katherine P

    2012-01-01

    Comprehension of insincere communication is an important aspect of social cognition requiring visual perspective taking, emotion reading, and understanding others' thoughts, opinions, and intentions. Someone who is lying intends to hide their insincerity from the listener, while a sarcastic speaker wants the listener to recognize they are speaking insincerely. We investigated whether face-to-face testing of comprehending insincere communication would effectively discriminate among neurodegenerative disease patients with different patterns of real-life social deficits. We examined ability to comprehend lies and sarcasm from a third-person perspective, using contextual cues, in 102 patients with one of four neurodegenerative diseases (behavioral variant frontotemporal dementia [bvFTD], Alzheimer's disease [AD], progressive supranuclear palsy [PSP], and vascular cognitive impairment) and 77 healthy older adults (normal controls--NCs). Participants answered questions about videos depicting social interactions involving deceptive, sarcastic, or sincere speech using The Awareness of Social Inference Test. All subjects equally understood sincere remarks, but bvFTD patients displayed impaired comprehension of lies and sarcasm compared with NCs. In other groups, impairment was not disease-specific but was proportionate to general cognitive impairment. Analysis of the task components revealed that only bvFTD patients were impaired on perspective taking and emotion reading elements and that both bvFTD and PSP patients had impaired ability to represent others' opinions and intentions (i.e., theory of mind). Test performance correlated with informants' ratings of subjects' empathy, perspective taking and neuropsychiatric symptoms in everyday life. Comprehending insincere communication is complex and requires multiple cognitive and emotional processes vulnerable across neurodegenerative diseases. However, bvFTD patients show uniquely focal and severe impairments at every level

  20. How specific are specific comprehension difficulties?

    DEFF Research Database (Denmark)

    Rønberg, Louise Flensted-Jensen; Petersen, Dorthe Klint

    2016-01-01

    as measured on a phonological coding measure. However, the proportion was smaller than the often reported 10-15 % and even smaller when average sight word recognition was also set as a criterion for word reading ability. Compared to average comprehenders, the poor comprehenders’ sight word recognition......This study explores the occurrence of poor comprehenders, i.e., children identified with reading comprehension difficulties in spite of age-appropriate word reading skills. It supports the findings that some children do show poor reading comprehension in spite of age-appropriate word reading...... and daily reading of literary texts were significantly below that of average readers. This study indicates that a lack of reading experience and, likewise, a lack of fluent word reading may be important factors in understanding nine-year-old poor comprehenders’ difficulties....

  1. Use of Bloom's Taxonomy in Developing Reading Comprehension Specifications

    Science.gov (United States)

    Luebke, Stephen; Lorie, James

    2013-01-01

    This article is a brief account of the use of Bloom's Taxonomy of Educational Objectives (Bloom, Engelhart, Furst, Hill, & Krathwohl, 1956) by staff of the Law School Admission Council in the 1990 development of redesigned specifications for the Reading Comprehension section of the Law School Admission Test. Summary item statistics for the…

  2. CoViCAD : comprehensive visualization of coronary artery disease

    NARCIS (Netherlands)

    Temeer, M.; Olivan Bescos, J.; Breeuwer, M.; Vilanova, A.; Gerritsen, F.A.; Gröller, E.

    2007-01-01

    We present novel, comprehensive visualization techniques for the diagnosis of patients with Coronary Artery Disease using segmented cardiac MRI data. We extent an accepted medical visualization technique called the bull’s eye plot by removing discontinuities, preserving the volumetric nature of the

  3. Comprehensive molecular diagnosis of Epstein-Barr virus-associated lymphoproliferative diseases using next-generation sequencing.

    Science.gov (United States)

    Ono, Shintaro; Nakayama, Manabu; Kanegane, Hirokazu; Hoshino, Akihiro; Shimodera, Saeko; Shibata, Hirofumi; Fujino, Hisanori; Fujino, Takahiro; Yunomae, Yuta; Okano, Tsubasa; Yamashita, Motoi; Yasumi, Takahiro; Izawa, Kazushi; Takagi, Masatoshi; Imai, Kohsuke; Zhang, Kejian; Marsh, Rebecca; Picard, Capucine; Latour, Sylvain; Ohara, Osamu; Morio, Tomohiro

    2018-05-18

    Epstein-Barr virus (EBV) is associated with several life-threatening diseases, such as lymphoproliferative disease (LPD), particularly in immunocompromised hosts. Some categories of primary immunodeficiency diseases (PIDs) including X-linked lymphoproliferative syndrome (XLP), are characterized by susceptibility and vulnerability to EBV infection. The number of genetically defined PIDs is rapidly increasing, and clinical genetic testing plays an important role in establishing a definitive diagnosis. Whole-exome sequencing is performed for diagnosing rare genetic diseases, but is both expensive and time-consuming. Low-cost, high-throughput gene analysis systems are thus necessary. We developed a comprehensive molecular diagnostic method using a two-step tailed polymerase chain reaction (PCR) and a next-generation sequencing (NGS) platform to detect mutations in 23 candidate genes responsible for XLP or XLP-like diseases. Samples from 19 patients suspected of having EBV-associated LPD were used in this comprehensive molecular diagnosis. Causative gene mutations (involving PRF1 and SH2D1A) were detected in two of the 19 patients studied. This comprehensive diagnosis method effectively detected mutations in all coding exons of 23 genes with sufficient read numbers for each amplicon. This comprehensive molecular diagnostic method using PCR and NGS provides a rapid, accurate, low-cost diagnosis for patients with XLP or XLP-like diseases.

  4. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  5. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

    Directory of Open Access Journals (Sweden)

    Tobias Eisenberger

    Full Text Available Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs. Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

  6. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

    Science.gov (United States)

    Eisenberger, Tobias; Decker, Christian; Hiersche, Milan; Hamann, Ruben C; Decker, Eva; Neuber, Steffen; Frank, Valeska; Bolz, Hanno J; Fehrenbach, Henry; Pape, Lars; Toenshoff, Burkhard; Mache, Christoph; Latta, Kay; Bergmann, Carsten

    2015-01-01

    Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

  7. Disease specific knowledge about cystic fibrosis, patient education and counselling in Poland

    Directory of Open Access Journals (Sweden)

    Sławomir Chomik

    2014-06-01

    Full Text Available introduction and objective. The presented study assesses levels of specific knowledge of the disease among cystic fibrosis (CF patients and their families, and evaluates the effectiveness of a targeted, disease specific education programme. materials and methods. A cross-sectional survey among 462 families with a CF child evaluated their knowledge of the disease. A one year follow up survey among 200 families assessed the effectiveness of an educational programme developed to correct gaps, errors and misconceptions identified in the previously administered survey. Self-administered, comprehensive, 5-domains, 45-item multiple-choice CF Disease Knowledge Questionnaire (CFDKQ was anonymously completed by 462 subjects. results. 228 respondents were male (49%, 234 female (51%. The level of disease-specific knowledge in the age groups 0–6 and 7–10 years, was significantly higher than in 11–14 and 15–18 years of age groups (p<0.005. General medical and Genetics/Reproduction knowledge was low in all patients. Significant predictors of patient and parental knowledge were age and domicile. Patients and parents rely heavily on doctors for information about CF (77%. The follow-up survey (CFDKQ emphasized that special education programmes significantly improved levels of disease specific knowledge (p<0.0001. conclusions. If left uncorrected, the misconceptions, gaps and errors in CF knowledge identified in the presented study could result in inadvertent non-adherence to treatment, and impact on the progression and outcome of the disease. Secondly, the results demonstrate the effectiveness of targeted, disease specific information in improving disease knowledge of CF patients and their families, and highlights the value and need for the development of educational programmes for chronically ill patients and their families.

  8. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review

    Science.gov (United States)

    Background: Metabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and Results: We searched MEDLINE and EMBASE from inception to Janua...

  9. Can Consumers Trust Web-Based Information About Celiac Disease? Accuracy, Comprehensiveness, Transparency, and Readability of Information on the Internet

    Science.gov (United States)

    McNally, Shawna L; Donohue, Michael C; Newton, Kimberly P; Ogletree, Sandra P; Conner, Kristen K; Ingegneri, Sarah E

    2012-01-01

    Background Celiac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content. Objectives To determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease. Methods Using the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality. Results We included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of

  10. Can consumers trust web-based information about celiac disease? Accuracy, comprehensiveness, transparency, and readability of information on the internet.

    Science.gov (United States)

    McNally, Shawna L; Donohue, Michael C; Newton, Kimberly P; Ogletree, Sandra P; Conner, Kristen K; Ingegneri, Sarah E; Kagnoff, Martin F

    2012-04-04

    Celiac disease is an autoimmune disease that affects approximately 1% of the US population. Disease is characterized by damage to the small intestinal lining and malabsorption of nutrients. Celiac disease is activated in genetically susceptible individuals by dietary exposure to gluten in wheat and gluten-like proteins in rye and barley. Symptoms are diverse and include gastrointestinal and extraintestinal manifestations. Treatment requires strict adherence to a gluten-free diet. The Internet is a major source of health information about celiac disease. Nonetheless, information about celiac disease that is available on various websites often is questioned by patients and other health care professionals regarding its reliability and content. To determine the accuracy, comprehensiveness, transparency, and readability of information on 100 of the most widely accessed websites that provide information on celiac disease. Using the search term celiac disease, we analyzed 100 of the top English-language websites published by academic, commercial, nonprofit, and other professional (nonacademic) sources for accuracy, comprehensiveness, transparency, and reading grade level. Each site was assessed independently by 3 reviewers. Website accuracy and comprehensiveness were probed independently using a set of objective core information about celiac disease. We used 19 general criteria to assess website transparency. Website readability was determined by the Flesch-Kincaid reading grade level. Results for each parameter were analyzed independently. In addition, we weighted and combined parameters to generate an overall score, termed website quality. We included 98 websites in the final analysis. Of these, 47 (48%) provided specific information about celiac disease that was less than 95% accurate (ie, the predetermined cut-off considered a minimum acceptable level of accuracy). Independent of whether the information posted was accurate, 51 of 98 (52%) websites contained less than

  11. A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration

    OpenAIRE

    Rivera, Andrea; White, Karen; Stöhr, Heidi; Steiner, Klaus; Hemmrich, Nadine; Grimm, Timo; Jurklies, Bernhard; Lorenz, Birgit; Scholl, Hendrik P. N.; Apfelstedt-Sylla, Eckhart; Weber, Bernhard H. F.

    2000-01-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in ...

  12. Subordinate clause comprehension and tense/agreement inconsistency in children with specific language impairment.

    Science.gov (United States)

    Souto, Sofía M; Leonard, Laurence B; Deevy, Patricia; Fey, Marc E; Bredin-Oja, Shelley L

    2016-01-01

    Several recent studies have suggested that the production errors of children with specific language impairment (SLI) such as The girl singing may be explained by a misinterpretation of grammatical adult input containing a similar structure (e.g., The boy hears the girl singing). Thirteen children with SLI and 13 younger typically developing children with comparable sentence comprehension test scores (TD-COMP) completed a comprehension task to assess their understanding of sentences involving a nonfinite subject-verb sequence in a subordinate clause such as The dad sees the boy running. TD-COMP children were more accurate on subordinate clause items than children with SLI despite similar performance on simple transitive (e.g., The horse sees the cow) and simple progressive (e.g., The cow is eating) items. However, no relationship was found between the SLI group's specific subordinate clause comprehension level and their specific level of auxiliary is production, casting some doubt on this type of structure as a source for inconsistent use of auxiliary is. The reader will learn that children with specific language impairment (SLI): (1) have difficulty understanding complex sentences that include nonfinite subject-verb sequences; (2) that this difficulty is apparent in comparison to younger typically developing peers who have similar scores not only on a sentence comprehension test, but also on simple sentences that correspond to the component parts of the complex sentences; and (3) that this weakness is concurrent with these children's inconsistent use of auxiliary is in production. Although novel verb studies show a clear connection between how children with SLI hear new verbs and how they use them, we do not yet have evidence that this connection is tied to a poor understanding of the input sentences that house the verbs. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A comprehensive outlook of Sannipata

    Science.gov (United States)

    Panja, Asit K; Chattopadhyaya, Abichal; Chaudhuri, Supriyo

    2011-01-01

    Nomenclature of the disease on the basis of vitiation of the body humors is stressed in ayurveda. Sannipatika, i.e., ‘conglomeration of vitiated tridosa’ is the final stage of process of manifestation of disease. In this specific state of pathogenesis, the disease becomes more advance and mostly irreversible. A detailed scientific study of Sannipatika-avastha has been documented in classics. Comprehensive analysis of sannipata-state and its ways of presentation is the main theme of the current article. PMID:22408295

  14. Comprehensive Care

    Science.gov (United States)

    ... Comprehensive Care Share this page Facebook Twitter Email Comprehensive Care Understand the importance of comprehensive MS care ... In this article A complex disease requires a comprehensive approach Today multiple sclerosis (MS) is not a ...

  15. Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

    Science.gov (United States)

    Papagno, C

    2001-07-01

    Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

  16. Comprehensive analysis of the specificity of transcription activator-like effector nucleases

    DEFF Research Database (Denmark)

    Juillerat, Alexandre; Dubois, Gwendoline; Valton, Julien

    2014-01-01

    A key issue when designing and using DNA-targeting nucleases is specificity. Ideally, an optimal DNA-targeting tool has only one recognition site within a genomic sequence. In practice, however, almost all designer nucleases available today can accommodate one to several mutations within...... their target site. The ability to predict the specificity of targeting is thus highly desirable. Here, we describe the first comprehensive experimental study focused on the specificity of the four commonly used repeat variable diresidues (RVDs; NI:A, HD:C, NN:G and NG:T) incorporated in transcription activator......-like effector nucleases (TALEN). The analysis of >15 500 unique TALEN/DNA cleavage profiles allowed us to monitor the specificity gradient of the RVDs along a TALEN/DNA binding array and to present a specificity scoring matrix for RVD/nucleotide association. Furthermore, we report that TALEN can only...

  17. Complex Sentence Comprehension and Working Memory in Children with Specific Language Impairment

    Science.gov (United States)

    Montgomery, James W.; Evans, Julia L.

    2009-01-01

    Purpose: This study investigated the association of 2 mechanisms of working memory (phonological short-term memory [PSTM], attentional resource capacity/allocation) with the sentence comprehension of school-age children with specific language impairment (SLI) and 2 groups of control children. Method: Twenty-four children with SLI, 18 age-matched…

  18. Disease specific protein corona

    Science.gov (United States)

    Rahman, M.; Mahmoudi, M.

    2015-03-01

    It is now well accepted that upon their entrance into the biological environments, the surface of nanomaterials would be covered by various biomacromolecules (e.g., proteins and lipids). The absorption of these biomolecules, so called `protein corona', onto the surface of (nano)biomaterials confers them a new `biological identity'. Although the formation of protein coronas on the surface of nanoparticles has been widely investigated, there are few reports on the effect of various diseases on the biological identity of nanoparticles. As the type of diseases may tremendously changes the composition of the protein source (e.g., human plasma/serum), one can expect that amount and composition of associated proteins in the corona composition may be varied, in disease type manner. Here, we show that corona coated silica and polystyrene nanoparticles (after interaction with in the plasma of the healthy individuals) could induce unfolding of fibrinogen, which promotes release of the inflammatory cytokines. However, no considerable releases of inflammatory cytokines were observed for corona coated graphene sheets. In contrast, the obtained corona coated silica and polystyrene nanoparticles from the hypofibrinogenemia patients could not induce inflammatory cytokine release where graphene sheets do. Therefore, one can expect that disease-specific protein coronas can provide a novel approach for applying nanomedicine to personalized medicine, improving diagnosis and treatment of different diseases tailored to the specific conditions and circumstances.

  19. Comprehension of Spacecraft Telemetry Using Hierarchical Specifications of Behavior

    Science.gov (United States)

    Havelund, Klaus; Joshi, Rajeev

    2014-01-01

    A key challenge in operating remote spacecraft is that ground operators must rely on the limited visibility available through spacecraft telemetry in order to assess spacecraft health and operational status. We describe a tool for processing spacecraft telemetry that allows ground operators to impose structure on received telemetry in order to achieve a better comprehension of system state. A key element of our approach is the design of a domain-specific language that allows operators to express models of expected system behavior using partial specifications. The language allows behavior specifications with data fields, similar to other recent runtime verification systems. What is notable about our approach is the ability to develop hierarchical specifications of behavior. The language is implemented as an internal DSL in the Scala programming language that synthesizes rules from patterns of specification behavior. The rules are automatically applied to received telemetry and the inferred behaviors are available to ground operators using a visualization interface that makes it easier to understand and track spacecraft state. We describe initial results from applying our tool to telemetry received from the Curiosity rover currently roving the surface of Mars, where the visualizations are being used to trend subsystem behaviors, in order to identify potential problems before they happen. However, the technology is completely general and can be applied to any system that generates telemetry such as event logs.

  20. Borrelia burgdorferi-specific IgA in Lyme Disease

    Directory of Open Access Journals (Sweden)

    Christina D'Arco

    2017-05-01

    Full Text Available The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223-modVlsE(275-291, a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8% from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease.

  1. Borrelia burgdorferi-specific IgA in Lyme Disease.

    Science.gov (United States)

    D'Arco, Christina; Dattwyler, Raymond J; Arnaboldi, Paul M

    2017-05-01

    The laboratory diagnosis of Lyme disease is currently dependent on the detection of IgM and IgG antibodies against Borrelia burgdorferi, the causative agent of the disease. The significance of serum IgA against B. burgdorferi remains unclear. The production of intrathecal IgA has been noted in patients with the late Lyme disease manifestation, neuroborreliosis, but production of antigen-specific IgA during early disease has not been evaluated. In the current study, we assessed serum IgA binding to the B. burgdorferi peptide antigens, C6, the target of the FDA-cleared C6 EIA, and FlaB(211-223)-modVlsE(275-291), a peptide containing a Borrelia flagellin epitope linked to a modified VlsE sequence, in patients with early and late Lyme disease. Specific IgA was detected in 59 of 152 serum samples (38.8%) from early Lyme disease patients. Approximately 50% of early Lyme disease patients who were seropositive for peptide-specific IgM and/or IgG were also seropositive for peptide-specific IgA. In a subpopulation of patients, high peptide-specific IgA could be correlated with disseminated disease, defined as multiple erythema migrans lesions, and neurological disease complications. These results suggest that there may be an association between elevated levels of antigen-specific IgA and particular disease manifestations in some patients with early Lyme disease. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. A new method for discovering disease-specific MiRNA-target regulatory networks.

    Directory of Open Access Journals (Sweden)

    Miriam Baglioni

    Full Text Available Genes and their expression regulation are among the key factors in the comprehension of the genesis and development of complex diseases. In this context, microRNAs (miRNAs are post-transcriptional regulators that play an important role in gene expression since they are frequently deregulated in pathologies like cardiovascular disease and cancer. In vitro validation of miRNA--targets regulation is often too expensive and time consuming to be carried out for every possible alternative. As a result, a tool able to provide some criteria to prioritize trials is becoming a pressing need. Moreover, before planning in vitro experiments, the scientist needs to evaluate the miRNA-target genes interaction network. In this paper we describe the miRable method whose purpose is to identify new potentially relevant genes and their interaction networks associate to a specific pathology. To achieve this goal miRable follows a system biology approach integrating together general-purpose medical knowledge (literature, Protein-Protein Interaction networks, prediction tools and pathology specific data (gene expression data. A case study on Prostate Cancer has shown that miRable is able to: 1 find new potential miRNA-targets pairs, 2 highlight novel genes potentially involved in a disease but never or little studied before, 3 reconstruct all possible regulatory subnetworks starting from the literature to expand the knowledge on the regulation of miRNA regulatory mechanisms.

  3. Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Lynne V. McFarland

    2018-05-01

    Full Text Available BackgroundAs the use and diversity of probiotic products expands, the choice of an appropriate type of probiotic is challenging for both medical care professionals and the public alike. Two vital factors in choosing the appropriate probiotic are often ignored, namely, the probiotic strain-specificity and disease-specificity for efficacy. Reviews and meta-analyses often pool together different types of probiotics, resulting in misleading conclusions of efficacy.MethodsA systematic review of the literature (1970–2017 assessing strain-specific and disease-specific probiotic efficacy was conducted. Trials were included for probiotics with an identifiable strain (either single strain or mixtures of strains that had at least two randomized, controlled trials for each type of disease indication. The goal was to determine if probiotic strains have strain and/or disease-specific efficacy.ResultsWe included 228 trials and found evidence for both strain specificity and disease specificity for the efficacy of specific probiotic strains. Significant efficacy evidence was found for 7 (70% of probiotic strain(s among four preventive indications and 11 (65% probiotic strain(s among five treatment indications. Strain-specific efficacy for preventing adult antibiotic-associated diarrhea was clearly demonstrated within the Lactobacillus species [e.g., by the mixture of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2 (Bio-K+®, by L. casei DN114001 (Actimel® and by Lactobacillus reuteri 55730], while other Lactobacillus strains did not show efficacy. Significant disease-specific variations in efficacy was demonstrated by L. rhamnosus GG and Saccharomyces boulardii CNCM I-745, as well as other probiotic strains.ConclusionStrong evidence was found supporting the hypothesis that the efficacy of probiotics is both strain-specific and disease-specific. Clinical guidelines and meta-analyses need to recognize the

  4. [Evaluation on intervention measures of comprehensive control for parasitic diseases in demonstration plot of Xiangyun County].

    Science.gov (United States)

    Wen-Juan, Li; Shao-Rong, Chen; Yan-Hong, Li; Wen, Fang; Chun-Rong, Ke; Li-Bo, Wang

    2011-10-01

    To evaluate the effect of comprehensive intervention measures to control and prevent parasitic diseases in the demonstration plot of Xiangyun County, so as to provide the evidence for establishing appropriate measures of parasitic diseases control and prevention. The baseline data of soil-transmitted nematode infections were obtained in 2006. A series of intervention measures, including health education, deworming, drinking water improvement,latrine improvement, and environment reconstruction, were performed for three years and the effect of the comprehensive intervention measures was evaluated by the national expert group in 2009. The awareness rate of parasitic disease knowledge of residents in 2009 (86.96%) was significantly higher than that in 2006 (35.20%) (Chi2 = 122.95, P transmitted nematode infections, the infection rates of Ascaris lumbricoides in both 2006 and 2009 were the highest and the rates were 18.74% and 2.08%, respectively. In the demonstration plots for parasitic diseases control and prevention of Xiangyun County, the effect of the comprehensive intervention measures which take health education as the forerunner and give priority to control source of parasite infection is remarkable. The measures implemented can achieve the purpose to reduce the infection rates of parasites and improve human health.

  5. Framework for Infectious Disease Analysis: A comprehensive and integrative multi-modeling approach to disease prediction and management.

    Science.gov (United States)

    Erraguntla, Madhav; Zapletal, Josef; Lawley, Mark

    2017-12-01

    The impact of infectious disease on human populations is a function of many factors including environmental conditions, vector dynamics, transmission mechanics, social and cultural behaviors, and public policy. A comprehensive framework for disease management must fully connect the complete disease lifecycle, including emergence from reservoir populations, zoonotic vector transmission, and impact on human societies. The Framework for Infectious Disease Analysis is a software environment and conceptual architecture for data integration, situational awareness, visualization, prediction, and intervention assessment. Framework for Infectious Disease Analysis automatically collects biosurveillance data using natural language processing, integrates structured and unstructured data from multiple sources, applies advanced machine learning, and uses multi-modeling for analyzing disease dynamics and testing interventions in complex, heterogeneous populations. In the illustrative case studies, natural language processing from social media, news feeds, and websites was used for information extraction, biosurveillance, and situation awareness. Classification machine learning algorithms (support vector machines, random forests, and boosting) were used for disease predictions.

  6. Eosinophils from Physiology to Disease: A Comprehensive Review

    Science.gov (United States)

    Yacoub, Mona-Rita; Ripa, Marco; Mannina, Daniele; Cariddi, Adriana; Saporiti, Nicoletta; Ciceri, Fabio; Castagna, Antonella; Dagna, Lorenzo

    2018-01-01

    Despite being the second least represented granulocyte subpopulation in the circulating blood, eosinophils are receiving a growing interest from the scientific community, due to their complex pathophysiological role in a broad range of local and systemic inflammatory diseases as well as in cancer and thrombosis. Eosinophils are crucial for the control of parasitic infections, but increasing evidence suggests that they are also involved in vital defensive tasks against bacterial and viral pathogens including HIV. On the other side of the coin, eosinophil potential to provide a strong defensive response against invading microbes through the release of a large array of compounds can prove toxic to the host tissues and dysregulate haemostasis. Increasing knowledge of eosinophil biological behaviour is leading to major changes in established paradigms for the classification and diagnosis of several allergic and autoimmune diseases and has paved the way to a “golden age” of eosinophil-targeted agents. In this review, we provide a comprehensive update on the pathophysiological role of eosinophils in host defence, inflammation, and cancer and discuss potential clinical implications in light of recent therapeutic advances. PMID:29619379

  7. 78 FR 8535 - Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement

    Science.gov (United States)

    2013-02-06

    ... develop and test innovative health care payment and service delivery models that show promise of reducing... test innovative payment and service delivery models that reduce spending under Medicare, Medicaid or...] Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement AGENCY: Centers for...

  8. Working memory and sentence comprehension of Hong Kong Chinese children with specific language impairment.

    Science.gov (United States)

    Siu, Elaine; Man, David W K

    2006-09-01

    Children with Specific Language Impairment present with delayed language development, but do not have a history of hearing impairment, mental deficiency, or associated social or behavioral problems. Non-word repetition was suggested as an index to reflect the capacity of phonological working memory. There is a paucity of such studies among Hong Kong Chinese children. This preliminary study aimed to examine the relationship between phonological working memory and Specific Language Impairment, through the processes of non-word repetition and sentence comprehension, of children with Specific Language Impairment and pre-school children with normal language development. Both groups of children were screened by a standardized language test. A list of Cantonese (the commonest dialect used in Hong Kong) multisyllabic nonsense utterances and a set of 18 sentences were developed for this study. t-tests and Pearson correlation were used to study the relationship between non-word repetition, working memory and specific language impairment. Twenty-three pre-school children with Specific Language Impairment (mean age = 68.30 months; SD = 6.90) and another 23 pre-school children (mean age = 67.30 months; SD = 6.16) participated in the study. Significant difference performance was found between the Specific Language Impairment group and normal language group in the multisyllabic nonsense utterances repetition task and the sentence comprehension task. Length effect was noted in Specific Language Impairment group children, which is consistent with the findings of other literature. In addition, correlations were also observed between the number of nonsense utterances repeated and the number of elements comprehended. Cantonese multisyllabic nonsense utterances might be worth further developing as a screening tool for the early detection of children with Specific Language Impairment.

  9. Syntactic comprehension and working memory in children with specific language impairment, autism or Down syndrome.

    Science.gov (United States)

    Fortunato-Tavares, Talita; Andrade, Claudia R F; Befi-Lopes, Debora; Limongi, Suelly O; Fernandes, Fernanda D M; Schwartz, Richard G

    2015-07-01

    This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.

  10. Role of Working Memory in Explaining the Performance of Individuals with Specific Reading Comprehension Difficulties: A Meta-Analysis

    Science.gov (United States)

    Carretti, Barbara; Borella, Erika; Cornoldi, Cesare; De Beni, Rossana

    2009-01-01

    It is well established that working memory is related to reading comprehension ability. However, its role in explaining specific reading comprehension difficulties is still under debate: the issue mainly concerns whether the contribution of working memory is dependent on task modality (verbal tasks being more predictive than visuo-spatial tasks)…

  11. Disease-specific self-efficacy in spasmodic dysphonia patients.

    Science.gov (United States)

    Hu, Amanda; Isetti, Derek; Hillel, Allen D; Waugh, Patricia; Comstock, Bryan; Meyer, Tanya K

    2013-03-01

    Self-efficacy (SE) is an optimistic self-belief that one can perform a novel task. This concept involves empowerment, self-esteem, and adaptation to a stressful situation. SE is a strong predictor of health behaviors. Our objectives were to study SE in spasmodic dysphonia (SD) and to develop a disease-specific SE-SD scale. Prospective study. Academic hospital. Disease-specific SE-SD items were developed with laryngologists, speech pathologists, and SD patients. These items, General SE Scale, Voice Handicap Index-10 (VHI-10), Consensus Auditory Perceptual Evaluation of Voice (CAPE-V), and Hospital Anxiety and Depression Scale (HADS), were administered to SD patients who presented for botulinum toxin injections. One hundred forty-five SD patients (mean age 59.5 ± 13.6 years) had a general SE score (Cronbach's α = 0.894) of 33.4 ± 5.2 out of 40. This was negatively correlated with HADS-A (r = -0.42, P < 0.001) and HADS-D (r = -0.42, P < .001), but not correlated with VHI-10 (r = -0.098, P = .243) and CAPE-V (r = -0.047, P = .57). Factor analysis selected 8 items from the general SE scale and 5 disease-specific SE-SD items to generate a 13-item disease-specific SE-SD scale (Cronbach's α = 0.907). Disease-specific SE-SD score was 42.1 ± 6.9 out of 52 and was negatively correlated with VHI-10 (r = -0.19, P = .005), HADS-A (r = -0.43, P < .001), and HADS-D (r = -0.57, P < .001), but not correlated with CAPE-V (r = -0.024, P = .60). SD patients established on botulinum toxin injections have high degrees of general and disease-specific SE. Patients with higher SE-SD demonstrate lower vocal handicap and lower levels of anxiety and depression. A 13-item disease-specific SE-SD scale has been developed.

  12. Specific Reading Comprehension Disability: Major Problem, Myth, or Misnomer?

    OpenAIRE

    Spencer, Mercedes; Quinn, Jamie M.; Wagner, Richard K.

    2014-01-01

    The goal of the present study was to test three competing hypotheses about the nature of comprehension problems of students who are poor in reading comprehension. Participants in the study were first, second, and third graders, totaling 9 cohorts and over 425,000 participants in all. The pattern of results was consistent across all cohorts: Less than one percent of first- through third-grade students who scored as poor in reading comprehension were adequate in both decoding and vocabulary. Al...

  13. Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

    Science.gov (United States)

    Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

    2017-12-01

    Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

  14. Using Pupillometry to Investigate Sentence Comprehension in Children with and without Specific Language Impairment

    Science.gov (United States)

    Lum, Jarrad A. G.; Youssef, George J.; Clark, Gillian M.

    2017-01-01

    Purpose: In this study pupillometry was used to investigate the allocation of attentional resources associated with sentence comprehension in children with and without specific language impairment (SLI). Method: Eighteen children with SLI (age: M = 6.4 years) and 18 typically developing (TD) children (age: M = 6.3 years) participated in the study.…

  15. Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery.

    Science.gov (United States)

    Jang, Jiho; Yoo, Jeong-Eun; Lee, Jeong-Ah; Lee, Dongjin R; Kim, Ji Young; Huh, Yong Jun; Kim, Dae-Sung; Park, Chul-Yong; Hwang, Dong-Youn; Kim, Han-Soo; Kang, Hoon-Chul; Kim, Dong-Wook

    2012-03-31

    The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

  16. Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

    Directory of Open Access Journals (Sweden)

    Wan Li

    Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

  17. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016 : a systematic analysis for the Global Burden of Disease Study 2016

    NARCIS (Netherlands)

    Hoek, H. W.; van Boven, Job; Postma, Maarten

    2017-01-01

    BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations

  18. Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease.

    NARCIS (Netherlands)

    Monninkhof, E.M.; Valk, P.D.L.P.M. van der; Palen, J.A.M. van der; Herwaarden, C.L.A. van; Zielhuis, G.A.

    2003-01-01

    The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD

  19. The discovery of how gender influences age immunological mechanisms in health and disease, and the identification of ageing gender-specific biomarkers, could lead to specifically tailored treatment and ultimately improve therapeutic success rates

    Directory of Open Access Journals (Sweden)

    Berghella Anna

    2012-11-01

    Full Text Available Abstract The control of human health and diseases in the elderly population is becoming a challenge, since mean age and life expectation are progressively increasing as well as chronic degenerative diseases. These disorders are of complex diagnosis and they are difficult to be treated, but it is hoped that the predictive medicine will lead to more specific and effective treatment by using specific markers to identify persons with high risk of developing disease, before the clinical manifestation. Peripheral blood targets and biomarkers are currently the most practical, non-invasive means of disease diagnosing, predicting prognosis and therapeutic response. Human longevity is directly correlated with the optimal functioning of the immune system. Recent findings indicate that the sexual dimorphism of T helper (Th cytokine pathways and the regulation of Th cell network homeostasis are normally present in the immune response and undergoes to adverse changes with ageing. Furthermore, immune senescence affects both men and women, but it does not affect them equally. Therefore, we hypothesize that the comprehension of the interferences between these gender specific pathways, the ageing immunological mechanism in pathological or healthy state and the current therapies, could lead to specifically tailored treatment and eventually improve the therapeutic success rates. Reaching this aim requires the identification of ageing gender-specific biomarkers that could easily reveal the above mentioned correlations.

  20. Specific Reading Comprehension Disability: Major Problem, Myth, or Misnomer?

    Science.gov (United States)

    Spencer, Mercedes; Quinn, Jamie M.; Wagner, Richard K.

    2014-01-01

    The goal of the present study was to test three competing hypotheses about the nature of comprehension problems of students who are poor in reading comprehension. Participants in the study were first, second, and third graders, totaling nine cohorts and over 425,000 participants in all. The pattern of results was consistent across all cohorts:…

  1. Validation of Ion TorrentTM Inherited Disease Panel with the PGMTM Sequencing Platform for Rapid and Comprehensive Mutation Detection

    Directory of Open Access Journals (Sweden)

    Abeer E. Mustafa

    2018-05-01

    Full Text Available Quick and accurate molecular testing is necessary for the better management of many inherited diseases. Recent technological advances in various next generation sequencing (NGS platforms, such as target panel-based sequencing, has enabled comprehensive, quick, and precise interrogation of many genetic variations. As a result, these technologies have become a valuable tool for gene discovery and for clinical diagnostics. The AmpliSeq Inherited Disease Panel (IDP consists of 328 genes underlying more than 700 inherited diseases. Here, we aimed to assess the performance of the IDP as a sensitive and rapid comprehensive gene panel testing. A total of 88 patients with inherited diseases and causal mutations that were previously identified by Sanger sequencing were randomly selected for assessing the performance of the IDP. The IDP successfully detected 93.1% of the mutations in our validation cohort, achieving high overall gene coverage (98%. The sensitivity for detecting single nucleotide variants (SNVs and short Indels was 97.3% and 69.2%, respectively. IDP, when coupled with Ion Torrent Personal Genome Machine (PGM, delivers comprehensive and rapid sequencing for genes that are responsible for various inherited diseases. Our validation results suggest the suitability of this panel for use as a first-line screening test after applying the necessary clinical validation.

  2. [Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

    Science.gov (United States)

    Zhang, J; Jin, R R; Li, J J; Li, J L; Su, X W; Deng, G J; Ma, S; Zhao, J; Wang, Y P; Bian, F; Qu, Y M; Shen, Z Z; Jiang, Y; Liu, Y L

    2018-04-10

    Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention ( OR =6.591, 95% CI : 5.188-8.373), salt reduction ( OR =1.352, 95% CI : 1.151-1.589), oil reduction ( OR =1.477, 95% CI : 1.249-1.746) and recommendation on physical activities ( OR =1.975, 95% CI : 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local

  3. Can the EVIDEM Framework Tackle Issues Raised by Evaluating Treatments for Rare Diseases: Analysis of Issues and Policies, and Context-Specific Adaptation.

    Science.gov (United States)

    Wagner, Monika; Khoury, Hanane; Willet, Jacob; Rindress, Donna; Goetghebeur, Mireille

    2016-03-01

    The multiplicity of issues, including uncertainty and ethical dilemmas, and policies involved in appraising interventions for rare diseases suggests that multicriteria decision analysis (MCDA) based on a holistic definition of value is uniquely suited for this purpose. The objective of this study was to analyze and further develop a comprehensive MCDA framework (EVIDEM) to address rare disease issues and policies, while maintaining its applicability across disease areas. Specific issues and policies for rare diseases were identified through literature review. Ethical and methodological foundations of the EVIDEM framework v3.0 were systematically analyzed from the perspective of these issues, and policies and modifications of the framework were performed accordingly to ensure their integration. Analysis showed that the framework integrates ethical dilemmas and issues inherent to appraising interventions for rare diseases but required further integration of specific aspects. Modification thus included the addition of subcriteria to further differentiate disease severity, disease-specific treatment outcomes, and economic consequences of interventions for rare diseases. Scoring scales were further developed to include negative scales for all comparative criteria. A methodology was established to incorporate context-specific population priorities and policies, such as those for rare diseases, into the quantitative part of the framework. This design allows making more explicit trade-offs between competing ethical positions of fairness (prioritization of those who are worst off), the goal of benefiting as many people as possible, the imperative to help, and wise use of knowledge and resources. It also allows addressing variability in institutional policies regarding prioritization of specific disease areas, in addition to existing uncertainty analysis available from EVIDEM. The adapted framework measures value in its widest sense, while being responsive to rare disease

  4. Generic and disease-specific measures of quality of life in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Bhattacharya, Sumangala; Vogel, A.; Hansen, M.L.

    2010-01-01

    The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD).......The aim of the study was to investigate the pattern of association of generic and disease-specific quality of life (QoL) scales with standard clinical outcome variables in Alzheimer's disease (AD)....

  5. Comprehensive evaluation of disease- and trait-specific enrichment for eight functional elements among GWAS-identified variants.

    Science.gov (United States)

    Markunas, Christina A; Johnson, Eric O; Hancock, Dana B

    2017-07-01

    Genome-wide association study (GWAS)-identified variants are enriched for functional elements. However, we have limited knowledge of how functional enrichment may differ by disease/trait and tissue type. We tested a broad set of eight functional elements for enrichment among GWAS-identified SNPs (p Enrichment analyses were conducted using logistic regression, with Bonferroni correction. Overall, a significant enrichment was observed for all functional elements, except sequence motifs. Missense SNPs showed the strongest magnitude of enrichment. eQTLs were the only functional element significantly enriched across all diseases/traits. Magnitudes of enrichment were generally similar across diseases/traits, where enrichment was statistically significant. Blood vs. brain tissue effects on enrichment were dependent on disease/trait and functional element (e.g., cardiovascular disease: eQTLs P TissueDifference  = 1.28 × 10 -6 vs. enhancers P TissueDifference  = 0.94). Identifying disease/trait-relevant functional elements and tissue types could provide new insight into the underlying biology, by guiding a priori GWAS analyses (e.g., brain enhancer elements for psychiatric disease) or facilitating post hoc interpretation.

  6. Exploring the potential relevance of human-specific genes to complex disease

    Directory of Open Access Journals (Sweden)

    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  7. The specific role of inhibition in reading comprehension in good and poor comprehenders.

    Science.gov (United States)

    Borella, Erika; Carretti, Barbara; Pelegrina, Santiago

    2010-01-01

    Difficulties in inhibitory processes have been shown to characterize the performance of poor comprehenders. However, the inhibitory inefficiency of poor comprehenders is most often assessed by their resistance to proactive interference, that is, the ability to suppress off-goal task information from working memory (WM). In two studies tasks assessing resistance to proactive interference (intrusion errors), response to distracters (Text With Distracters task) and prepotent response inhibition (Stroop and Hayling tests), along with WM measures, were administered to children aged 10 to 11, both good and poor comprehenders. The aim of the study was to specifically determine whether general or specific inhibitory factors affect poor comprehenders' reading difficulties. Results showed that poor comprehenders, compared to good ones, are impaired in WM tasks and in inhibitory tasks that assess resistance to proactive interference. This suggests that reading comprehension difficulties of poor comprehenders are related to specific inhibitory problems.

  8. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

    2000-10-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

  9. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    Science.gov (United States)

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  10. High throughput protease profiling comprehensively defines active site specificity for thrombin and ADAMTS13.

    Science.gov (United States)

    Kretz, Colin A; Tomberg, Kärt; Van Esbroeck, Alexander; Yee, Andrew; Ginsburg, David

    2018-02-12

    We have combined random 6 amino acid substrate phage display with high throughput sequencing to comprehensively define the active site specificity of the serine protease thrombin and the metalloprotease ADAMTS13. The substrate motif for thrombin was determined by >6,700 cleaved peptides, and was highly concordant with previous studies. In contrast, ADAMTS13 cleaved only 96 peptides (out of >10 7 sequences), with no apparent consensus motif. However, when the hexapeptide library was substituted into the P3-P3' interval of VWF73, an exosite-engaging substrate of ADAMTS13, 1670 unique peptides were cleaved. ADAMTS13 exhibited a general preference for aliphatic amino acids throughout the P3-P3' interval, except at P2 where Arg was tolerated. The cleaved peptides assembled into a motif dominated by P3 Leu, and bulky aliphatic residues at P1 and P1'. Overall, the P3-P2' amino acid sequence of von Willebrand Factor appears optimally evolved for ADAMTS13 recognition. These data confirm the critical role of exosite engagement for substrates to gain access to the active site of ADAMTS13, and define the substrate recognition motif for ADAMTS13. Combining substrate phage display with high throughput sequencing is a powerful approach for comprehensively defining the active site specificity of proteases.

  11. Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific patterns?

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Brynskov, Jørn; Hegedüs, Laszlo

    2007-01-01

    ) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant...

  12. The Effect of Neuro-Linguistic Programming (NLP) on Reading Comprehension in English for Specific Purposes Courses

    Science.gov (United States)

    Farahani, Fahimeh

    2018-01-01

    Neuro-Linguistic Programming (NLP) has potential to help language learners; however, it has received scant attention. The present study was an attempt to investigate the effect of NLP techniques on reading comprehension of English as a Foreign Language (EFL) learners at an English for Specific Purposes (ESP) course. To achieve this goal, two…

  13. Alcohol dependence and risk of somatic diseases and mortality

    DEFF Research Database (Denmark)

    Holst, Charlotte; Tolstrup, Janne Schurmann; Sørensen, Holger Jelling

    2017-01-01

    AIMS: To (1) estimate sex-specific risks of a comprehensive spectrum of somatic diseases in alcohol-dependent individuals versus a control population, and in the same population to (2) estimate sex-specific risks of dying from the examined somatic diseases. DESIGN: Register-based matched cohort...

  14. Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.

    Science.gov (United States)

    Wlodarski, Tomasz; Kutner, Jan; Towpik, Joanna; Knizewski, Lukasz; Rychlewski, Leszek; Kudlicki, Andrzej; Rowicka, Maga; Dziembowski, Andrzej; Ginalski, Krzysztof

    2011-01-01

    Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

  15. Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.

    Directory of Open Access Journals (Sweden)

    Tomasz Wlodarski

    Full Text Available Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity. Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.

  16. SPECIFICITY OF THE PRECIPITIN REACTION IN TOBACCO MOSAIC DISEASE.

    Science.gov (United States)

    Beale, H P

    1931-09-30

    1. Leaf extracts of Sudan grass, Hippeastrum equestre Herb., lily, and Abutilon striatum Dicks. (A. Thompsoni hort.), each affected with its respective mosaic disease, and peach affected with yellows disease, were tested for their ability to precipitate antiserum for virus extract of tobacco mosaic disease. No precipitate occurred. 2. Nicotiana glutinosa L., N. rustica L., and Martynia louisiana Mill. were added to the list of hosts of tobacco mosaic virus which have been tested with antiserum for the same virus in N. tabacum L. var. Turkish. The object was to determine the presence or absence of material reacting with the specific precipitins such as that already demonstrated in extracts of tomato, pepper, and petunia affected with the same virus. The presence of specific substances was demonstrated in every case. 3. The viruses of ringspot and cucumber mosaic diseases were multiplied in Turkish tobacco and leaf extracts of the affected plants were used in turn as antigens in precipitin tests with antiserum for tobacco mosaic virus extract of Turkish tobacco. A slight precipitation resulted in the tubes containing undiluted antiserum and virus extract such as occurs when juice from normal tobacco is used with undiluted antiserum. No precipitate was demonstrable that was specific for virus extracts of tobacco affected with either ringspot or cucumber mosaic disease. 4. The results favor the interpretation that the specific antigenic substance in virus extract of tobacco mosaic disease is foreign antigenic material, possibly virus itself, not altered host protein.

  17. Allergen-specific immunotherapy and risk of autoimmune disease

    DEFF Research Database (Denmark)

    Linneberg, Allan; Madsen, Flemming; Skaaby, Tea

    2012-01-01

    After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....

  18. Variation of a test's sensitivity and specificity with disease prevalence

    NARCIS (Netherlands)

    Leeflang, Mariska M. G.; Rutjes, Anne W. S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M. M.

    2013-01-01

    Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23

  19. Validation of a Comprehensive Early Childhood Allergy Questionnaire.

    Science.gov (United States)

    Minasyan, Anna; Babajanyan, Arman; Campbell, Dianne E; Nanan, Ralph

    2015-09-01

    Parental questionnaires to assess incidence of pediatric allergic disease have been validated for use in school-aged children. Currently, there is no validated questionnaire-based assessment of food allergy, atopic dermatitis (AD), and asthma for infants and young children. The Comprehensive Early Childhood Allergy Questionnaire was designed for detecting AD, asthma, and IgE-mediated food allergies in children aged 1-5 years. A nested case-control design was applied. Parents of 150 children attending pediatric outpatient clinics completed the questionnaire before being clinically assessed by a pediatrician for allergies. Sensitivity, specificity, and reproducibility of the questionnaire were assessed. Seventy-seven children were diagnosed with one or more current allergic diseases. The questionnaire demonstrated high overall sensitivity of 0.93 (95% CI 0.86-0.98) with a specificity of 0.79 (95% CI 0.68-0.88). Questionnaire reproducibility was good with a kappa agreement rate for symptom-related questions of 0.45-0.90. Comprehensive Early Childhood Allergy Questionnaire accurately and reliably reflects the presence of allergies in children aged 1-5 years. Its use is warranted as a tool for determining prevalence of allergies in this pediatric age group. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. The specificity of emotion inferences in text comprehension: the role of top-down and bottom-up processes

    OpenAIRE

    Gillioz, Christelle; Gygax, Pascal

    2013-01-01

    The aim of this thesis was to investigate the influence of individual differences and the nature of the information presented to readers on emotion inferences in text comprehension, in particular on the specificity of these emotion inferences. Research on emotion inferences has led some researchers to suggest that emotion inferences made during reading are specific (e.g., Gernsbacher et al., 1992) whereas others (e.g., Gygax et al., 2007) proposed that readers do not need to elaborate a compl...

  1. Disease-specific direct-to-consumer advertising for reminding consumers to take medications.

    Science.gov (United States)

    Bhutada, Nilesh S; Rollins, Brent L

    2015-01-01

    To assess the relationship between disease-specific direct-to-consumer (DTC) advertising, via traditional advertising effectiveness measures, and consumers' self-reported medication-taking behavior. Data were gathered for 514 respondents (age 18 and above) using an online survey panel. Participants were exposed to a disease-specific (i.e., nonbranded) DTC advertising for depression. The advertising stimulus created for the study was based on the Food and Drug Administration guidelines for disease-specific DTC advertising and modeled after current print disease-specific DTC advertising. Participants reviewed the advertising stimulus through the online program and then responded to a questionnaire containing closed-ended questions assessing the constructs. Data were analyzed using chi-square tests. All tests were interpreted at an a priori alpha of 0.05. Significantly more respondents who were highly involved, paid more attention to the advertisement, and were responsive to DTC advertisements in the past indicated that the disease-specific DTC advertising stimulus reminded them to take their depression and other medications. These exploratory results show disease-specific DTC advertising can help people remember to take their prescription medication when viewed, which may lead to more positive medication-taking behavior and increased medication adherence. Additionally, given the fair balance and legal issues surrounding product-specific DTC advertising, disease-specific DTC advertising can serve as an effective component of the marketing mix for pharmaceutical manufacturers. Future research should attempt to study the impact of disease-specific DTC advertising on consumers' actual medication adherence using standardized adherence measures such as prescription records.

  2. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, Ryan M.; Bhutta, Zulfiqar A.; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Zian; Coates, Matthew M.; Coggeshall, Megan; Dandona, Lalit; Dicker, Daniel J.; Erskine, Holly E.; Ferrari, Alize J.; Fitzmaurice, Christina; Foreman, Kyle; Forouzanfar, Mohammad H.; Fraser, Maya S.; Pullman, Nancy; Gething, Peter W.; Goldberg, Ellen M.; Graetz, Nicholas; Haagsma, Juanita A.; Hay, Simon I.; Huynh, Chantal; Johnson, Catherine; Kassebaum, Nicholas J.; Kinfu, Yohannes; Kulikoff, Xie Rachel; Kutz, Michael; Kyu, Hmwe H.; Larson, Heidi J.; Leung, Janni; Liang, Xiaofeng; Lim, Stephen S.; Lind, Margaret; Lozano, Rafael; Marquez, Neal; Mensah, George A.; Mikesell, Joe; Mokdad, Ali H.; Mooney, Meghan D.; Nguyen, Grant; Nsoesie, Elaine; Pigott, David M.; Amare, Azmeraw T.; Hoek, Hans W.; Singh, Abhishek; Tura, Abera Kenay

    2016-01-01

    Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes

  3. Variation of a test's sensitivity and specificity with disease prevalence.

    Science.gov (United States)

    Leeflang, Mariska M G; Rutjes, Anne W S; Reitsma, Johannes B; Hooft, Lotty; Bossuyt, Patrick M M

    2013-08-06

    Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p disease prevalence; there was no such systematic effect for sensitivity. The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

  4. A comprehensive review and update on Crohn's disease.

    Science.gov (United States)

    Gajendran, Mahesh; Loganathan, Priyadarshini; Catinella, Anthony P; Hashash, Jana G

    2018-02-01

    The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups. The annual incidence of CD in North America is reported to be 3.1-20.2 per 100,000 with a prevalence of 201 per 100,000 population. Based on the epidemiological, genetic and immunological data, CD is considered to be a heterogeneous disorder with multifactorial etiology in which genetics and environment interact to manifest the disease. Several genes have been studied so for with respect to CD, but thus far the strong and replicated associations have been identified with NOD2, IL23R and ATG16L1 genes. The risk factors implicated with CD include smoking, low fiber- high carbohydrate diet, altered microbiome and medications such as non-steroidal anti-inflammatory drugs. CD is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to perianal area. In terms of distribution of the disease 25% of the patients have colitis only, 25% is ileitis only and 50% have ileocolitis. The Montreal classification is based on the age at diagnosis ( 40), disease location (Ileal, colonic, Ileocolonic) and the disease behavior (nonstricturing/nonpenetrating, stricturing, penetrating). The key features for diagnosing CD comprises a combination of radiographic, endoscopic and pathological findings demonstrating focal, asymmetric, transmural or granulomatous features. Abdominal Computed tomography (CT

  5. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015

    NARCIS (Netherlands)

    Wang, Haidong; Naghavi, Mohsen; Allen, Christine; Barber, R.M.; Bhutta, Zulfiqar; Carter, Austin; Casey, Daniel C.; Charlson, Fiona J.; Chen, Alan Z.; Coates, M.; Geleijnse, J.M.

    2016-01-01

    Background
    Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249

  6. "Reading" Paintings: Evidence for Trans-Symbolic and Symbol-Specific Comprehension Processes

    Science.gov (United States)

    Loughlin, Sandra; Grossnickle, Emily; Dinsmore, Daniel; Alexander, Patricia

    2015-01-01

    Art-based reading instruction and interventions for elementary and middle school students are growing in popularity despite scant theoretical rationale and empirical research support. This study explored the degree to which painting comprehension processes map onto text comprehension processes in this population. In particular, we used think aloud…

  7. Disease specific therapies in leukodystrophies and leukoencephalopathies

    NARCIS (Netherlands)

    Helman, Guy; van Haren, Keith; Bonkowsky, Joshua L.; Bernard, Genevieve; Pizzino, Amy; Braverman, Nancy; Suhr, Dean; Patterson, Marc C.; Ali Fatemi, S.; Leonard, Jeff; van der Knaap, Marjo S.; Back, Stephen A.; Damiani, Stephen; Goldman, Steven A.; Takanohashi, Asako; Petryniak, Magdalena; Rowitch, David; Messing, Albee; Wrabetz, Lawrence; Schiffmann, Raphael; Eichler, Florian; Escolar, Maria L.; Vanderver, Adeline

    2015-01-01

    Leukodystrophies are a heterogeneous, often progressive group of disorders manifesting a wide range of symptoms and complications. Most of these disorders have historically had no etiologic or disease specific therapeutic approaches. Recently, a greater understanding of the pathologic mechanisms

  8. Improving listening comprehension skills relying on metacognitive strategies - focus on vocabulary and specific l2 instruction

    Directory of Open Access Journals (Sweden)

    Jerotijević-Tišma Danica

    2016-01-01

    Full Text Available The present paper aims at investigating the application of an instructional method specifically focused on the expansion of metacognitive awareness and its effect on Serbian EFL students’ listening comprehension. The current study is a follow-up research of a similar study by Vandergrift and Tafaghodtari (2010. However, we sought to expand the previous research by investigating the relationship between the students’ current level of L2 (target language vocabulary and listening test scores. Our study likewise differed in the sample of participants, the target language, teaching and testing material used, and the duration of the very experiment. To answer the proposed research questions we conducted an experiment with 57 Serbian secondary school EFL (English as a Foreign Language learners divided into experimental (n=27 and control group (n=30. The results of the pre- and post-tests of the two groups showed the beneficial effects of developing metacognitive strategies and the strong positive correlation between the level of vocabulary and listening comprehension. The paper underlines important pedagogical implications especially regarding the enhancement of metacognitive awareness and vocabulary proficiency of students in order to improve performance on listening comprehension tasks.

  9. Development of a disease-specific quality of life questionnaire in Addison's disease.

    Science.gov (United States)

    Løvås, Kristian; Curran, Suzanne; Oksnes, Marianne; Husebye, Eystein S; Huppert, Felicia A; Chatterjee, V Krishna K

    2010-02-01

    Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL). We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's alpha and Rasch analysis. Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's alpha 0.95 and Person Separation Index 0.94 (Rasch analysis). We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

  10. ADO: a disease ontology representing the domain knowledge specific to Alzheimer's disease.

    Science.gov (United States)

    Malhotra, Ashutosh; Younesi, Erfan; Gündel, Michaela; Müller, Bernd; Heneka, Michael T; Hofmann-Apitius, Martin

    2014-03-01

    Biomedical ontologies offer the capability to structure and represent domain-specific knowledge semantically. Disease-specific ontologies can facilitate knowledge exchange across multiple disciplines, and ontology-driven mining approaches can generate great value for modeling disease mechanisms. However, in the case of neurodegenerative diseases such as Alzheimer's disease, there is a lack of formal representation of the relevant knowledge domain. Alzheimer's disease ontology (ADO) is constructed in accordance to the ontology building life cycle. The Protégé OWL editor was used as a tool for building ADO in Ontology Web Language format. ADO was developed with the purpose of containing information relevant to four main biological views-preclinical, clinical, etiological, and molecular/cellular mechanisms-and was enriched by adding synonyms and references. Validation of the lexicalized ontology by means of named entity recognition-based methods showed a satisfactory performance (F score = 72%). In addition to structural and functional evaluation, a clinical expert in the field performed a manual evaluation and curation of ADO. Through integration of ADO into an information retrieval environment, we show that the ontology supports semantic search in scientific text. The usefulness of ADO is authenticated by dedicated use case scenarios. Development of ADO as an open ADO is a first attempt to organize information related to Alzheimer's disease in a formalized, structured manner. We demonstrate that ADO is able to capture both established and scattered knowledge existing in scientific text. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  11. Tissue-specific functional networks for prioritizing phenotype and disease genes.

    Directory of Open Access Journals (Sweden)

    Yuanfang Guan

    Full Text Available Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.

  12. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Isojima

    2017-12-01

    Full Text Available Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  13. Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.

    Science.gov (United States)

    Isojima, Tsuyoshi; Yokoya, Susumu

    2017-12-01

    Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

  14. Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited

    DEFF Research Database (Denmark)

    Martens, Pernille; Worm, Signe Westring; Lundgren, Bettina

    2004-01-01

    Serotype-specific mortality from invasive Streptococcus pneumoniae disease revisited.Martens P, Worm SW, Lundgren B, Konradsen HB, Benfield T. Department of Infectious Diseases 144, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark. pernillemartens@yahoo.com BACKGROUND: Invasive infection...... with Streptococcus pneumoniae (pneumococci) causes significant morbidity and mortality. Case series and experimental data have shown that the capsular serotype is involved in the pathogenesis and a determinant of disease outcome. METHODS: Retrospective review of 464 cases of invasive disease among adults diagnosed...

  15. Is Word-Problem Solving a Form of Text Comprehension?

    Science.gov (United States)

    Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.; Hamlett, Carol L.; Wang, Amber Y.

    2015-01-01

    This study’s hypotheses were that (a) word-problem (WP) solving is a form of text comprehension that involves language comprehension processes, working memory, and reasoning, but (b) WP solving differs from other forms of text comprehension by requiring WP-specific language comprehension as well as general language comprehension. At the start of the 2nd grade, children (n = 206; on average, 7 years, 6 months) were assessed on general language comprehension, working memory, nonlinguistic reasoning, processing speed (a control variable), and foundational skill (arithmetic for WPs; word reading for text comprehension). In spring, they were assessed on WP-specific language comprehension, WPs, and text comprehension. Path analytic mediation analysis indicated that effects of general language comprehension on text comprehension were entirely direct, whereas effects of general language comprehension on WPs were partially mediated by WP-specific language. By contrast, effects of working memory and reasoning operated in parallel ways for both outcomes. PMID:25866461

  16. Variation of a test’s sensitivity and specificity with disease prevalence

    Science.gov (United States)

    Leeflang, Mariska M.G.; Rutjes, Anne W.S.; Reitsma, Johannes B.; Hooft, Lotty; Bossuyt, Patrick M.M.

    2013-01-01

    Background: Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. Methods: We used data from 23 meta-analyses, each of which included 10–39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. Results: Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p disease prevalence; there was no such systematic effect for sensitivity. Interpretation: The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. PMID:23798453

  17. Assessment of disease-specific knowledge in Australian children with inflammatory bowel disease and their parents.

    Science.gov (United States)

    Day, Andrew S; Mylvaganam, Gaithri; Shalloo, Nollaig; Clarkson, Cathy; Leach, Steven T; Lemberg, Daniel A

    2017-08-01

    Disease-specific knowledge may influence disease outcome and quality of life in children with inflammatory bowel disease (IBD). This prospective study aimed to define IBD-related knowledge in a group of Australian children with IBD and their parents using a validated measure of disease-specific knowledge, the Inflammatory Bowel Disease Knowledge Inventory Device (IBD-KID). Children (less than 18 years) diagnosed with IBD who were members of the Australian patient support organisation were identified. Each family was sent copies of the IBD-KID. Children aged 10-18 years and all parents were asked to complete the IBD-KID and to also provide demographic details and disease characteristics. Replies were received from 196 families: 262 parents and 128 children completed questionnaires. Most children had a diagnosis of Crohn disease (65%) and 51% were male. Children diagnosed in the preceding 6 years scored higher than those with longer time since diagnosis. Parents had better scores in the IBD-KID than the children (P parents and children had poor understanding of key management issues for IBD (such as side effects of steroids), important outcomes (e.g. growth) and the use of complementary therapies. Consistent patterns of IBD-related knowledge were noted in this large group of Australian children with IBD and their parents. Measurement of disease-related knowledge with the IBD-KID can identify gaps in understanding, thereby permitting focused educational activities. Although these knowledge gaps may impact upon outcomes, further prospective studies are now required to elucidate the relationships between enhanced knowledge and specific outcomes. © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  18. Intermittent Theta-Burst Stimulation of the Right Dorsolateral Prefrontal Cortex to Promote Metaphor Comprehension in Parkinson Disease: A Case Study.

    Science.gov (United States)

    Tremblay, Christina; Monetta, Laura; Langlois, Mélanie; Schneider, Cyril

    2016-01-01

    This single-case research-designed study explored whether intermittent theta-burst stimulation (iTBS) of the right dorsolateral prefrontal cortex (DLPFC) could improve metaphor comprehension in people with Parkinson disease (PD) and language impairments. A right-handed participant with PD diagnosed 9 years ago, receiving long-term treatment with levodopa, and with metaphor comprehension impairment was recruited to undergo 10 sessions of sham stimulation (in 2wk), a washout period (6wk), and then 10 sessions of iTBS (in 2wk). Clinical scores of metaphor comprehension and motor evaluation (Unified Parkinson Disease Rating Scale part III) and transcranial magnetic stimulation to test the excitability of the primary motor cortex (M1) were used at baseline, postsham, post-iTBS, and at 3 follow-ups (8, 14, and 20wk post-iTBS). Metaphor comprehension was improved after iTBS, and the highest scores were obtained 8 weeks later (P=.01). This improvement was correlated with the increase of the right M1 excitability (r=-.86, P=.03) and with the decrease of transcallosal inhibition latency from the left to the right hemisphere (r=-.88, P=.02). Sham yielded no effect (P>.05). Administration of iTBS over the right DLPFC improved metaphor comprehension likely by a long-term influence on brain synaptic plasticity, including improvement of interhemispheric dialogue. More studies are warranted to confirm these findings in larger samples of participants with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  19. An initial exploration for comprehensive assessment of IgG4-related lung disease: analyses on the cases enrolled from a systematic review.

    Science.gov (United States)

    Wang, An; Fan, Jie; Chen, Xiaofeng; Wang, Shaohua

    2018-03-01

    The existence of two diagnostic systems, the Boston and Japan criteria, for immunoglobulin G4-related disease (IgG4-RD) confuse the medical practice. We aimed to develop a comprehensive assessment based on the weight of each diagnostic item in the existing criteria to improve the diagnostic efficiency of Boston criteria. We assessed the patients enrolled by a systematic review of the literatures using the Boston criteria, Japan criteria and a tentative comprehensive assessment respectively, and evaluated the efficiency of each system and their consistency. Our analysis showed that the distinction in pathological diagnostic items was similar for the Boston criteria (IgG4+/IgG+ ratio, Pcomprehensive assessment (IgG4+/IgG+ ratio and the number of pathological features, Pcomprehensive assessment. The current two diagnostic systems have poor consistency. Comprehensive assessment has good agreement with the Boston criteria, but can identify those cases in Boston Category 3 who could still be diagnosed as IgG4-related lung disease. Considering the weight of diagnostic items, the scoring system is a tentative exploration that should be improved with further experience in diagnosing IgG4-related lung disease.

  20. Comprehensive proteomic analysis of human pancreatic juice

    DEFF Research Database (Denmark)

    Grønborg, Mads; Bunkenborg, Jakob; Kristiansen, Troels Zakarias

    2004-01-01

    Proteomic technologies provide an excellent means for analysis of body fluids for cataloging protein constituents and identifying biomarkers for early detection of cancers. The biomarkers currently available for pancreatic cancer, such as CA19-9, lack adequate sensitivity and specificity...... contributing to late diagnosis of this deadly disease. In this study, we carried out a comprehensive characterization of the "pancreatic juice proteome" in patients with pancreatic adenocarcinoma. Pancreatic juice was first fractionated by 1-dimensional gel electrophoresis and subsequently analyzed by liquid...... in this study could be directly assessed for their potential as biomarkers for pancreatic cancer by quantitative proteomics methods or immunoassays....

  1. Muscle-Specific Mis-Splicing and Heart Disease Exemplified by RBM20.

    Science.gov (United States)

    Rexiati, Maimaiti; Sun, Mingming; Guo, Wei

    2018-01-05

    Alternative splicing is an essential post-transcriptional process to generate multiple functional RNAs or proteins from a single transcript. Progress in RNA biology has led to a better understanding of muscle-specific RNA splicing in heart disease. The recent discovery of the muscle-specific splicing factor RNA-binding motif 20 (RBM20) not only provided great insights into the general alternative splicing mechanism but also demonstrated molecular mechanism of how this splicing factor is associated with dilated cardiomyopathy. Here, we review our current knowledge of muscle-specific splicing factors and heart disease, with an emphasis on RBM20 and its targets, RBM20-dependent alternative splicing mechanism, RBM20 disease origin in induced Pluripotent Stem Cells (iPSCs), and RBM20 mutations in dilated cardiomyopathy. In the end, we will discuss the multifunctional role of RBM20 and manipulation of RBM20 as a potential therapeutic target for heart disease.

  2. Enteroclysis in adult celiac disease: diagnostic value of specific radiographic features

    International Nuclear Information System (INIS)

    Lomoschitz, F.; Schima, W.; Schober, E.; Turetschek, K.; Kaider, A.; Vogelsang, H.

    2003-01-01

    The purpose of this study was to compare the diagnostic accuracy of various radiographic findings at enteroclysis in adult patients with untreated celiac disease. Twenty-seven adult patients underwent enteroclysis because of unspecific intestinal symptoms before definitive biopsy proof of celiac disease. Enteroclysis of 123 subjects with similar clinical presentation, including abdominal pain, diarrhea, occult intestinal bleeding, and weight loss, who had a definitive diagnosis other than celiac disease, served as controls. The radiographic features previously described in the literature as indicative of adult celiac disease (i.e., fold thickening, decrease of jejunal folds, increase of ileal folds, small bowel dilatation, flocculation) were evaluated in blinded fashion in all studies and the subjective likelihood of diagnosis of celiac disease was assessed. Assessing every finding separately, each feature proved to have a high specificity (78-100%) but low sensitivity (19-59%) for celiac disease. Reversal of jejunoileal fold pattern was the single best feature (specificity 100%, 95% CI 97-100%; sensitivity 59%, 95% CI 40-78%); however, combination of criteria enables establishment of the diagnosis of celiac disease quite accurately (specificity 100%, 95% CI 98-100%; sensitivity 78%, 95% CI 58-91%). Reversal of jejunoileal fold pattern as a single finding as well as combination at least three of the following features, i.e., fold thickening, decrease of jejunal folds (''colonization''), increase of ileal folds (''jejunization''), dilatation, and flocculation, make enteroclysis an accurate tool for diagnosis of celiac disease in adult patients with suspected intestinal disease. (orig.)

  3. Quality of life in patients with anorectal malformation or Hirschsprung's disease: development of a disease-specific questionnaire

    NARCIS (Netherlands)

    Hanneman, M. J.; Sprangers, M. A.; de Mik, E. L.; Ernest van Heurn, L. W.; de Langen, Z. J.; Looyaard, N.; Madern, G. C.; Rieu, P. N.; van der Zee, D. C.; van Silfhout, M.; Aronson, D. C.

    2001-01-01

    PURPOSE: Hirschsprung's disease and anorectal malformation are congenital diseases of the digestive tract with sequelae into adulthood. The quality of life of patients with these diseases is largely unknown. The aim of the study was 1) to construct a self-report disease-specific instrument to assess

  4. Validation of the Comprehensive ICF Core Set for obstructive pulmonary diseases from the perspective of physiotherapists.

    Science.gov (United States)

    Rauch, Alexandra; Kirchberger, Inge; Stucki, Gerold; Cieza, Alarcos

    2009-12-01

    The 'Comprehensive ICF Core Set for obstructive pulmonary diseases' (OPD) is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with OPD. To optimize a multidisciplinary and patient-oriented approach in pulmonary rehabilitation, in which physiotherapy plays an important role, the ICF offers a standardized language and understanding of functioning. For it to be a useful tool for physiotherapists in rehabilitation of patients with OPD, the objective of this study was to validate this Comprehensive ICF Core Set for OPD from the perspective of physiotherapists. A three-round survey based on the Delphi technique of physiotherapists who are experienced in the treatment of OPD asked about the problems, resources and aspects of environment of patients with OPD that physiotherapists treat in clinical practice (physiotherapy intervention categories). Responses were linked to the ICF and compared with the existing Comprehensive ICF Core Set for OPD. Fifty-one physiotherapists from 18 countries named 904 single terms that were linked to 124 ICF categories, 9 personal factors and 16 'not classified' concepts. The identified ICF categories were mainly third-level categories compared with mainly second-level categories of the Comprehensive ICF Core Set for OPD. Seventy of the ICF categories, all personal factors and 15 'not classified' concepts gained more than 75% agreement among the physiotherapists. Of these ICF categories, 55 (78.5%) were covered by the Comprehensive ICF Core Set for OPD. The validity of the Comprehensive ICF Core Set for OPD was largely supported by the physiotherapists. Nevertheless, ICF categories that were not covered, personal factors and not classified terms offer opportunities towards the final ICF Core Set for OPD and further research to strengthen physiotherapists' perspective in pulmonary rehabilitation.

  5. Short-term Evaluation of a Comprehensive Education Program Including Inhaler Training and Disease Management on Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Yoo, Kwang Ha; Chung, Wou Young; Park, Joo Hun; Hwang, Sung Chul; Kim, Tae Eun; Oh, Min Jung; Kang, Dae Ryong; Rhee, Chin Kook; Yoon, Hyoung Kyu; Kim, Tae Hyung; Kim, Deog Kyeom; Park, Yong Bum; Kim, Sang Ha; Yum, Ho Kee

    2017-10-01

    Proper education regarding inhaler usage and optimal management of chronic obstructive pulmonary disease (COPD) is essential for effectively treating patients with COPD. This study was conducted to evaluate the effects of a comprehensive education program including inhaler training and COPD management. We enlisted 127 patients with COPD on an outpatient basis at 43 private clinics in Korea. The patients were educated on inhaler usage and disease management for three visits across 2 weeks. Physicians and patients were administered a COPD assessment test (CAT) and questionnaires about the correct usage of inhalers and management of COPD before commencement of this program and after their third visit. The outcomes of 127 COPD patients were analyzed. CAT scores (19.6±12.5 vs. 15.1±12.3) improved significantly after this program (pmanagement and the correct technique for using inhalers than those who did not have improved CAT scores (peducation program including inhaler training and COPD management at a primary care setting improved CAT scores and led to patients' better understanding of COPD management. Copyright©2017. The Korean Academy of Tuberculosis and Respiratory Diseases

  6. The impact of strain-specific immunity on Lyme disease incidence is spatially heterogeneous.

    Science.gov (United States)

    Khatchikian, Camilo E; Nadelman, Robert B; Nowakowski, John; Schwartz, Ira; Wormser, Gary P; Brisson, Dustin

    2017-12-01

    Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne infection in the US. Recent studies have demonstrated that the incidence of human Lyme disease would have been even greater were it not for the presence of strain-specific immunity, which protects previously infected patients against subsequent infections by the same B. burgdorferi strain. Here, spatial heterogeneity is incorporated into epidemiological models to accurately estimate the impact of strain-specific immunity on human Lyme disease incidence. The estimated reduction in the number of Lyme disease cases is greater in epidemiologic models that explicitly include the spatial distribution of Lyme disease cases reported at the county level than those that utilize nationwide data. strain-specific immunity has the greatest epidemiologic impact in geographic areas with the highest Lyme disease incidence due to the greater proportion of people that have been previously infected and have developed strain-specific immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Enteroclysis in adult celiac disease: diagnostic value of specific radiographic features

    Energy Technology Data Exchange (ETDEWEB)

    Lomoschitz, F.; Schima, W.; Schober, E.; Turetschek, K. [Department of Radiology and Ludwig Boltzmann Institute for Clinical and Experimental Radiologic Research, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kaider, A. [Department of Medical Computer Sciences, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Vogelsang, H. [Department of Internal Medicine IV, Division of Gastroenterology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2003-04-01

    The purpose of this study was to compare the diagnostic accuracy of various radiographic findings at enteroclysis in adult patients with untreated celiac disease. Twenty-seven adult patients underwent enteroclysis because of unspecific intestinal symptoms before definitive biopsy proof of celiac disease. Enteroclysis of 123 subjects with similar clinical presentation, including abdominal pain, diarrhea, occult intestinal bleeding, and weight loss, who had a definitive diagnosis other than celiac disease, served as controls. The radiographic features previously described in the literature as indicative of adult celiac disease (i.e., fold thickening, decrease of jejunal folds, increase of ileal folds, small bowel dilatation, flocculation) were evaluated in blinded fashion in all studies and the subjective likelihood of diagnosis of celiac disease was assessed. Assessing every finding separately, each feature proved to have a high specificity (78-100%) but low sensitivity (19-59%) for celiac disease. Reversal of jejunoileal fold pattern was the single best feature (specificity 100%, 95% CI 97-100%; sensitivity 59%, 95% CI 40-78%); however, combination of criteria enables establishment of the diagnosis of celiac disease quite accurately (specificity 100%, 95% CI 98-100%; sensitivity 78%, 95% CI 58-91%). Reversal of jejunoileal fold pattern as a single finding as well as combination at least three of the following features, i.e., fold thickening, decrease of jejunal folds (''colonization''), increase of ileal folds (''jejunization''), dilatation, and flocculation, make enteroclysis an accurate tool for diagnosis of celiac disease in adult patients with suspected intestinal disease. (orig.)

  8. CDDUX: A disease-specific health-related quality-of-life questionnaire for children with celiac disease

    NARCIS (Netherlands)

    van Doorn, Roesja K.; Winkler, Lex M. F.; Zwinderman, Koos H.; Mearin, M. Luisa; Koopman, Hendrik M.

    2008-01-01

    Objective: The development of a disease-specific, health-related, quality-of-life questionnaire for children ages 8 to 18 with celiac disease (CD), together with a parent-as-proxy version. Materials and Methods: We used a focus-group method (bottom-up approach) to investigate the impact of CD on

  9. Capturing structured, pulmonary disease-specific data elements in electronic health records.

    Science.gov (United States)

    Gronkiewicz, Cynthia; Diamond, Edward J; French, Kim D; Christodouleas, John; Gabriel, Peter E

    2015-04-01

    Electronic health records (EHRs) have the potential to improve health-care quality by allowing providers to make better decisions at the point of care based on electronically aggregated data and by facilitating clinical research. These goals are easier to achieve when key, disease-specific clinical information is documented as structured data elements (SDEs) that computers can understand and process, rather than as free-text/natural-language narrative. This article reviews the benefits of capturing disease-specific SDEs. It highlights several design and implementation considerations, including the impact on efficiency and expressivity of clinical documentation and the importance of adhering to data standards when available. Pulmonary disease-specific examples of collection instruments are provided from two commonly used commercial EHRs. Future developments that can leverage SDEs to improve clinical quality and research are discussed.

  10. Metaphor-related figurative language comprehension in clinical populations: a critical review

    Directory of Open Access Journals (Sweden)

    Maity Siqueira

    2016-12-01

    Full Text Available This paper aims to critically review current studies with respect to definitions,methods, and results on the comprehension of metaphor, metonymy,idioms, and proverbs under the following clinical conditions: aphasia,Alzheimer’s disease, autism, brain injuries, specific language impairment,and Williams Syndrome. A comprehensive search of experimentalpsycholinguistic research was conducted using EBSCOhost, PsychInfo,PUBMED, and Web of Science databases. Thirty-eight studies met thereview inclusion criteria. Results point to deficits in figurative languagecomprehension in all conditions considered, lack of clear definitions ofthe phenomena investigated, and varied methods throughout the sample.Patients’ difficulties are attributed to multiple factors, such as a lack ofTheory of Mind, executive dysfunctions, and poor semantic knowledge.The study of nonliteral aspects of language comprehension in clinicalpopulations reveals a range of disparate impairments. There was no specificfeature about metaphor-related phenomena identified that could, on its own,account for the difficulty some populations have to understand figurativelanguage. Rather, metaphor-related language comprehension difficultiesare often part of pragmatic, linguistic, and/or cognitive impairments.Keywords: Figurative language. Metaphor. Metonymy. Proverb. Clinicalpopulations

  11. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  12. Disease-Specific Mortality of Differentiated Thyroid Cancer Patients in Korea: A Multicenter Cohort Study

    Directory of Open Access Journals (Sweden)

    Min Ji Jeon

    2017-11-01

    Full Text Available BackgroundLittle is known regarding disease-specific mortality of differentiated thyroid cancer (DTC patients and its risk factors in Korea.MethodsWe retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005.ResultsMean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97% and underwent total thyroidectomy (85%. Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9% occurred; the 10-year disease-specific survival (DSS rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%. Older age (≥45 years at diagnosis, male, follicular thyroid cancer (FTC versus PTC, larger tumor size (>2 cm, presence of extrathyroidal extension (ETE, lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM stage were independent risk factors of disease-specific mortality of DTC patients.ConclusionThe rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients.

  13. The Effect of Neuro-Linguistic Programming (NLP on Reading Comprehension in English for Specific Purposes Courses

    Directory of Open Access Journals (Sweden)

    Fahimeh Farahani

    2018-01-01

    Full Text Available Neuro-Linguistic Programming (NLP has potential to help language learners; however, it has received scant attention. The present study was an attempt to investigate the effect of NLP techniques on reading comprehension of English as a Foreign Language (EFL learners at an English for Specific Purposes (ESP course. To achieve this goal, two intact classes of students were selected to form an experimental group (n=30 and a control group (n=30. A reading pretest (based on the course content was given to all participants. The sensory learning styles of the participants were diagnosed using Reid's (1987 leaning style questionnaire, and the participants in the experimental group were familiarized with NLP techniques to be able to implement these techniques in their reading. In the control group, the conventional approach to teach ESP reading was used. Considering the analysis of posttest results through ANCOVA, it was found that implementation of NLP techniques can have significant effect on reading comprehension of Iranian undergraduate EFL learners. Pedagogical implications are discussed.

  14. Strategy-based listening and pragmatic comprehension

    Directory of Open Access Journals (Sweden)

    Corsetti, Cristiane Ruzicki

    2014-01-01

    Full Text Available This article addresses the role of strategy-based listening as an alternative methodological approach to develop pragmatic comprehension in L2 contexts. Pragmatic comprehension refers to the understanding of speech acts and conversational implicatures. Listening comprehension comprises both bottom-up and top-down processes. Strategy-based listening encompasses the activation of pragmatic knowledge through pre-listening activities and the development of specific listening micro-skills. An empirical project which included a classroom project carried out with a group of eight learners preparing for the IELTS examination in 2009 corroborated the following assumptions: in order to achieve listening proficiency, learners need practice in making inferences as semantic and pragmatic inferences are embedded in verbal communication; semantic and pragmatic aspects affecting the meaning of utterances can be highlighted via comprehension activities focusing on specific listening subskills. The results of the classroom project suggested that strategy-based listening is potentially capable of directly enhancing pragmatic comprehension but were inconclusive with regards to pragmatic production

  15. DincRNA: a comprehensive web-based bioinformatics toolkit for exploring disease associations and ncRNA function.

    Science.gov (United States)

    Cheng, Liang; Hu, Yang; Sun, Jie; Zhou, Meng; Jiang, Qinghua

    2018-06-01

    DincRNA aims to provide a comprehensive web-based bioinformatics toolkit to elucidate the entangled relationships among diseases and non-coding RNAs (ncRNAs) from the perspective of disease similarity. The quantitative way to illustrate relationships of pair-wise diseases always depends on their molecular mechanisms, and structures of the directed acyclic graph of Disease Ontology (DO). Corresponding methods for calculating similarity of pair-wise diseases involve Resnik's, Lin's, Wang's, PSB and SemFunSim methods. Recently, disease similarity was validated suitable for calculating functional similarities of ncRNAs and prioritizing ncRNA-disease pairs, and it has been widely applied for predicting the ncRNA function due to the limited biological knowledge from wet lab experiments of these RNAs. For this purpose, a large number of algorithms and priori knowledge need to be integrated. e.g. 'pair-wise best, pairs-average' (PBPA) and 'pair-wise all, pairs-maximum' (PAPM) methods for calculating functional similarities of ncRNAs, and random walk with restart (RWR) method for prioritizing ncRNA-disease pairs. To facilitate the exploration of disease associations and ncRNA function, DincRNA implemented all of the above eight algorithms based on DO and disease-related genes. Currently, it provides the function to query disease similarity scores, miRNA and lncRNA functional similarity scores, and the prioritization scores of lncRNA-disease and miRNA-disease pairs. http://bio-annotation.cn:18080/DincRNAClient/. biofomeng@hotmail.com or qhjiang@hit.edu.cn. Supplementary data are available at Bioinformatics online.

  16. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  17. Improving the Specificity of EEG for Diagnosing Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    François-B. Vialatte

    2011-01-01

    Full Text Available Objective. EEG has great potential as a cost-effective screening tool for Alzheimer's disease (AD. However, the specificity of EEG is not yet sufficient to be used in clinical practice. In an earlier study, we presented preliminary results suggesting improved specificity of EEG to early stages of Alzheimer's disease. The key to this improvement is a new method for extracting sparse oscillatory events from EEG signals in the time-frequency domain. Here we provide a more detailed analysis, demonstrating improved EEG specificity for clinical screening of MCI (mild cognitive impairment patients. Methods. EEG data was recorded of MCI patients and age-matched control subjects, in rest condition with eyes closed. EEG frequency bands of interest were θ (3.5–7.5 Hz, α1 (7.5–9.5 Hz, α2 (9.5–12.5 Hz, and β (12.5–25 Hz. The EEG signals were transformed in the time-frequency domain using complex Morlet wavelets; the resulting time-frequency maps are represented by sparse bump models. Results. Enhanced EEG power in the θ range is more easily detected through sparse bump modeling; this phenomenon explains the improved EEG specificity obtained in our previous studies. Conclusions. Sparse bump modeling yields informative features in EEG signal. These features increase the specificity of EEG for diagnosing AD.

  18. CDC Best Practices for Comprehensive Tobacco Control Programs - 2007

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

  19. CDC Best Practices for Comprehensive Tobacco Control Programs - 2014

    Data.gov (United States)

    U.S. Department of Health & Human Services — Centers for Disease Control and Prevention (CDC). Best Practices for Comprehensive Tobacco Control Programs. Funding. CDC's Best Practices for Comprehensive Tobacco...

  20. Microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease: A comprehensive meta-analysis

    OpenAIRE

    LI, HUI; FU, WEI-PING; HONG, ZE-HUI

    2012-01-01

    Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the detoxification the products of smoking and is proposed to be a genetic factor for the development of chronic obstructive pulmonary disease (COPD). Two functional polymorphisms of EPHX1, T113C and A139G, have been analyzed in numerous studies to assess the COPD risk attributed to these variants. However, the conclusions were controversial. We performed a comprehensive meta-analysis to clarify these findings. A total of 24 studie...

  1. Effectiveness of disease-specific self-management education on health outcomes in patients with chronic obstructive pulmonary disease: An updated systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Tao; Tan, Jing-Yu; Xiao, Lily Dongxia; Deng, Renli

    2017-08-01

    To update a previously published systematic review on the effectiveness of self-management education (SME) for patients with chronic obstructive pulmonary disease (COPD). Electronic databases were accessed (from inception to July 2016) to find relevant randomized controlled trials. Studies that compared SME with routine methods of care in COPD patients were retrieved. Both data synthesis and descriptive analysis were used for outcome assessment (e.g. quality of life and healthcare utilization). Twenty-four studies were included. Data synthesis showed better quality of life among COPD patients receiving SME. Significant reductions in COPD-related hospital admissions and emergency department visits were identified in the SME group. SME may positively affect the reduction of COPD patients' emotional distress. No significant reduction in smoking rate and mortality rate was observed between groups. No clear evidence supports the improvement of pulmonary functions, dyspnea, and nutritional status in COPD patients with the use of SME. SME can be a useful strategy to improve quality of life and disease-specific knowledge in patients with COPD. It also reduces respiratory-related hospital admissions and emergency department visits in COPD patients. Inclusion of SME as one of the key components for the comprehensive management of COPD is encouraged. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cystinosis in adult and adolescent patients: Recommendations for the comprehensive care of cystinosis

    Directory of Open Access Journals (Sweden)

    Gema Ariceta

    2015-05-01

    Conclusions: Guidelines for the comprehensive care of cystinosis provide a support tool for health professionals who look after these patients. They are based on the following main pillars: (a a multidisciplinary approach; (b appropriate disease monitoring and control of white blood cell (WBC cystine levels; (c the importance of adherence to cysteamine treatment; and (d the promotion of patient self-care by means of disease education programmes. All these recommendations will lead us, in a second phase, to create a coordinated model of transition from paediatric to adult care services which will cover the specific needs of cystinosis.

  3. Immunogenetic mechanisms for the coexistence of organ-specific and systemic autoimmune diseases.

    Science.gov (United States)

    Fridkis-Hareli, Masha

    2008-02-15

    Organ-specific autoimmune diseases affect particular targets in the body, whereas systemic diseases engage multiple organs. Both types of autoimmune diseases may coexist in the same patient, either sequentially or concurrently, sustained by the presence of autoantibodies directed against the corresponding autoantigens. Multiple factors, including those of immunological, genetic, endocrine and environmental origin, contribute to the above condition. Due to association of certain autoimmune disorders with HLA alleles, it has been intriguing to examine the immunogenetic basis for autoantigen presentation leading to the production of two or more autoantibodies, each distinctive of an organ-specific or systemic disease. This communication offers the explanation for shared autoimmunity as illustrated by organ-specific blistering diseases and the connective tissue disorders of systemic nature. Several hypothetical mechanisms implicating HLA determinants, autoantigenic peptides, T cells, and B cells have been proposed to elucidate the process by which two autoimmune diseases are induced in the same individual. One of these scenarios, based on the assumption that the patient carries two disease-susceptible HLA genes, arises when a single T cell epitope of each autoantigen recognizes its HLA protein, leading to the generation of two types of autoreactive B cells, which produce autoantibodies. Another mechanism functioning whilst an epitope derived from either autoantigen binds each of the HLA determinants, resulting in the induction of both diseases by cross-presentation. Finally, two discrete epitopes originating from the same autoantigen may interact with each of the HLA specificities, eliciting the production of both types of autoantibodies. Despite the lack of immediate or unequivocal experimental evidence supporting the present hypothesis, several approaches may secure a better understanding of shared autoimmunity. Among these are animal models expressing the transgenes

  4. Towards comprehensive and transparent reporting: context-specific additions to the ICF taxonomy for medical evaluations of work capacity involving claimants with chronic widespread pain and low back pain.

    Science.gov (United States)

    Schwegler, Urban; Anner, Jessica; Glässel, Andrea; Brach, Mirjam; De Boer, Wout; Cieza, Alarcos; Trezzini, Bruno

    2014-08-29

    Medical evaluations of work capacity provide key information for decisions on a claimant's eligibility for disability benefits. In recent years, the evaluations have been increasingly criticized for low transparency and poor standardization. The International Classification of Functioning, Disability and Health (ICF) provides a comprehensive spectrum of categories for reporting functioning and its determinants in terms of impairments and contextual factors and could facilitate transparent and standardized documentation of medical evaluations of work capacity. However, the comprehensiveness of the ICF taxonomy in this particular context has not been empirically examined. In this study, we wanted to identify potential context-specific additions to the ICF for its application in medical evaluations of work capacity involving chronic widespread pain (CWP) and low back pain (LBP). A retrospective content analysis of Swiss medical reports was conducted by using the ICF for data coding. Concepts not appropriately classifiable with ICF categories were labeled as specification categories (i.e. context-specific additions) and were assigned to predefined specification areas (i.e. precision, coverage, personal factors, and broad concepts). Relevant specification categories for medical evaluations of work capacity involving CWP and LBP were determined by calculating their relative frequency across reports and setting a relevance threshold. Forty-three specification categories for CWP and fifty-two for LBP reports passed the threshold. In both groups of reports, precision was the most frequent specification area, followed by personal factors. The ICF taxonomy represents a universally applicable standard for reporting health and functioning information. However, when applying the ICF for comprehensive and transparent reporting in medical evaluations of work capacity involving CWP and LBP context-specific additions are needed. This is particularly true for the documentation of

  5. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  6. Is Word-Problem Solving a Form of Text Comprehension?

    Science.gov (United States)

    Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.; Hamlett, Carol L.; Wang, Amber Y.

    2015-01-01

    This study's hypotheses were that (a) word-problem (WP) solving is a form of text comprehension that involves language comprehension processes, working memory, and reasoning, but (b) WP solving differs from other forms of text comprehension by requiring WP-specific language comprehension as well as general language comprehension. At the start of…

  7. The Comprehension Problems of Children with Poor Reading Comprehension despite Adequate Decoding: A Meta-Analysis.

    Science.gov (United States)

    Spencer, Mercedes; Wagner, Richard K

    2018-06-01

    The purpose of this meta-analysis was to examine the comprehension problems of children who have a specific reading comprehension deficit (SCD), which is characterized by poor reading comprehension despite adequate decoding. The meta-analysis included 86 studies of children with SCD who were assessed in reading comprehension and oral language (vocabulary, listening comprehension, storytelling ability, and semantic and syntactic knowledge). Results indicated that children with SCD had deficits in oral language ( d = -0.78, 95% CI [-0.89, -0.68], but these deficits were not as severe as their deficit in reading comprehension ( d = -2.78, 95% CI [-3.01, -2.54]). When compared to reading comprehension age-matched normal readers, the oral language skills of the two groups were comparable ( d = 0.32, 95% CI [-0.49, 1.14]), which suggests that the oral language weaknesses of children with SCD represent a developmental delay rather than developmental deviance. Theoretical and practical implications of these findings are discussed.

  8. Determining T-cell specificity to understand and treat disease

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker; Newell, Evan W.

    2017-01-01

    Adaptive immune responses and immunopathogeneses are based on the ability of T cells to respond to specific antigens. Consequently, understanding T-cell recognition patterns in health and disease involves studying the complexity and genetic heterogeneity of the antigen recognition pathway, which...

  9. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

    Science.gov (United States)

    Boldt, Karsten; van Reeuwijk, Jeroen; Lu, Qianhao; Koutroumpas, Konstantinos; Nguyen, Thanh-Minh T; Texier, Yves; van Beersum, Sylvia E C; Horn, Nicola; Willer, Jason R; Mans, Dorus A; Dougherty, Gerard; Lamers, Ideke J C; Coene, Karlien L M; Arts, Heleen H; Betts, Matthew J; Beyer, Tina; Bolat, Emine; Gloeckner, Christian Johannes; Haidari, Khatera; Hetterschijt, Lisette; Iaconis, Daniela; Jenkins, Dagan; Klose, Franziska; Knapp, Barbara; Latour, Brooke; Letteboer, Stef J F; Marcelis, Carlo L; Mitic, Dragana; Morleo, Manuela; Oud, Machteld M; Riemersma, Moniek; Rix, Susan; Terhal, Paulien A; Toedt, Grischa; van Dam, Teunis J P; de Vrieze, Erik; Wissinger, Yasmin; Wu, Ka Man; Apic, Gordana; Beales, Philip L; Blacque, Oliver E; Gibson, Toby J; Huynen, Martijn A; Katsanis, Nicholas; Kremer, Hannie; Omran, Heymut; van Wijk, Erwin; Wolfrum, Uwe; Kepes, François; Davis, Erica E; Franco, Brunella; Giles, Rachel H; Ueffing, Marius; Russell, Robert B; Roepman, Ronald

    2016-05-13

    Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine.

  10. The challenges of reshaping disease specific and care oriented community based services towards comprehensive goals: a situation appraisal in the Western Cape Province, South Africa.

    Science.gov (United States)

    Schneider, Helen; Schaay, Nikki; Dudley, Lilian; Goliath, Charlyn; Qukula, Tobeka

    2015-09-30

    Similar to other countries in the region, South Africa is currently reorienting a loosely structured and highly diverse community care system that evolved around HIV and TB, into a formalized, comprehensive and integrated primary health care outreach programme, based on community health workers (CHWs). While the difficulties of establishing national CHW programmes are well described, the reshaping of disease specific and care oriented community services, based outside the formal health system, poses particular challenges. This paper is an in-depth case study of the challenges of implementing reforms to community based services (CBS) in one province of South Africa. A multi-method situation appraisal of CBS in the Western Cape Province was conducted over eight months in close collaboration with provincial stakeholders. The appraisal mapped the roles and service delivery, human resource, financing and governance arrangements of an extensive non-governmental organisation (NGO) contracted and CHW based service delivery infrastructure that emerged over 15-20 years in this province. It also gathered the perspectives of a wide range of actors - including communities, users, NGOs, PHC providers and managers - on the current state and future visions of CBS. While there was wide support for new approaches to CBS, there are a number of challenges to achieving this. Although largely government funded, the community based delivery platform remains marginal to the formal public primary health care (PHC) and district health systems. CHW roles evolved from a system of home based care and are limited in scope. There is a high turnover of cadres, and support systems (supervision, monitoring, financing, training), coordination between CHWs, NGOs and PHC facilities, and sub-district capacity for planning and management of CBS are all poorly developed. Reorienting community based services that have their origins in care responses to HIV and TB presents an inter-related set of resource

  11. Assessing Disease Class-Specific Diagnostic Ability: A Practical Adaptive Test Approach.

    Science.gov (United States)

    Papa, Frank J.; Schumacker, Randall E.

    Measures of the robustness of disease class-specific diagnostic concepts could play a central role in training programs designed to assure the development of diagnostic competence. In the pilot study, the authors used disease/sign-symptom conditional probability estimates, Monte Carlo procedures, and artificial intelligence (AI) tools to create…

  12. Executive Dysfunction among Children with Reading Comprehension Deficits

    Science.gov (United States)

    Locascio, Gianna; Mahone, E. Mark; Eason, Sarah H.; Cutting, Laurie E.

    2010-01-01

    Emerging research supports the contribution of executive function (EF) to reading comprehension; however, a unique pattern has not been established for children who demonstrate comprehension difficulties despite average word recognition ability (specific reading comprehension deficit; S-RCD). To identify particular EF components on which children…

  13. How To Tutor Students with Reading Comprehension Problems.

    Science.gov (United States)

    Parker, Richard; Hasbrouck, Jan E.; Denton, Carolyn

    2002-01-01

    Suggestions for tutoring students with reading comprehension problems include careful selection of books with readable text segments, use of comprehension strategies such as paraphrasing brief sections, and reading to find specific information. Several reading comprehension strategies for students are summarized. (Contains 7 references.) (DB)

  14. Profiling classroom reading comprehension development practices ...

    African Journals Online (AJOL)

    Of specific concern is the lack of representation of the sampled South African learners at the PIRLS international benchmarks, revealing a distinct lack of their development of thinking and reasoning abilities for reading comprehension. To shed light on potential reasons for learners' reading comprehension difficulties, this ...

  15. Behavior, nutrition and lifestyle in a comprehensive health and disease paradigm: skills and knowledge for a predictive, preventive and personalized medicine.

    Science.gov (United States)

    Trovato, Guglielmo M

    2012-03-22

    Health and disease of individuals and of populations are the result of three groups of risk factors: genetics, environment and behavior. Assessment, interventions and tailored changes are possible with integrated approaches more effective if respectful of individuals and different cultures. Assessment tools and integrated interventional strategies are available, but widespread knowledge, skills and competence of well trained individual Medical Doctors still lack. Mediterranean diet is an appropriate reference paradigm because encompasses consistent research background, affordable sustainability, widespread comprehensibility and attractiveness inside a cultural framework of competences and skills in which the Medical Doctors can personally manage the need of prediction (early diagnosis), prevention (intervention on healthy persons) and tailored therapy and follow-up for patients. This profile is flexible and adjustable according to specific needs and preferences due to different economic and ethno-cultural milieus. It can enhanced through on-site/e-learning Continuous Medical Education (CME), by training and using friendly and affordable equipments.

  16. Hemophilia and von Willebrand's disease: 1. Diagnosis, comprehensive care and assessment. Association of Hemophilia Clinic Directors of Canada.

    Science.gov (United States)

    1995-07-01

    To present current strategies for the assessment and comprehensive care of patients with hemophilia and von Willebrand's disease. Hospital care, home care, single-provider care and multidisciplinary care. Morbidity and quality of life associated with bleeding and treatment. Relevant clinical studies and reports published from 1974 to 1994 were examined. A search was conducted of own reprint files, MEDLINE, citations in the articles reviewed and references provided by colleagues. In the MEDLINE search the following terms were used singly or in combination: "hemophilia," "von Willebrand's disease," "Factor VIII," "Factor IX," "von Willebrand factor," "diagnosis," "management," "home care," "comprehensive care," "inhibitor," "AIDS," "hepatitis," "life expectancy," "complications," "practice guidelines," "consensus statement" and "controlled trial." The in-depth review included only articles written in English from North America and Europe that were relevant to human disease and to a predetermined outline. The availability of treatment products in Canada was also considered. Minimizing morbidity and maximizing functional status and quality of life were given a high value. The optimal use of treatment procedures and home care offers patients the advantages of minimized disability, improved survival and financial benefit. It is also cost effective. Potential harm, including the risk of hepatitis B, hepatitis C and HIV infection, has now been minimized through viral inactivation of plasma-derived coagulation-factor concentrates and through the use of recombinant clotting factor concentrates and other non-plasma-derived hemostatic agents. Patients with hemophilia and severe von Willebrand's disease should be followed in comprehensive care centres that offer expertise in the diagnosis, assessment and management of bleeding and complications and that can meet the educational and counselling needs of patients, family members and health care providers. Eligible patients should

  17. Quality of life in paediatric inflammatory bowel disease measured by a generic and a disease-specific questionnaire

    NARCIS (Netherlands)

    Loonen, H. J.; Grootenhuis, M. A.; Last, B. F.; Koopman, H. M.; Derkx, H. H. F.

    2002-01-01

    This study assessed the impact of inflammatory bowel disease (IBD) on the health-related quality of life (HRQoL) of children and adolescents. using both a generic and a disease-specific instrument. Three questionnaires were sent to all patients (8-18 y old) from the database of two large

  18. Comprehensive embryo testing. Experts' opinions regarding future directions: an expert panel study on comprehensive embryo testing.

    Science.gov (United States)

    Hens, Kristien; Dondorp, Wybo J; Geraedts, Joep P M; de Wert, Guido M

    2013-05-01

    What do scientists in the field of preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) consider to be the future direction of comprehensive embryo testing? Although there are many biological and technical limitations, as well as uncertainties regarding the meaning of genetic variation, comprehensive embryo testing will impact the IVF/PGD practice and a timely ethical reflection is needed. Comprehensive testing using microarrays is currently being introduced in the context of PGD and PGS, and it is to be expected that whole-genome sequencing will also follow. Current ethical and empirical sociological research on embryo testing focuses on PGD as it is practiced now. However, empirical research and systematic reflection regarding the impact of comprehensive techniques for embryo testing is missing. In order to understand the potential of this technology and to be able to adequately foresee its implications, we held an expert panel with seven pioneers in PGD. We conducted an expert panel in October 2011 with seven PGD pioneers from Belgium, The Netherlands, Germany and the UK. Participants expected the use of comprehensive techniques in the context of PGD. However, the introduction of these techniques in embryo testing requires timely ethical reflection as it involves a shift from choosing an embryo without a particular genetic disease (i.e. PGD) or most likely to result in a successful pregnancy (i.e. PGS) to choosing the best embryo based on a much wider set of criteria. Such ethical reflection should take account of current technical and biological limitations and also of current uncertainties with regard to the meaning of genetic variance. However, ethicists should also not be afraid to look into the future. There was a general agreement that embryo testing will be increasingly preceded by comprehensive preconception screening, thus enabling smart combinations of genetic testing. The group was composed of seven participants from

  19. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  20. Systemic and Disease-Specific Risk Factors in Vascular Dementia: Diagnosis and Prevention

    Directory of Open Access Journals (Sweden)

    Efraim Jaul

    2017-10-01

    Full Text Available In order to prevent the onset of vascular dementia (VaD in aging individuals, it is critical to detect clinically relevant vascular and systemic pathophysiological changes to signal the onset of its preceding prodromal stages. Identifying behavioral and neurobiological markers that are highly sensitive to VaD classification vs. other dementias is likely to assist in developing novel preventive treatment strategies that could delay the onset of disruptive psychomotor symptoms, decrease hospitalizations, and increase the quality of life in clinically-high-risk aging individuals. In light of empirical diagnostic and clinical findings associated with VaD pathophysiology, the current investigation will suggest a few clinically-validated biomarker measures of prodromal VaD cognitive impairments that are correlated with vascular symptomology, and VaD endophenotypes in non-demented aging people. In prodromal VaD individuals, distinguishing VaD from other dementias (e.g., Alzheimer's disease could facilitate specific early preventive interventions that significantly delay more severe cognitive deterioration or indirectly suppress the onset of dementia with vascular etiology. Importantly, the authors conclude that primary prevention strategies should examine aging individuals by employing comprehensive geriatric assessment approach, taking into account their medical history, and longitudinally noting their vascular, systemic, cognitive, behavioral, and clinical functional status. Secondary prevention strategies may include monitoring chronic medication as well as promoting programs that facilitate social interaction and every-day activities.

  1. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Chase, Gary; Lu, Mei

    2004-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  2. Molecular Differentiation of Risk for Disease Progression: Delineating Stage-Specific Therapeutic Targets for Disease Management in Breast Cancer

    National Research Council Canada - National Science Library

    Worsham, Maria J; Raju, Usha; Lu, Mei

    2006-01-01

    .... The aim of this research is to 1a: identify an informative set of specific genetic alterations that underlie the pathogenesis of disease progression to serve as targets for management of disease at the earliest stages and 1b...

  3. Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis--A Comprehensive Review and Guide to Therapy. I. Systemic Disease.

    Science.gov (United States)

    Kohanim, Sahar; Palioura, Sotiria; Saeed, Hajirah N; Akpek, Esen K; Amescua, Guillermo; Basu, Sayan; Blomquist, Preston H; Bouchard, Charles S; Dart, John K; Gai, Xiaowu; Gomes, José A P; Gregory, Darren G; Iyer, Geetha; Jacobs, Deborah S; Johnson, Anthony J; Kinoshita, Shigeru; Mantagos, Iason S; Mehta, Jodhbir S; Perez, Victor L; Pflugfelder, Stephen C; Sangwan, Virender S; Sippel, Kimberly C; Sotozono, Chie; Srinivasan, Bhaskar; Tan, Donald T H; Tandon, Radhika; Tseng, Scheffer C G; Ueta, Mayumi; Chodosh, James

    2016-01-01

    The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Hypertext comprehension of deaf and hard-of-hearing students and students with specific language impairment.

    Science.gov (United States)

    Blom, Helen; Segers, Eliane; Hermans, Daan; Knoors, Harry; Verhoeven, Ludo

    2017-02-01

    This paper provides insight into the reading comprehension of hierarchically structured hypertexts within D/HH students and students with SLI. To our knowledge, it is the first study on hypertext comprehension in D/HH students and students with SLI, and it also considers the role of working memory. We compared hypertext versus linear text comprehension in D/HH students and students with SLI versus younger students without language problems who had a similar level of decoding and vocabulary. The results demonstrated no difference in text comprehension between the hierarchically structured hypertext and the linear text. Text comprehension of D/HH students and students with SLI was comparable to that of the students without language problems. In addition, there was a similar positive predictive value of visuospatial and not verbal working memory on hypertext comprehension for all three groups. The findings implicate that educational settings can make use of hierarchically structured hypertexts as well as linear texts and that children can navigate in the digital world from young age on, even if language or working memory problems are present. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. University Students with Poor Reading Comprehension

    Science.gov (United States)

    Georgiou, George K.; Das, J. P.

    2015-01-01

    The present study aimed to examine the nature of the working memory and general cognitive ability deficits experienced by university students with a specific reading comprehension deficit. A total of 32 university students with poor reading comprehension but average word-reading skills and 60 age-word-matched controls with no comprehension…

  6. Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

    Science.gov (United States)

    Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

    2017-07-01

    The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Automated real time constant-specificity surveillance for disease outbreaks

    Directory of Open Access Journals (Sweden)

    Brownstein John S

    2007-06-01

    Full Text Available Abstract Background For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. Results We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p Conclusion Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.

  8. Cardiovascular Disease Modeling Using Patient-Specific Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Atsushi Tanaka

    2015-08-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs has opened up a new scientific frontier in medicine. This technology has made it possible to obtain pluripotent stem cells from individuals with genetic disorders. Because iPSCs carry the identical genetic anomalies related to those disorders, iPSCs are an ideal platform for medical research. The pathophysiological cellular phenotypes of genetically heritable heart diseases such as arrhythmias and cardiomyopathies, have been modeled on cell culture dishes using disease-specific iPSC-derived cardiomyocytes. These model systems can potentially provide new insights into disease mechanisms and drug discoveries. This review focuses on recent progress in cardiovascular disease modeling using iPSCs, and discusses problems and future perspectives concerning their use.

  9. Cardiac rehabilitation: a comprehensive review

    OpenAIRE

    Lear, Scott A; Ignaszewski, Andrew

    2001-01-01

    Abstract Cardiac rehabilitation (CR) is a commonly used treatment for men and women with cardiovascular disease. To date, no single study has conclusively demonstrated a comprehensive benefit of CR. Numerous individual studies, however, have demonstrated beneficial effects such as improved risk-factor profile, slower disease progression, decreased morbidity, and decreased mortality. This paper will review the evidence for the use of CR and discuss the implications and limitations of these stu...

  10. Specific Profile of Tau Isoforms in Argyrophylic Grain Disease

    Directory of Open Access Journals (Sweden)

    Alberto Rábano

    2013-01-01

    Full Text Available Argyrophylic grain disease (AGD is a neurodegenerative condition that has been classified among the sporadic tauopathies. Entities in this group present intracellular aggregates of hyperphosphorylated tau, giving rise to characteristic neuronal and glial inclusions. In different tauopathies, the proportion of several tau isoforms present in the aggregates shows specific patterns. AGD has been tentatively classified in the 4R group (predominance of 4R tau isoforms together with progressive supranuclear palsy and corticobasal degeneration. Pick's disease is included in the 3R group (predominance of 3R isoforms, whereas tau pathology of Alzheimer's disease represents and intermediate group (3 or 4 repeats [3R plus 4R, respectively] isoforms. In this work, we have analyzed tau present in aggregates isolated from brain samples of patients with argyrophylic grain disease. Our results indicate that the main tau isoform present in aggregates obtained from patients with AGD is a hyperphosphorylated isoform containing exons 2 and 10 but lacking exon 3.

  11. Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

    Directory of Open Access Journals (Sweden)

    Rachel S. Lee

    2011-01-01

    Full Text Available The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ.

  12. The comprehension of Italian relative clauses in poor readers and in children with Specific Language Impairment

    Directory of Open Access Journals (Sweden)

    Fabrizio Arosio

    2017-02-01

    Full Text Available Children with Specific Language Impairment (SLI and children with Developmental Dyslexia (DD have problems comprehending relative clauses (RCs and find object RCs more difficult than subject RCs, as do typically developing children. Few studies have compared these groups directly, leaving it unclear whether the problems observed in children with DD are similar to those described in SLI. Work with typically developing children has shown that the comprehension of passive RCs is less challenging than that of object RCs. It is argued that this asymmetry depends on intervention effects as modelized in a Relativized Minimality framework. Since movement is challenging for children with SLI and those with DD, examining and comparing their comprehension of object RCs and passive RCs can broaden our understanding of their language deficits. In fact, both structures involve movement, but the moved element and the movement configuration are different. In our study we investigated the comprehension of subject RCs, object RCs and passive RCs in 12 Italian monolingual children with SLI (mean age: 7;6, 13 Italian monolingual children with DD (mean age: 10;7 and 50 typically developing controls matched for age, grammar and vocabulary. Results from a picture selection task show that: (i subject RCs are unproblematic for all children; (ii object RCs are challenging for children with SLI, children with DD and younger typically developing controls; (iii passive RCs are better understood than object RCs in all groups, but still problematic for children with SLI and younger typically developing controls. Our data show that intervention effects are found in children with SLI and children with DD and that those with SLI have a deficit in transferring thematic roles to moved elements. Our results point out that some of the children with DD have a mild grammatical deficit that was undetected or escaped standardized tests.

  13. Development of a quality-of-life instrument for autoimmune bullous disease: the Autoimmune Bullous Disease Quality of Life questionnaire.

    Science.gov (United States)

    Sebaratnam, Deshan F; Hanna, Anna Marie; Chee, Shien-ning; Frew, John W; Venugopal, Supriya S; Daniel, Benjamin S; Martin, Linda K; Rhodes, Lesley M; Tan, Jeremy Choon Kai; Wang, Charles Qian; Welsh, Belinda; Nijsten, Tamar; Murrell, Dédée F

    2013-10-01

    Quality-of-life (QOL) evaluation is an increasingly important outcome measure in dermatology, with disease-specific QOL instruments being the most sensitive to changes in disease status. To develop a QOL instrument specific to autoimmune bullous disease (AIBD). A comprehensive item generation process was used to build a 45-item pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire, distributed to 70 patients with AIBD. Experts in bullous disease refined the pilot ABQOL before factor analysis was performed to yield the final ABQOL questionnaire of 17 questions. We evaluated validity and reliability across a range of indices. Australian dermatology outpatient clinics and private dermatology practices. PATIENTS AND EXPOSURE: Patients with a histological diagnosis of AIBD. The development of an AIBD-specific QOL instrument. Face and content validity were established through the comprehensive patient interview process and expert review. In terms of convergent validity, the ABQOL was found to have a moderate correlation with scores on the Dermatology Life Quality Index (R = 0.63) and the General Health subscale of the 36-Item Short Form Health Survey (R = 0.69; P = .009) and low correlation with the Pemphigus Disease Area Index (R = 0.42) and Autoimmune Bullous Disease Skin Disorder Intensity Score (R = 0.48). In terms of discriminant validity, the ABQOL was found to be more sensitive than the Dermatology Life Quality Index (P = .02). The ABQOL was also found to be a reliable instrument evaluated by internal consistency (Cronbach α coefficient, 0.84) and test-retest reliability (mean percentage variation, 0.92). The ABQOL has been shown to be a valid and reliable instrument that may serve as an end point in clinical trials. Future work should include incorporating patient weighting on questions to further increase content validity and translation of the measure to other languages. anzctr.org.au Identifier: ACTRN12612000750886.

  14. [Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

    Science.gov (United States)

    Bachmann, H

    1987-11-01

    Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

  15. Prediction of disease-related genes based on weighted tissue-specific networks by using DNA methylation.

    Science.gov (United States)

    Li, Min; Zhang, Jiayi; Liu, Qing; Wang, Jianxin; Wu, Fang-Xiang

    2014-01-01

    Predicting disease-related genes is one of the most important tasks in bioinformatics and systems biology. With the advances in high-throughput techniques, a large number of protein-protein interactions are available, which make it possible to identify disease-related genes at the network level. However, network-based identification of disease-related genes is still a challenge as the considerable false-positives are still existed in the current available protein interaction networks (PIN). Considering the fact that the majority of genetic disorders tend to manifest only in a single or a few tissues, we constructed tissue-specific networks (TSN) by integrating PIN and tissue-specific data. We further weighed the constructed tissue-specific network (WTSN) by using DNA methylation as it plays an irreplaceable role in the development of complex diseases. A PageRank-based method was developed to identify disease-related genes from the constructed networks. To validate the effectiveness of the proposed method, we constructed PIN, weighted PIN (WPIN), TSN, WTSN for colon cancer and leukemia, respectively. The experimental results on colon cancer and leukemia show that the combination of tissue-specific data and DNA methylation can help to identify disease-related genes more accurately. Moreover, the PageRank-based method was effective to predict disease-related genes on the case studies of colon cancer and leukemia. Tissue-specific data and DNA methylation are two important factors to the study of human diseases. The same method implemented on the WTSN can achieve better results compared to those being implemented on original PIN, WPIN, or TSN. The PageRank-based method outperforms degree centrality-based method for identifying disease-related genes from WTSN.

  16. Modeling the Cumulative Effects of Social Exposures on Health: Moving beyond Disease-Specific Models

    Directory of Open Access Journals (Sweden)

    Heather L. White

    2013-03-01

    Full Text Available The traditional explanatory models used in epidemiology are “disease specific”, identifying risk factors for specific health conditions. Yet social exposures lead to a generalized, cumulative health impact which may not be specific to one illness. Disease-specific models may therefore misestimate social factors’ effects on health. Using data from the Canadian Community Health Survey and Canada 2001 Census we construct and compare “disease-specific” and “generalized health impact” (GHI models to gauge the negative health effects of one social exposure: socioeconomic position (SEP. We use logistic and multinomial multilevel modeling with neighbourhood-level material deprivation, individual-level education and household income to compare and contrast the two approaches. In disease-specific models, the social determinants under study were each associated with the health conditions of interest. However, larger effect sizes were apparent when outcomes were modeled as compound health problems (0, 1, 2, or 3+ conditions using the GHI approach. To more accurately estimate social exposures’ impacts on population health, researchers should consider a GHI framework.

  17. Integrating Multiple On-line Knowledge Bases for Disease-Lab Test Relation Extraction.

    Science.gov (United States)

    Zhang, Yaoyun; Soysal, Ergin; Moon, Sungrim; Wang, Jingqi; Tao, Cui; Xu, Hua

    2015-01-01

    A computable knowledge base containing relations between diseases and lab tests would be a great resource for many biomedical informatics applications. This paper describes our initial step towards establishing a comprehensive knowledge base of disease and lab tests relations utilizing three public on-line resources. LabTestsOnline, MedlinePlus and Wikipedia are integrated to create a freely available, computable disease-lab test knowledgebase. Disease and lab test concepts are identified using MetaMap and relations between diseases and lab tests are determined based on source-specific rules. Experimental results demonstrate a high precision for relation extraction, with Wikipedia achieving the highest precision of 87%. Combining the three sources reached a recall of 51.40%, when compared with a subset of disease-lab test relations extracted from a reference book. Moreover, we found additional disease-lab test relations from on-line resources, indicating they are complementary to existing reference books for building a comprehensive disease and lab test relation knowledge base.

  18. Erdheim-Chester disease: a comprehensive review.

    Science.gov (United States)

    Abdelfattah, Ahmed Maher; Arnaout, Karim; Tabbara, Imad A

    2014-07-01

    Erdheim-Chester disease is a rare form of non-Langerhans' cell histiocytosis characterized by multi-system infiltration by xanthogranulomas composed of foamy histiocytes surrounded by fibrosis. Approximately 400 cases have been reported in the literature, and the recent increase in the number of cases is likely due to the increased awareness of its associated morbidity and mortality. The etiology of this disease remains unknown, the clinical course is variable and treatment is still not well-established. The objective of this review is to describe the pathogenesis, clinical manifestations, and diagnosis of this rare disorder, and to review its prognosis and treatment. Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis. It was first described in 1930. Approximately 400 cases have been reported in the literature. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Comprehensive analysis of the mutation spectrum in 301 German ALS families.

    Science.gov (United States)

    Müller, Kathrin; Brenner, David; Weydt, Patrick; Meyer, Thomas; Grehl, Torsten; Petri, Susanne; Grosskreutz, Julian; Schuster, Joachim; Volk, Alexander E; Borck, Guntram; Kubisch, Christian; Klopstock, Thomas; Zeller, Daniel; Jablonka, Sibylle; Sendtner, Michael; Klebe, Stephan; Knehr, Antje; Günther, Kornelia; Weis, Joachim; Claeys, Kristl G; Schrank, Berthold; Sperfeld, Anne-Dorte; Hübers, Annemarie; Otto, Markus; Dorst, Johannes; Meitinger, Thomas; Strom, Tim M; Andersen, Peter M; Ludolph, Albert C; Weishaupt, Jochen H

    2018-04-12

    Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions. Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families. 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1 , whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes. We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Molecular property diagnostic suite (MPDS): Development of disease-specific open source web portals for drug discovery.

    Science.gov (United States)

    Nagamani, S; Gaur, A S; Tanneeru, K; Muneeswaran, G; Madugula, S S; Consortium, Mpds; Druzhilovskiy, D; Poroikov, V V; Sastry, G N

    2017-11-01

    Molecular property diagnostic suite (MPDS) is a Galaxy-based open source drug discovery and development platform. MPDS web portals are designed for several diseases, such as tuberculosis, diabetes mellitus, and other metabolic disorders, specifically aimed to evaluate and estimate the drug-likeness of a given molecule. MPDS consists of three modules, namely data libraries, data processing, and data analysis tools which are configured and interconnected to assist drug discovery for specific diseases. The data library module encompasses vast information on chemical space, wherein the MPDS compound library comprises 110.31 million unique molecules generated from public domain databases. Every molecule is assigned with a unique ID and card, which provides complete information for the molecule. Some of the modules in the MPDS are specific to the diseases, while others are non-specific. Importantly, a suitably altered protocol can be effectively generated for another disease-specific MPDS web portal by modifying some of the modules. Thus, the MPDS suite of web portals shows great promise to emerge as disease-specific portals of great value, integrating chemoinformatics, bioinformatics, molecular modelling, and structure- and analogue-based drug discovery approaches.

  1. [Office employees physiological and psychological state effects of workplace peculiarities comprehensive analysis].

    Science.gov (United States)

    2012-01-01

    Consumer goods company clerkship working condition hygienic evaluation, psychological state and cardio-vascular system analyses have shown that work tension is governing factor for organism functional strain development in comparison with occupational environment factors. Received data confirm determined before indices comprehension as specific for psychological and cardio-vascular system state reserves decrease degree under mental work tension elevation. For purpose of functional strain and overstrain manifestation before occupational disease incipient character forming early warning "Methodical recommendation on occupational stress under office employees arduous mental work evaluation" was developed.

  2. The Contribution of Specific Diseases to Educational Disparities in Disability-Free Life Expectancy

    Science.gov (United States)

    Nusselder, Wilma J.; Looman, Caspar W.N.; Mackenbach, Johan P.; Huisman, Martijn; van Oyen, Herman; Deboosere, Patrick; Gadeyne, Sylvie; Kunst, Anton E.

    2005-01-01

    Objectives. We examined the contribution that specific diseases, as causes of both death and disability, make to educational disparities in disability-free life expectancy (DFLE). Methods. We used disability data from the Belgian Health Interview Survey (1997) and mortality data from the National Mortality Follow-Up Study (1991–1996) to assess education-related disparities in DFLE and to partition these differences into additive contributions of specific diseases. Results. The DFLE advantage of higher-educated compared with lower-educated persons was 8.0 years for men and 5.9 years for women. Arthritis (men, 1.3 years; women, 2.2 years), back complaints (men, 2.1 years), heart disease/stroke (men, 1.5 years; women, 1.6 years), asthma/chronic obstructive pulmonary disease (COPD) (men, 1.2 years; women, 1.5 years), and “other diseases” (men, 2.4 years) contributed the most to this difference. Conclusions. Disabling diseases, such as arthritis, back complaints, and asthma/COPD, contribute substantially to differences in DFLE by education. Public health policy aiming to reduce existing disparities in the DFLE and to improve population health should not only focus on fatal diseases but also on these nonfatal diseases. PMID:16195519

  3. Automated real time constant-specificity surveillance for disease outbreaks.

    Science.gov (United States)

    Wieland, Shannon C; Brownstein, John S; Berger, Bonnie; Mandl, Kenneth D

    2007-06-13

    For real time surveillance, detection of abnormal disease patterns is based on a difference between patterns observed, and those predicted by models of historical data. The usefulness of outbreak detection strategies depends on their specificity; the false alarm rate affects the interpretation of alarms. We evaluate the specificity of five traditional models: autoregressive, Serfling, trimmed seasonal, wavelet-based, and generalized linear. We apply each to 12 years of emergency department visits for respiratory infection syndromes at a pediatric hospital, finding that the specificity of the five models was almost always a non-constant function of the day of the week, month, and year of the study (p accounting for not only the expected number of visits, but also the variance of the number of visits. The expectation-variance model achieves constant specificity on all three time scales, as well as earlier detection and improved sensitivity compared to traditional methods in most circumstances. Modeling the variance of visit patterns enables real-time detection with known, constant specificity at all times. With constant specificity, public health practitioners can better interpret the alarms and better evaluate the cost-effectiveness of surveillance systems.

  4. Effect of a comprehensive plan for periodontal disease care on oral health-related quality of life in patients with periodontal disease in Taiwan.

    Science.gov (United States)

    Wang, Tze-Fang; Fang, Chun-Han; Hsiao, Kai-Jong; Chou, Chyuan

    2018-02-01

    A comprehensive plan for periodontal disease (PD) care in Taiwan provides non-surgical and supportive periodontal treatment. The aim of this study was to determine whether the care plan could improve the oral health-related quality of life of patients with PD.This study was conducted by purposive sampling and a quasi-experimental design. Patients with PD were assigned to either comprehensive periodontal treatment (n = 32) or a simple cleaning regimen (n = 32). Their oral health-related quality of life (OHRQoL) was measured using the Taiwanese version of the Brief World Health Organization Quality of Life (WHOQOL-BREF) scale (general QoL) and the Oral Health Impact Profile (OHIP-14) (OHRQoL). Both scales were completed 14, 28, and 90 days after the initial assessment. The extent of PD in the experimental group was determined again at the end of the study.On the 28-item WHOQOL-BREF scale, the scores of the experimental group were higher than those of the control group on 5 items and the environmental domain at 14 days. There was a significant improvement in the experimental group on 2 items at 28 days and at 90 days after periodontal treatment (both P improvement in the experimental group in total score at 28 and 90 days after periodontal treatment (both P plan for PD care showed some improvement in QoL, including in the environmental domain, and on the total score for OHRQoL. Comprehensive periodontal treatment also alleviated periodontal symptoms.

  5. Disease-specific and inflammation-independent stromal alterations in spondylarthritis synovitis

    NARCIS (Netherlands)

    Yeremenko, Nataliya; Noordenbos, Troy; Cantaert, Tineke; van Tok, Melissa; van de Sande, Marleen; Cañete, Juan D.; Tak, Paul P.; Baeten, Dominique

    2013-01-01

    The molecular processes driving the distinct patterns of synovial inflammation and tissue remodeling in spondylarthritis (SpA) as compared to rheumatoid arthritis (RA) remain largely unknown. Therefore, we aimed to identify novel and unsuspected disease-specific pathways in SpA by a systematic and

  6. Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Bogdanos Dimitrios P

    2012-08-01

    Full Text Available Abstract Background Glycoprotein 2 (GP2 was discovered as the major autoantigen of Crohn’s disease (CD-specific pancreatic autoantibodies (PAB. We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes. Methods Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF in 271 sera, 169 with CD and 102 with ulcerative colitis (UC. As healthy controls 160 adult blood donors and 65 children were included. Results Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2% than in UC (9/102, 8.9% patients and in controls (9/225, 4% (p  Conclusions Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.

  7. Lesion localization of speech comprehension deficits in chronic aphasia.

    Science.gov (United States)

    Pillay, Sara B; Binder, Jeffrey R; Humphries, Colin; Gross, William L; Book, Diane S

    2017-03-07

    Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension. Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language. ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG). Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia. © 2017 American Academy of Neurology.

  8. A comprehensive test specification for pulse fission counters

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, D L [Control and Instrumentation Division, Atomic Energy Establishment, Winfrith, Dorchester, Dorset (United Kingdom)

    1962-02-15

    The following test specification is based on the memorandum AERE - M 728 which it now replaces It contains a standard acceptance test procedure for the many U.K.A.E.A, designed pulse fission counters now commercially available. This test specification may be used for any pulse fission counter provided a specification sheet as shown in Appendix 3 is supplied to the contractor quoting this report and including specified values for the measured quantities. (author)

  9. Longitudinal patterns of predominant asthma disease activity in pediatric patients enrolled in an asthma-specific disease management program.

    Science.gov (United States)

    Scott, Lyne; Nichols, Breck; Choi Kwong, Kenny Yat; Morphew, Tricia; Jones, Craig A

    2008-08-01

    To determine if patterns of predominant asthma disease activity are more closely related than baseline asthma severity to measures of morbidity (acute asthma attack, emergency room visit/hospitalization, missed school days, and/or steroid burst). Retrospective analysis was performed for inner-city Los Angeles asthmatic children (3 to 18 years of age) during their first year of enrollment in an asthma-specific disease management program. All measures of morbidity were more closely related to patterns of predominant disease activity than baseline severity. We conclude that patterns of predominant disease activity are a more significant predictor of asthma morbidity than is baseline severity.

  10. Immunoglobulin G4 -related kidney disease: A comprehensive pictorial review of the imaging spectrum, Mimickers, and clinicopathological characteristics

    International Nuclear Information System (INIS)

    Seo, Ni Eun; Kim, Jin Hee; Byun, Jae Ho; Lee, Seung Soo; Kim, Hyoung Jung; Lee, Moon Gyu

    2015-01-01

    Immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) has recently been demonstrated to be an important part of IgG4-related sclerosing disease (IgG4-SD). However, since IgG4-KD is still relatively unfamiliar to radiologists and physicians as compared to IgG4-SD involving other organs, it could, therefore, be easily missed. In this article, we present a comprehensive pictorial review of IgG4-KD with regards to the imaging spectrum, mimickers, and clinicopathologic characteristics, based on our clinical experience with 48 patients during the past 13 years, as well as a literature review. Awareness of the broad imaging spectrum of IgG4-KD and differential diagnosis from its mimickers will thus facilitate its early diagnosis and treatment

  11. Association of Immunological Cell Profiles with Specific Clinical Phenotypes of Scleroderma Disease

    Science.gov (United States)

    Calzada, David; Mayayo, Teodoro; González-Rodríguez, María Luisa; Rabasco, Antonio María; Lahoz, Carlos

    2014-01-01

    This study aimed to search the correlation among immunological profiles and clinical phenotypes of scleroderma in well-characterized groups of scleroderma patients, comparing forty-nine scleroderma patients stratified according to specific clinical phenotypes with forty-nine healthy controls. Five immunological cell subpopulations (B, CD4+ and CD8+ T-cells, NK, and monocytes) and their respective stages of apoptosis and activation were analyzed by flow cytometry, in samples of peripheral blood mononuclear cells (PBMCs). Analyses of results were stratified according to disease stage, time since the diagnosis, and visceral damage (pulmonary fibrosis, pulmonary hypertension, and cardiac affliction) and by time of treatment with corticosteroids. An increase in the percentages of monocytes and a decrease in the B cells were mainly related to the disease progression. A general apoptosis decrease was found in all phenotypes studied, except in localized scleroderma. An increase of B and NK cells activation was found in patients diagnosed more than 10 years ago. Specific cell populations like monocytes, NK, and B cells were associated with the type of affected organ. This study shows how, in a heterogeneous disease, proper patient's stratification according to clinical phenotypes allows finding specific cellular profiles. Our data may lead to improvements in the knowledge of prognosis factors and to aid in the analysis of future specific therapies. PMID:24818126

  12. Disease-specific hashtags and the creation of Twitter medical communities in hematology and oncology.

    Science.gov (United States)

    Pemmaraju, Naveen; Thompson, Michael A; Qazilbash, Muzaffar

    2017-10-01

    Twitter is being increasingly used for information gathering and dissemination of ideas in both medical practice and scientific research. A major limitation to its use has been the surplus of available information and difficulty in categorizing that information into topics of individual interest. However, a Twitter feature known as the hashtag (#), which denotes a specific category or topic, helps in streamlining this wealth of information. The creation and adoption of disease-specific hashtags by healthcare stakeholders has led to a greater uniformity of medical discussions that can be retrieved and referenced at later time-points. As new disease-specific hashtags are created for hematologic and oncologic diseases, more users can connect across the world, even for the rarest of cancer subtypes. A major challenge for this emerging application will be the development of specific and easily identifiable hashtags over time to add more clarity, while still trying to grow Twitter users and expand its reach. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

  14. Disease-specific health status as a predictor of mortality in patients with heart failure

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H; Versteeg, Henneke; Zijlstra, Wobbe P

    2014-01-01

    AIMS: Some, but not all, studies have shown that patient-reported health status, including symptoms, functioning, and health-related quality of life, provides additional information to traditional clinical factors in predicting prognosis in heart failure patients. To evaluate the overall evidence......, the association of disease-specific health status on mortality in heart failure was examined through a systematic review and meta-analysis. METHODS AND RESULTS: Prospective cohort studies that assessed the independent association of disease-specific health status with mortality in heart failure were selected....... Searching PubMed (until March 2013) resulted in 17 articles in the systematic review and 17 studies in the meta-analysis. About half of the studies reported a significant relationship between disease-specific health status and mortality in heart failure, while the remainder found no association. A larger...

  15. Current roles of specific bacteria in the pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Lucy McMullen

    2015-12-01

    Full Text Available The relevance of alterations in gut microbiota in the pathogenesis of inflammatory bowel disease (IBD remains unclear. Currently there is conflicting evidence with regards to the roles of specific bacterial species. Escherichia coli (particularly the adherent invasive strain are more prevalent in those with IBD and are associated with higher risk of IBD. However, the organisms are also present in healthy individuals and colonisation does not correlate with the degree of inflammation in IBD. Campylobacter concisus is more prevalent in those with IBD and higher levels of C. concisus specific IgG antibodies are found in the serum of those with IBD compared to healthy controls. Further, C. concisus has immunogenic properties that stimulate an antibody response suggesting the bacteria might trigger or exacerbate disease. Conversely most mycobacteria are unlikely to be causative as they are not presentin microbial stool cultures early in disease. In various studies,Mycobacterium aviumparatuberculosishas been detected both more frequently and not at all in individuals with Crohn's disease. Similar conflict exists with respect to Yersinia enterocolitica,Bacteroidesvulgatus and Helicobacter hepaticus, which are also more prevalent in IBD. However, these organisms appear more likely to contribute to disease persistence than initial disease development. This review aims to summarise the current understanding of key bacterial species implicated in the pathogenesis of IBD.

  16. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Nagasawa

    Full Text Available BACKGROUND: Immunoglobulin (IgA nephropathy (IgAN is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. METHODS AND FINDINGS: We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062. Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012. Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002. Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019. There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046, and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037 by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. CONCLUSION: This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  17. Periodontal disease bacteria specific to tonsil in IgA nephropathy patients predicts the remission by the treatment.

    Science.gov (United States)

    Nagasawa, Yasuyuki; Iio, Kenichiro; Fukuda, Shinji; Date, Yasuhiro; Iwatani, Hirotsugu; Yamamoto, Ryohei; Horii, Arata; Inohara, Hidenori; Imai, Enyu; Nakanishi, Takeshi; Ohno, Hiroshi; Rakugi, Hiromi; Isaka, Yoshitaka

    2014-01-01

    Immunoglobulin (Ig)A nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. Some bacteria were reported to be the candidate of the antigen or the pathogenesis of IgAN, but systematic analysis of bacterial flora in tonsil with IgAN has not been reported. Moreover, these bacteria specific to IgAN might be candidate for the indicator which can predict the remission of IgAN treated by the combination of tonsillectomy and steroid pulse. We made a comprehensive analysis of tonsil flora in 68 IgAN patients and 28 control patients using Denaturing gradient gel electrophoresis methods. We also analyzed the relationship between several bacteria specific to the IgAN and the prognosis of the IgAN. Treponema sp. were identified in 24% IgAN patients, while in 7% control patients (P = 0.062). Haemophilus segnis were detected in 53% IgAN patients, while in 25% control patients (P = 0.012). Campylobacter rectus were identified in 49% IgAN patients, while in 14% control patients (P = 0.002). Multiple Cox proportional-hazards model revealed that Treponema sp. or Campylobactor rectus are significant for the remission of proteinuria (Hazard ratio 2.35, p = 0.019). There was significant difference in remission rates between IgAN patients with Treponema sp. and those without the bacterium (p = 0.046), and in remission rates between IgAN patients with Campylobacter rectus and those without the bacterium (p = 0.037) by Kaplan-Meier analysis. Those bacteria are well known to be related with the periodontal disease. Periodontal bacteria has known to cause immune reaction and many diseases, and also might cause IgA nephropathy. This insight into IgAN might be useful for diagnosis of the IgAN patients and the decision of treatment of IgAN.

  18. Hypertext comprehension of deaf and hard-of-hearing students and students with specific language impairment

    NARCIS (Netherlands)

    Blom, H.C.; Segers, P.C.J.; Hermans, D.; Knoors, H.E.T.; Verhoeven, L.T.W.

    2017-01-01

    This paper provides insight into the reading comprehension of hierarchically structured hypertexts within D/HH students and students with SLI. To our knowledge, it is the first study on hypertext comprehension in D/HH students and students with SLI, and it also considers the role of working memory.

  19. Women-specific factors to consider in risk, diagnosis and treatment of cardiovascular disease.

    Science.gov (United States)

    Harvey, Ronée E; Coffman, Kirsten E; Miller, Virginia M

    2015-03-01

    In the era of individualized medicine, gaps in knowledge remain about sex-specific risk factors, diagnostic and treatment options that might reduce mortality from cardiovascular disease (CVD) and improve outcomes for both women and men. In this review, contributions of biological mechanisms involving the sex chromosomes and the sex hormones on the cardiovascular system will be discussed in relationship to the female-specific risk factors for CVD: hypertensive disorders of pregnancy, menopause and use of hormonal therapies for contraception and menopausal symptoms. Additionally, sex-specific factors to consider in the differential diagnosis and treatment of four prevalent CVDs (hypertension, stroke, coronary artery disease and congestive heart failure) will be reviewed with emphasis on areas where additional research is needed.

  20. Comprehensive Diabetes and Non-Communicable Disease Educator in the Low-Resource Settings.

    Science.gov (United States)

    Bhattarai, M D

    2016-01-01

    The role of self-management education in diabetes and other major non-communicable diseases is clearly evident. To take care of and educate people with diabetes and other major NCD under the supervision of medical professionals and for education of other health care professionals, Comprehensive Diabetes and NCD Educators are needed in the routine service in peripheral health clinics and hospitals. The areas of training of CDNCD educator should match with the cost-effective interventions for diabetes and other major NCD that are feasible and planned for implementation in primary care in the low resource settings. Most of such interventions are part of diabetes education as required for Diabetes Self-Management Education programmes and traditional Diabetes Educator. The addition of use of inhaled steroids and bronchodilator in chronic respiratory disease and identification of presenting features of cancer, also required for many people with diabetes with various such common co-morbidities, will complete the areas of training of traditional Diabetes Educator as that of CDNCD Educator. Staff nurse and health assistants, who are as such already providing routine clinical service to all patients including with diabetes and major NCD in peripheral health clinics and hospitals, are most appropriate for CDNCD Educator training. The training of CDNCD Educator, like that of traditional Diabetes Educator, requires fulfilment of sufficient hours of practical work experience under supervision and achievement of the essential competencies entailing at least 6 month or more of intensive training schedules to be eligible to appear in its final certifying examination.

  1. GIDEON: a comprehensive Web-based resource for geographic medicine

    Directory of Open Access Journals (Sweden)

    Berger Stephen A

    2005-04-01

    Full Text Available Abstract GIDEON (Global Infectious Diseases and Epidemiology Network is a web-based computer program designed for decision support and informatics in the field of Geographic Medicine. The first of four interactive modules generates a ranked differential diagnosis based on patient signs, symptoms, exposure history and country of disease acquisition. Additional options include syndromic disease surveillance capability and simulation of bioterrorism scenarios. The second module accesses detailed and current information regarding the status of 338 individual diseases in each of 220 countries. Over 50,000 disease images, maps and user-designed graphs may be downloaded for use in teaching and preparation of written materials. The third module is a comprehensive source on the use of 328 anti-infective drugs and vaccines, including a listing of over 9,500 international trade names. The fourth module can be used to characterize or identify any bacterium or yeast, based on laboratory phenotype. GIDEON is an up-to-date and comprehensive resource for Geographic Medicine.

  2. Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide

    Science.gov (United States)

    Hajipour, Mohammad Javad; Raheb, Jamshid; Akhavan, Omid; Arjmand, Sareh; Mashinchian, Omid; Rahman, Masoud; Abdolahad, Mohammad; Serpooshan, Vahid; Laurent, Sophie; Mahmoudi, Morteza

    2015-05-01

    The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the `personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred

  3. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

    2008-01-01

    to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also......Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...

  4. Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

    Science.gov (United States)

    2014-01-01

    While the antigenic specificity and pathogenic relevance of immunologic reactivity to gluten in celiac disease have been extensively researched, the immune response to nongluten proteins of wheat has not been characterized. We aimed to investigate the level and molecular specificity of antibody response to wheat nongluten proteins in celiac disease. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a nongluten protein extract from the wheat cultivar Triticum aestivum Butte 86. Antibodies were further analyzed for reactivity to specific nongluten proteins by two-dimensional gel electrophoresis and immunoblotting. Immunoreactive molecules were identified by tandem mass spectrometry. Compared with healthy controls, patients exhibited significantly higher levels of antibody reactivity to nongluten proteins. The main immunoreactive nongluten antibody target proteins were identified as serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. The results demonstrate that, in addition to the well-recognized immune reaction to gluten, celiac disease is associated with a robust humoral response directed at a specific subset of the nongluten proteins of wheat. PMID:25329597

  5. Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Zhi-Bo Wang; Xiaoqing Zhang; Xue-Jun Li

    2013-01-01

    Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease.Here,we developed a closely representative cell model of SMA by knocking down the disease-determining gene,survival motor neuron (SMN),in human embryonic stem cells (hESCs).Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons.Notably,the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated.Furthermore,these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-A7 (lacking exon 7)knockdown,and were specific to spinal motor neurons.Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes,including specific axonal defects and motor neuron loss.Finally,knockdown of SMNFL led to excessive mitochondrial oxidative stress in human motor neuron progenitors.The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine,a potent antioxidant,which prevented disease-related apoptosis and subsequent motor neuron death.Thus,we report here the successful establishment of an hESC-based SMA model,which exhibits disease gene isoform specificity,cell type specificity,and phenotype reversibility.Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA.

  6. Interstitial lung disease in systemic autoimmune rheumatic diseases: a comprehensive review.

    Science.gov (United States)

    Atzeni, Fabiola; Gerardi, Maria Chiara; Barilaro, Giuseppe; Masala, Ignazio Francesco; Benucci, Maurizio; Sarzi-Puttini, Piercarlo

    2018-01-01

    Interstitial lung diseases (ILDs) are among the most serious complications associated with systemic rheumatic diseases, and lead to significant morbidity and mortality; they may also be the first manifestation of connective tissue diseases (CTDs). The aim of this narrative review is to summarise the data concerning the pathogenesis of CTD/ILD and its distinguishing features in different rheumatic diseseas. Areas covered: The pathogenesis, clinical aspects and treatment of ILD associated with rheumatic systemic diseases and CTDs were reviewed by searching the PubMed, Medline, and Cochrane Library databases for papers published between 1995 and February 2017 using combinations of words or terms. Articles not written in English were excluded. Expert commentary: The management of CTD-ILD is challenging because of the lack of robust data regarding the treatments used, the heterogeneity of the diseases themselves, and the scarcity of well-defined outcome measures. Treatment decisions are often made clinically on the basis of functional, radiographic progression, and exacerbating factors such as age and the burden of comorbidities. Given the complexities of diagnosis and the paucity of treatment trials, the management of CTD patients with ILD requires multidisciplinary collaboration between rheumatologists and pulmonologists in CTD-ILD clinics.

  7. Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination.

    Science.gov (United States)

    van Wijk, Nick; Broersen, Laus M; de Wilde, Martijn C; Hageman, Robert J J; Groenendijk, Martine; Sijben, John W C; Kamphuis, Patrick J G H

    2014-01-01

    Synapse loss and synaptic dysfunction are pathological processes already involved in the early stages of Alzheimer's disease (AD). Synapses consist principally of neuronal membranes, and the neuronal and synaptic losses observed in AD have been linked to the degeneration and altered composition and structure of these membranes. Consequently, synapse loss and membrane-related pathology provide viable targets for intervention in AD. The specific nutrient combination Fortasyn Connect (FC) is designed to ameliorate synapse loss and synaptic dysfunction in AD by addressing distinct nutritional needs believed to be present in these patients. This nutrient combination comprises uridine, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium, and is present in Souvenaid, a medical food intended for use in early AD. It has been hypothesized that FC counteracts synaptic loss and reduces membrane-related pathology in AD by providing nutritional precursors and cofactors that act together to support neuronal membrane formation and function. Preclinical studies formed the basis of this hypothesis which is being validated in a broad clinical study program investigating the potential of this nutrient combination in AD. Memory dysfunction is one key early manifestation in AD and is associated with synapse loss. The clinical studies to date show that the FC-containing medical food improves memory function and preserves functional brain network organization in mild AD compared with controls, supporting the hypothesis that this intervention counteracts synaptic dysfunction. This review provides a comprehensive overview of basic scientific studies that led to the creation of FC and of its effects in various preclinical models.

  8. A non-specific biomarker of disease activity in HIV/AIDS patients ...

    African Journals Online (AJOL)

    Background: A general non-specific marker of disease activity that could alert the clinician and prompt further investiga- tion would be of ... laration of Helsinki, the National Health Act and the ..... CD8+ lymphocytes and neopterin are related to.

  9. Negative cancer stereotypes and disease-specific self-concept in head and neck cancer.

    Science.gov (United States)

    Wong, Janice C; Payne, Ada Y M; Mah, Kenneth; Lebel, Sophie; Lee, Ruth N F; Irish, Jonathan; Rodin, Gary; Devins, Gerald M

    2013-05-01

    Life-threatening diseases, such as head and neck cancer (HNCa), can stimulate the emergence of a new disease-specific self-concept. We hypothesized that (i) negative cancer-stereotypes invoke distancing, which inhibits the adoption of a disease-specific self-concept and (ii) patient characteristics, disease and treatment factors, and cancer-related stressors moderate the phenomenon. Head and neck cancer outpatients (N = 522) completed a semantic-differential measure of disease-specific self-concept (perceived similarity to the 'cancer patient') and other self-report measures in structured interviews. Negative cancer-stereotypes were represented by the number of semantic-differential dimensions (0-3) along which respondents evaluated the stereotypic 'cancer patient' negatively (i.e., negative valence). We tested the two-way interactions between negative valence and hypothesized moderator variables. We observed significant negative valence × moderator interactions for the following: (i) patient characteristics (education, employment, social networks); (ii) disease and treatment factors (cancer-symptom burden); and (iii) cancer-related stressors (uncertainty, lack of information, and existential threats). Negative cancer stereotypes were consistently associated with distancing of self from the stereotypic 'cancer patient,' but the effect varied across moderator variables. All significant moderators (except employment and social networks) were associated with increasing perceived similarity to the 'cancer patient' when respondents maintained negative stereotypes; perceived similarity decreased when people were employed or had extensive social networks. Moderator effects were less pronounced when respondents did not endorse negative cancer stereotypes. When they hold negative stereotypes, people with HNCa distance themselves from a 'cancer patient' identity to preserve self-esteem or social status, but exposure to cancer-related stressors and adaptive demands may

  10. [SWOT analysis of laboratory certification and accreditation on detection of parasitic diseases].

    Science.gov (United States)

    Xiong, Yan-hong; Zheng, Bin

    2014-04-01

    This study analyzes the strength, weakness, opportunity and threat (SWOT) of laboratory certification and accreditation on detection of parasitic diseases by SWOT analysis comprehensively, and it puts forward some development strategies specifically, in order to provide some indicative references for the further development.

  11. Clinical validity of a disease-specific health status questionnaire: the peripheral artery questionnaire.

    Science.gov (United States)

    Hoeks, Sanne E; Smolderen, Kim G; Scholte Op Reimer, Wilma J M; Verhagen, Hence J M; Spertus, John A; Poldermans, Don

    2009-02-01

    Measuring patient-centered outcomes is becoming increasingly important in patients with peripheral arterial disease (PAD), both as a means of determining the benefits of treatment and as an aid for disease management. In order to monitor health status in a reliable and sensitive way, the disease-specific measure Peripheral Artery Questionnaire (PAQ) was developed. However, to date, its correlation with traditional clinical indices is unknown. The primary aim of this study was to better establish the clinical validity of the PAQ by examining its association with functional indices related to PAD. Furthermore, we hypothesized that the clinical validity of this disease-specific measure is better as compared with the EuroQol-5-dimensional (EQ-5D), a standardized generic instrument. Data on 711 consecutive PAD patients undergoing surgery were collected from 11 Dutch hospitals in 2004. At 3-year follow-up, questionnaires including the PAQ, EQ-5D, and EuroQol-Visual Analogue Scale (EQ VAS) were completed in 84% of survivors. The PAQ was analyzed according to three domains, as established by a factor analyses in the Dutch population, and the summary score. Baseline clinical indices included the presence and severity of claudication intermittent (CI) and the Lee Cardiac Risk Index. All three PAQ domains (Physical Function, Perceived Disability, and Treatment Satisfaction) were significantly associated with CI symptoms (P values PAQ summary scores as compared with asymptomatic patients (58.6 +/- 27.8 vs 68.6 +/- 27.8, P = PAQ summary score and the subscale scores for Physical Functioning and Perceived Disability demonstrated a clear dose-response relation for walking distance and the Lee Risk Index (P values PAQ proved to be good as the PAQ subscales discriminated well between patients with or without symptomatic PAD and its severity as defined by walking distance. Furthermore, the PAQ subscales were directly proportional to the presence and number of risk factors relevant

  12. Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; van der Velde, J. L.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; DunnGalvin, A.; Hourihane, J. O.'B.; Duiverman, E. J.; Dubois, A. E. J.

    2010-01-01

    Health-related quality of life (HRQL) has never been measured with both generic and disease-specific questionnaires in the same group of food allergic patients. The aim of this study was to compare HRQL of food allergic patients as measured with generic and disease-specific questionnaires. Generic

  13. Health-related quality of life of food allergic patients measured with generic and disease-specific questionnaires

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; van der Velde, J. L.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; DunnGalvin, A.; Hourihane, J. O'B.; Duiverman, E. J.; Dubois, A. E. J.

    P>Background: Health-related quality of life (HRQL) has never been measured with both generic and disease-specific questionnaires in the same group of food allergic patients. The aim of this study was to compare HRQL of food allergic patients as measured with generic and disease-specific

  14. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

    Directory of Open Access Journals (Sweden)

    Kazuichi Okazaki

    2012-01-01

    Full Text Available Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team and the other from lymph proliferation (Umehara team supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP, compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

  15. Specific diagnosis of brain disease with double isotope brain scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J; Lotritsch, K H; Hilbrand, E; Meixner, M; Barolin, G; Scholz, H [Landesunfallkrankenhaus, Feldkirch (Austria). Dept. of Nuclear Medicine; Landesnervenkrankenhaus, Feldkirch (Austria). Dept. of Neurology)

    1976-02-01

    25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double siotope imaging technique using sup(99m)TcO/sub 4/- and sup(99m)Tc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. sup(99m)Tc-EHDP is shown to be the tracer of choice for the imaging of CVA's and sup(99m)TcO/sub 4/- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.

  16. Specific capture of target bacteria onto sensor surfaces for infectious disease diagnosis

    International Nuclear Information System (INIS)

    Kim, Jong-Hoon; Inoue, Shinnosuke; Chung, Jae-Hyun; Cangelosi, Gerard A; Lee, Kyong-Hoon

    2014-01-01

    A long-sought goal for infectious disease care is a rapid and accurate diagnostic tool that is compatible with the needs of low-resource settings. To identify target biomarkers of infectious diseases, immunoassays utilizing the binding affinity between antigen and antibody have been widely used. In immunoassays, the interaction between antigen and antibody on sensor surfaces should be precisely controlled for specific identification of targets. This paper studies the specific capturing mechanisms of target bacteria onto sensor surfaces through investigation of combined effects of capillary action and binding affinity. As a model system, cells of both Escherichia coli and the Bacillus Calmette-Guérin strain of Mycobacterium bovis were used to study specific and nonspecific capturing mechanisms onto a microtip sensor. The capillary action was observed to arrange the concentrated cells onto the two-dimensional sensor surface. Due to the capillary-induced organization of target cells on the antibody-functionalized sensor surface, the number of the captured target cells was three times greater than that of the non-targeted cells. The capturing and detection capabilities varied with the width of a microtip. The specific capturing mechanism can be used to enhance the sensitivity and specificity of an immunoassay. (paper)

  17. Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer's disease: ADAS-cog subscale results from the Alphase Study.

    Science.gov (United States)

    Saumier, D; Duong, A; Haine, D; Garceau, D; Sampalis, J

    2009-11-01

    Tramiprosate (homotaurine, ALZHEMEDTM) was recently investigated for its efficacy, safety and disease-modification effects in a Phase III clinical study in mild to moderate Alzheimer's disease (AD) patients (the Alphase study). The primary cognitive endpoint measure of that study was the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). To characterize potential cognitive benefits of tramiprosate, the present study describes exploratory analyses performed on scores obtained from the specific ADAS-cog subscales in order to determine whether specific domains of cognition may be differentially affected by tramiprosate, which would not have been evident from the measure's total score. Multi-center, double-blind, randomized, placebo-controlled study. 67 investigative sites in the United States and Canada. A total of 1,052 patients were randomized. Patients were randomized to receive twice a day Placebo (n=353), tramiprosate 100 mg (n=352) and tramiprosate 150 mg (n=347). ADAS-cog assessments were conducted every three months over the 78-week study period. Exploratory analyses were performed by comparing ADAS-cog subscale scores between Placebo and each active treatment arm at each visit. The findings of this analysis revealed statistically significant differences or statistical trends in favour of tramiprosate on six ADAS-cog subscales, namely Following Commands, Language Comprehension, Ideational Praxis, Object Naming, Remembering Test Instructions, and Spoken Language Ability. Differences in favor of Placebo were only observed on the Constructional Praxis subscale. This exploratory analysis suggests that tramiprosate may have some benefit on memory, language and praxis skills in mild to moderate AD individuals. Future clinical studies of tramiprosate should include specialized neuropsychological tests to validate its effects within these cognitive domains.

  18. Assessing reading comprehension in adolescent low achievers : Subskills identification and task specificity

    NARCIS (Netherlands)

    van Steensel, R.; Oostdam, R.; van Gelderen, A.

    2013-01-01

    On the basis of a validation study of a new test for assessing low-achieving adolescents’ reading comprehension skills – the SALT-reading – we analyzed two issues relevant to the field of reading test development. Using the test results of 200 seventh graders, we examined the possibility of

  19. Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

    Science.gov (United States)

    Passweg, Jakob; Baldomero, Helen; Stern, Martin; Bargetzi, Mario; Ghielmini, Michele; Leibundgut, Kurt; Duchosal, Michel; Hess, Urs; Seger, Reinhard; Buhrfeind, Eva; Schanz, Urs; Gratwohl, Alois

    2010-06-12

    Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

  20. A content analysis of peripheral arterial disease patient-reported outcome measures using the International Classification of Functioning, Disability and Health.

    Science.gov (United States)

    Osborne, Candice Lee; Kauvar, David Seth

    2017-10-17

    The purpose of this study was to link, classify and describe the content of peripheral arterial disease (PAD)-specific patient-reported outcome measures using the International Classification of Functioning. The results were then analyzed to determine if these assessments provide clinicians and researchers with a comprehensive understanding of the lived experience of patients with PAD. Each meaningful concept in identified PAD assessments was linked to the International Classification of Functioning, Disability and Health to determine included and excluded content areas. An overall perspective was assigned to each assessment item. Inter-rater reliability was established using a kappa statistic. The body functions component is most frequently addressed overall followed by the activities and participation component. International Classification of Functioning chapter and category distribution vary greatly between assessments and no assessment comprehensively examines community participation and relationships. The majority of the assessment items are of the health status-disability and quality of life perspectives. The results of this study suggest the need for the development of a comprehensive PAD assessment that includes a more even distribution of International Classification of Functioning topics and subtopics. A more comprehensive assessment would better capture the lived experience of this patient population. Implications for Rehabilitation A better understanding of the data collected using the current peripheral arterial disease-specific patient-reported outcome measures may contribute to the development of more comprehensive assessment tools that will ultimately lead to improved patient care. This study contributes to the preliminary foundation for the development of a peripheral arterial disease International Classification of Functioning, Disability and Health Core Set. Clinicians and researchers interested in using peripheral arterial disease-specific

  1. Can Neglected Tropical Diseases Compromise Human Wellbeing in Sex-, Age-, and Trait-Specific Ways?

    Directory of Open Access Journals (Sweden)

    David C Geary

    2016-04-01

    Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.

  2. Are NOD2 polymorphisms linked to a specific disease endophenotype of Crohn's disease?

    DEFF Research Database (Denmark)

    Jensen, Stina Rikke; Nielsen, Ole Haagen; Pedersen, Susanne Brix

    2011-01-01

    is not yet clarified. The enhanced number of pathogenic E. coli in the ileal mucosa of CD as compared to healthy controls may result from a genetically based failure in one of the intestinal bacteria sensing systems, like NOD2, making the ileal epithelium more prone to colonization with microbes harboring...... specific properties such as AIEC. Increasing the focus on defining subgroups of patients with similar disease initiations, mechanisms of action, and manifestations in CD may be pivotal for the development and implementation of future individualized treatment strategies of benefit for the single patient...

  3. Chronic phase of Chagas disease: why should it be treated? A comprehensive review

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2011-09-01

    Full Text Available The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii promote tissue regeneration to prevent fibrosis, (iii reverse existing fibrosis, (iv prevent cardiomyopathy, megaoesophagus and megacolon and (v reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

  4. Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks

    Directory of Open Access Journals (Sweden)

    Keil Andreas

    2004-10-01

    Full Text Available Abstract Background How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension. Results Amplitude-modulated (sinusoidal 41.5 Hz auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a an incomprehensible string of words, (b the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates, increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b relative to all other conditions, and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c, tone and melody relative to the other conditions, leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material. Conclusions We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

  5. Readability and comprehensibility of informed consent forms for clinical trials

    Directory of Open Access Journals (Sweden)

    Anvita Pandiya

    2010-01-01

    A shortened Informed Consent Form, with information that a reasonable person would want to understand along with specific information that the person wants in particular would be a good option to improve understanding or comprehensibility. Additional informational meetings with a qualified person like a counselor could help in comprehension. Questionnaires designed to test comprehension of patient, peer review, patient writing the salient features could help evaluate the comprehensibility of the Informed Consent Form.

  6. The peripheral artery questionnaire: a new disease-specific health status measure for patients with peripheral arterial disease.

    Science.gov (United States)

    Spertus, John; Jones, Philip; Poler, Sherri; Rocha-Singh, Krishna

    2004-02-01

    The most common indication for treating patients with peripheral arterial disease is to improve their health status: their symptoms, function, and quality of life. Quantifying health status requires a valid, reproducible, and sensitive disease-specific measure. The Peripheral Artery Questionnaire (PAQ) is a 20-item questionnaire developed to meet this need by quantifying patients' physical limitations, symptoms, social function, treatment satisfaction, and quality of life. Psychometric and clinical properties of the PAQ were evaluated in a prospective cohort study of 44 patients undergoing elective percutaneous peripheral revascularization. To establish reproducibility, 2 assessments were performed 2 weeks apart and before revascularization. The change in scores before and 6 weeks after revascularization were used to determine the instruments' responsiveness and were compared with the Short Form-36 and the Walking Impairment Questionnaire. A series of cross-sectional analyses were performed to establish the construct validity of the PAQ. The 7 domains of the PAQ were internally reliable, with Cronbach alpha = 0.80 to 0.94. The test-retest reliability analyses revealed insignificant mean changes of 0.6 to 2.3 points (P = not significant for all). Conversely, the change after revascularization ranged from 13.7 to 41.9 points (P PAQ to clinical improvement. The PAQ Summary Scale was the most sensitive of all scales tested. Construct validity was established by demonstrating correlations with other measures of patient health status. The PAQ is a valid, reliable, and responsive disease-specific measure for patients with peripheral arterial disease. It may prove to be a useful end point in clinical trials and a potential aid in disease management.

  7. Addressing non-communicable diseases in the Seychelles: towards a comprehensive plan of action.

    Science.gov (United States)

    Bovet, Pascal; Viswanathan, Bharathi; Shamlaye, Conrad; Romain, Sarah; Gedeon, Jude

    2010-06-01

    This article reviews the different steps taken during the past 20 years for the prevention and control of non-communicable diseases (NCDs) in the Seychelles. National surveys revealed high levels of several cardiovascular risk factors and prompted an organized response, starting with the creation of an NCD unit in the Ministry of Health. Information campaigns and nationwide activities raised awareness and rallied increasingly broad and high-level support. Significant policy was developed including comprehensive tobacco legislation and a School Nutrition Policy that bans soft drinks in schools. NCD guidelines were developed and specialized 'NCD nurses' were trained to complement doctors in district health centers. Decreasing smoking prevalence is evidence of success, but the raising so-called diabesity epidemic calls for an integrated multi-sector policy to mould an environment conducive to healthy behaviors. Essential components of these efforts include: effective surveillance mechanisms supplemented by focused research; generating broad interest and consensus; mobilizing leadership and commitment at all levels; involving local and international expertise; building on existing efforts; and seeking integrated, multi-disciplinary and multi-sector approaches.

  8. The Organization and Anatomy of Narrative Comprehension and Expression in Lewy Body Spectrum Disorders

    Science.gov (United States)

    Ash, Sharon; Xie, Sharon; Gross, Rachel Goldmann; Dreyfuss, Michael; Boller, Ashley; Camp, Emily; Morgan, Brianna; O’Shea, Jessica; Grossman, Murray

    2012-01-01

    Objective Patients with Lewy body spectrum disorders (LBSD) such as Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD), and dementia with Lewy bodies (DLB) exhibit deficits in both narrative comprehension and narrative expression. The present research examines the hypothesis that these impairments are due to a material-neutral deficit in organizational executive resources rather than to impairments of language per se. We predicted that comprehension and expression of narrative would be similarly affected and that deficits in both expression and comprehension of narrative would be related to the same anatomic distribution of prefrontal disease. Method We examined 29 LBSD patients and 26 healthy seniors on their comprehension and expression of narrative discourse. For comprehension, we measured accuracy and latency in judging events with high and low associativity from familiar scripts such as “going fishing.” The expression task involved maintaining the connectedness of events while narrating a story from a wordless picture book. Results LBSD patients were impaired on measures of narrative organization during both comprehension and expression relative to healthy seniors. Measures of organization during narrative expression and comprehension were significantly correlated with each other. These measures both correlated with executive measures but not with neuropsychological measures of lexical semantics or grammar. Voxel-based morphometry revealed overlapping regressions relating frontal atrophy to narrative comprehension, narrative expression, and measures of executive control. Conclusions Difficulty with narrative discourse in LBSD stems in part from a deficit of organization common to comprehension and expression. This deficit is related to prefrontal cortical atrophy in LBSD. PMID:22309984

  9. Age-specific epigenetic drift in late-onset Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Sun-Chong Wang

    Full Text Available Despite an enormous research effort, most cases of late-onset Alzheimer's disease (LOAD still remain unexplained and the current biomedical science is still a long way from the ultimate goal of revealing clear risk factors that can help in the diagnosis, prevention and treatment of the disease. Current theories about the development of LOAD hinge on the premise that Alzheimer's arises mainly from heritable causes. Yet, the complex, non-Mendelian disease etiology suggests that an epigenetic component could be involved. Using MALDI-TOF mass spectrometry in post-mortem brain samples and lymphocytes, we have performed an analysis of DNA methylation across 12 potential Alzheimer's susceptibility loci. In the LOAD brain samples we identified a notably age-specific epigenetic drift, supporting a potential role of epigenetic effects in the development of the disease. Additionally, we found that some genes that participate in amyloid-beta processing (PSEN1, APOE and methylation homeostasis (MTHFR, DNMT1 show a significant interindividual epigenetic variability, which may contribute to LOAD predisposition. The APOE gene was found to be of bimodal structure, with a hypomethylated CpG-poor promoter and a fully methylated 3'-CpG-island, that contains the sequences for the epsilon4-haplotype, which is the only undisputed genetic risk factor for LOAD. Aberrant epigenetic control in this CpG-island may contribute to LOAD pathology. We propose that epigenetic drift is likely to be a substantial mechanism predisposing individuals to LOAD and contributing to the course of disease.

  10. Disease-specific health-related quality of life instruments for IgE-mediated food allergy.

    Science.gov (United States)

    Salvilla, S A; Dubois, A E J; Flokstra-de Blok, B M J; Panesar, S S; Worth, A; Patel, S; Muraro, A; Halken, S; Hoffmann-Sommergruber, K; DunnGalvin, A; Hourihane, J O'B; Regent, L; de Jong, N W; Roberts, G; Sheikh, A

    2014-07-01

    This is one of seven interlinked systematic reviews undertaken on behalf of the European Academy of Allergy and Clinical Immunology as part of their Guidelines for Food Allergy and Anaphylaxis, which focuses on instruments developed for IgE-mediated food allergy. Disease-specific questionnaires are significantly more sensitive than generic ones in measuring the response to interventions or future treatments, as well as estimating the general burden of food allergy. The aim of this systematic review was therefore to identify which disease-specific, validated instruments can be employed to enable assessment of the impact of, and investigations and interventions for, IgE-mediated food allergy on health-related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease-specific quality of life (QOL) tools relating to IgE-mediated food allergy. From the 17 eligible studies, we identified seven disease-specific HRQL instruments, which were then subjected to detailed quality appraisal. This revealed that these instruments have undergone formal development and validation processes, and have robust psychometric properties, and therefore provide a robust means of establishing the impact of food allergy on QOL. Suitable instruments are now available for use in children, adolescents, parents/caregivers, and adults. Further work must continue to develop a clinical minimal important difference for food allergy and for making these instruments available in a wider range of European languages. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations.

    Science.gov (United States)

    Go, M F; Chan, K Y; Versalovic, J; Koeuth, T; Graham, D Y; Lupski, J R

    1995-07-01

    Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species. Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program. Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease. Cluster analysis of REP-PCR DNA fingerprints of H. pylori strains suggests that duodenal ulcer isolates, as a group, are more similar to one another and different from gastritis isolates. These results suggest that disease-specific strains may exist.

  12. Comprehensive Locoregional Treatment and Systemic Therapy for Postmastectomy Isolated Locoregional Recurrence

    International Nuclear Information System (INIS)

    Kuo, S.-H.; Huang, C.-S.; Kuo, W.-H.; Cheng, A.-L.; Chang, K.-J.; Chia-Hsien Cheng, Jason

    2008-01-01

    Purpose: To assess the impact of comprehensive locoregional therapy and systemic therapy on disease control and survival for postmastectomy patients with isolated locoregional recurrence (ILRR). Methods and Materials: A total of 115 postmastectomy breast cancer patients treated for ILRR were included. Of the patients, 98 underwent comprehensive locoregional treatment (local tumor excision plus postoperative radiotherapy), and 17 received definitive radiotherapy alone. Involved-field radiotherapy was given to 69 patients, whereas entire-field radiotherapy (both involved-field and elective-field, involving the chest wall and regional lymphatics) was given to 46 patients. Systemic therapy consisting of hormone therapy, chemotherapy, or both was given to 69% of patients. Results: Patients treated with comprehensive locoregional treatment had a significantly better 5-year invasive disease-free survival (IDFS) and overall survival (OS) after ILRR than patients treated with definitive radiotherapy alone (IDFS rate, 51% vs. 16%, p = 0.006; OS rate, 62% vs. 37%, p = 0.017). Patients with the most comprehensive locoregional treatment (recurrent tumor excision and entire-field radiotherapy) and systemic therapy had a significantly better 5-year IDFS and OS than patients given either treatment or neither treatment (IDFS rate, 52% vs. 39%, p = 0.011; OS rate, 63% vs. 50%, p = 0.026). Multivariate analysis revealed that positive axillary lymph nodes, Grade III tumor, negative estrogen and progesterone receptor status at primary diagnosis, disease-free interval of less than 2 years, and less comprehensive locoregional treatment were significantly associated with worse IDFS and OS. Conclusions: Use of comprehensive locoregional therapy and systemic therapy can achieve good survival outcome in a substantial proportion of postmastectomy patients with ILRR

  13. Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

    Science.gov (United States)

    Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

    2015-09-04

    comprehensive genetic characterization of a large collection of Chinese USH patients. Up to 90 % of USH patients have disease caused by mutations in known USH disease genes. By combining NGS-based molecular diagnosis and patient clinical information, a more accurate diagnosis, prognosis and personalized treatment of USH patients can be achieved.

  14. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  15. Design of comprehensive Alzheimer's disease centers to address unmet national needs.

    Science.gov (United States)

    Trojanowski, John Q; Arnold, Steven E; Karlawish, Jason H; Brunden, Kurt; Cary, Mark; Davatzikos, Christos; Detre, John; Gaulton, Glen; Grossman, Murray; Hurtig, Howard; Jedrziewski, Kathryn; McCluskey, Leo; Naylor, Mary; Polsky, Daniel; Schellenberg, Gerard D; Siderowf, Andrew; Shaw, Leslie M; Van Deerlin, Vivianna; Wang, Li-San; Werner, Rachel; Xie, Sharon X; Lee, Virginia M-Y

    2010-03-01

    The problem of Alzheimer's disease (AD) exemplifies the challenges of dealing with a broad range of aging-related chronic disorders that require long-term, labor-intensive, and expensive care. As the baby boom generation ages and brain diseases become more prevalent, the need to confront the pending health care crisis is more urgent than ever before. Indeed, there is now a critical need to expand significantly the national effort to solve the problem of AD, with special focus on prevention. The Campaign to Prevent Alzheimer's Disease by 2020 (PAD2020) aims to create a new paradigm for planning and supporting the organization of worldwide cooperative research networks to develop new technologies for early detection and treatments of aging-related memory and motor impairments. PAD 2020 is developing an implementation plan to justify (1) increasing the federal budget for research, (2) developing novel national resources to discover new interventions for memory and motor disorders, and (3) creating innovative and streamlined decision-making processes for selecting and supporting new ideas. Since 1978 the National Institute on Aging or National Institute of Health (NIH) established an extensive national network of AD research facilities at academic institutions including AD Centers (ADCs), Consortium to Establish a Registry for AD, AD Cooperative Study (ADCS), AD Drug Discovery Program, National Alzheimer's Coordinating Center, National Cell Repository for AD, and AD Neuroimaging Initiative. However, despite the success of these programs and their critical contributions, they are no longer adequate to meet the challenges presented by AD. PAD 2020 is designed to address these changes by improving the efficiency and effectiveness of these programs. For example, the ADCs (P30s and P50s) can be enhanced by converting some into Comprehensive Alzheimer's Disease Centers (CADCs) to support not only research, but also by being demonstration projects on care/treatment, clinical

  16. Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients

    Directory of Open Access Journals (Sweden)

    Meng-Lu Liu

    2016-01-01

    Full Text Available Subtype-specific neurons obtained from adult humans will be critical to modeling neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS. Here, we show that adult human skin fibroblasts can be directly and efficiently converted into highly pure motor neurons without passing through an induced pluripotent stem cell stage. These adult human induced motor neurons (hiMNs exhibit the cytological and electrophysiological features of spinal motor neurons and form functional neuromuscular junctions (NMJs with skeletal muscles. Importantly, hiMNs converted from ALS patient fibroblasts show disease-specific degeneration manifested through poor survival, soma shrinkage, hypoactivity, and an inability to form NMJs. A chemical screen revealed that the degenerative features of ALS hiMNs can be remarkably rescued by the small molecule kenpaullone. Taken together, our results define a direct and efficient strategy to obtain disease-relevant neuronal subtypes from adult human patients and reveal their promising value in disease modeling and drug identification.

  17. Prediction of the development of reading comprehension: a longitudinal study

    NARCIS (Netherlands)

    Verhoeven, L.T.W.; Leeuwe, J.F.J. van

    2008-01-01

    Specific effects of word decoding, vocabulary and listening comprehension abilities on the development of reading comprehension were longitudinally examined for a representative sample of 2143 Dutch children throughout the elementary school period. An attempt was made to test two theoretical

  18. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    Science.gov (United States)

    Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

    2016-01-01

    Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the

  19. Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

    Directory of Open Access Journals (Sweden)

    Katerina Markopoulou

    Full Text Available Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L, which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may

  20. Quality of life and symptoms in patients with malignant diseases admitted to a comprehensive cancer centre

    DEFF Research Database (Denmark)

    Strömgren, Lene Annette Sand; Niemann, Carsten Utoft; Tange, Ulla Brix

    2014-01-01

    PURPOSE: Quality of life and symptomatology in patients with malignancies admitted to comprehensive cancer centres are rarely investigated. Thus, this study aimed to investigate symptomatology and health-related quality of life of inpatients with cancer. METHODS: A prospective, cross......-sample test, rank tests and Fisher's exact test. RESULTS: One hundred twenty-four patients were analysed, mean age = 59 years (SD = 13.7), 42 % admitted to haematological department; lung cancer was the most frequent diagnosis (15 %). Low health-related quality of life and severe symptom burden, especially...... in oncology patients (P = 0.0194 and 0.0064, respectively). CONCLUSIONS: Patients in the wards of haematology and oncology had pronounced symptomatology and low quality of life. A more systematic focus on the amelioration of problems with functioning and symptoms among inpatients with malignant diseases...

  1. A comprehensive radiology information system

    International Nuclear Information System (INIS)

    Jost, R.G.

    1985-01-01

    DECrad version II was recently tested by members of the Radiology Information System Consortium (RISC) and was found to meet the specifications prepared by the consortium. It is a comprehensive tailorable system that can be interfaced to practically any HIS. This paper provides an overall view of the major functions of the system which include registration, scheduling, tracking, film library management, reporting, statistics, and teaching modules. The evolution of the specification and user experiences is reported

  2. Imaging of congenital heart disease in adults: choice of modalities.

    Science.gov (United States)

    Orwat, Stefan; Diller, Gerhard-Paul; Baumgartner, Helmut

    2014-01-01

    Major advances in noninvasive imaging of adult congenital heart disease have been accomplished. These tools play now a key role in comprehensive diagnostic work-up, decision for intervention, evaluation for the suitability of specific therapeutic options, monitoring of interventions and regular follow-up. Besides echocardiography, magnetic resonance (CMR) and computed tomography (CT) have gained particular importance. The choice of imaging modality has thus become a critical issue. This review summarizes strengths and limitations of the different imaging modalities and how they may be used in a complementary fashion. Echocardiography obviously remains the workhorse of imaging routinely used in all patients. However, in complex disease and after surgery echocardiography alone frequently remains insufficient. CMR is particularly useful in this setting and allows reproducible and accurate quantification of ventricular function and comprehensive assessment of cardiac anatomy, aorta, pulmonary arteries and venous return including complex flow measurements. CT is preferred when CMR is contraindicated, when superior spatial resolution is required or when "metallic" artefacts limit CMR imaging. In conclusion, the use of currently available imaging modalities in adult congenital heart disease needs to be complementary. Echocardiography remains the basis tool, CMR and CT should be added considering specific open questions and the ability to answer them, availability and economic issues.

  3. Contribution of Electronic Medical Records to the Management of Rare Diseases

    Directory of Open Access Journals (Sweden)

    Dominique Bremond-Gignac

    2015-01-01

    Full Text Available Purpose. Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients’ data with ophthalmology-specific EMR. Methods. Ophthalmology-specific EMR software (Softalmo software Corilus was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. Results. A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. Discussion. EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. Conclusion. Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease.

  4. Contribution of Electronic Medical Records to the Management of Rare Diseases.

    Science.gov (United States)

    Bremond-Gignac, Dominique; Lewandowski, Elisabeth; Copin, Henri

    2015-01-01

    Electronic health record systems provide great opportunity to study most diseases. Objective of this study was to determine whether electronic medical records (EMR) in ophthalmology contribute to management of rare eye diseases, isolated or in syndromes. Study was designed to identify and collect patients' data with ophthalmology-specific EMR. Ophthalmology-specific EMR software (Softalmo software Corilus) was used to acquire ophthalmological ocular consultation data from patients with five rare eye diseases. The rare eye diseases and data were selected and collected regarding expertise of eye center. A total of 135,206 outpatient consultations were performed between 2011 and 2014 in our medical center specialized in rare eye diseases. The search software identified 29 congenital aniridia, 6 Axenfeld/Rieger syndrome, 11 BEPS, 3 Nanophthalmos, and 3 Rubinstein-Taybi syndrome. EMR provides advantages for medical care. The use of ophthalmology-specific EMR is reliable and can contribute to a comprehensive ocular visual phenotype useful for clinical research. Routinely EMR acquired with specific software dedicated to ophthalmology provides sufficient detail for rare diseases. These software-collected data appear useful for creating patient cohorts and recording ocular examination, avoiding the time-consuming analysis of paper records and investigation, in a University Hospital linked to a National Reference Rare Center Disease.

  5. Effects of reciprocal teaching on reading comprehension of low-achieving adolescents. The importance of specific teacher skills

    NARCIS (Netherlands)

    M. Okkinga; Dr. A.J.S. van Gelderen; R. van Steensel

    2016-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects

  6. Effects of reciprocal teaching on reading comprehension of low-achieving adolescents. The importance of specific teacher skills

    NARCIS (Netherlands)

    Okkinga, Mariska; van Steensel, Roel; van Gelderen, Amos J.S.; Sleegers, Peter J.C.

    2018-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects

  7. Comprehensive genetic study of fatty acids helps explain the role of noncoding inflammatory bowel disease associated SNPs and fatty acid metabolism in disease pathogenesis.

    Science.gov (United States)

    Jezernik, Gregor; Potočnik, Uroš

    2018-03-01

    Fatty acids and their derivatives play an important role in inflammation. Diet and genetics influence fatty acid profiles. Abnormalities of fatty acid profiles have been observed in inflammatory bowel diseases (IBD), a group of complex diseases defined by chronic gastrointestinal inflammation. IBD associated fatty acid profile abnormalities were observed independently of nutritional status or disease activity, suggesting a common genetic background. However, no study so far has attempted to look for overlap between IBD loci and fatty acid associated loci or investigate the genetics of fatty acid profiles in IBD. To this end, we conducted a comprehensive genetic study of fatty acid profiles in IBD using iCHIP, a custom microarray platform designed for deep sequencing of immune-mediated disease associated loci. This study identifies 10 loci associated with fatty acid profiles in IBD. The most significant associations were a locus near CBS (p = 7.62 × 10 -8 ) and a locus in LRRK2 (p = 1.4 × 10 -7 ). Of note, this study replicates the FADS gene cluster locus, previously associated with both fatty acid profiles and IBD pathogenesis. Furthermore, we identify 18 carbon chain trans-fatty acids (p = 1.12 × 10 -3 ), total trans-fatty acids (p = 4.49 × 10 -3 ), palmitic acid (p = 5.85 × 10 -3 ) and arachidonic acid (p = 8.58 × 10 -3 ) as significantly associated with IBD pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Tract specific analysis in patients with sickle cell disease

    Science.gov (United States)

    Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

    2015-12-01

    Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

  9. A protocol for comprehensive assessment of bulbar dysfunction in amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Yunusova, Yana; Green, Jordan R; Wang, Jun; Pattee, Gary; Zinman, Lorne

    2011-02-21

    Improved methods for assessing bulbar impairment are necessary for expediting diagnosis of bulbar dysfunction in ALS, for predicting disease progression across speech subsystems, and for addressing the critical need for sensitive outcome measures for ongoing experimental treatment trials. To address this need, we are obtaining longitudinal profiles of bulbar impairment in 100 individuals based on a comprehensive instrumentation-based assessment that yield objective measures. Using instrumental approaches to quantify speech-related behaviors is very important in a field that has primarily relied on subjective, auditory-perceptual forms of speech assessment(1). Our assessment protocol measures performance across all of the speech subsystems, which include respiratory, phonatory (laryngeal), resonatory (velopharyngeal), and articulatory. The articulatory subsystem is divided into the facial components (jaw and lip), and the tongue. Prior research has suggested that each speech subsystem responds differently to neurological diseases such as ALS. The current protocol is designed to test the performance of each speech subsystem as independently from other subsystems as possible. The speech subsystems are evaluated in the context of more global changes to speech performance. These speech system level variables include speaking rate and intelligibility of speech. The protocol requires specialized instrumentation, and commercial and custom software. The respiratory, phonatory, and resonatory subsystems are evaluated using pressure-flow (aerodynamic) and acoustic methods. The articulatory subsystem is assessed using 3D motion tracking techniques. The objective measures that are used to quantify bulbar impairment have been well established in the speech literature and show sensitivity to changes in bulbar function with disease progression. The result of the assessment is a comprehensive, across-subsystem performance profile for each participant. The profile, when compared to

  10. How working memory relates to children's reading comprehension: The importance of domain-specificity in storage and processing

    NARCIS (Netherlands)

    Nouwens, S.; Groen, M.A.; Verhoeven, L.T.W.

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the

  11. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  12. Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimer's Disease

    Science.gov (United States)

    Wilke, Scott A.; Raam, Tara; Antonios, Joseph K.; Bushong, Eric A.; Koo, Edward H.; Ellisman, Mark H.; Ghosh, Anirvan

    2014-01-01

    The earliest stages of Alzheimer's disease (AD) are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber (MF) synapse between dentate gyrus (DG) and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy (SBEM) to analyze MF microcircuitry in a mouse model of familial Alzheimer's disease (FAD). FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease. PMID:24454724

  13. A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

    Science.gov (United States)

    Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

    2017-12-20

    Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

  14. Controlling the Regional Identity of hPSC-Derived Neurons to Uncover Neuronal Subtype Specificity of Neurological Disease Phenotypes

    Directory of Open Access Journals (Sweden)

    Kent Imaizumi

    2015-12-01

    Full Text Available The CNS contains many diverse neuronal subtypes, and most neurological diseases target specific subtypes. However, the mechanism of neuronal subtype specificity of disease phenotypes remains elusive. Although in vitro disease models employing human pluripotent stem cells (PSCs have great potential to clarify the association of neuronal subtypes with disease, it is currently difficult to compare various PSC-derived subtypes. This is due to the limited number of subtypes whose induction is established, and different cultivation protocols for each subtype. Here, we report a culture system to control the regional identity of PSC-derived neurons along the anteroposterior (A-P and dorsoventral (D-V axes. This system was successfully used to obtain various neuronal subtypes based on the same protocol. Furthermore, we reproduced subtype-specific phenotypes of amyotrophic lateral sclerosis (ALS and Alzheimer’s disease (AD by comparing the obtained subtypes. Therefore, our culture system provides new opportunities for modeling neurological diseases with PSCs.

  15. Application of a disease-specific mapping function to estimate utility gains with effective treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Rupnow Marcia FT

    2005-09-01

    Full Text Available Abstract Background Most tools for estimating utilities use clinical trial data from general health status models, such as the 36-Item Short-Form Health Survey (SF-36. A disease-specific model may be more appropriate. The objective of this study was to apply a disease-specific utility mapping function for schizophrenia to data from a large, 1-year, open-label study of long-acting risperidone and to compare its performance with an SF-36-based utility mapping function. Methods Patients with schizophrenia or schizoaffective disorder by DSM-IV criteria received 25, 50, or 75 mg long-acting risperidone every 2 weeks for 12 months. The Positive and Negative Syndrome Scale (PANSS and SF-36 were used to assess efficacy and health-related quality of life. Movement disorder severity was measured using the Extrapyramidal Symptom Rating Scale (ESRS; data concerning other common adverse effects (orthostatic hypotension, weight gain were collected. Transforms were applied to estimate utilities. Results A total of 474 patients completed the study. Long-acting risperidone treatment was associated with a utility gain of 0.051 using the disease-specific function. The estimated gain using an SF-36-based mapping function was smaller: 0.0285. Estimates of gains were only weakly correlated (r = 0.2. Because of differences in scaling and variance, the requisite sample size for a randomized trial to confirm observed effects is much smaller for the disease-specific mapping function (156 versus 672 total subjects. Conclusion Application of a disease-specific mapping function was feasible. Differences in scaling and precision suggest the clinically based mapping function has greater power than the SF-36-based measure to detect differences in utility.

  16. 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.

  17. Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

    Science.gov (United States)

    Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

    2015-07-01

    We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

  18. Disease-specific health-related quality of life in patients with esophageal achalasia before and after therapy.

    Science.gov (United States)

    Garrigues, V; Ortiz, V; Casanova, C; Bujanda, L; Moreno-Osset, E; Rodríguez-Téllez, M; Montserrat, A; Brotons, A; Fort, E; Ponce, J

    2010-07-01

    To evaluate disease-specific health-related quality of life (HRQoL) in patients with symptomatic esophageal achalasia before and after therapy. Symptoms and disease-specific HRQoL were evaluated before and 3 months after therapy. Therapy selection, either dilatation or myotomy, depended exclusively on the opinion of the physician on charge of the patient. Symptom severity was graded from 0 to 3, using a scoring system. A disease-specific questionnaire for achalasia developed and validated in Spanish language with 18 items and four subscales (AE-18) was used to evaluate HRQoL. Changes after therapy in HRQoL and its association with clinical improvement were analyzed. Sixty-five patients were prospectively included in eight hospitals in Spain. Of them, 47 were treated with dilatation, and 18 with laparoscopic Heller myotomy. After therapy, AE-18 global and subscales scores improved significantly. Changes in HRQoL were associated with improvement in symptoms. An important improvement in symptoms (>or=50%) was needed to obtain a minimal clinically important improvement (>or=20%) in HRQoL. Disease-specific HRQoL improves in patients with symptomatic achalasia after therapy with dilatation or myotomy. The degree of improvement of HRQoL depends on the degree of improvement of esophageal symptoms.

  19. Effects of Reciprocal Teaching on Reading Comprehension of Low-Achieving Adolescents. The Importance of Specific Teacher Skills

    Science.gov (United States)

    Okkinga, Mariska; van Steensel, Roel; van Gelderen, Amos J. S.; Sleegers, Peter J. C.

    2018-01-01

    Low-achieving adolescents are known to have difficulties with reading comprehension. This article discusses how reciprocal teaching can improve low-achieving adolescents' reading comprehension in whole-classroom settings (as opposed to small-group settings) and to what extent intervention effects are dependent on teacher behaviour. Over the course…

  20. Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

    Science.gov (United States)

    Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

    2018-04-12

    To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

  1. Comprehensive Performance Nutrition for Special Operations Forces.

    Science.gov (United States)

    Daigle, Karen A; Logan, Christi M; Kotwal, Russ S

    2015-01-01

    Special Operations Forces (SOF) training, combat, and contingency operations are unique and demanding. Performance nutrition within the Department of Defense has emphasized that nutrition is relative to factors related to the desired outcome, which includes successful performance of mentally and physically demanding operations and missions of tactical and strategic importance, as well as nonoperational assignments. Discussed are operational, nonoperational, and patient categories that require different nutrition strategies to facilitate category-specific performance outcomes. Also presented are 10 major guidelines for a SOF comprehensive performance nutrition program, practical nutrition recommendations for Special Operators and medical providers, as well as resources for dietary supplement evaluation. Foundational health concepts, medical treatment, and task-specific performance factors should be considered when developing and systematically implementing a comprehensive SOF performance nutrition program. When tailored to organizational requirements, SOF unit- and culture-specific nutrition education and services can optimize individual Special Operator performance, overall unit readiness, and ultimately, mission success. 2015.

  2. Cardiovascular magnetic resonance in carotid atherosclerotic disease

    Directory of Open Access Journals (Sweden)

    Chen Huijun

    2009-12-01

    Full Text Available Abstract Atherosclerosis is a chronic, progressive, inflammatory disease affecting many vascular beds. Disease progression leads to acute cardiovascular events such as myocardial infarction, stroke and death. The diseased carotid alone is responsible for one third of the 700,000 new or recurrent strokes occurring yearly in the United States. Imaging plays an important role in the management of atherosclerosis, and cardiovascular magnetic resonance (CMR of the carotid vessel wall is one promising modality in the evaluation of patients with carotid atherosclerotic disease. Advances in carotid vessel wall CMR allow comprehensive assessment of morphology inside the wall, contributing substantial disease-specific information beyond luminal stenosis. Although carotid vessel wall CMR has not been widely used to screen for carotid atherosclerotic disease, many trials support its potential for this indication. This review summarizes the current state of knowledge regarding carotid vessel wall CMR and its potential clinical application for management of carotid atherosclerotic disease.

  3. Multiple sclerosis care: an integrated disease-management model.

    Science.gov (United States)

    Burks, J

    1998-04-01

    A disease-management model must be integrated, comprehensive, individual patient focused and outcome driven. In addition to high quality care, the successful model must reduce variations in care and costs. MS specialists need to be intimately involved in the long-term care of MS patients, while not neglecting primary care issues. A nurse care manager is the "glue" between the managed care company, health care providers and the patient/family. Disease management focuses on education and prevention, and can be cost effective as well as patient specific. To implement a successful program, managed care companies and health care providers must work together.

  4. Development of comprehensive image processing technique for differential diagnosis of liver disease by using multi-modality images. Pixel-based cross-correlation method using a profile

    International Nuclear Information System (INIS)

    Inoue, Akira; Okura, Yasuhiko; Akiyama, Mitoshi; Ishida, Takayuki; Kawashita, Ikuo; Ito, Katsuyoshi; Matsunaga, Naofumi; Sanada, Taizo

    2009-01-01

    Imaging techniques such as high magnetic field imaging and multidetector-row CT have been markedly improved recently. The final image-reading systems easily produce more than a thousand diagnostic images per patient. Therefore, we developed a comprehensive cross-correlation processing technique using multi-modality images, in order to decrease the considerable time and effort involved in the interpretation of a radiogram (multi-formatted display and/or stack display method, etc). In this scheme, the criteria of an attending radiologist for the differential diagnosis of liver cyst, hemangioma of liver, hepatocellular carcinoma, and metastatic liver cancer on magnetic resonance images with various sequences and CT images with and without contrast enhancement employ a cross-correlation coefficient. Using a one-dimensional cross-correlation method, comprehensive image processing could be also adapted for various artifacts (some depending on modality imaging, and some on patients), which may be encountered at the clinical scene. This comprehensive image-processing technique could assist radiologists in the differential diagnosis of liver diseases. (author)

  5. Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

    Science.gov (United States)

    Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo

    2017-03-01

    The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. How Working Memory Relates to Children's Reading Comprehension: The Importance of Domain-Specificity in Storage and Processing

    Science.gov (United States)

    Nouwens, Suzan; Groen, Margriet A.; Verhoeven, Ludo

    2017-01-01

    Working memory is considered a well-established predictor of individual variation in reading comprehension in children and adults. However, how storage and processing capacities of working memory in both the phonological and semantic domain relate to reading comprehension is still unclear. In the current study, we investigated the contribution of…

  7. The prospective relationship between work stressors and cardiovascular disease, using a comprehensive work stressor measure for exposure assessment.

    Science.gov (United States)

    Szerencsi, Karolina; van Amelsvoort, Ludovic; Prins, Martin; Kant, Ijmert

    2014-02-01

    The currently used instruments which measure the psychosocial work environment have been criticized. We analyzed the association between work stressors and cardiovascular disease, using the Maastricht Cohort Study Work Stressor Score (MCS-WSS), a comprehensive measure which has been associated with work strain. At baseline 11,489 employees of the Maastricht Cohort Study were participating. This prospective cohort study started in 1998 in the Netherlands and includes a heterogeneous population of employees. The psychosocial work environment, cardiovascular risk factors and the occurrence of cardiovascular disease were measured with questionnaires at various time points during follow-up, the last follow-up was in 2008. For a subsample of employees, CVD extracted from medical records was available. The MCS-WSS consists of items from emotional demands, psychological demands, role clarity, career possibilities, working overtime, job insecurity, cognitive demands, skills discretion and decision authority. Each item has its own contribution in inducing work strain, represented by its own weighting factor. The association between a high exposure to work stressors at baseline and cardiovascular morbidity was assessed with Cox regression analyses. Analyses were adjusted for age, gender, educational level, smoking, body mass index, alcohol consumption and leisure physical activity. During a median follow-up of 49 months, 309 employees developed incident cardiovascular disease. Overall, no significant associations were found between a high exposure to work stressors at baseline and cardiovascular morbidity. The results of this study indicate that high exposure to work stressors has no considerable impact on cardiovascular disease.

  8. Listening comprehension in preschoolers: the role of memory.

    Science.gov (United States)

    Florit, Elena; Roch, Maja; Altoè, Gianmarco; Levorato, Maria Chiara

    2009-11-01

    The current study analyzed the relationship between text comprehension and memory skills in preschoolers. We were interested in verifying the hypothesis that memory is a specific contributor to listening comprehension in preschool children after controlling for verbal abilities. We were also interested in analyzing the developmental path of the relationship between memory skills and listening comprehension in the age range considered. Forty-four, 4-year-olds (mean age = 4 years and 6 months, SD = 4 months) and 40, 5-year-olds (mean age = 5 years and 4 months, SD = 5 months) participated in the study. The children were administered measures to evaluate listening comprehension ability (story comprehension), short-term and working memory skills (forward and backward word span), verbal intelligence and receptive vocabulary. Results showed that both short-term and working memory predicted unique and independent variance in listening comprehension after controlling for verbal abilities, with working memory explaining additional variance over and above short-term memory. The predictive power of memory skills was stable in the age range considered. Results also confirm a strong relation between verbal abilities and listening comprehension in 4- and 5-year-old children.

  9. Specific deficit of colour-colour short-term memory binding in sporadic and familial Alzheimer's disease.

    Science.gov (United States)

    Parra, Mario A; Sala, Sergio Della; Abrahams, Sharon; Logie, Robert H; Méndez, Luis Guillermo; Lopera, Francisco

    2011-06-01

    Short-term memory binding of visual features which are processed across different dimensions (shape-colour) is impaired in sporadic Alzheimer's disease, familial Alzheimer's disease, and in asymptomatic carriers of familial Alzheimer's disease. This study investigated whether Alzheimer's disease also impacts on within-dimension binding processes. The study specifically explored whether visual short-term memory binding of features of the same type (colour-colour) is sensitive to Alzheimer's disease. We used a neuropsychological battery and a short-term memory binding task to assess patients with sporadic Alzheimer's disease (Experiment 1), familial Alzheimer's disease (Experiment 2) due to the mutation E280A of the Presenilin-1 gene and asymptomatic carriers of the mutation. The binding task assessed change detection within arrays of unicoloured objects (Colour Only) or bicoloured objects the colours of which had to be remembered separately (Unbound Colours) or together (Bound Colours). Performance on the Bound Colours condition (1) explained the largest proportion of variance between patients (sporadic and familial Alzheimer's disease), (2) combined more sensitivity and specificity for the disease than other more traditional neuropsychological tasks, (3) identified asymptomatic carriers of the mutation even when traditional neuropsychological measures and other measures of short-term memory did not and, (4) contrary to shape-colour binding, correlated with measures of hippocampal functions. Colour-colour binding and shape-colour binding both appear to be sensitive to AD even though they seem to rely on different brain mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Determining Specific Window Period for Common Scab Disease Infection in Potato Tubers

    Directory of Open Access Journals (Sweden)

    Bhim Bahadur Khatri

    2017-05-01

    Full Text Available A series of experiments was conducted under glasshouse and hydroponic conditions to determine the specific window period for common scab disease infection in potato tubers. The study was performed in a glasshouse system where separate tubers from the root zone were inoculated at different intervals during plant growth along with a novel hydroponic system to inoculate individual tubers at specific times of development growth allowing non-destructive observations of common scab symptoms developing. The window of tuber susceptibility to common scab disease infection was shown to vary with the season or conditions under which the plants were grown. Different internodes on tubers were found susceptible to infection at different times during tuber development. Basal internodes, which are the first sections of the tuber to expand, were susceptible to infection in the beginning of tuber development, whereas apical internodes only became susceptible later in tuber growth when the basal internodes were no longer susceptible.

  11. ALLERGEN-SPECIFIC IMMUNOTHERAPY: VACCINES FOR ALLERGIC DISEASES

    Directory of Open Access Journals (Sweden)

    A. S. Fedorov

    2015-01-01

    Full Text Available Allergen-specific immunotherapy (ASIT is the most effective method of allergy treatment which consists of exposure to small doses of antigen responsible for development of allergic condition in the particular patient. Therefore, one may achieve desensitization to this antigen. The history of ASIT application lasts for more than 100 years, and, over this time, huge clinical evidence for the usage of the method has been accumulated. Use of ASIT causes reduction of allergy symptoms and treatment needs and, moreover, it has the potential for long-term clinical benefit, by preventing the development of allergy and its symptoms. The treatment affects basic immunological mechanisms responsible for the development of clinical symptoms. ASIT is an antiinflammatory, pathogenetic and prophylactic treatment of allergic airway disease. The review considers the results of major clinical trials of the ASIT applications for treatment of allergic diseases of the respiratory system (allergic rhinitis and bronchial asthma. Various schemes of ASIT are discussed including its different variants (injectable and sublingual ASIT, the issues of preparation choice for ASIT from those currently available on the pharmaceutical market, patient selection criteria, and the issues of modern molecular allergodiagnostic (allergic sensitization mapping of the patient at molecular level, in order to optimize them. Immunological mechanisms of ASIT are also considered, since appropriate views are rather contraversial. The ASIT effect is mediated through the following basic immunological mechanisms: the suppressed increase of the eosinophil concentrations, reduced duration of the delayed hypersensitivity phase, as well as initiation and maintenance of the Th2-to-Th1-like immune response transition. Regulatory T-cells play a major role in implementation of the immunological mechanism in ASIT, they have a significant impact on the Th2 response suppression. Such suppression may proceed

  12. Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

    Science.gov (United States)

    Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

    2016-01-01

    Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

  13. Targeting Specific HATs for Neurodegenerative Disease Treatment: Translating Basic Biology to Therapeutic Possibilities

    Directory of Open Access Journals (Sweden)

    Sheila K. Pirooznia

    2013-03-01

    Full Text Available Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HATs activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and

  14. Memory mechanisms supporting syntactic comprehension.

    Science.gov (United States)

    Caplan, David; Waters, Gloria

    2013-04-01

    Efforts to characterize the memory system that supports sentence comprehension have historically drawn extensively on short-term memory as a source of mechanisms that might apply to sentences. The focus of these efforts has changed significantly in the past decade. As a result of changes in models of short-term working memory (ST-WM) and developments in models of sentence comprehension, the effort to relate entire components of an ST-WM system, such as those in the model developed by Baddeley (Nature Reviews Neuroscience 4: 829-839, 2003) to sentence comprehension has largely been replaced by an effort to relate more specific mechanisms found in modern models of ST-WM to memory processes that support one aspect of sentence comprehension--the assignment of syntactic structure (parsing) and its use in determining sentence meaning (interpretation) during sentence comprehension. In this article, we present the historical background to recent studies of the memory mechanisms that support parsing and interpretation and review recent research into this relation. We argue that the results of this research do not converge on a set of mechanisms derived from ST-WM that apply to parsing and interpretation. We argue that the memory mechanisms supporting parsing and interpretation have features that characterize another memory system that has been postulated to account for skilled performance-long-term working memory. We propose a model of the relation of different aspects of parsing and interpretation to ST-WM and long-term working memory.

  15. Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature.

    Science.gov (United States)

    Haberman, Yael; Tickle, Timothy L; Dexheimer, Phillip J; Kim, Mi-Ok; Tang, Dora; Karns, Rebekah; Baldassano, Robert N; Noe, Joshua D; Rosh, Joel; Markowitz, James; Heyman, Melvin B; Griffiths, Anne M; Crandall, Wallace V; Mack, David R; Baker, Susan S; Huttenhower, Curtis; Keljo, David J; Hyams, Jeffrey S; Kugathasan, Subra; Walters, Thomas D; Aronow, Bruce; Xavier, Ramnik J; Gevers, Dirk; Denson, Lee A

    2014-08-01

    Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.

  16. Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease

    Science.gov (United States)

    Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas

    2010-01-01

    Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection. PMID:20696822

  17. Are generic and disease-specific health related quality of life correlated? The case of chronic lung disease due to sulfur mustard

    Directory of Open Access Journals (Sweden)

    Shervin Assari

    2009-09-01

    Full Text Available

    • BACKGROUND: The aim of this study was to investigate the association between the two most commonly used generic and disease specific health-related quality of life (HRQoL measures in patients with chronic lung disease due to SM: Medical Outcomes Study Short Form 36-Item (SF-36 and St George's Respiratory Questionnaire (SGRQ.
    • METHODS: This is a secondary analysis of Iranian Chemical Warfare Victims Health Assessment Study (ICWVHAS during October 2007 in Isfahan, Iran. In that survey, conducted in an outpatient setting, 292 patients with chronic lung disease due to SM were selected from all provinces in Iran. The total score and sub scores of correlations of SGRQ and SF-36 were assessed. Correlation of quality-of-life scores were evaluated using Pearson’s coefficient.
    • RESULTS: Samples were 276 patients who were selected for our analysis. No significant correlation was found between the total score or sub scores of SF-36 and the total score or sub scores of SGRQ (p > 0.05.
    • CONCLUSIONS: In patients with chronic lung disease due to SM, the SF-36 and SGRQ assess different aspects of HRQoL. Therefore applying both of them together, at least in the research setting is suggested.
    • KEYWORDS: Chronic Lung Disease, Health Related Quality of Life, Generic Health Related Quality of Life, Disease Specific Health Related Quality of Life, Sulfur Mustard.

  18. Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

    Science.gov (United States)

    Ai, Rizi; Laragione, Teresina; Hammaker, Deepa; Boyle, David L; Wildberg, Andre; Maeshima, Keisuke; Palescandolo, Emanuele; Krishna, Vinod; Pocalyko, David; Whitaker, John W; Bai, Yuchen; Nagpal, Sunil; Bachman, Kurtis E; Ainsworth, Richard I; Wang, Mengchi; Ding, Bo; Gulko, Percio S; Wang, Wei; Firestein, Gary S

    2018-05-15

    Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets.

  19. Specific reduction of calcium-binding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases

    International Nuclear Information System (INIS)

    Iacopino, A.M.; Christakos, S.

    1990-01-01

    The present studies establish that there are specific, significant decreases in the neuronal calcium-binding protein (28-kDa calbindin-D) gene expression in aging and in neurodegenerative diseases. The specificity of the changes observed in calbindin mRNA levels was tested by reprobing blots with calmodulin, cyclophilin, and B-actin cDNAs. Gross brain regions of the aging rat exhibited specific, significant decreases in calbindin·mRNA and protein levels in the cerebellum, corpus striatum, and brain-stem region but not in the cerebral cortex or hippocampus. Discrete areas of the aging human brain exhibited significant decreases in calbindin protein and mRNA in the cerebellum, corpus striatum, and nucleus basalis but not in the neocortex, hippocampus, amygdala, locus ceruleus, or nucleus raphe dorsalis. Comparison of diseased human brain tissue with age- and sex-matched controls yielded significant decreases calbindin protein and mRNA in the substantia nigra (Parkinson disease), in the corpus striatum (Huntington disease), in the nucleus basalis (Alzheimer disease), and in the hippocampus and nucleus raphe dorsalis (Parkinson, Huntington, and Alzheimer diseases) but not in the cerebellum, neocortex, amygdala, or locus ceruleus. These findings suggest that decreased calbindin gene expression may lead to a failure of calcium buffering or intraneuronal calcium homeostasis, which contributes to calcium-mediated cytotoxic events during aging and in the pathogenesis of neurodegenerative diseases

  20. Modulation of Trypanosoma cruzi-specific T-cell responses after chemotherapy for chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    María Cecilia Albareda

    2015-05-01

    Full Text Available The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th1 and interleukin (IL-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

  1. Assessing children's inference generation: what do tests of reading comprehension measure?

    Science.gov (United States)

    Bowyer-Crane, Claudine; Snowling, Margaret J

    2005-06-01

    Previous research suggests that children with specific comprehension difficulties have problems with the generation of inferences. This raises important questions as to whether poor comprehenders have poor comprehension skills generally, or whether their problems are confined to specific inference types. The main aims of the study were (a) using two commonly used tests of reading comprehension to classify the questions requiring the generation of inferences, and (b) to investigate the relative performance of skilled and less-skilled comprehenders on questions tapping different inference types. The performance of 10 poor comprehenders (mean age 110.06 months) was compared with the performance of 10 normal readers (mean age 112.78 months) on two tests of reading comprehension. A qualitative analysis of the NARA II (form 1) and the WORD comprehension subtest was carried out. Participants were then administered the NARA II, WORD comprehension subtest and a test of non-word reading. The NARA II was heavily reliant on the generation of knowledge-based inferences, while the WORD comprehension subtest was biased towards the retention of literal information. Children identified by the NARA II as having comprehension difficulties performed in the normal range on the WORD comprehension subtests. Further, children with comprehension difficulties performed poorly on questions requiring the generation of knowledge-based and elaborative inferences. However, they were able to answer questions requiring attention to literal information or use of cohesive devices at a level comparable to normal readers. Different reading tests tap different types of inferencing skills. Lessskilled comprehenders have particular difficulty applying real-world knowledge to a text during reading, and this has implications for the formulation of effective intervention strategies.

  2. Calcific Aortic Valve Disease Is Associated with Layer-Specific Alterations in Collagen Architecture.

    Directory of Open Access Journals (Sweden)

    Heather N Hutson

    Full Text Available Disorganization of the valve extracellular matrix (ECM is a hallmark of calcific aortic valve disease (CAVD. However, while microarchitectural features of the ECM can strongly influence the biological and mechanical behavior of tissues, little is known about the ECM microarchitecture in CAVD. In this work, we apply advanced imaging techniques to quantify spatially heterogeneous changes in collagen microarchitecture in CAVD. Human aortic valves were obtained from individuals between 50 and 75 years old with no evidence of valvular disease (healthy and individuals who underwent valve replacement surgery due to severe stenosis (diseased. Second Harmonic Generation microscopy and subsequent image quantification revealed layer-specific changes in fiber characteristics in healthy and diseased valves. Specifically, the majority of collagen fiber changes in CAVD were found to occur in the spongiosa, where collagen fiber number increased by over 2-fold, and fiber width and density also significantly increased. Relatively few fibrillar changes occurred in the fibrosa in CAVD, where fibers became significantly shorter, but did not otherwise change in terms of number, width, density, or alignment. Immunohistochemical staining for lysyl oxidase showed localized increased expression in the diseased fibrosa. These findings reveal a more complex picture of valvular collagen enrichment and arrangement in CAVD than has previously been described using traditional analysis methods. Changes in fiber architecture may play a role in regulating the pathobiological events and mechanical properties of valves during CAVD. Additionally, characterization of the ECM microarchitecture can inform the design of fibrous scaffolds for heart valve tissue engineering.

  3. Language impairment in Alzheimer's disease and benefits of acetylcholinesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Ferris SH

    2013-08-01

    Full Text Available Steven H Ferris,1 Martin Farlow21Alzheimer's Disease Center, Comprehensive Center on Brain Aging, New York University Langone Medical Center, New York, NY, 2Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USAAbstract: Alzheimer's disease is characterized by progressively worsening deficits in several cognitive domains, including language. Language impairment in Alzheimer's disease primarily occurs because of decline in semantic and pragmatic levels of language processing. Given the centrality of language to cognitive function, a number of language-specific scales have been developed to assess language deficits throughout progression of the disease and to evaluate the effects of pharmacotherapy on language function. Trials of acetylcholinesterase inhibitors, used for the treatment of clinical symptoms of Alzheimer's disease, have generally focused on overall cognitive effects. However, in the current report, we review data indicating specific beneficial effects of acetylcholinesterase inhibitors on language abilities in patients with Alzheimer’s disease, with a particular focus on outcomes among patients in the moderate and severe disease stages, during which communication is at risk and preservation is particularly important.Keywords: Alzheimer's disease, donepezil, cognition, language, communication, clinical trials

  4. Bayesian Estimation of Fish Disease Prevalence from Pooled Samples Incorporating Sensitivity and Specificity

    Science.gov (United States)

    Williams, Christopher J.; Moffitt, Christine M.

    2003-03-01

    An important emerging issue in fisheries biology is the health of free-ranging populations of fish, particularly with respect to the prevalence of certain pathogens. For many years, pathologists focused on captive populations and interest was in the presence or absence of certain pathogens, so it was economically attractive to test pooled samples of fish. Recently, investigators have begun to study individual fish prevalence from pooled samples. Estimation of disease prevalence from pooled samples is straightforward when assay sensitivity and specificity are perfect, but this assumption is unrealistic. Here we illustrate the use of a Bayesian approach for estimating disease prevalence from pooled samples when sensitivity and specificity are not perfect. We also focus on diagnostic plots to monitor the convergence of the Gibbs-sampling-based Bayesian analysis. The methods are illustrated with a sample data set.

  5. Bicuspid Aortic Valve Disease: A Comprehensive Review

    OpenAIRE

    Mordi, Ify; Tzemos, Nikolaos

    2012-01-01

    Bicuspid aortic valve is the commonest congenital cardiac abnormality in the general population. This paper article will discuss our current knowledge of the anatomy, pathophysiology, genetics, and clinical aspects of bicuspid aortic valve disease.

  6. [Specific features of gastroesophageal reflux disease associated with obesity and overweight].

    Science.gov (United States)

    Livzan, M A; Lapteva, I V; Krolevets, T S; Kiselev, I E

    2016-01-01

    To reveal the specific features of gastroesophageal reflux disease (GERD) associated with obesity and overweight, by investigating the clinical and endoscopic manifestations of the disease, 24-hour pH-metry scores, and leptin levels. A total of 131 patients with GERD were examined. The data about complaints and those from life and medical histories were collected; anthropometric measurements and the results of blood biochemical tests, esophagoduodenoscopy (EPDS), and pH-metry were assessed; and the serum levels of leptin and its receptor were estimated. The patients were allocated into a study group (104 obese and/or overweight patients) and a comparison one (27 normal weight people). Waist circumference, hip circumference, and blood glucose levels proved to be statistically significantly higher in the study group (pstudy group and 5.47 (3.35-7.68) ng/ml in the comparison group; the median levels of the receptors were 18.83 (14.98-25.11) ng/ml and 30.93 (24.68-33.53) ng/ml, respectively). This group showed a moderate negative correlation between these indicators (rs=-0.451; pstudy group displayed higher pH values in the gastric cardia and body (prefluxate having with a low pH value (refluxate having a pH below 4.0 (rs=0.543; preflux episodes longer than 5 minutes in the esophagus, and to the De Meester index for this indicator (rs=0.471; pdisease, which determines the specific features of the disease (alkaline or mixed refluxate) and the need for individualized therapy.

  7. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    DEFF Research Database (Denmark)

    Dydensborg Sander, Stine; Størdal, Ketil; Plato Hansen, Tine

    2016-01-01

    PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

  8. Retrieval of radiology reports citing critical findings with disease-specific customization.

    Science.gov (United States)

    Lacson, Ronilda; Sugarbaker, Nathanael; Prevedello, Luciano M; Ivan, Ip; Mar, Wendy; Andriole, Katherine P; Khorasani, Ramin

    2012-01-01

    Communication of critical results from diagnostic procedures between caregivers is a Joint Commission national patient safety goal. Evaluating critical result communication often requires manual analysis of voluminous data, especially when reviewing unstructured textual results of radiologic findings. Information retrieval (IR) tools can facilitate this process by enabling automated retrieval of radiology reports that cite critical imaging findings. However, IR tools that have been developed for one disease or imaging modality often need substantial reconfiguration before they can be utilized for another disease entity. THIS PAPER: 1) describes the process of customizing two Natural Language Processing (NLP) and Information Retrieval/Extraction applications - an open-source toolkit, A Nearly New Information Extraction system (ANNIE); and an application developed in-house, Information for Searching Content with an Ontology-Utilizing Toolkit (iSCOUT) - to illustrate the varying levels of customization required for different disease entities and; 2) evaluates each application's performance in identifying and retrieving radiology reports citing critical imaging findings for three distinct diseases, pulmonary nodule, pneumothorax, and pulmonary embolus. Both applications can be utilized for retrieval. iSCOUT and ANNIE had precision values between 0.90-0.98 and recall values between 0.79 and 0.94. ANNIE had consistently higher precision but required more customization. Understanding the customizations involved in utilizing NLP applications for various diseases will enable users to select the most suitable tool for specific tasks.

  9. The humankind genome: from genetic diversity to the origin of human diseases.

    Science.gov (United States)

    Belizário, Jose E

    2013-12-01

    Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

  10. Non-specific Inflammatory Disease Showed Abnormal FDG Uptake in Lower Extremities

    International Nuclear Information System (INIS)

    Chun, Kyung Ah; Kong, Eun Jung; Cho, Ihn Ho; Hong, Young Hoon; Lee, Choong Ki

    2008-01-01

    Including malignancy, various disease can show abnormal uptake in bone marrow. 1,2) We report a case of non-specific inflammatory FDG uptake in bone marrow mimicking malignancy. A 35-year old woman with fever of unknown origin (FUO) underwent 18 F-FDG PET/CT to find out fever focus and unknown malignancy. 18 F-FDG was injected and imaged 1hr after injection with Discovery ST (GE, USA). 18 F-FDG PET/CT whole body image showed abnormal uptake in lower extremities. MRI and biopsy was also done in the sites of abnormal uptake. PET and MRI suspect malignancy, but biopsy result was non-specific inflammatory process. The patient was improved her clinical condition after antibiotics therapy

  11. Exercise thallium-201 myocardial imaging in left main coronary artery disease: sensitive but not specific

    International Nuclear Information System (INIS)

    Rehn, T.; Griffith, L.S.; Achuff, S.C.; Bailey, I.K.; Bulkley, B.H.; Burow, R.; Pitt, B.; Becker, L.C.

    1981-01-01

    To determine the usefulness of thallium-201 scintigraphy for identifying left main coronary artery disease, the results of scintigraphy at rest and during exercise were compared in 24 patients with 50 percent or greater narrowing of the left main coronary artery and 80 patients with 50 percent or greater narrowing of one or more of the major coronary arteries but without left main coronary involvement. By segmental analysis of the scintigrams, perfusion defects were assigned to the left anterior descending, left circumflex or right coronary artery, singly or in combination, and the pattern of simultaneous left anterior descending and circumflex arterial defects was used to identify left main coronary artery disease. Of the 24 patients with left main coronary artery disease, 22 (92 percent) had abnormal exercise scintigrams. Despite this high sensitivity, the pattern of perfusion defects was not specific; the ''left main pattern'' was found in 3 patients (13 percent) with left main coronary artery disease but also in 3 (33 percent) of 9 patients with combined left anterior descending and left circumflex arterial disease, 4 (19 percent) of 21 patients with three vessel disease and 3 (6 percent) of 50 patients with one or two vessel disease but excluding the group with left anterior descending plus left circumflex arterial disease. The pattern of perfusion defects in the patients with left main coronary artery disease was determined by the location and severity of narrowings in the coronary arteries downstream from the left main arterial lesion. Concomitant lesions in other arteries were found in all patients with left main coronary disease (one vessel in 1 patient, two vessels in 7 patients and three vessels in 16). For this reason, it is unlikely that even with improvements in radiopharmaceutical agents and imaging techniques, myocardial perfusion scintigraphy will be sufficiently specific for definitive identification of left main coronary artery disease

  12. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  13. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  14. Methodological principles of radiation influence upon specific function of female organism and gynecological diseases

    International Nuclear Information System (INIS)

    Tsvelev, Yu.V.; Kira, E.F.

    1994-01-01

    1025 women permanently residing at the territory subjected to radioactive contamination due to the Chernobyl NPP accident underwent dispensary examination in 1991-1992. Study of ionizing radiation influence on specific functions (menstrual, reproductive, secretory and gynecological) of female organism is carried out. It is found that the highest percentage in the structure of gynecological diseases is accounted for inflammatory diseases of uterine appendages and neck of the uterus. 1 tab

  15. Epilogue: Reading Comprehension Is Not a Single Ability-Implications for Assessment and Instruction.

    Science.gov (United States)

    Kamhi, Alan G; Catts, Hugh W

    2017-04-20

    In this epilogue, we review the 4 response articles and highlight the implications of a multidimensional view of reading for the assessment and instruction of reading comprehension. We reiterate the problems with standardized tests of reading comprehension and discuss the advantages and disadvantages of recently developed authentic tests of reading comprehension. In the "Instruction" section, we review the benefits and limitations of strategy instruction and highlight suggestions from the response articles to improve content and language knowledge. We argue that the only compelling reason to administer a standardized test of reading comprehension is when these tests are necessary to qualify students for special education services. Instruction should be focused on content knowledge, language knowledge, and specific task and learning requirements. This instruction may entail the use of comprehension strategies, particularly those that are specific to the task and focus on integrating new knowledge with prior knowledge.

  16. Validation of a New Questionnaire with Generic and Disease-Specific Qualities: The Mcgill Copd Quality of Life Questionnaire

    Directory of Open Access Journals (Sweden)

    Smita Pakhale

    2012-01-01

    Full Text Available BACKGROUND: A validated health-related quality of life questionnaire in chronic obstructive pulmonary disease (COPD with advantages of both generic- and disease-specific questionnaires is needed to capture patients’ perspectives of severity and impact of the disease. The McGill COPD questionnaire was created to include these advantages in English and French. It assesses three domains: symptoms, physical function and feelings with 29 items (12 from the 36-item Short-Form Health Survey with 17 from the previously developed COPD-specific module.

  17. [Effect of comprehensive control and prevention for chronic disease in demonstration plot of Chongqing].

    Science.gov (United States)

    Qi, Li; Ding, Xian-bin; Mao, De-qiang; Feng, Lian-gui; Wang, Yu-lin; Jiao, Yan; Zhang, Chun-hua; Lü, Xiao-yan; Li, Hong; Xia, Yi-yin

    2013-03-01

    To evaluate the effect of comprehensive control and prevention for chronic diseases in demonstration plot of Chongqing. Residents were enrolled through multi-stage stratified random sampling method from 17 districts or counties which had successfully established demonstration plots and 21 districts or counties which had not established demonstration plots (non-demonstration plot for short) yet on May, 2012. Questionnaire was designed to survey awareness of health knowledge, health behaviors and utilization of health supportive tools. The results were analyzed by SPSS 15.0 software. We investigated 15 108 residents, 6156 of which were in demonstration plot and others (8951) were not. The findings revealed the percentage of the people who were aware the national action of health lifestyle in demonstration plot and in non-demonstration plot were 44.4% (2734/6157) and 40.2% (3598/8951), respectively, and the awareness of the hypertension risk of too much sodium were 72.4% (4458/6156) and 67.5% (6042/8951), respectively, and the awareness of the cardinal vascular disease (CVD) risk of obesity and overweight were 77.2% (4753/6157) and 69.6% (6230/8951), respectively. About the residents' health behaviors in demonstration plot and in non-demonstration plot, the utilization rates of salt restriction scoop or pot were 23.5% (1447/6157) and 17.9% (1602/8951), and the utilization rates of oil restriction pot were 16.7% (1028/6157) and 11.8% (1064/8951), respectively. Totally, 33 of the 37 indexes were shown higher in demonstration plot than that in non-demonstration plot (P plot was more effective, and the remarkable improvement of health knowledge and behaviors level had been achieved in demonstration plot.

  18. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

    Directory of Open Access Journals (Sweden)

    Christina M Lill

    Full Text Available More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD. To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8 association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8. All meta-analysis results are freely available on a dedicated online database (www.pdgene.org, which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

  19. Assessing the Relation between Language Comprehension and Performance in General Chemistry

    Science.gov (United States)

    Pyburn, Daniel T.; Pazicni, Samuel; Benassi, Victor A.; Tappin, Elizabeth E.

    2013-01-01

    Few studies have focused specifically on the role that language plays in learning chemistry. We report here an investigation into the ability of language comprehension measures to predict performance in university introductory chemistry courses. This work is informed by theories of language comprehension, which posit that high-skilled…

  20. Genotator: A disease-agnostic tool for genetic annotation of disease

    Directory of Open Access Journals (Sweden)

    Jung Jae-Yoon

    2010-10-01

    Full Text Available Abstract Background Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. Methods We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. Results Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. Conclusions As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked

  1. Genotator: a disease-agnostic tool for genetic annotation of disease.

    Science.gov (United States)

    Wall, Dennis P; Pivovarov, Rimma; Tong, Mark; Jung, Jae-Yoon; Fusaro, Vincent A; DeLuca, Todd F; Tonellato, Peter J

    2010-10-29

    Disease-specific genetic information has been increasing at rapid rates as a consequence of recent improvements and massive cost reductions in sequencing technologies. Numerous systems designed to capture and organize this mounting sea of genetic data have emerged, but these resources differ dramatically in their disease coverage and genetic depth. With few exceptions, researchers must manually search a variety of sites to assemble a complete set of genetic evidence for a particular disease of interest, a process that is both time-consuming and error-prone. We designed a real-time aggregation tool that provides both comprehensive coverage and reliable gene-to-disease rankings for any disease. Our tool, called Genotator, automatically integrates data from 11 externally accessible clinical genetics resources and uses these data in a straightforward formula to rank genes in order of disease relevance. We tested the accuracy of coverage of Genotator in three separate diseases for which there exist specialty curated databases, Autism Spectrum Disorder, Parkinson's Disease, and Alzheimer Disease. Genotator is freely available at http://genotator.hms.harvard.edu. Genotator demonstrated that most of the 11 selected databases contain unique information about the genetic composition of disease, with 2514 genes found in only one of the 11 databases. These findings confirm that the integration of these databases provides a more complete picture than would be possible from any one database alone. Genotator successfully identified at least 75% of the top ranked genes for all three of our use cases, including a 90% concordance with the top 40 ranked candidates for Alzheimer Disease. As a meta-query engine, Genotator provides high coverage of both historical genetic research as well as recent advances in the genetic understanding of specific diseases. As such, Genotator provides a real-time aggregation of ranked data that remains current with the pace of research in the disease

  2. The European Union as a Comprehensive Police Actor

    Directory of Open Access Journals (Sweden)

    Stephen Anthony Rozée

    2011-12-01

    Full Text Available The European Union (EU has responded to changing security threats by seeking to increase cooperation between the law enforcement agencies of the Member States, granting further powers to Europol and other intelligence-sharing institutions, and by undertaking police missions beyond EU borders. The literature relating to EU policing is generally focused on the ‘internal’ and ‘external’ dimensions, or on specific aspects of police activity. This tendency to concentrate on narrow or isolated areas of policing has led to a significant gap regarding the broader analysis of the EU as a comprehensive police actor. Important questions about the nature of EU policing as a whole, as well as the contribution of policing activities to the EU’s security agenda, remain unexplored in the literature. This article aims to define what is meant by ‘comprehensive policing’ and to indentify criteria by which the comprehensiveness of EU-level policing may be measured. In addition to this, an integrated actorness/police comprehensiveness framework will be presented as a tool for assessing the EU as a comprehensive police actor.

  3. Translating advances in reading comprehension research to educational practice

    Directory of Open Access Journals (Sweden)

    Danielle S. McNamara

    2011-07-01

    Full Text Available The authors review five major findings in reading comprehension and their implications for educational practice. First, research suggests that comprehension skills are separable from decoding processes and important at early ages, suggesting that comprehension skills should be targeted early, even before the child learns to read. Second, there is an important distinction between reading processes and products, as well as their causal relationship: processes lead to certain products. Hence, instructional approaches and strategies focusing on processes are needed to improve students’ reading performance (i.e., product. Third, inferences are a crucial component of skilled comprehension. Hence, children need scaffolding and remediation to learn to generate inferences, even when they know little about the text topic. Fourth, comprehension depends on a complex interaction between the reader, the characteristics of the text, and the instructional task, highlighting the need for careful selection of instructional materials for individual students and specific groups of students. Finally, educators may benefit from heightened awareness of the limitations and inadequacies of standardized reading comprehension assessments, as well as the multidimensionality of comprehension to better understand their students’ particular strengths and weaknesses.

  4. Translating advances in reading comprehension research to educational practice

    Directory of Open Access Journals (Sweden)

    Danielle S. McNAMARA

    2011-11-01

    Full Text Available The authors review five major findings in reading comprehension and their implications for educational practice. First, research suggests that comprehension skills are separable from decodingprocesses and important at early ages, suggesting that comprehension skills should be targeted early, even before the child learns to read. Second, there is an important distinction between readingprocesses and products, as well as their causal relationship: processes lead to certain products. Hence, instructional approaches and strategies focusing on processes are needed to improve students’reading performance (i.e., product. Third, inferences are a crucial component of skilled comprehension. Hence, children need scaffolding and remediation to learn to generate inferences, even when they know little about the text topic. Fourth, comprehension depends on a complex interaction between the reader, the characteristics of the text, and the instructional task, highlighting the need for careful selection of instructional materials for individual students and specific groups of students. Finally, educators may benefit from heightened awareness of the limitations and inadequacies of standardized reading comprehension assessments, as well as the multidimensionality of comprehension to better understand their students’ particular strengths and weaknesses.

  5. Alzheimer's Disease and Glaucoma: Imaging the Biomarkers of Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Denise A. Valenti

    2010-01-01

    Full Text Available Imaging through the visual system in Alzheimer's disease, with the technology currently in widespread use for the diagnosis and management of eye disease such as glaucoma and macular degeneration, is proving to be promising. In vivo cross-section imaging during an annual comprehensive eye exam has been available for a decade for glaucoma and macular degeneration, and this same imaging, using Optical Coherence Tomography, has been demonstrated to show deficits specific to AD and mild cognitive impairment. These deficits are in the form of nerve fiber layer tissue drop out in the retina and optic nerve. The retrograde loss of nerve fiber layer tissue in the retina and optic nerve may be an early biomarker of AD, and these deficits in the nerve fiber layer of the retina and optic nerve may be the earliest sign of AD, even prior to damage to the hippocampal region that impacts memory.

  6. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease.

    Science.gov (United States)

    Bloom, Seth M; Bijanki, Vinieth N; Nava, Gerardo M; Sun, Lulu; Malvin, Nicole P; Donermeyer, David L; Dunne, W Michael; Allen, Paul M; Stappenbeck, Thaddeus S

    2011-05-19

    The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here, we fulfilled Koch's postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively reisolated them in culture. The bacteria colonized IBD-susceptible and -nonsusceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease, but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Commensal Bacteroides species induce colitis in host-genotype-specific fashion in a mouse model of inflammatory bowel disease

    Science.gov (United States)

    Bloom, Seth M.; Bijanki, Vinieth N.; Nava, Gerardo M.; Sun, Lulu; Malvin, Nicole P.; Donermeyer, David L.; Dunne, W. Michael; Allen, Paul M.; Stappenbeck, Thaddeus S.

    2011-01-01

    SUMMARY The intestinal microbiota is important for induction of inflammatory bowel disease (IBD). IBD is associated with complex shifts in microbiota composition, but it is unclear whether specific bacterial subsets induce IBD and, if so, whether their proportions in the microbiota are altered during disease. Here we fulfilled Koch’s postulates in host-genotype-specific fashion using a mouse model of IBD with human-relevant disease-susceptibility mutations. From screening experiments we isolated common commensal Bacteroides species, introduced them into antibiotic-pretreated mice, and quantitatively re-isolated them in culture. The bacteria colonized IBD-susceptible and non-susceptible mice equivalently, but induced disease exclusively in susceptible animals. Conversely, commensal Enterobacteriaceae were >100-fold enriched during spontaneous disease but an Enterobacteriaceae isolate failed to induce disease in antibiotic-pretreated mice despite robust colonization. We thus demonstrate that IBD-associated microbiota alterations do not necessarily reflect underlying disease etiology. These findings establish important experimental criteria and a conceptual framework for understanding microbial contributions to IBD. PMID:21575910

  8. Using Appropriate Strategies to Improve Students' Comprehension ...

    African Journals Online (AJOL)

    Using Appropriate Strategies to Improve Students' Comprehension of Chemistry Texts: A Guide for Chemistry Teachers. ... African Research Review ... Unfortunately, contemporary research insight into science reading is lacking and science educators tend to focus on methods of teaching specific subject matter and ...

  9. Comprehensive numerical modelling of tokamaks

    International Nuclear Information System (INIS)

    Cohen, R.H.; Cohen, B.I.; Dubois, P.F.

    1991-01-01

    We outline a plan for the development of a comprehensive numerical model of tokamaks. The model would consist of a suite of independent, communicating packages describing the various aspects of tokamak performance (core and edge transport coefficients and profiles, heating, fueling, magnetic configuration, etc.) as well as extensive diagnostics. These codes, which may run on different computers, would be flexibly linked by a user-friendly shell which would allow run-time specification of packages and generation of pre- and post-processing functions, including workstation-based visualization of output. One package in particular, the calculation of core transport coefficients via gyrokinetic particle simulation, will become practical on the scale required for comprehensive modelling only with the advent of teraFLOP computers. Incremental effort at LLNL would be focused on gyrokinetic simulation and development of the shell

  10. Measuring disease-specific quality of life in rare populations: a practical approach to cross-cultural translation

    Directory of Open Access Journals (Sweden)

    Riedlinger Arne

    2009-10-01

    Full Text Available Abstract Background Disease-specific quality of life (QoL measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. Procedure A measurement study was conducted in the United Kingdom (UK, France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. Results This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT, were performed in children with immune thrombocytopenic purpura (ITP. The KIT was translated from North American English into UK English, French, German, and Spanish. Conclusion This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.

  11. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ... to Know? Why Is Comprehensive Care or Team Approach Important? 2013 PSA Featuring Katie Couric What Are ...

  12. Specific schistosomiasis treatment as a strategy for disease control

    Directory of Open Access Journals (Sweden)

    José Rodrigues Coura

    2010-07-01

    Full Text Available The great hope for schistosomiasis treatment began with the development of oxamniquine and praziquantel. These drugs can be administered orally in a single dose and have a high curative power with minor side effects. In this study, we carried out a field experiment involving a population of 3,782 people. The population was examined at four localities in Minas Gerais within the valleys of the Doce and Jequitinhonha Rivers. In this cohort, there were 1,790 patients infected with Schistosoma mansoni (47.3% and we showed that only 1,403 (78.4% could be treated with oxamniquine in a single dose of 12.5-20 mg/kg orally. The other 387 (21.6% were not treated during the first stage because of contraindications (pregnancy or impeditive diseases, absences or refusals. It was observed that, on average, 8.8-17% of the infected patients continued to excrete S. mansoni eggs at the end of the 2nd month after treatment and 30-32% of the cohort was infected by the end of the 24th month. In one of the areas that we followed-up for a total of 30 years, the prevalence of the infection with S. mansoni fell from 60.8-19.3% and the hepatosplenic form of the disease dropped from 5.8-1.3%. We conclude that specific treatment of schistosomiasis reduces the prevalence of infection in the short-term and the morbidity due to schistosomiasis in medium to long-term time frames, but does not help to control disease transmission.

  13. Asia Pacific Consensus Statements on Crohn's disease. Part 1: Definition, diagnosis, and epidemiology: (Asia Pacific Crohn's Disease Consensus--Part 1).

    Science.gov (United States)

    Ooi, Choon Jin; Makharia, Govind K; Hilmi, Ida; Gibson, Peter R; Fock, Kwong Ming; Ahuja, Vineet; Ling, Khoon Lin; Lim, Wee Chian; Thia, Kelvin T; Wei, Shu-chen; Leung, Wai Keung; Koh, Poh Koon; Gearry, Richard B; Goh, Khean Lee; Ouyang, Qin; Sollano, Jose; Manatsathit, Sathaporn; de Silva, H Janaka; Rerknimitr, Rungsun; Pisespongsa, Pises; Abu Hassan, Muhamad Radzi; Sung, Joseph; Hibi, Toshifumi; Boey, Christopher C M; Moran, Neil; Leong, Rupert W L

    2016-01-01

    Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology with the goal of developing best management practices, coordinating research, and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis, and management of Crohn's disease. The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses, and treatment availability. It does not intend to be all comprehensive and future revisions are likely to be required in this ever-changing field. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  14. Comprehensive analysis of the related factors of early hypothyroidism occurring in patients with Graves' disease after 131I treatment

    International Nuclear Information System (INIS)

    Tan Jian; Wang Peng; Zhang Lijuan; He Yajing; Wang Renfei

    2005-01-01

    Objective: To make a comprehensive analysis of the related factors of early hypothyroidism occurring in patients with Graves' disease after 131 I treatment. Methods: The information of 131 I treated Graves' disease was collected including general data, clinical observation, laboratory data, thyroid function test, etc. Then a retrospective statistical analysis was carried out, using cluster analysis, factor analysis, discriminant analysis, multivariate regression analysis, etc. Results: 1) Cluster analysis and factor analysis showed that among clinical observation such as clinical course, treatment course, patients' state and disease occurrance, the first three factors correlated highly; among laboratory data such as thyrotrophin receptor antibody (TRAb), thyroid-stimulating immunoglobulins (TSI), thyroglobulin antibody (TgAb) and thyroid microsomal antibody (TMAb), both the first two and the last two correlated highly, each two factors had the similar effect. 2) Fsher discriminant analysis showed that among the thyroid weight, the effective half life, the maximum 131 I uptake percentage, total dose of 131 I and the average dose of 131 I per gram of thyroid, the last one had the most predicting value for incidence of early hypothyroidism. 3) Logistic regression analysis showed that among all the related factors of early hypothyroidism occurred after 131 I treated Graves' disease, thyroid weight, average dose of 131 I per gram of thyroid, the maximum 131 I uptake percentage and the level of TSI were effective factors. Conclusions: The occurrence of early hypothyroidism for 131 I-treated Graves' disease is probably affected by many factors. If more factors are taken into consideration before therapy and the theraputic dose is well adjusted accordingly, it can reduce the incidence of early hypothroidism to a certain extent. (authors)

  15. Sector-wide or disease-specific? Implications of trends in development assistance for health for the SDG era.

    Science.gov (United States)

    Buffardi, Anne L

    2018-04-01

    The record of the Millennium Development Goals broadly reflects the trade-offs of disease-specific financing: substantial progress in particular areas, facilitated by time-bound targets that are easy to measure and communicate, which shifted attention and resources away from other areas, masked inequalities and exacerbated fragmentation. In many ways, the Sustainable Development Goals reflect a profound shift towards a more holistic, system-wide approach. To inform responses to this shift, this article builds upon existing work on aggregate trends in donor financing, bringing together what have largely been disparate analyses of sector-wide and disease-specific financing approaches. Looking across the last 26 years, the article examines how international donors have allocated development assistance for health (DAH) between these two approaches and how attempts to bridge them have fared in practice. Since 1990, DAH has overwhelmingly favoured disease-specific earmarks over health sector support, with the latter peaking in 1998. Attempts to integrate system strengthening elements into disease-specific funding mechanisms have varied by disease, and more integrated funding platforms have failed to gain traction. Health sector support largely remains an unfulfilled promise: proportionately low amounts (albeit absolute increases) which have been inconsistently allocated, and the overall approach inconsistently applied in practice. Thus, the expansive orientation of the Sustainable Development Goals runs counter to trends over the last several decades. Financing proposals and efforts to adapt global health institutions must acknowledge and account for the persistent challenges in the financing and implementation of integrated, cross-sector policies. National and subnational experimentation may offer alternatives within and beyond the health sector.

  16. Hidden Language Impairments in Children: Parallels between Poor Reading Comprehension and Specific Language Impairment?

    Science.gov (United States)

    Nation, Kate; Clarke, Paula; Marshall, Catherine M.; Durand, Marianne

    2004-01-01

    This study investigates the oral language skills of 8-year-old children with impaired reading comprehension. Despite fluent and accurate reading and normal nonverbal ability, these children are poor at understanding what they have read. Tasks tapping 3 domains of oral language, namely phonology, semantics, and morphosyntax, were administered,…

  17. Reading comprehension as part of the teaching learning process of English for specific purposes

    Directory of Open Access Journals (Sweden)

    Yaima Rosa Reyes Piñero

    2012-06-01

    Full Text Available This article presents and characterizes a system of interdisciplinary tasks which contributes to reading comprehension as a basic objective of the teaching learning process of English in the first year students of Marxism-Leninism and History career of the University of Pedagogical Sciences in Pinar del Río.

  18. Salivary Gland Pathology in IgG4-Related Disease: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Ilaria Puxeddu

    2018-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a rare fibroinflammatory condition that can affect almost any organ, characterized by swollen lesions and often by eosinophilia and elevated serum IgG4 concentrations. The diagnosis of IgG4-RD is a challenging task: in fact, single or multiple organs can be affected and clinical, serological, and histological findings can be heterogeneous. In IgG4-RD, the involvement of salivary glands is observed in 27% to 53% of patients. Several organ-specific conditions, now recognized as different manifestations of IgG4-related sialadenitis (IgG4-RS, were viewed in the past as individual disease entities. The study of salivary glands may sometimes be complex, because of the number of pathological conditions that may affect them, often with overlapping clinical pictures. Integration of different imaging techniques is often required in the case of swelling of salivary glands, even though biopsy remains the gold standard for a definite diagnosis of IgG4-RS. Thus, in this review, we discuss new insights in the pathogenesis of IgG4-RD, focusing on its clinical aspects and the tools that are currently available for a correct differential diagnosis when the salivary glands are involved.

  19. Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

    Science.gov (United States)

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-12-14

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

  20. Use of Meta-comprehensive Strategies to Strengthen Reading Comprehension in Second-Cycle Students from a Public School at Bogotá, Colombia

    Directory of Open Access Journals (Sweden)

    Bibian Alexandra Rodríguez Ribero

    2016-06-01

    Full Text Available This research inquired about the effect of a classroom intervention in metacomprehension strategies, specifically self-questioning, on reading comprehension improvement in third and fourth - graders. Reading comprehension was understood as a process that relates content, text and inferences, and is facilitated by metacomprehension or metacognitive processes applied to reading comprehension. The participants were third- and fourth-grade students: the intervention group (which had an initial assessment, and were submitted to classroom intervention in metacomprehension using self-questioning—implemented by the first three authors—, and had a final assessment, and the control group (which had initial assessment, the usual classroom work with other teachers, and final assessment. The Comprensión Lingüística Progresiva (clp, Alliende, Condemarín & Milicic, 2004—a reading comprehension test—and the students’ metacomprehensive strategies questionnaire were administered to students in both groups, in the initial and final assessments. This information was complemented with interview data from other teachers (different from the authors in order to know their perspective on reading comprehension underlying their reading teaching practices. Results showed a rise in reading comprehension tests scores and diversification in the use of metacomprehensive strategies only in the intervention group, and different conceptions of reading comprehension in other teachers, which had nothing to do with metacomprehension strategies.

  1. Executive dysfunction among children with reading comprehension deficits.

    Science.gov (United States)

    Locascio, Gianna; Mahone, E Mark; Eason, Sarah H; Cutting, Laurie E

    2010-01-01

    Emerging research supports the contribution of executive function (EF) to reading comprehension; however, a unique pattern has not been established for children who demonstrate comprehension difficulties despite average word recognition ability (specific reading comprehension deficit; S-RCD). To identify particular EF components on which children with S-RCD struggle, a range of EF skills was compared among 86 children, ages 10 to 14, grouped by word reading and comprehension abilities: 24 average readers, 44 with word recognition deficits (WRD), and 18 S-RCD. An exploratory principal components analysis of EF tests identified three latent factors, used in subsequent group comparisons: Planning/ Spatial Working Memory, Verbal Working Memory, and Response Inhibition. The WRD group exhibited deficits (relative to controls) on Verbal Working Memory and Inhibition factors; S-RCD children performed more poorly than controls on the Planning factor. Further analyses suggested the WRD group's poor performance on EF factors was a by-product of core deficits linked to WRD (after controlling for phonological processing, this group no longer showed EF deficits). In contrast, the S-RCD group's poor performance on the planning component remained significant after controlling for phonological processing. Findings suggest reading comprehension difficulties are linked to executive dysfunction; in particular, poor strategic planning/organizing may lead to reading comprehension problems.

  2. Proverb comprehension impairments in schizophrenia are related to executive dysfunction.

    Science.gov (United States)

    Thoma, Patrizia; Hennecke, Marie; Mandok, Tobias; Wähner, Alfred; Brüne, Martin; Juckel, Georg; Daum, Irene

    2009-12-30

    The study aimed to investigate the pattern of proverb comprehension impairment and its relationship to proverb familiarity and executive dysfunction in schizophrenia. To assess the specificity of the impairment pattern to schizophrenia, alcohol-dependent patients were included as a psychiatric comparison group, as deficits of executive function and theory of mind as well as dysfunction of the prefrontal cortex, which have been related to proverb comprehension difficulties, are common in both disorders. Twenty-four schizophrenia patients, 20 alcohol-dependent patients and 34 healthy controls were administered a multiple-choice proverb interpretation task incorporating ratings of subjective familiarity and measures of executive function. Schizophrenia patients chose the correct abstract and meaningful interpretations less frequently and instead chose the incorrect concrete (both meaningless and meaningful) proverb interpretations more often than alcohol-dependent patients and healthy controls. Relative to healthy controls, schizophrenia patients also chose more abstract-meaningless response alternatives and were impaired in all executive domains. Impaired divided attention was most consistently associated with proverb interpretation deficits in both patient groups. Taken together, schizophrenia patients showed a specific pattern of proverb comprehension impairments related to executive dysfunction and symptoms. The comparison with the alcohol-dependent subgroup suggests that a more comprehensive and severe impairment of complex higher-order cognitive functions including executive behavioural control and non-literal language comprehension might be associated with frontal dysfunction in schizophrenia as compared to alcohol use disorder.

  3. Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Hager, Henrik; Steiniche, Torben

    2008-01-01

    Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has...... led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5...... of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens...

  4. Site-Specific Antioxidative Therapy for Prevention of Atherosclerosis and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Hajime Otani

    2013-01-01

    Full Text Available Oxidative stress has been implicated in pathophysiology of aging and age-associated disease. Antioxidative medicine has become a practice for prevention of atherosclerosis. However, limited success in preventing cardiovascular disease (CVD in individuals with atherosclerosis using general antioxidants has prompted us to develop a novel antioxidative strategy to prevent atherosclerosis. Reducing visceral adipose tissue by calorie restriction (CR and regular endurance exercise represents a causative therapy for ameliorating oxidative stress. Some of the recently emerging drugs used for the treatment of CVD may be assigned as site-specific antioxidants. CR and exercise mimetic agents are the choice for individuals who are difficult to continue CR and exercise. Better understanding of molecular and cellular biology of redox signaling will pave the way for more effective antioxidative medicine for prevention of CVD and prolongation of healthy life span.

  5. A 2-d classification of diseases based on age-specific death rates

    Science.gov (United States)

    Richmond, Peter; Roehner, Bertrand M.

    2018-02-01

    Age specific mortality curves exhibit an age tc (about 10 years) which plays a crucial role in that the mortality curve decreases hyperbolically in the age interval A before tc and increases exponentially in the interval B following tc. For those familiar with reliability theory, region A is called the "burn in" phase and B is the "wear out" phase. Using the exponents of the hyperbolic and exponential phases, we introduce a new 2 dimensional map of diseases. This permits the classification of diseases into three broad classes: AS1, AS2 and S. Class AS1 includes all diseases arising from congenital malformations which dominate infant and child mortality; class AS2 includes degenerative diseases such as dementia and Alzheimer's which dominate old age mortality. In class S, which includes most infectious and metabolic diseases, the exponents from both aging phases contribute to positions on the map. Cancer is one of these mixed cases but is closer to class AS2 than AS1. A second line classification is needed to resolve S cases and to this end we introduce a 3rd dimension, namely (calendar) time. Using historical data we show that in their response to treatment (particularly vaccination), S diseases fall into three sub-classes. (i) Class E diseases (e.g. measles or meningococcal disease) which have been almost eliminated at all ages (ii) class C diseases (e.g. tuberculosis) which can be cured but whose cure becomes less effective at old age. (iii) Class U diseases for which radical cures are still unknown. Regarding the future, the fact that the wear-out process of numerous diseases already starts around the age of 25 means that a major extension of the human lifespan beyond 120 certainly also requires to uncover the secret of the "elixir of eternal youth" which has driven timeless human efforts and still seems unlikely in the foreseeable future.

  6. Sensitivity and specificity of thallium-201 perfusion scintigrams under exercise in the diagnosis of coronary artery disease

    International Nuclear Information System (INIS)

    Verani, M.S.; Marcus, M.L.; Razzak, M.A.; Ehrhardt, J.C.

    1978-01-01

    The specificity and sensitivity of thallium-201 myocardial perfusion imaging (MPI), under exercise, in patients with suspected coronary-obstructive disease was compared with graded exercise ECG tests (GTX) in patients with angiographically normal (N = 34) and obstructed (N = 48) coronary arteries. Of the 34 patients with normal coronaries, only one had a perfusion defect on the MPI (specificity 97%). Of the 48 patients with coronary obstructive disease (>50% obstruction of at least one coronary vessel), MPI was positive in 38 (sensitivity 79%). In contrast, the GTX had a specificity of 62% and sensitivity of 88% if nondiagnostic GTX tests are excluded. When the MPI and the GTX were used in combination, however, the sensitivity of detecting patients with coronary obstructive disease was increased to 94% (p < 0.01). The MPI was particularly useful in the evaluation of the 26 patients with nondiagnostic GTX. In this group, 24 of the 26 patients were correctly identified by the MPI with respect to the presence or absence of coronary-obstructive disease. In the 14 patients with a history of classical angina but with normal coronaries, the MPI was negative in 13 and positive in one, thus suggesting that in the majority of these patients transient transmural myocardial ischemia probably does not occur during exercise. The presence or absence of angiographically demonstrable coronary collateral vessels did not seem to influence the exercise MPI in patients with coronary-obstructive disease. Thus, although the MPI does not correctly identify all patients with either coronary-obstructive disease or normal coronary arteries, it is helpful in patients who have a nondiagnostic GTX. Furthermore, when used in combination with the GTX, the MPI significantly increases the likelihood that significant coronary-obstructive disease is present when both tests are positive, and that coronary disease is absent when both tests are negative

  7. Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training.

    Science.gov (United States)

    Zimmermann, Ronan; Gschwandtner, Ute; Benz, Nina; Hatz, Florian; Schindler, Christian; Taub, Ethan; Fuhr, Peter

    2014-04-08

    In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: -1.49 to -0.11) than patients trained with CogniPlus. In our study, patients with PD derived at least the same degree of cognitive benefit from non-cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

  8. [Epigenetic regulations and cerebral plasticity: towards new therapeutic options in neurodegenerative diseases?

    Science.gov (United States)

    Merienne, Karine; Boutillier, Anne-Laurence

    2016-01-01

    Although revealed in the 1950's, epigenetics is still a fast-growing field. Its delineations continuously evolve and become clarified. In particular, "neuroepigenetics", a notion that encompasses epigenetic regulations associated with neuronal processes, appears very promising. Indeed, the challenge to be undertaken in this sub-field is double. On the one hand, it should bring molecular comprehension of specific neuronal processes, some of them falling within the long term regulations, such as learning and memory. On the other hand, it could bring therapeutic options for brain diseases, e.g. neurodegenerative diseases such as Alzheimer's or Huntington's diseases. © Société de Biologie, 2017.

  9. High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison's disease patients.

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein S; Pearce, Simon H; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2014-09-01

    The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. Copyright © 2014 by The American Association of Immunologists, Inc.

  10. Systematization and sophistication of a comprehensive sensitivity analysis program. Phase 2

    International Nuclear Information System (INIS)

    Oyamada, Kiyoshi; Ikeda, Takao

    2004-02-01

    This study developed minute estimation by adopting comprehensive sensitivity analytical program for reliability of TRU waste repository concepts in a crystalline rock condition. We examined each components and groundwater scenario of geological repository and prepared systematic bases to examine the reliability from the point of comprehensiveness. Models and data are sophisticated to examine the reliability. Based on an existing TRU waste repository concepts, effects of parameters to nuclide migration were quantitatively classified. Those parameters, that will be decided quantitatively, are such as site character of natural barrier and design specification of engineered barriers. Considering the feasibility of those figures of specifications, reliability is re-examined on combinations of those parameters within a practical range. Future issues are; Comprehensive representation of hybrid geosphere model including the fractured medium and permeable matrix medium. Sophistication of tools to develop the reliable combinations of parameters. It is significant to continue this study because the disposal concepts and specification of TRU nuclides containing waste on various sites shall be determined rationally and safely through these studies. (author)

  11. Asia-Pacific consensus statements on Crohn's disease. Part 2: Management.

    Science.gov (United States)

    Ooi, Choon Jin; Makharia, Govind K; Hilmi, Ida; Gibson, Peter R; Fock, Kwong Ming; Ahuja, Vineet; Ling, Khoon Lin; Lim, Wee Chian; Thia, Kelvin T; Wei, Shu-chen; Leung, Wai Keung; Koh, Poh Koon; Gearry, Richard B; Goh, Khean Lee; Ouyang, Qin; Sollano, Jose; Manatsathit, Sathaporn; de Silva, H Janaka; Rerknimitr, Rungsun; Pisespongsa, Pises; Abu Hassan, Muhamad Radzi; Sung, Joseph; Hibi, Toshifumi; Boey, Christopher C M; Moran, Neil; Leong, Rupert W L

    2016-01-01

    The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  12. Unsupervised method for automatic construction of a disease dictionary from a large free text collection.

    Science.gov (United States)

    Xu, Rong; Supekar, Kaustubh; Morgan, Alex; Das, Amar; Garber, Alan

    2008-11-06

    Concept specific lexicons (e.g. diseases, drugs, anatomy) are a critical source of background knowledge for many medical language-processing systems. However, the rapid pace of biomedical research and the lack of constraints on usage ensure that such dictionaries are incomplete. Focusing on disease terminology, we have developed an automated, unsupervised, iterative pattern learning approach for constructing a comprehensive medical dictionary of disease terms from randomized clinical trial (RCT) abstracts, and we compared different ranking methods for automatically extracting con-textual patterns and concept terms. When used to identify disease concepts from 100 randomly chosen, manually annotated clinical abstracts, our disease dictionary shows significant performance improvement (F1 increased by 35-88%) over available, manually created disease terminologies.

  13. Spontaneous growth in growth hormone deficiency from birth until 7 years of age: development of disease-specific growth curves.

    Science.gov (United States)

    Mayer, M; Schmitt, K; Kapelari, K; Frisch, H; Köstl, G; Voigt, M

    2010-01-01

    Little is known about spontaneous growth of growth hormone (GH)-deficient children during infancy and childhood. Retrospectively, we calculated disease-specific pretreatment percentiles for height, weight, BMI and growth velocity of 113 GH-deficient boys and 41 GH-deficient girls from birth until 7 years of age, by mean and standard deviation. Infants with idiopathic GH deficiency (GHD) grow in disease-specific percentile channels. There is a significant difference in length and weight from birth onward compared to regional reference (pgrowth velocity, despite a wide variance in the first years, so height deficit became more evident with increasing age. GHD is a congenital disease no matter when height deficit becomes clinically evident, because GH-deficient children grow in disease-specific percentile channels with a highly significantly reduced length and weight, which demonstrates that GH is essential for adequate growth in infancy and early childhood. Copyright (c) 2010 S. Karger AG, Basel.

  14. Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease.

    Science.gov (United States)

    Chen, Jack J; Swope, David M; Dashtipour, Khashayar

    2007-09-01

    Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B (MAO-B) prolong the duration of action of both endogenously and exogenously derived dopamine. Rasagiline [N-propargyl-l(R)-aminoindan] is a second-generation propargylamine pharmacophore that selectively and irreversibly inhibits brain MAO-B and is specifically designed for the treatment of Parkinson's disease (PD). The aim of this study was to review the pharmacology, tolerability, and clinical efficacy of rasagiline in the treatment of PD. MEDLINE (1966-April 2007), the Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-April 2007) were searched for original research and review articles published in English. The search terms were monoamine oxidase, neuroprotection, Parkinson disease, propargylamine, rasagiline, and selegiline. The reference lists of articles were also consulted, as was information provided by the manufacturer of rasagiline. Data from 63 clinical and laboratory studies were analyzed. Based on the results from those studies, we concluded that rasagiline PO QD, at the therapeutic dosage range of 0.5 to 1 rag/d, is effective and well tolerated and completely, selectively, and specifically inhibited MAO-B. Pharmacologically, rasagiline was found to be Rasagiline was effective both as monotherapy in early PD and as adjunctive treatment in patients with advancing PD and motor fluctuations. As monotherapy, rasagiline provided modest yet clinically meaningful benefit. A randomized, double-blind, placebo-controlled study found that, after 26 weeks of treatment, the adjusted effect size for total Unified Parkinson's Disease Rating Scale score was -4.20 (95% CI, -5.66 to -2.73) for rasagiline 1 mg/d versus placebo (P rasagiline is initiated early (before the need for dopaminergic agents) rather than later. In patients with more advanced disease who received treatment with dopaminergic agents, rasagiline and entacapone were associated

  15. A comprehensive review of amyotrophic lateral sclerosis

    Science.gov (United States)

    Zarei, Sara; Carr, Karen; Reiley, Luz; Diaz, Kelvin; Guerra, Orleiquis; Altamirano, Pablo Fernandez; Pagani, Wilfredo; Lodin, Daud; Orozco, Gloria; Chinea, Angel

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5–10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease. PMID:26629397

  16. Strategies and methods to study female-specific cardiovascular health and disease: a guide for clinical scientists.

    Science.gov (United States)

    Ouyang, Pamela; Wenger, Nanette K; Taylor, Doris; Rich-Edwards, Janet W; Steiner, Meir; Shaw, Leslee J; Berga, Sarah L; Miller, Virginia M; Merz, Noel Bairey

    2016-01-01

    In 2001, the Institute of Medicine's (IOM) report, "Exploring the Biological Contributions to Human Health: Does Sex Matter?" advocated for better understanding of the differences in human diseases between the sexes, with translation of these differences into clinical practice. Sex differences are well documented in the prevalence of cardiovascular (CV) risk factors, the clinical manifestation and incidence of cardiovascular disease (CVD), and the impact of risk factors on outcomes. There are also physiologic and psychosocial factors unique to women that may affect CVD risk, such as issues related to reproduction. The Society for Women's Health Research (SWHR) CV Network compiled an inventory of sex-specific strategies and methods for the study of women and CV health and disease across the lifespan. References for methods and strategy details are provided to gather and evaluate this information. Some items comprise robust measures; others are in development. To address female-specific CV health and disease in population, physiology, and clinical trial research, data should be collected on reproductive history, psychosocial variables, and other factors that disproportionately affect CVD in women. Variables related to reproductive health include the following: age of menarche, menstrual cycle regularity, hormone levels, oral contraceptive use, pregnancy history/complications, polycystic ovary syndrome (PCOS) components, menopause age, and use and type of menopausal hormone therapy. Other factors that differentially affect women's CV risk include diabetes mellitus, autoimmune inflammatory disease, and autonomic vasomotor control. Sex differences in aging as well as psychosocial variables such as depression and stress should also be considered. Women are frequently not included/enrolled in mixed-sex CVD studies; when they are included, information on these variables is generally not collected. These omissions limit the ability to determine the role of sex-specific

  17. Effects of Phonological Abilities and Linguistic Comprehension on the Development of Reading.

    Science.gov (United States)

    de Jong, Peter F.; van der Leij, Aryan

    2002-01-01

    Examines specific effects of phonological abilities and linguistic comprehension on the development of word-decoding ability and reading comprehension, respectively, of 141 Dutch children from the end of first grade to the end of third grade. Finds that partly different determinants underlie the development of word-decoding ability and reading…

  18. Speech comprehension aided by multiple modalities: behavioural and neural interactions

    Science.gov (United States)

    McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K.

    2014-01-01

    Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources – e.g. voice, face, gesture, linguistic context – to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with

  19. [The diagnostic value of ultrasonic elastography and ultrasonography comprehensive score in cervical lesions].

    Science.gov (United States)

    Lu, R; Xiao, Y

    2017-07-18

    Objective: To evaluate the clinical value of ultrasonic elastography and ultrasonography comprehensive scoring method in the diagnosis of cervical lesions. Methods: A total of 116 patients were selected from the Department of Gynecology of the first hospital affiliated with Central South University from March 2014 to September 2015.All of the lesions were preoperatively examined by Doppler Ultrasound and elastography.The elasticity score was determined by a 5-point scoring method. Calculation of the strain ratio was based on a comparison of the average strain measured in the lesion with the adjacent tissue of the same depth, size, and shape.All these ultrasonic parameters were quantified, added, and arrived at ultrasonography comprehensive scores.To use surgical pathology as the gold standard, the sensitivity, specificity, accuracy of Doppler Ultrasound, elasticity score and strain ratio methods and ultrasonography comprehensive scoring method were comparatively analyzed. Results: (1) The sensitivity, specificity, and accuracy of Doppler Ultrasound in diagnosing cervical lesions were 82.89% (63/76), 85.0% (34/40), and 83.62% (97/116), respectively.(2) The sensitivity, specificity, and accuracy of the elasticity score method were 77.63% (59/76), 82.5% (33/40), and 79.31% (92/116), respectively; the sensitivity, specificity, and accuracy of the strain ratio measure method were 84.21% (64/76), 87.5% (35/40), and 85.34% (99/116), respectively.(3) The sensitivity, specificity, and accuracy of ultrasonography comprehensive scoring method were 90.79% (69/76), 92.5% (37/40), and 91.38% (106/116), respectively. Conclusion: (1) It was obvious that ultrasonic elastography had certain diagnostic value in cervical lesions. Strain ratio measurement can be more objective than elasticity score method.(2) The combined application of ultrasonography comprehensive scoring method, ultrasonic elastography and conventional sonography was more accurate than single parameter.

  20. Implementation of Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Health Authority by the Agency for Toxic Substances and Disease Registry

    International Nuclear Information System (INIS)

    Siegel, M.R.

    1990-01-01

    The Superfund Amendments and Reauthorization Act (SARA) of 1986 greatly expanded the health authority of the Comprehensive Environmental Response, Compensation, and Liability Act. One of the federal agencies most affected by SARA is the Agency for Toxic Substances and Disease Registry (ATSDR) of the U.S. Public Health Service. Among other responsibilities, ATSDR was mandated to conduct health assessments within strict time frames for each site on or proposed for the U.S. Environmental Protection Agency's National Priorities List. The author will review ATSDR's efforts to address this new statutory mandate, especially for federal facilities, and will focus on different conceptual frameworks for implementing the health assessment program

  1. Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific

    International Nuclear Information System (INIS)

    Taki, Junichi; Nakajima, Kenichi; Hwang, Eui-Hyo; Matsunari, Ichiro; Tonami, Norihisa; Komai, Kiyonobu; Yoshita, Mitsuhiro; Sakajiri, Kenichi

    2000-01-01

    The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63±9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61±0.29) was significantly lower than that in the control group (2.24±0.14, P<0.01), P-nism (2.15±0.31, P<0.01), MSA (2.08±0.31, P<0.05) and PSP (2.30±0.24, P<0.01). The delayed H/M ratio in PD (1.47±0.34) was also significantly lower than that in the control group (2.37±0.14, P<0.01), P-nism (2.13±0.38, P<0.01), PSP (2.36±0.36, P<0.01) and MSA (2.17±0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%±8.0% vs 11%±4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of the lower leg muscles in MSA

  2. LipidPedia: a comprehensive lipid knowledgebase.

    Science.gov (United States)

    Kuo, Tien-Chueh; Tseng, Yufeng Jane

    2018-04-10

    Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging. Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms. LipidPedia is available at http://lipidpedia.cmdm.tw. yjtseng@csie.ntu.edu.tw. Supplementary data are available at Bioinformatics online.

  3. The Contribution of Attentional Control and Working Memory to Reading Comprehension and Decoding

    Science.gov (United States)

    Arrington, C. Nikki; Kulesz, Paulina A.; Francis, David J.; Fletcher, Jack M.; Barnes, Marcia A.

    2014-01-01

    Little is known about how specific components of working memory, namely, attentional processes including response inhibition, sustained attention, and cognitive inhibition, are related to reading decoding and comprehension. The current study evaluated the relations of reading comprehension, decoding, working memory, and attentional control in…

  4. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC. Keywords: Metabolomics, Lipid peroxidation, Lipidomics, Myocardial infarction, Isoprostanes, Coronary heart disease (CHD

  5. High frequency of cytolytic 21-Hydroxylase specific CD8+ T cells in autoimmune Addison’s disease patients1

    Science.gov (United States)

    Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein; Pearce, Simon H.; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo

    2016-01-01

    The mechanisms behind the destruction of the adrenal glands in autoimmune Addison’s disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in over 90% of patients, but these autoantibodies are not thought to mediate the disease. Here we demonstrate highly frequent 21-hydroxylase specific T cells detectable in 20 patients with Addison’s disease. Using overlapping 18aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8+ and CD4+ T cell responses in a large proportion of Addison’s patients both ex-vivo and after in-vitro culture of peripheral blood lymphocytes up to 20 years after diagnosis. In a large proportion of patients, CD8+ 21-hydroxylase specific T cells and CD4+ 21-hydroxylase specific T cells were very abundant and detectable in ex-vivo assays. HLA class-I tetramer-guided isolation of 21-hydroxylase specific CD8+ T cells showed their ability to lyse 21-hydroxylase positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate strong cytotoxic T lymphocyte responses to 21-hydroxylase often occur in-vivo, and that reactive cytotoxic T lymphocytes have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. PMID:25063864

  6. The role of self-efficacy in inflammatory bowel disease management: preliminary validation of a disease-specific measure.

    Science.gov (United States)

    Keefer, Laurie; Kiebles, Jennifer L; Taft, Tiffany H

    2011-02-01

    Inflammatory bowel diseases (IBDs) require self-management skills that may be influenced by self-efficacy (SE). Self-efficacy represents an individual's perception of his or her ability to organize and execute the behaviors necessary to manage disease. The goal of this study was to develop a valid and reliable measure of IBD-specific SE that can be used in clinical and research contexts. One hundred and twenty-two adults with a verified IBD diagnosis participated in the study. Data were pooled from 2 sources: patients from an outpatient university gastroenterology clinic (n=42) and a sample of online respondents (n=80). All participants (N=122) completed the IBD Self-Efficacy Scale (IBD-SES) and the Inflammatory Bowel Disease Questionnaire. Additionally, online participants completed the Brief Symptom Inventory-18 and the Rosenberg Self-Esteem Scale, whereas those in the clinic sample completed the Perceived Health Competence Scale, the Perceived Stress Questionnaire, and the Short Form Version 2 Health Survey. The IBD-SES was initially constructed to identify 4 distinct theoretical domains of self-efficacy: (1) managing stress and emotions, (2) managing medical care, (3) managing symptoms and disease, and (4) maintaining remission. The 29-item IBD-SES has high internal consistency (r=0.96), high test-retest reliability (r=0.90), and demonstrates strong construct and concurrent validity with established measures. The IBD-SES is a critical first step toward addressing an important psychological construct that could influence treatment outcomes in IBD.

  7. Emergency preparedness: a comprehensive plan

    International Nuclear Information System (INIS)

    Wilson, R.H.

    1975-01-01

    The Atlantic Richfield Hanford Company (ARHCO) has developed comprehensive plans for coping with emergencies ranging from criticality to civil disturbance. A unique notification system provides for immediate contact with key personnel by using a central communications center, crash alarm warning networks, and a continuing telephone cascade notification system. There is also the capability of immediately contacting other contractor key personnel. Certain jobs have been predetermined as necessary for coping with an emergency. An emergency staff consisting of responsible management, with alternates, has been preselected to automatically fill these jobs when notified. Control centers for headquarters and ''field'' are established with telephone and radio communication capabilities and are also supplied with some source materials to assist initiating plans for containing an emergency for recovery. A comprehensive emergency procedures manual has been developed, which contains information of company-wide application and procedures for specific facilities covering almost all accident situations

  8. Neuronal basis of speech comprehension.

    Science.gov (United States)

    Specht, Karsten

    2014-01-01

    Verbal communication does not rely only on the simple perception of auditory signals. It is rather a parallel and integrative processing of linguistic and non-linguistic information, involving temporal and frontal areas in particular. This review describes the inherent complexity of auditory speech comprehension from a functional-neuroanatomical perspective. The review is divided into two parts. In the first part, structural and functional asymmetry of language relevant structures will be discus. The second part of the review will discuss recent neuroimaging studies, which coherently demonstrate that speech comprehension processes rely on a hierarchical network involving the temporal, parietal, and frontal lobes. Further, the results support the dual-stream model for speech comprehension, with a dorsal stream for auditory-motor integration, and a ventral stream for extracting meaning but also the processing of sentences and narratives. Specific patterns of functional asymmetry between the left and right hemisphere can also be demonstrated. The review article concludes with a discussion on interactions between the dorsal and ventral streams, particularly the involvement of motor related areas in speech perception processes, and outlines some remaining unresolved issues. This article is part of a Special Issue entitled Human Auditory Neuroimaging. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Prospective assessment of disease-specific quality of life in adults with eosinophilic esophagitis.

    Science.gov (United States)

    Stern, E; Taft, T; Zalewski, A; Gonsalves, N; Hirano, I

    2017-10-27

    Eosinophilic esophagitis (EoE) is an important cause of upper gastrointestinal dysfunction in children and adults. The EoE-quality of life (QOL)-A was validated as a disease-specific measure of quality of life in EoE. This study characterized the extent of QOL concerns in a cohort of adult EoE patients and delineated the relationships between QOL and other disease activity measures. One hundred sixty-seven patients enrolled in this prospective cohort study. Patients with established and suspected EoE undergoing endoscopy at a single university-based medical center were recruited. EoE was diagnosed on the basis of the clinical criteria and histologic demonstration of ≥15 eos/hpf while on proton pump inhibition therapy. Sixty five patients undergoing repeat endoscopy during the enrollment period participated twice. Patients provided demographic information and completed symptom assessments and the EoE-QOL-A. Analyses included comparisons with overall QOL as well as QOL subscales. Outcome measures included endoscopic activity using a validated instrument, the EoE Endoscopic Reference Score, and histology. Overall QOL was significantly correlated with dysphagia frequency, intensity, and severity (P food impaction in the last 30 days had significantly worse overall QOL (P = 0.009). There was no correlation between overall QOL and years since diagnosis, symptom duration, endoscopic features, or histologic findings. Patient symptoms correlated with endoscopic features of edema, rings, and stricture severity. Histologic activity was highly correlated with severity of endoscopic features. Patients who underwent repeat endoscopy with histologic response demonstrated improved eating and social QOL; however, overall QOL was unchanged. In adults with EoE, patient reported QOL is associated with symptom severity but not endoscopic or histologic features. Disease-specific QOL may complement parameters of biologic activity in the assessment of overall disease burden in EoE.

  10. Toward comprehensive detection of sight threatening retinal disease using a multiscale AM-FM methodology

    Science.gov (United States)

    Agurto, C.; Barriga, S.; Murray, V.; Murillo, S.; Zamora, G.; Bauman, W.; Pattichis, M.; Soliz, P.

    2011-03-01

    In the United States and most of the western world, the leading causes of vision impairment and blindness are age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. In the last decade, research in automatic detection of retinal lesions associated with eye diseases has produced several automatic systems for detection and screening of AMD, DR, and glaucoma. However. advanced, sight-threatening stages of DR and AMD can present with lesions not commonly addressed by current approaches to automatic screening. In this paper we present an automatic eye screening system based on multiscale Amplitude Modulation-Frequency Modulation (AM-FM) decompositions that addresses not only the early stages, but also advanced stages of retinal and optic nerve disease. Ten different experiments were performed in which abnormal features such as neovascularization, drusen, exudates, pigmentation abnormalities, geographic atrophy (GA), and glaucoma were classified. The algorithm achieved an accuracy detection range of [0.77 to 0.98] area under the ROC curve for a set of 810 images. When set to a specificity value of 0.60, the sensitivity of the algorithm to the detection of abnormal features ranged between 0.88 and 1.00. Our system demonstrates that, given an appropriate training set, it is possible to use a unique algorithm to detect a broad range of eye diseases.

  11. Negative blood oxygen level dependent signals during speech comprehension.

    Science.gov (United States)

    Rodriguez Moreno, Diana; Schiff, Nicholas D; Hirsch, Joy

    2015-05-01

    Speech comprehension studies have generally focused on the isolation and function of regions with positive blood oxygen level dependent (BOLD) signals with respect to a resting baseline. Although regions with negative BOLD signals in comparison to a resting baseline have been reported in language-related tasks, their relationship to regions of positive signals is not fully appreciated. Based on the emerging notion that the negative signals may represent an active function in language tasks, the authors test the hypothesis that negative BOLD signals during receptive language are more associated with comprehension than content-free versions of the same stimuli. Regions associated with comprehension of speech were isolated by comparing responses to passive listening to natural speech to two incomprehensible versions of the same speech: one that was digitally time reversed and one that was muffled by removal of high frequencies. The signal polarity was determined by comparing the BOLD signal during each speech condition to the BOLD signal during a resting baseline. As expected, stimulation-induced positive signals relative to resting baseline were observed in the canonical language areas with varying signal amplitudes for each condition. Negative BOLD responses relative to resting baseline were observed primarily in frontoparietal regions and were specific to the natural speech condition. However, the BOLD signal remained indistinguishable from baseline for the unintelligible speech conditions. Variations in connectivity between brain regions with positive and negative signals were also specifically related to the comprehension of natural speech. These observations of anticorrelated signals related to speech comprehension are consistent with emerging models of cooperative roles represented by BOLD signals of opposite polarity.

  12. Lung fibrosis quantified by HRCT in scleroderma patients with different disease forms and ANA specificities

    Directory of Open Access Journals (Sweden)

    S. Mancin

    2011-09-01

    Full Text Available Objective: to define the prevalence of interstitial lung fibrosis in systemic sclerosis (SSc and its relationship with the different clinical forms of disease and ANA specificities. Methods: fifty patients with SSc were submitted to pulmonary high resolution computed tomography (HRCT. Lung abnormalities were evaluated according to Warrick’s score that considers both the severity and the extent of fibrotic lesions. Results: pulmonary HRCT abnormalities were observed in 84% of SSc patients. Ground glass aspects (60%, irregular pleural margins (56% and septal/subpleural lines (68% were the most common lesions. The distribution of these abnormalities favoured the posterior basilar segments of both lungs. HRCT findings were significantly more frequent in males and in patients with the cutaneous diffuse form of SSc and with the specific antibody anti-Scl70. Conclusions: HRCT is a very useful method for the diagnosis of interstitial lung fibrosis in SSc. Warrick’s score permits to quantify the HRCT findings and to evaluate their relationship with the disease clinical forms and ANA specificities.

  13. Amyloid-β peptide-specific DARPins as a novel class of potential therapeutics for Alzheimer disease.

    Science.gov (United States)

    Hanenberg, Michael; McAfoose, Jordan; Kulic, Luka; Welt, Tobias; Wirth, Fabian; Parizek, Petra; Strobel, Lisa; Cattepoel, Susann; Späni, Claudia; Derungs, Rebecca; Maier, Marcel; Plückthun, Andreas; Nitsch, Roger M

    2014-09-26

    Passive immunization with anti-amyloid-β peptide (Aβ) antibodies is effective in animal models of Alzheimer disease. With the advent of efficient in vitro selection technologies, the novel class of designed ankyrin repeat proteins (DARPins) presents an attractive alternative to the immunoglobulin scaffold. DARPins are small and highly stable proteins with a compact modular architecture ideal for high affinity protein-protein interactions. In this report, we describe the selection, binding profile, and epitope analysis of Aβ-specific DARPins. We further showed their ability to delay Aβ aggregation and prevent Aβ-mediated neurotoxicity in vitro. To demonstrate their therapeutic potential in vivo, mono- and trivalent Aβ-specific DARPins (D23 and 3×D23) were infused intracerebroventricularly into the brains of 11-month-old Tg2576 mice over 4 weeks. Both D23 and 3×D23 treatments were shown to result in improved cognitive performance and reduced soluble Aβ levels. These findings demonstrate the therapeutic potential of Aβ-specific DARPins for the treatment of Alzheimer disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Comprehensive Stuttering Treatment for Adolescents: A Case Study.

    Science.gov (United States)

    Coleman, Craig E

    2018-01-09

    This article will focus on a hypothetical case study to highlight comprehensive assessment and treatment for adolescent children who stutter. Assessment and treatment are laid out with a literature review utilizing the components of the International Classification of Functioning, Disability and Health model. Specific assessment and treatment strategies and approaches are discussed. Using the International Classification of Functioning, Disability and Health model can help guide clinicians through the assessment and treatment process to ensure that all areas of stuttering are considered. Comprehensive assessment and treatment helps clinicians address all relevant elements of a stuttering disorder, rather than focusing exclusively on reducing speech disruptions.

  15. Comprehensive analysis of transport aircraft flight performance

    Science.gov (United States)

    Filippone, Antonio

    2008-04-01

    This paper reviews the state-of-the art in comprehensive performance codes for fixed-wing aircraft. The importance of system analysis in flight performance is discussed. The paper highlights the role of aerodynamics, propulsion, flight mechanics, aeroacoustics, flight operation, numerical optimisation, stochastic methods and numerical analysis. The latter discipline is used to investigate the sensitivities of the sub-systems to uncertainties in critical state parameters or functional parameters. The paper discusses critically the data used for performance analysis, and the areas where progress is required. Comprehensive analysis codes can be used for mission fuel planning, envelope exploration, competition analysis, a wide variety of environmental studies, marketing analysis, aircraft certification and conceptual aircraft design. A comprehensive program that uses the multi-disciplinary approach for transport aircraft is presented. The model includes a geometry deck, a separate engine input deck with the main parameters, a database of engine performance from an independent simulation, and an operational deck. The comprehensive code has modules for deriving the geometry from bitmap files, an aerodynamics model for all flight conditions, a flight mechanics model for flight envelopes and mission analysis, an aircraft noise model and engine emissions. The model is validated at different levels. Validation of the aerodynamic model is done against the scale models DLR-F4 and F6. A general model analysis and flight envelope exploration are shown for the Boeing B-777-300 with GE-90 turbofan engines with intermediate passenger capacity (394 passengers in 2 classes). Validation of the flight model is done by sensitivity analysis on the wetted area (or profile drag), on the specific air range, the brake-release gross weight and the aircraft noise. A variety of results is shown, including specific air range charts, take-off weight-altitude charts, payload-range performance

  16. Comprehension of complex biological processes by analytical methods: how far can we go using mass spectrometry?

    International Nuclear Information System (INIS)

    Gerner, C.

    2013-01-01

    Comprehensive understanding of complex biological processes is the basis for many biomedical issues of great relevance for modern society including risk assessment, drug development, quality control of industrial products and many more. Screening methods provide means for investigating biological samples without research hypothesis. However, the first boom of analytical screening efforts has passed and we again need to ask whether and how to apply screening methods. Mass spectrometry is a modern tool with unrivalled analytical capacities. This applies to all relevant characteristics of analytical methods such as specificity, sensitivity, accuracy, multiplicity and diversity of applications. Indeed, mass spectrometry qualifies to deal with complexity. Chronic inflammation is a common feature of almost all relevant diseases challenging our modern society; these diseases are apparently highly diverse and include arteriosclerosis, cancer, back pain, neurodegenerative diseases, depression and other. The complexity of mechanisms regulating chronic inflammation is the reason for the practical challenge to deal with it. The presentation shall give an overview of capabilities and limitations of the application of this analytical tool to solve critical questions with great relevance for our society. (author)

  17. Toxoplasmosis--a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries.

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H

    2014-01-01

    Toxoplasmosis is becoming a global health hazard as it infects 30-50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Prevalence data published between 1995-2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and

  18. Disease-specific health-related quality of life instruments for IgE-mediated food allergy

    DEFF Research Database (Denmark)

    Salvilla, S A; Dubois, A E J; Flokstra-de Blok, B M J

    2014-01-01

    of the impact of, and investigations and interventions for, IgE-mediated food allergy on health-related quality of life (HRQL). Using a sensitive search strategy, we searched seven electronic bibliographic databases to identify disease-specific quality of life (QOL) tools relating to IgE-mediated food allergy...

  19. Comprehensive Psychiatric Evaluation

    Science.gov (United States)

    ... Facts for Families Guide Facts for Families - Vietnamese Comprehensive Psychiatric Evaluation No. 52; Updated October 2017 Evaluation ... with serious emotional and behavioral problems need a comprehensive psychiatric evaluation. Comprehensive psychiatric evaluations usually require a ...

  20. Economic aspects of rare diseases.

    Science.gov (United States)

    Borski, Krzysztof

    2015-01-01

    Economic problems related to the prevention, diagnosis and treatment of rare diseases are presented paying particular attention to the costs of financing treatment, including the issue of its refund, which is a fundamental and difficult to solve economic problem of the health care system. Rare diseases, despite the low frequency of occurrence, together cover a large group of diseases being a serious medical, social and economic problem. The adoption of Polish National Plan for Rare Diseases resulting from the recommendations of the Council of the European Union, the extension of institutional activities related to the area of public health and social initiatives seeking innovative solutions to create a model of social support for patients and their families, with very high complexity of the issues regarding rare diseases, results in the need for a coherent, comprehensive, system operations and adoption of comprehensive solutions.

  1. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy

    Science.gov (United States)

    Satoh, Minoru; Tanaka, Shin; Ceribelli, Angela; Calise, S. John; Chan, Edward K. L.

    2018-01-01

    Autoantibodies specific for idiopathic inflammatory myopathy (myositis-specific autoantibodies (MSAs)) are clinically useful biomarkers to help the diagnosis of polymyositis/dermatomyositis (PM/DM). Many of these are also associated with a unique clinical subset of PM/DM, making them useful in predicting and monitoring certain clinical manifestations. Classic MSAs known for over 30 years include antibodies to Jo-1 (histidyl transfer RNA (tRNA) synthetase) and other aminoacyl tRNA synthetases (ARS), anti-Mi-2, and anti-signal recognition particle (SRP). Anti-Jo-1 is the first autoantibodies to ARS detected in 15–25 % of patients. In addition to anti-Jo-1, antibodies to seven other aminoacyl tRNA synthetases (ARS) have been reported with prevalence, usually 1–5 % or lower. Patients with any antiARS antibodies are associated with anti-synthetase syndrome characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, and others. Several recent studies suggested heterogeneity in clinical features among different anti-ARS antibody-positive patients and anti-ARS may also be found in idiopathic ILD without myositis. Anti-Mi-2 is a classic marker for DM and associated with good response to steroid treatment and good prognosis. Anti-SRP is specific for PM and associated with treatment-resistant myopathy histologically characterized as necrotizing myopathy. In addition to classic MSAs, several new autoantibodies with strong clinical significance have been described in DM. Antibodies to transcription intermediary factor 1γ/α (TIF1γ/α, p155/140) are frequently found in DM associated with malignancy while anti-melanoma differentiation-associated gene 5 (MDA5; CADM140) are associated with clinically amyopathic DM (CADM) complicated by rapidly progressive ILD. Also, anti-MJ/nuclear matrix protein 2 (NXP-2) and anti-small ubiquitin-like modifier-1 (SUMO-1) activating enzyme (SAE) are recognized as new DM-specific autoantibodies. Addition of

  2. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around

  3. Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

    Science.gov (United States)

    Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

    2018-01-01

    Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD

  4. The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome

    Directory of Open Access Journals (Sweden)

    M. Biglari

    2015-11-01

    Full Text Available Irritable Bowel Syndrome (IBS is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL. Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years. HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF questionnaires. Patients also completed Speilberger`s “State/Trait Anxiety Inventory” and “Beck Depression Inventory-II” for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P P value < 0.001. Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

  5. Comprehensive Stuttering Treatment or Adolescents: A Case Study

    Science.gov (United States)

    Coleman, Craig E.

    2018-01-01

    Purpose: This article will focus on a hypothetical case study to highlight comprehensive assessment and treatment for adolescent children who stutter. Method: Assessment and treatment are laid out with a literature review utilizing the components of the International Classification of Functioning, Disability and Health model. Specific assessment…

  6. Specific learning disability in mathematics: a comprehensive review.

    Science.gov (United States)

    Soares, Neelkamal; Evans, Teresa; Patel, Dilip R

    2018-01-01

    Math skills are necessary for success in the childhood educational and future adult work environment. This article reviews the changing terminology for specific learning disabilities (SLD) in math and describes the emerging genetics and neuroimaging studies that relate to individuals with math disability (MD). It is important to maintain a developmental perspective on MD, as presentation changes with age, instruction, and the different models (educational and medical) of identification. Intervention requires a systematic approach to screening and remediation that has evolved with more evidence-based literature. Newer directions in behavioral, educational and novel interventions are described.

  7. Children's hypertext comprehension

    NARCIS (Netherlands)

    Segers, P.C.J.; Segers, E.; Broek, P. van den

    2017-01-01

    The present chapter gives an overview of the literature on hypertext comprehension, children's hypertext comprehension and individual variation therein, ending with a perspective for future research. Hypertext comprehension requires the reader to make bridging inferences between the different parts

  8. ESAP Students' Comprehension of Multiple Technical Reading Texts: Insights from Personal Epistemological Beliefs

    Science.gov (United States)

    Karimi, Mohammad Nabi; Atai, Mohamood Reza

    2014-01-01

    Given the importance associated with multiple-document literacy in the present-day knowledge societies and the dearth of research in English Language Teaching in general and English for Specific/Academic Purposes (ESAP) contexts in particular on multiple-document comprehension and the significance of reader beliefs in this type of comprehension,…

  9. Profiles of microbial fatty acids in the human metabolome are disease-specific

    Directory of Open Access Journals (Sweden)

    Zhanna A Ktsoyan

    2011-01-01

    Full Text Available The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense crosstalk and signalling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF, and in patients with peptic ulceration (PU resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified. This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.

  10. Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

    Science.gov (United States)

    Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

    2016-09-01

    Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus

  11. Agrammatic Comprehension of Wh-Extraction in Danish, English and French

    DEFF Research Database (Denmark)

    Nyvad, Anne Mette

    2010-01-01

    This dissertation discusses the comprehension deficit in agrammatic aphasia and how it relates to wh-extraction. Ostensibly, Broca’s aphasics are unable to understand certain types of syntactic movement structure when the semantic and pragmatic cues are withheld. The present study seeks to examine...... whether results hitherto obtained in crosslinguistic research on wh-extraction, specifically in English and French, also pertain to Danish agrammatic comprehenders, but it also widens the scope of interest: Biclausal structures involving wh-questions have not yet been subject to a systematic investigation......) widely-held account of the comprehension patterns in agrammatism. Focus is on comprehension, but data from research on agrammatic production will be offered when relevant to the theoretical discussion....

  12. Comprehensive overview of prostatitis.

    Science.gov (United States)

    Khan, Farhan Ullah; Ihsan, Awais Ullah; Khan, Hidayat Ullah; Jana, Ruby; Wazir, Junaid; Khongorzul, Puregmaa; Waqar, Muhammad; Zhou, Xiaohui

    2017-10-01

    Prostatitis is a common urinary tract syndrome that many doctors find problematic to treat effectively. It is the third most commonly found urinary tract disease in men after prostate cancer and Benign Prostate Hyperplasia (BPH). Prostatitis may account for 25% of all office visits made to the urological clinics complaining about the genital and urinary systems all over the world. In the present study, we classified prostatitis and comprehensively elaborated the etiology, pathogenesis, diagnosis, and treatment of acute bacterial prostatitis (category I), chronic bacterial prostatitis (category II), chronic pelvic pain syndrome (CPPS) (category III), and asymptomatic prostatitis (category IV). In addition, we also tried to get some insights about other types of prostatitis-like fungal, viral and gonococcal prostatitis. The aim of this review is to present the detail current perspective of prostatitis in a single review. To the best of our knowledge currently, there is not a single comprehensive review, which can completely elaborate this important topic in an effective way. Furthermore, this review will provide a solid platform to conduct future studies on different aspects such as risk factors, mechanism of pathogenesis, proper diagnosis, and rational treatment plans for fungal, viral, and gonococcal prostatitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Advanced Selling: A Comprehensive Course Sales Project

    Science.gov (United States)

    Yarrington-Young, Susan; Castleberry, Stephen B.; Coleman, Joshua T.

    2016-01-01

    A comprehensive project for the Advanced Selling course that has been tested at three universities is introduced. After selecting an industry and a company, students engage in a complete industry analysis, a company sales analysis, a sales-specific SWOT analysis, complete a ride day with a salesperson in that firm, then present their findings in a…

  14. Emerging infectious diseases: a guide to diseases, causative agents, and surveillance

    National Research Council Canada - National Science Library

    Beltz, Lisa A

    2011-01-01

    "This important resource offers a comprehensive introduction to emerging and reemerging infectious disease, including the underlying mechanisms of microbial emergence, the technology used to detect...

  15. Comprehensive proteomic analysis of the wheat pathogenic fungus Zymoseptoria tritici

    DEFF Research Database (Denmark)

    Yang, Fen; Yin, Qi

    2016-01-01

    Zymoseptoria tritici causes Septoria tritici blotch disease of wheat. To obtain a comprehensive protein dataset of this fungal pathogen, proteomes of Z. tritici growing in nutrient-limiting and rich media and in vivo at a late stage of wheat infection were fractionated by 1D gel or strong cation...

  16. An update on the epigenetics of psychotic diseases and autism.

    Science.gov (United States)

    Abdolmaleky, Hamid Mostafavi; Zhou, Jin-Rong; Thiagalingam, Sam

    2015-01-01

    The examination of potential roles of epigenetic alterations in the pathogenesis of psychotic diseases have become an essential alternative in recent years as genetic studies alone are yet to uncover major gene(s) for psychosis. Here, we describe the current state of knowledge from the gene-specific and genome-wide studies of postmortem brain and blood cells indicating that aberrant DNA methylation, histone modifications and dysregulation of micro-RNAs are linked to the pathogenesis of mental diseases. There is also strong evidence supporting that all classes of psychiatric drugs modulate diverse features of the epigenome. While comprehensive environmental and genetic/epigenetic studies are uncovering the origins, and the key genes/pathways affected in psychotic diseases, characterizing the epigenetic effects of psychiatric drugs may help to design novel therapies in psychiatry.

  17. Myositis specific autoantibodies; specificity and clinical applications.

    NARCIS (Netherlands)

    Hengstman, G.J.D.

    2005-01-01

    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as

  18. Dietary sodium in chronic kidney disease: a comprehensive approach.

    Science.gov (United States)

    Wright, Julie A; Cavanaugh, Kerri L

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

  19. Autosomal dominant polycystic kidney disease and pain - a review of the disease from aetiology, evaluation, past surgical treatment options to current practice.

    Science.gov (United States)

    Badani, K K; Hemal, A K; Menon, M

    2004-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD), often referred to as "adult" polycystic kidney disease, is one of the commonest hereditary disorders. It affects approximately 4 to 6 million individuals worldwide. The disease progresses to end-stage renal disease and it accounts for 10-15% of patients requiring dialysis in the United States. A comprehensive Medline search for aetiology, evaluation, screening, cellular biology, and treatment was utilized to locate, extract, and synthesize relevant data with respect to this topic. Special attention was focused on urologic literature and surgical textbooks regarding operative treatment of pain associated with ADPKD. Now, patients with ADPKD have more treatment options. More specifically, several therapeutic alternatives are now available for the management of pain in these patients. A recent review of literature supports the performance of open or laparoscopic cyst decortication procedures for control of pain and infection without the worry of causing further renal impairment in those with preserved renal function.

  20. Unique dietary patterns and chronic disease risk profiles of adult men: the Framingham nutrition studies.

    Science.gov (United States)

    Millen, Barbara E; Quatromoni, Paula A; Pencina, Michael; Kimokoti, Ruth; Nam, Byung-H O; Cobain, Sonia; Kozak, Waldemar; Appugliese, Danielle P; Ordovas, Jose; D'Agostino, Ralph B

    2005-11-01

    To identify the dietary patterns of adult men and examine their relationships with nutrient intake and chronic disease risk over long-term follow-up. Baseline 145-item food frequency questionnaires from 1,666 Framingham Offspring-Spouse cohort men were used to identify comprehensive dietary patterns. Independent 3-day dietary records at baseline and 8 years later provided estimates of subjects' nutrient intake by dietary pattern. Chronic disease risk factor status was compared at baseline and 16-year follow-up across all male dietary patterns. Cluster analysis was applied to food frequency data to identify non-overlapping male dietary patterns. Analysis of covariance and logistic regression were used to compare nutrient intake, summary nutritional risk scores, and chronic disease risk status at baseline and follow-up by male dietary pattern. Five distinct and comprehensive dietary patterns of Framingham Offspring-Spouse men were identified and ordered according to overall nutritional risk: Transition to Heart Healthy, Higher Starch, Average Male, Lower Variety, and Empty Calories. Nutritional risk was high and varied by dietary pattern; key nutrient contrasts were stable over 8-year follow-up. Chronic disease risk also varied by dietary pattern and specific subgroup differences persisted over 16 years, notably rates of overweight/obesity and smoking. Quantitative cluster analysis applied to food frequency questionnaire data identified five distinct, comprehensive, and stable dietary patterns of adult Framingham Offspring-Spouse cohort men. The close associations between the dietary patterns, nutritional risk, and chronic disease profiles of men emphasize the importance of targeted preventive nutrition interventions to promote health in the male population.

  1. GeneView: a comprehensive semantic search engine for PubMed.

    Science.gov (United States)

    Thomas, Philippe; Starlinger, Johannes; Vowinkel, Alexander; Arzt, Sebastian; Leser, Ulf

    2012-07-01

    Research results are primarily published in scientific literature and curation efforts cannot keep up with the rapid growth of published literature. The plethora of knowledge remains hidden in large text repositories like MEDLINE. Consequently, life scientists have to spend a great amount of time searching for specific information. The enormous ambiguity among most names of biomedical objects such as genes, chemicals and diseases often produces too large and unspecific search results. We present GeneView, a semantic search engine for biomedical knowledge. GeneView is built upon a comprehensively annotated version of PubMed abstracts and openly available PubMed Central full texts. This semi-structured representation of biomedical texts enables a number of features extending classical search engines. For instance, users may search for entities using unique database identifiers or they may rank documents by the number of specific mentions they contain. Annotation is performed by a multitude of state-of-the-art text-mining tools for recognizing mentions from 10 entity classes and for identifying protein-protein interactions. GeneView currently contains annotations for >194 million entities from 10 classes for ∼21 million citations with 271,000 full text bodies. GeneView can be searched at http://bc3.informatik.hu-berlin.de/.

  2. Development of a disease-specific instrument to measure quality of life in patients with alopecia areata.

    Science.gov (United States)

    Endo, Yuichiro; Miyachi, Yoshiki; Arakawa, Akiko

    2012-01-01

    Alopecia areata (AA) is a common hair loss disorder that frequently follows a chronic course. Although AA is apparently associated with disturbance of quality of life (QoL), no disease-specific instrument to measure the QoL has been developed. This study was conducted to develop a disease-specific self-administered instrument to measure AA patients' QoL (AAQ). A two-step cross-sectional study was conducted. Items were generated from qualitative interviews with five patients with AA (two men and three women, age 28±6.4 years). Then, a preliminary questionnaire was produced and delivered to the patients (n=122). The AAQ was examined in terms of statistical performance. The AAQ included 7 items in the following three subscales: 'restriction of activity', 'concealment' and 'adaptation'. The reliability of internal consistency was fair with Cronbach's alpha coefficients of 0.59-81 for each subscale. Confirmatory factor analysis and correlation analysis demonstrated that the AAQ had good construct validity. Interestingly, the AAQ was only correlated with subjective severity scores as rated by the patients, but not with objective disease severity assessed by investigators.

  3. The Relationship between Listening Comprehension of Text and Sentences in Preschoolers: Specific or Mediated by Lower and Higher Level Components?

    Science.gov (United States)

    Florit, Elena; Roch, Maja; Levorato, M. Chiara

    2013-01-01

    Two studies explored the relation between listening comprehension of text and listening comprehension of sentences in preschoolers aged 4 to 5 years, 11 months. The first study analyzed this relationship taking into account the role of lower level components, namely, word knowledge and verbal working memory, as possible mediators. These components…

  4. HSP: bystander antigen in atopic diseases?

    Directory of Open Access Journals (Sweden)

    Joost A Aalberse

    2012-05-01

    Full Text Available Over the last years insight in the complex interactions between innate and adaptive immunity in the regulation of an inflammatory response has increased enormously. This has revived the interest in stress proteins; proteins that are expressed during cell stress. As these proteins can attract and trigger an immunological response they can act as important mediators in this interaction. In this respect, of special interest are proteins that may act as modulators of both innate and adaptive immunity. Heat shock proteins (HSPs are stress proteins that have these, and more, characteristics. More than two decades of studies on HSPs has revealed that they are part of intrinsic, natural mechanisms that steer inflammation. This has provoked comprehensive explorations of the role of HSPs in various human inflammatory diseases.Most studies have focused on classical autoimmune diseases. This has led to the development of clinical studies with HSPs that have shown promise in Phase II/III clinical trials. Remarkably, only very little is yet known of the role of HSPs in atopic diseases. In allergic disease a number of studies have investigated the possibility that allergen-specific regulatory T cell (Treg function is defective in individuals with allergic diseases. This raises the question whether methods can be identified to improve the Treg repertoire. Studies from other inflammatory diseases have suggested HSPs may have such a beneficial effect on the T cell repertoire. Based on the immune mechanisms of atopic diseases, in this review we will argue that, as in other human inflammatory conditions, understanding immunity to HSPs is likely also relevant for atopic diseases. Specifically, we will discuss why certain HSPs such as HSP60 connect the immune response to environmental antigens with regulation of the inflammatory response.Thus they provide a molecular link that may eventually even help to better understand the immune pathological basis of the hygiene

  5. Von Hippel-Lindau disease: an evaluation of natural history and functional disability.

    Science.gov (United States)

    Feletti, Alberto; Anglani, Mariagiulia; Scarpa, Bruno; Schiavi, Francesca; Boaretto, Francesca; Zovato, Stefania; Taschin, Elisa; Gardi, Mario; Zanoletti, Elisabetta; Piermarocchi, Stefano; Murgia, Alessandra; Pavesi, Giacomo; Opocher, Giuseppe

    2016-07-01

    Although many studies have been published about specific lesions characterizing von Hippel-Lindau(VHL) disease, none have dealt with the natural history of the whole disease and the consequent disabilities. We aim to define the comprehensive natural history of VHL disease and to describe the functional disabilities and their impact upon patients' quality of life, thereby tailoring the follow-up schedule accordingly. We performed a prospective analysis on 128 VHL-affected patients beginning in 1996. For each affected organ, we defined intervals between the first and subsequent VHL-related manifestations and compared them with current VHL surveillance protocols. We looked for any association of the number of involved organs with age, sex, type of VHL gene mutation, and functional domain mutation. Ultimately, we assessed the organ-specific disabilities caused by VHL disease. Hemangioblastomas show different patterns of progression depending on their location, whereas both renal cysts and carcinomas have similar progression rates. Surgery for pheochromocytoma and CNS hemangioblastoma is performed earlier than for pancreatic or renal cancer. The number of involved organs is associated with age but not with sex, type of VHL gene mutation, or functional domain mutation. A thorough analysis of functional disabilities showed that age is related to the first-appearing functional impairment, but it is not predictive of the final number of disabilities. Our study defines the disease progression and provides a comprehensive view of the syndrome over time. We analyzed for the first time the functional disability of VHL patients, assessing the progression for each function. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Formulating a comprehensive strategy to counter the menace of malnutrition in developing countries

    Directory of Open Access Journals (Sweden)

    Saurabh RamBihariLal Shrivastava

    2014-01-01

    Full Text Available The indispensable role of optimal nutrition in ensuring absolute health status and holistic development of a society is well acknowledged. Malnutrition is considered as a disease of human society that can begin in the womb and eventually lasts till the death. A wide range of socio-cultural and infectious parameters have been determined that can ultimately precipitate malnutrition. Considering the multi-factorial origin of the disease, the strategy to combat malnutrition should also be comprehensive and multi-pronged comprising measures to combat the condition at every level concurrently in the entire nation. The corrective policy essentially requires the coordinated approach of different stakeholders and should be targeted at four different levels - family, community, national, and international. To conclude, diet is a crucial element in the natural history of many public health-related diseases, and owing to the multiple factors that eventually determine the dietary habits, a comprehensive approach is the need of the hour.

  7. Radioimmunoassay for detection of VP1 specific neutralizing antibodies of foot and mouse disease virus

    International Nuclear Information System (INIS)

    Patzer, E.J.; Jackson, M.L.; Moore, D.M.

    1985-01-01

    A solid-phase radioimmunoassay was developed for the detection of antibodies against a specific region of the VP1 protein of the A24 and O1 serotypes of foot and mouth disease virus. The antibody titers from the radioimmunoassay showed a positive correlation with neutralizing antibody titers determined by a mouse protection assay. The specificity of the assay resides in the peptide used as antigen. The assay is rapid, reproducible and does not require the use of whole virions. (orig.)

  8. Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zabel Claus

    2011-09-01

    Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

  9. Communicating projected survival with treatments for chronic kidney disease: patient comprehension and perspectives on visual aids.

    Science.gov (United States)

    Dowen, Frances; Sidhu, Karishma; Broadbent, Elizabeth; Pilmore, Helen

    2017-09-21

    Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Visual aids, can be beneficial adjuncts to discussing survival in CKD.

  10. Designing information visualizations for elite soccer children's different levels of comprehension

    DEFF Research Database (Denmark)

    Herdal, Thor; Pedersen, Jeppe Gerner; Knudsen, Søren

    2016-01-01

    We describe a study that sought to understand elite soccer children's use of visualizations to learn about, and improve their own sports performance. We specifically investigate how visualizations support the players' data comprehension. In this process, we design and evaluate visualizations base...... on real data. Finally, we discuss how the players' level of comprehension might depend on factors such as their general literacy and visualization literacy, and the role of visualization in coaching children....

  11. Comprehensive School Reform and Achievement: A Meta-Analysis

    Science.gov (United States)

    Borman, Geoffrey D.; Hewes, Gina M.; Overman, Laura T.; Brown, Shelly

    2003-01-01

    This meta-analysis reviews research on the achievement effects of comprehensive school reform (CSR) and summarizes the specific effects of 29 widely implemented models. There are limitations on the overall quantity and quality of the research base, but the overall effects of CSR appear promising. The combined quantity, quality, and statistical…

  12. Electronic Integrated Disease Surveillance System and Pathogen Asset Control System

    Directory of Open Access Journals (Sweden)

    Tom G. Wahl

    2012-06-01

    Full Text Available Electronic Integrated Disease Surveillance System (EIDSS has been used to strengthen and support monitoring and prevention of dangerous diseases within One Health concept by integrating veterinary and human surveillance, passive and active approaches, case-based records including disease-specific clinical data based on standardised case definitions and aggregated data, laboratory data including sample tracking linked to each case and event with test results and epidemiological investigations. Information was collected and shared in secure way by different means: through the distributed nodes which are continuously synchronised amongst each other, through the web service, through the handheld devices. Electronic Integrated Disease Surveillance System provided near real time information flow that has been then disseminated to the appropriate organisations in a timely manner. It has been used for comprehensive analysis and visualisation capabilities including real time mapping of case events as these unfold enhancing decision making. Electronic Integrated Disease Surveillance System facilitated countries to comply with the IHR 2005 requirements through a data transfer module reporting diseases electronically to the World Health Organisation (WHO data center as well as establish authorised data exchange with other electronic system using Open Architecture approach. Pathogen Asset Control System (PACS has been used for accounting, management and control of biological agent stocks. Information on samples and strains of any kind throughout their entire lifecycle has been tracked in a comprehensive and flexible solution PACS. Both systems have been used in a combination and individually. Electronic Integrated Disease Surveillance System and PACS are currently deployed in the Republics of Kazakhstan, Georgia and Azerbaijan as a part of the Cooperative Biological Engagement Program (CBEP sponsored by the US Defense Threat Reduction Agency (DTRA.

  13. Electronic integrated disease surveillance system and pathogen asset control system.

    Science.gov (United States)

    Wahl, Tom G; Burdakov, Aleksey V; Oukharov, Andrey O; Zhilokov, Azamat K

    2012-06-20

    Electronic Integrated Disease Surveillance System (EIDSS) has been used to strengthen and support monitoring and prevention of dangerous diseases within One Health concept by integrating veterinary and human surveillance, passive and active approaches, case-based records including disease-specific clinical data based on standardised case definitions and aggregated data, laboratory data including sample tracking linked to each case and event with test results and epidemiological investigations. Information was collected and shared in secure way by different means: through the distributed nodes which are continuously synchronised amongst each other, through the web service, through the handheld devices. Electronic Integrated Disease Surveillance System provided near real time information flow that has been then disseminated to the appropriate organisations in a timely manner. It has been used for comprehensive analysis and visualisation capabilities including real time mapping of case events as these unfold enhancing decision making. Electronic Integrated Disease Surveillance System facilitated countries to comply with the IHR 2005 requirements through a data transfer module reporting diseases electronically to the World Health Organisation (WHO) data center as well as establish authorised data exchange with other electronic system using Open Architecture approach. Pathogen Asset Control System (PACS) has been used for accounting, management and control of biological agent stocks. Information on samples and strains of any kind throughout their entire lifecycle has been tracked in a comprehensive and flexible solution PACS.Both systems have been used in a combination and individually. Electronic Integrated Disease Surveillance System and PACS are currently deployed in the Republics of Kazakhstan, Georgia and Azerbaijan as a part of the Cooperative Biological Engagement Program (CBEP) sponsored by the US Defense Threat Reduction Agency (DTRA).

  14. Specific proof of various stages of Osler's disease of the brain via high field magnetic resonance tomography (1. 5 Tesla)

    Energy Technology Data Exchange (ETDEWEB)

    Billet, F; Bluemm, R G; Beyer, H K

    1988-08-01

    MR is a sensitive noninvasive examination method for diagnosing parenchymatous cryptic arteriovenous malformations and sequels of cerebral haemorrhage. In a patient with recurring nosebleed and brain stem syndrome eleven so-called cryptic arteriovenous malformations or their haemorrhage sequels were diagnosed via magnetic resonance tomography. Basing on these specific findings, nosebleeding, and a positive family anamnesis, the findings could be classified as belonging to manifestations of Osler's disease (hereditary haemorrhagic telangiectasia). This rare disease is characterised by a triad of signs: telangiectasias, recurring bleeding, and heredity. In this article the specific MR image is compared with the CT pattern and the results are discussed against the background of literature on Osler's disease which is also known as Rendu-Osler-Weber disease.

  15. Nailfold capillaroscopy: Specific features in Fabry disease.

    Science.gov (United States)

    Wasik, Jan S; Simon, Roger W; Meier, Thomas; Steinmann, Beat; Amann-Vesti, Beatrice R

    2009-01-01

    Fabry disease is a rare X-linked disorder caused by deficiency of alpha-galactosidase A. The metabolic defect results in the progressive accumulation of globotriaosylceramide within vascular cells leading to renal, cardiac and cerebrovascular manifestations. The aim of this study was to evaluate nailfold capillaroscopy as a non-invasive diagnostic tool in Fabry disease and to characterize morphological and functional changes of the capillaries in vivo. Twenty-five consecutive patients with Fabry disease (17 males) without enzyme-replacement therapy had been studied by fluorescence nailfold capillaroscopy. Macrocirculation of digital arteries was tested by digital pulse volume recording and patients had been asked about the presence of Raynaud phenomenon. Significant more bushy capillaries and clusters were present in Fabry patients (72%) compared to healthy controls (10%). No avascular fields had been seen, and in only one patient atypical architecture and in another one a giant capillary was present. Enhanced natrium-fluorescein diffusion into the pericapillary area has been observed in three male patients. Six patients (one female) reported Raynaud phenomenon of all fingers. In Fabry disease morphological and functional microangiopathy of nailfold capillaries is present. Furthermore, these new findings might explain, at least in part, the unusual high frequency of Raynaud phenomenon in Fabry patients, which has not been described so far. Our data suggest that capillaroscopy might be used as an additional non-invasive diagnostic tool for Fabry disease.

  16. Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

    Science.gov (United States)

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H.

    2014-01-01

    Background Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (ptoxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more

  17. Non-Communicable Diseases in Emergencies: A Call to Action

    Science.gov (United States)

    Demaio, Alessandro; Jamieson, Jennifer; Horn, Rebecca; de Courten, Maximilian; Tellier, Siri

    2013-01-01

    Recent years have demonstrated the devastating health consequences of complex emergencies and natural disasters and thereby highlighted the importance of comprehensive and collaborative approaches to humanitarian responses and risk reduction. Simultaneously, noncommunicable diseases are now recognised as a real and growing threat to population health and development; a threat that is magnified by and during emergencies. Noncommunicable diseases, however, continue to receive little attention from humanitarian organisations in the acute phase of disaster and emergency response. This paper calls on all sectors to recognise and address the specific health challenges posed by noncommunicable diseases in emergencies and disaster situations. This publication aims to highlight the need for: • Increased research on morbidity and mortality patterns due to noncommunicable diseases during and following emergencies; • Raised awareness through greater advocacy for the issue and challenges of noncommunicable diseases during and following emergencies; • Incorporation of noncommunicable diseases into existing emergency-related policies, standards, and resources; • Development of technical guidelines on the clinical management of noncommunicable diseases in emergencies; • Greater integration and coordination in health service provision during and following emergencies; • Integrating noncommunicable diseases into practical and academic training of emergency workers and emergency-response coordinators. PMID:24056956

  18. EMC² = comprehension: A reading strategy instruction framework for all teachers

    Directory of Open Access Journals (Sweden)

    Nanda M Klapwijk

    2015-02-01

    Full Text Available Comprehension is a critical part of the reading process, and yet learners continue to struggle with it and teachers continue to neglect it in their teaching. Many reasons exist for the lack of focus on reading comprehension instruction, but for the most part, teachers simply do not seem to view comprehension as part of the reading process, are not able to teach the concept, and are seemingly not taught to do so during their teacher training years. In addition to this, comprehension continues to be viewed as part of 'language teaching', and is therefore viewed as the so-called 'language teacher's' domain. In support of effective comprehension instruction in the unique, multilingual South African education environment, this article proposes a framework for reading strategy instruction, aimed specifically at teachers. The framework was developed from a research study, and refined through subsequent application in a university course as well as a further study. The framework acknowledges that reading is a multifaceted and complex process, and accordingly, provides sufficient structure for teachers. It further addresses the issue of comprehension instruction through the use of selected reading strategies, designed to be applied by all teachers in all subjects in a flexible and easy manner.

  19. Solid Waste/Disease Relationships, A Literature Survey.

    Science.gov (United States)

    Hanks, Thrift G.

    Presented is a comprehensive survey of the literature on the relationships between disease and solid wastes. Diseases are grouped on the basis of waste type or disease vector, such as chemical waste, human fecal waste, animal fecal waste, rodent-borne disease, mosquito-borne disease and miscellaneous communicable disease. The following format is…

  20. Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

    Science.gov (United States)

    Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

  1. Working memory contributions to reading comprehension components in middle childhood children.

    Science.gov (United States)

    Chrysochoou, Elisavet; Bablekou, Zoe; Tsigilis, Nikolaos

    2011-01-01

    This study examined working memory contributions to reading comprehension subskills in Greek children (mean age 9 years, 1 month). The phonological loop of the Baddeley and Hitch working memory model was assessed with 3 recall tasks (words, nonwords, and digits) and a word list matching task. The central executive (CE) was assessed with 3 tasks (listening, counting, and backward digit recall). Participants were also given a receptive vocabulary task, a reading fluency task, and written stories accompanied by comprehension questions. Canonical correlation analyses showed that the comprehension variables were related to the CE rather than the phonological loop measures. CE functions were more strongly associated with elaborative inference generation (involving significant offline processing) and comprehension control (involving metacognitive monitoring). Smaller yet significant associations were observed between the CE and the necessary inference and literal comprehension measures, whereas a moderate relationship was found in the case of the simile comprehension variable. Among the CE variables, listening recall demonstrated the highest loading on the canonical function, followed by moderate yet significant counting and backward digit recall loadings. Vocabulary was found to fully mediate several associations between working memory and comprehension measures; however, the relationship between listening recall and elaborative inferences was partly mediated. Reading fluency and, on several occasions, Greek vocabulary knowledge did not mediate the relationships between CE measures and comprehension skills assessed. This study demonstrates the usefulness of CE measures for identifying young children's possible difficulties in carrying out specific reading comprehension processes.

  2. GPS Civil Monitoring Performance Specification

    Science.gov (United States)

    2009-02-10

    This Civil Monitoring Performance Specification (CMPS) is published and maintained at : the direction of the Program Manager for Civil Applications, Global Positioning Systems : Wing (GPSW). The purpose of this document is to provide a comprehensive ...

  3. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS.

    Directory of Open Access Journals (Sweden)

    Soo Jin Park

    Full Text Available Central nervous system (CNS inflammatory demyelinating diseases (IDDs are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS, neuromyelitis optica spectrum disorder (NMOSD, and idiopathic transverse myelitis (ITM. Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls. Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs.

  4. Self-reported dietary adherence, disease-specific symptoms, and quality of life are associated with healthcare provider follow-up in celiac disease.

    Science.gov (United States)

    Hughey, Jacob J; Ray, Bonnie K; Lee, Anne R; Voorhees, Kristin N; Kelly, Ciaran P; Schuppan, Detlef

    2017-12-11

    The only treatment for celiac disease (CeD) is a lifelong gluten-free diet (GFD). The restrictive nature of the GFD makes adherence a challenge. As an integral part of CeD management, multiple professional organizations recommend regular follow-up with a healthcare provider (HCP). Many CeD patients also participate in patient advocacy groups (PAGs) for education and support. Previous work found that follow-up of CeD patients is highly variable. Here we investigated the self-reported factors associated with HCP follow-up among individuals diagnosed with CeD who participate in a PAG. We conducted a survey of members of Beyond Celiac (a PAG), collecting responses from 1832 U.S. adults ages 19-65 who reported having CeD. The survey queried HCP follow-up related to CeD and included validated instruments for dietary adherence (CDAT), disease-specific symptoms (CSI), and quality of life (CD-QOL). Overall, 27% of respondents diagnosed with CeD at least five years ago reported that they had not visited an HCP about CeD in the last five years. The most frequent reason for not visiting an HCP was "doing fine on my own" (47.6%). Using multiple logistic regression, we identified significant associations between whether a respondent reported visiting an HCP about CeD in the last five years and the scores for all three validated instruments. In particular, as disease-specific symptoms and quality of life worsened, the probability of having visited an HCP increased. Conversely, as dietary adherence worsened, the probability decreased. Our results suggest that many individuals with CeD manage their disease without ongoing support from an HCP. Our results thus emphasize the need for greater access to high quality CeD care, and highlight an opportunity for PAGs to bring together patients and HCPs to improve management of CeD.

  5. Measurement properties of asthma-specific quality-of-life measures: protocol for a systematic review.

    Science.gov (United States)

    Apfelbacher, Christian; Paudyal, Priya; Bülbül, Alpaslan; Smith, Helen

    2014-07-24

    Asthma is a frequent chronic inflammatory disease of the airways, and the assessment of health-related quality of life (HrQoL) is important in both research and routine care. Various asthma-specific measures of HrQoL exist but there is uncertainty which measures are best suited for use in research and routine care. Therefore, the aim of the proposed research is a comprehensive systematic assessment of the measurement properties of the existing measures that were developed to measure asthma-specific quality of life. This study is a systematic review of the measurement properties of asthma-specific measures of health-related quality of life. PubMed and Embase will be searched using a selection of relevant search terms. Eligible studies will be primary empirical studies evaluating, describing or comparing measurement properties of asthma-specific HRQL tools. Eligibility assessment and data abstraction will be performed independently by two reviewers. Evidence tables will be generated for study characteristics, instrument characteristics, measurement properties and interpretability. The quality of the measurement properties will be assessed using predefined criteria. Methodological quality of studies will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis will be undertaken if more than one study have investigated a particular measurement property. The proposed systematic review will produce a comprehensive assessment of measurement properties of existing measures of asthma-specific health-related quality of life. We also aim to derive recommendations in order to help researchers and practitioners alike in the choice of instrument. PROSPERO registration number: CRD42014010491.

  6. Forecasting and Analyzing the Disease Burden of Aged Population in China, Based on the 2010 Global Burden of Disease Study

    Directory of Open Access Journals (Sweden)

    Chengzhen Bao

    2015-06-01

    Full Text Available Background: Forecasting the disease burden of the elderly will contribute to make a comprehensive assessment about physical and mental status of the elderly in China and provide a basis for reducing the negative consequences of aging society to a minimum. Methods: This study collected data from a public database online provided by Global Burden of Disease Study 2010. Grey model GM (1, 1 was used to forecast all-cause and disease-specific rates of disability adjusted life years (DALYs in 2015 and 2020. Results: After cross-sectional and longitudinal analysis, we found that non-communicable diseases (NCDs were still the greatest threats in the elderly, followed by injuries. As for 136 predicted causes, more than half of NCDs increased obviously with age, less than a quarter of communicable, material, neonatal, and nutritional disorders or injuries had uptrend. Conclusions: The findings display the health condition of the Chinese elderly in the future, which will provide critical information for scientific and sociological researches on preventing and reducing the risks of aging society.

  7. A validated disease specific prediction equation for resting metabolic rate in underweight patients with COPD

    Directory of Open Access Journals (Sweden)

    Anita Nordenson

    2010-09-01

    Full Text Available Anita Nordenson2, Anne Marie Grönberg1,2, Lena Hulthén1, Sven Larsson2, Frode Slinde11Department of Clinical Nutrition, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden; 2Department of Internal Medicine/Respiratory Medicine and Allergology, Sahlgrenska Academy at University of Gothenburg, SwedenAbstract: Malnutrition is a serious condition in chronic obstructive pulmonary disease (COPD. Successful dietary intervention calls for calculations of resting metabolic rate (RMR. One disease-specific prediction equation for RMR exists based on mainly male patients. To construct a disease-specific equation for RMR based on measurements in underweight or weight-losing women and men with COPD, RMR was measured by indirect calorimetry in 30 women and 11 men with a diagnosis of COPD and body mass index <21 kg/m2. The following variables, possibly influencing RMR were measured: length, weight, middle upper arm circumference, triceps skinfold, body composition by dual energy x-ray absorptiometry and bioelectrical impedance, lung function, and markers of inflammation. Relations between RMR and measured variables were studied using univariate analysis according to Pearson. Gender and variables that were associated with RMR with a P value <0.15 were included in a forward multiple regression analysis. The best-fit multiple regression equation included only fat-free mass (FFM: RMR (kJ/day = 1856 + 76.0 FFM (kg. To conclude, FFM is the dominating factor influencing RMR. The developed equation can be used for prediction of RMR in underweight COPD patients.Keywords: pulmonary disease, chronic obstructive, basal metabolic rate, malnutrition, body composition

  8. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  9. Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease.

    Science.gov (United States)

    Lu, Qiyu; Sun, Yi; Duan, Yuyin; Li, Bin; Xia, Jianming; Yu, Songhua; Zhang, Guimin

    2018-03-16

    Valvular heart disease is a leading cause of cardiovascular mortality, especially in China. More than a half of valvular heart diseases are caused by acute rheumatic fever. microRNA is involved in many physiological and pathological processes. However, the miRNA profile of the rheumatic valvular heart disease is unknown. This research is to discuss microRNAs and their target gene pathways involved in rheumatic heart valve disease. Serum miRNA from one healthy individual and four rheumatic heart disease patients were sequenced. Specific differentially expressed miRNAs were quantified by Q-PCR in 40 patients, with 20 low-to-moderate rheumatic mitral valve stenosis patients and 20 severe mitral valve stenosis patients. The target relationship between certain miRNA and predicted target genes were analysis by Luciferase reporter assay. The IL-1β and IL1R1 expression levels were analyzed by immunohistochemistry and western blot in the mitral valve from surgery of mitral valve replacement. The results showed that 13 and 91 miRNAs were commonly upregulated or downregulated in all four patients. Nine miRNAs, 1 upregulated and 8 downregulated, that had a similar fold change in all 4 patients were selected for quantitative PCR verification. The results showed similar results from miRNA sequencing. Within these 9 tested miRNAs, hsa-miR-205-3p and hsa-miR-3909 showed a low degree of dispersion between the members of each group. Hsa miR-205-3p and hsa-miR-3909 were predicted to target the 3'UTR of IL-1β and IL1R1 respectively. This was verified by luciferase reporter assays. Immunohistochemistry and Western blot results showed that the mitral valve from rheumatic valve heart disease showed higher levels of IL- 1β and IL1R1 expression compared with congenital heart valve disease. This suggested a difference between rheumatic heart valve disease and other types of heart valve diseases, with more inflammatory responses in the former. In the present study, by next generation

  10. The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome.

    Science.gov (United States)

    Jamali, Raika; Biglari, Mohammad

    2015-11-01

    Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL). Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL) in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years). HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL) and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires. Patients also completed Speilberger`s "State/Trait Anxiety Inventory" and "Beck Depression Inventory-II" for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P < 0.001). In linear regression analysis, a strong correlation was observed between the HRQOL scores of IBS-QOL and the WHOQOL-BREF questionnaires (standard β = 0.86 (95%CI: 1.15 - 1.44), P value < 0.001). Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

  11. Strategies identification in an experimental reading comprehension task

    Directory of Open Access Journals (Sweden)

    Stanković Sanda

    2010-01-01

    Full Text Available Standardized reading comprehension tests (RCTs usually consist of a small number of texts each accompanied by several multiple-choice questions, with texts and questions simultaneously presented. The score the common measure of reading comprehension ability in RCTs is the score. Literature review suggests that strategies subjects employ may influence their performance on RCT, however the score itself provides no information on the specific strategy employed. Knowledge of test-taking strategies could have impact on understanding of the actual purpose and benefits of using RCTs in pedagogical and psychological practice. With the ultimate objective of constructing a first standard RCT in Serbian language, the preliminary step we took was to conduct an experimental reading comprehension task (ERCT consisting of 27 short texts displayed in succession, each followed by a single multiplechoice question. Using qualitative analysis of subjects’ responses in semi-structured postexperimental interview, we identified four overall strategies used on ERCT. Our results show that groups of students who used specific strategies differed significantly from one another in text reading time, with no differences found regarding the question reading and answering time. More importantly, there were no significant between-group differences found in terms of ERCT score. These findings suggest that choice of strategy is a way to optimize the relation between one’s own potential and ERCT task requirements. RCT based on ERCT principles would allow for a flexible choice of strategy which would not influence the final score.

  12. The stress of being chronically ill: from disease-specific to task-specific aspects.

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D. de; Schreurs, K.; Bensing, J.

    2004-01-01

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  13. The stress of being chronically ill: from disease-specific to task-specific aspects

    NARCIS (Netherlands)

    Heijmans, M.; Rijken, M.; Foets, M.; Ridder, D.T.D. de; Schreurs, K.; Bensing, J.

    The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors.

  14. Physiologic assessment of coronary artery disease: Focus on fractional flow reserve

    International Nuclear Information System (INIS)

    Hwang, Do Yeon; Koo, Bon Kwon; Lee, Joo Myung

    2016-01-01

    The presence of myocardial ischemia is the most important prognostic factor in patients with ischemic heart disease. Fractional flow reserve (FFR) is a gold standard invasive method used to detect the stenosis-specific myocardial ischemia. FFR-guided revascularization strategy is superior to angiography-guided strategy. The recently developed hyperemia-free index, instantaneous wave free ratio is being actively investigated. A non-invasive FFR derived from coronary CT angiography is now used in clinical practice. Due to rapid expansion of invasive and non-invasive physiologic assessment, comprehensive understanding of the role and potential pitfalls of each modality are required for its application. In this review, we focus on the basic and clinical aspects of physiologic assessment in ischemic heart disease

  15. Physiologic assessment of coronary artery disease: Focus on fractional flow reserve

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Do Yeon; Koo, Bon Kwon [Dept. of Radiology, Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul (Korea, Republic of); Lee, Joo Myung [Dept. of Internal Medicine and Cardiovascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    The presence of myocardial ischemia is the most important prognostic factor in patients with ischemic heart disease. Fractional flow reserve (FFR) is a gold standard invasive method used to detect the stenosis-specific myocardial ischemia. FFR-guided revascularization strategy is superior to angiography-guided strategy. The recently developed hyperemia-free index, instantaneous wave free ratio is being actively investigated. A non-invasive FFR derived from coronary CT angiography is now used in clinical practice. Due to rapid expansion of invasive and non-invasive physiologic assessment, comprehensive understanding of the role and potential pitfalls of each modality are required for its application. In this review, we focus on the basic and clinical aspects of physiologic assessment in ischemic heart disease.

  16. Fragrance allergy and quality of life - development and validation of a disease-specific quality of life instrument.

    Science.gov (United States)

    Heisterberg, Maria V; Menné, Torkil; Johansen, Jeanne D

    2014-02-01

    Fragrance allergy is a lifelong condition that may give rise to permanent or recurrent contact dermatitis and may affect quality of life (QoL). The effect on QoL has not yet been investigated, and no disease-specific QoL instrument for fragrance allergy exists. To develop and validate a disease-specific instrument to investigate QoL among fragrance-allergic subjects. A fragrance QoL instrument (FQL index) was developed on the basis of narratives from 68 fragrance-allergic subjects, and consisted of 13 items. It was tested in a postal survey among 1650 participants patch tested at Gentofte University Hospital (2000–2010). The survey included other QoL instruments [Dermatology Life Quality Index (DLQI) and Short Form 36 (SF36) version 2] and questions on eczema severity (response rate of 66%). A retest was conducted after 3–6 months (response rate of 72.5%). The FQL index showed a significant and strong correlation with the DLQI (rS = 0.70), and disease severity, but a weak correlation with SF36 [mental component summary score, rS = − 0.22; physical component summary score, rS = − 0.31]. Good reliability and responsiveness to changes in disease severity were seen. The FQL index is a good instrument with which to investigate QoL in subjects with fragrance allergy. Good correlations with the DLQI and self-estimated disease severity were seen, and it showed good reliability, reproducibility and ability to distinguish changes in disease severity.

  17. Applications of Patient-Specific Induced Pluripotent Stem Cells; Focused on Disease Modeling, Drug Screening and Therapeutic Potentials for Liver Disease

    OpenAIRE

    Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

    2010-01-01

    The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of...

  18. Peripheral sympathetic dysfunction in patients with Parkinson's disease without autonomic failure is heart selective and disease specific

    Energy Technology Data Exchange (ETDEWEB)

    Taki, Junichi; Nakajima, Kenichi; Hwang, Eui-Hyo; Matsunari, Ichiro; Tonami, Norihisa [Department of Nuclear Medicine, Kanazawa University School of Medicine, Kanazawa (Japan); Komai, Kiyonobu; Yoshita, Mitsuhiro; Sakajiri, Kenichi [Department of the Neurology, Kanazawa University School of Medicine, Kanazawa (Japan)

    2000-05-01

    The study was undertaken to investigate by means of iodine-123-labelled metaiodobenzylguanidine (MIBG) scintigraphy the peripheral sympathetic function in patients with Parkinson's disease (PD) without autonomic failure and in patients with related neurodegenerative diseases with parkinsonism. Seventy patients (33 men and 37 women, mean age 63{+-}9.7 years) with parkinsonism and ten control subjects underwent MIBG scintigraphy. Of these 70 patients, 41 were diagnosed as having idiopathic PD, 9 multiple system atrophy (MSA), 6 progressive supranuclear palsy (PSP) and 2 corticobasal degeneration (CBD); the remaining 12 were diagnosed as having neurodegenerative disease with parkinsonism (P-nism) that did not meet the diagnostic criteria of any specific disease. Cardiac planar and tomographic imaging studies and subsequent whole-body imaging were performed 20 min and 3 h after the injection of 111 MBq MIBG. The early MIBG heart to mediastinum (H/M) ratio in PD (1.61{+-}0.29) was significantly lower than that in the control group (2.24{+-}0.14, P<0.01), P-nism (2.15{+-}0.31, P<0.01), MSA (2.08{+-}0.31, P<0.05) and PSP (2.30{+-}0.24, P<0.01). The delayed H/M ratio in PD (1.47{+-}0.34) was also significantly lower than that in the control group (2.37{+-}0.14, P<0.01), P-nism (2.13{+-}0.38, P<0.01), PSP (2.36{+-}0.36, P<0.01) and MSA (2.17{+-}0.36, P<0.01). In patients with PD, early and delayed H/M ratios were significantly decreased in disease stages I, II and III (established using the Hoehn and Yahr criteria) as compared with control subjects, and there were no significant differences among the stages. Only PD showed a significantly higher washout rate (WR) than that in the control subjects (27%{+-}8.0% vs 11%{+-}4.2%, P<0.01). Early and delayed uptake ratios of the lung, parotid gland, thyroid gland, liver and femoral muscles in each of the patient groups were not significantly different from those in control subjects. Only the early and delayed uptake ratios of

  19. Death Penalty Decisions: Instruction Comprehension, Attitudes, and Decision Mediators.

    Science.gov (United States)

    Patry, Marc W; Penrod, Steven D

    2013-01-01

    A primary goal of this research was to empirically evaluate a set of assumptions, advanced in the Supreme Court's ruling in Buchanan v. Angelone (1998), about jury comprehension of death penalty instructions. Further, this research examined the use of evidence in capital punishment decision making by exploring underlying mediating factors upon which death penalty decisions may be based. Manipulated variables included the type of instructions and several variations of evidence. Study 1 was a paper and pencil study of 245 undergraduate mock jurors. The experimental design was an incomplete 4×2×2×2×2 factorial model resulting in 56 possible conditions. Manipulations included four different types of instructions, presence of a list of case-specific mitigators to accompany the instructions, and three variations in the case facts: age of the defendant, bad prior record, and defendant history of emotional abuse. Study 2 was a fully-crossed 2×2×2×2×2 experiment with four deliberating mock juries per cell. Manipulations included jury instructions (original or revised), presence of a list of case-specific mitigators, defendant history of emotional abuse, bad prior record, and heinousness of the crime. The sample of 735 jury-eligible participants included 130 individuals who identified themselves as students. Participants watched one of 32 stimulus videotapes based on a replication of a capital sentencing hearing. The present findings support previous research showing low comprehension of capital penalty instructions. Further, we found that higher instruction comprehension was associated with higher likelihood of issuing life sentence decisions. The importance of instruction comprehension is emphasized in a social cognitive model of jury decision making at the sentencing phase of capital cases.

  20. The research of Proactive Coping Behavior of Patients with Chronic Non-Specific Lung Disease

    Directory of Open Access Journals (Sweden)

    Marija A. Yaroslavskaya

    2011-01-01

    Full Text Available The purpose of the research was to study the patterns of using proactive coping and adherences to it's different types in patients with chronic non-specifi c lung diseases. Participants of the study (N=180 were 30 to 60 years old. The Proactive Coping Inventory was used to assess the patients' psychological status. According to the results of the study patients with chronic non-specifi c lung diseases use dif-ferent types of proactive coping behavior while solving problematic and stressful situations. The research revealed that patients with bronchial asthma don't have the skills of independent decision making, definition of objectives, considering of options in solving conflicts or other inconvenient situations sufficiently developed. Patients with chronic obstructive pulmonary disease are less satisfied with the emotional support that they receive from their relatives and closest people, it's harder for them to reveal their feelings and emotions than for those who suffer from bronchial asthma and healthy ones. The results of the study may be useful in developing educational systems of proactive coping behavior skills for patients with chronic non-specific lung diseases for their health and well-being support.

  1. A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial) - design, intervention, and population

    DEFF Research Database (Denmark)

    Zwisler, A.D.O.; Schou, O.; Soja, A.M.B.

    2005-01-01

    , or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor...... that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high...

  2. A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population

    DEFF Research Database (Denmark)

    Zwisler, Ann-Dorthe Olsen; Soja, Anne Merete Boas; Brønnum-Hansen, Henrik

    2005-01-01

    , or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor...... that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high...

  3. The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Christopher J. Ricketts

    2018-04-01

    Full Text Available Summary: Renal cell carcinoma (RCC is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD ChRCC that associated with extremely poor survival. : Ricketts et al. find distinctive features of each RCC subtype, providing the foundation for development of subtype-specific therapeutic and management strategies. Somatic alteration of BAP1, PBRM1, and metabolic pathways correlates with subtype-specific decreased survival, while CDKN2A alteration, DNA hypermethylation, and Th2 immune signature correlate with decreased survival within all subtypes. Keywords: clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, CDKN2A, DNA hypermethylation, immune signature, chromatin remodeling, TCGA, PanCanAtlas

  4. Development and validation of a score for evaluating comprehensive stroke care capabilities: J-ASPECT Study

    OpenAIRE

    Kada, Akiko; Nishimura, Kunihiro; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru

    2017-01-01

    Background Although the Brain Attack Coalition recommended establishing centers of comprehensive care for stroke and cerebrovascular disease patients, a scoring system for such centers was lacking. We created and validated a comprehensive stroke center (CSC) score, adapted to Japanese circumstances. Methods Of the selected 1369 certified training institutions in Japan, 749 completed an acute stroke care capabilities survey. Hospital performance was determined using a 25-item score, evaluating...

  5. Study on comprehensive evaluation methods for nuclear fuel cycle

    International Nuclear Information System (INIS)

    Arie, Kazuo

    1999-03-01

    This investigation on comprehensive-evaluation-methods for nuclear fuel cycle has been performed through open-literature search. As the results, no proper comprehensive-evaluation-method has been found which integrate several factors to be considered into only one factor. In the evaluation of future advanced nuclear energy systems, it is required to evaluate from both view points of natural resources and natural environment, in addition to the other factors such as safety, economy, and proliferation resistance. It is recommended that clarification of specific items or targets to be evaluated is most important as the first thing to be done. Second, methodology for the evaluation should be discussed. (author)

  6. Mortality from circulatory diseases by specific country of birth across six European countries: test of concept

    NARCIS (Netherlands)

    Bhopal, Raj S.; Rafnsson, Snorri B.; Agyemang, Charles; Fagot-Campagna, Anne; Giampaoli, Simona; Hammar, Niklas; Harding, Seeromanie; Hedlund, Ebba; Juel, Knud; Mackenbach, Johan P.; Primatesta, Paola; Rey, Gregoire; Rosato, Michael; Wild, Sarah; Kunst, Anton E.

    2012-01-01

    Background: Important differences in cardiovascular disease (CVD) mortality by country of birth have been shown within European countries. We now focus on CVD mortality by specific country of birth across European countries. Methods: For Denmark, England and Wales, France, The Netherlands, Scotland

  7. Survival after Liver Transplantation in the United States: A Disease-Specific Analysis of the UNOS database

    Czech Academy of Sciences Publication Activity Database

    Roberts, M.S.; Angus, D.C.; Bryce, C.L.; Valenta, Zdeněk; Weissfeld, L.

    2004-01-01

    Roč. 10, č. 7 (2004), s. 886-897 ISSN 1527-6465 Source of funding: V - iné verejné zdroje Keywords : disease-specific survival * liver transplantation * cox PH model Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 3.984, year: 2004

  8. Comprehensive proteomic analysis of the wheat pathogenic fungus Zymoseptoria tritici.

    Science.gov (United States)

    Yang, Fen; Yin, Qi

    2016-01-01

    Zymoseptoria tritici causes Septoria tritici blotch disease of wheat. To obtain a comprehensive protein dataset of this fungal pathogen, proteomes of Z. tritici growing in nutrient-limiting and rich media and in vivo at a late stage of wheat infection were fractionated by 1D gel or strong cation exchange (SCX) chromatography and analyzed by LC-MS/MS. A total of 5731, 5376 and 3168 Z. tritici proteins were confidently identified from these conditions, respectively. Of these in vitro and in planta proteins, 9 and 11% were predicted to contain signal peptides, respectively. Functional classification analysis revealed the proteins were involved in the various cellular activities. Comparison of three distinct protein expression profiles demonstrates the elevated carbohydrate, lipid and secondary metabolisms, transport, protein processing and energy production specifically in the host environment, in contrast to the enhancement of signaling, defense, replication, transcription and cell division in vitro. The data provide useful targets towards a better understanding of the molecular basis of Z. tritici growth, development, stress response and pathogenicity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients.

    Directory of Open Access Journals (Sweden)

    Arndt Rolfs

    Full Text Available Gaucher disease (GD is the most common lysosomal storage disorder (LSD. Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs.Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD.

  10. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states

    Directory of Open Access Journals (Sweden)

    Cunningham TJ

    2014-09-01

    Full Text Available Timothy J Cunningham,1 Earl S Ford,1 Janet B Croft,1 Melissa T Merrick,2 Italia V Rolle,3 Wayne H Giles1 1Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; 2Division of Violence Prevention, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, GA, USA; 3Office on Smoking and Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA Purpose: Adverse childhood experiences (ACEs before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD in the general population. Materials and methods: Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs and their corresponding 95% confidence intervals (CIs for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Results: Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61, sexual abuse (PR =1.69, 95% CI: 1.36, 2.10, living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81, witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72, and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80 during childhood compared to those with no individual ACEs

  11. Quantification of liver fat: A comprehensive review.

    Science.gov (United States)

    Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

    2016-04-01

    Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Use of the Menopause-Specific Quality of Life (MENQOL) questionnaire in research and clinical practice: a comprehensive scoping review.

    Science.gov (United States)

    Sydora, Beate C; Fast, Hilary; Campbell, Sandy; Yuksel, Nese; Lewis, Jacqueline E; Ross, Sue

    2016-09-01

    The Menopause-Specific Quality of Life (MENQOL) questionnaire was developed as a validated research tool to measure condition-specific QOL in early postmenopausal women. We conducted a comprehensive scoping review to explore the extent of MENQOL's use in research and clinical practice to assess its value in providing effective, adequate, and comparable participant assessment information. Thirteen biomedical and clinical databases were systematically searched with "menqol" as a search term to find articles using MENQOL or its validated derivative MENQOL-Intervention as investigative or clinical tools from 1996 to November 2014 inclusive. Review articles, conference abstracts, proceedings, dissertations, and incomplete trials were excluded. Additional articles were collected from references within key articles. Three independent reviewers extracted data reflecting study design, intervention, sample characteristics, MENQOL questionnaire version, modifications and language, recall period, and analysis detail. Data analyses included categorization and descriptive statistics. The review included 220 eligible papers of various study designs, covering 39 countries worldwide and using MENQOL translated into more than 25 languages. A variety of modifications to the original questionnaire were identified, including omission or addition of items and alterations to the validated methodological analysis. No papers were found that described MENQOL's use in clinical practice. Our study found an extensive and steadily increasing use of MENQOL in clinical and epidemiological research over 18 years postpublication. Our results stress the importance of proper reporting and validation of translations and variations to ensure outcome comparison and transparency of MENQOL's use. The value of MENQOL in clinical practice remains unknown.

  13. Specificity of anti-tau antibodies when analyzing mice models of Alzheimer's disease: problems and solutions.

    Directory of Open Access Journals (Sweden)

    Franck R Petry

    Full Text Available Aggregates of hyperphosphorylated tau protein are found in a group of diseases called tauopathies, which includes Alzheimer's disease. The causes and consequences of tau hyperphosphorylation are routinely investigated in laboratory animals. Mice are the models of choice as they are easily amenable to transgenic technology; consequently, their tau phosphorylation levels are frequently monitored by Western blotting using a panel of monoclonal/polyclonal anti-tau antibodies. Given that mouse secondary antibodies can recognize endogenous mouse immunoglobulins (Igs and the possible lack of specificity with some polyclonal antibodies, non-specific signals are commonly observed. Here, we characterized the profiles of commonly used anti-tau antibodies in four different mouse models: non-transgenic mice, tau knock-out (TKO mice, 3xTg-AD mice, and hypothermic mice, the latter a positive control for tau hyperphosphorylation. We identified 3 tau monoclonal antibody categories: type 1, characterized by high non-specificity (AT8, AT180, MC1, MC6, TG-3, type 2, demonstrating low non-specificity (AT270, CP13, CP27, Tau12, TG5, and type 3, with no non-specific signal (DA9, PHF-1, Tau1, Tau46. For polyclonal anti-tau antibodies, some displayed non-specificity (pS262, pS409 while others did not (pS199, pT205, pS396, pS404, pS422, A0024. With monoclonal antibodies, most of the interfering signal was due to endogenous Igs and could be eliminated by different techniques: i using secondary antibodies designed to bind only non-denatured Igs, ii preparation of a heat-stable fraction, iii clearing Igs from the homogenates, and iv using secondary antibodies that only bind the light chain of Igs. All of these techniques removed the non-specific signal; however, the first and the last methods were easier and more reliable. Overall, our study demonstrates a high risk of artefactual signal when performing Western blotting with routinely used anti-tau antibodies, and proposes

  14. Comprehension-Driven Program Analysis (CPA) for Malware Detection in Android Phones

    Science.gov (United States)

    2015-07-01

    Android source . 3.1.2.2 Analyzers An analyzer conforms to specifications defined by the Security Toolbox. Specifically an analyzer encapsulates a...COMPREHENSION-DRIVEN PROGRAM ANALYSIS (CPA) FOR MALWARE DETECTION IN ANDROID PHONES IOWA STATE UNIVERSITY JULY 2015 FINAL...average 1 hour per response, including the time for reviewing instructions, searching existing data sources , gathering and maintaining the data needed

  15. Development and Validation of an Online Dynamic Assessment for Raising Students' Comprehension of Science Text

    Science.gov (United States)

    Wang, Jing-Ru; Chen, Shin-Feng

    2016-01-01

    This article reports on the development of an online dynamic approach for assessing and improving students' reading comprehension of science texts--the dynamic assessment for reading comprehension of science text (DARCST). The DARCST blended assessment and response-specific instruction into a holistic learning task for grades 5 and 6 students. The…

  16. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Willing, B.; Halfvarson, J.; Dicksved, J.; Rosenquist, M.; Jarnerot, G.; Engstrand, L.; Tysk, C.; Jansson, J. K

    2008-08-15

    Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.

  17. The dimensions of reading comprehension in Dutch children: Is differentiation by text and question type necessary?

    NARCIS (Netherlands)

    Muijselaar, M.M.L.; Swart, N.M.; Steenbeek-Planting, E.G.; Droop, W.; Verhoeven, L.T.W.; Jong, P.F. de

    2017-01-01

    Many recent studies have aimed to demonstrate that specific types of reading comprehension depend on different underlying cognitive abilities. In these studies, it is often implicitly assumed that reading comprehension is a multidimensional construct. The general aim of this study was to examine the

  18. Reading Comprehension, Working Memory and Higher-Level Language Skills in Children with SLI and/or Dyslexia

    Science.gov (United States)

    Wong, Anita M.-Y.; Ho, Connie S.-H.; Au, Terry K.-F.; McBride, Catherine; Ng, Ashley K.-H.; Yip, Lesley P.-W.; Lam, Catherine C.-C.

    2017-01-01

    This study examined (1) whether working memory and higher-level languages skills--inferencing and comprehension monitoring--accounted for individual differences among Chinese children in Chinese reading comprehension, after controlling for age, Chinese word reading and oral language skills, and (2) whether children with specific language…

  19. Oxidative stress in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shyamal K Goswami

    2015-01-01

    Full Text Available Oxidative stress caused by various oxygen containing free radicals and reactive species (collectively called "Reactive Oxygen Species" or ROS has long been attributed to cardiovascular diseases. In human body, major oxidizing species are super oxide, hydrogen peroxide, hydroxyl radical, peroxy nitrite etc. ROS are produced from distinct cellular sources, enzymatic and non-enzymatic; have specific physicochemical properties and often have specific cellular targets. Although early studies in nineteen sixties and seventies highlighted the deleterious effects of these species, later it was established that they also act as physiological modulators of cellular functions and diseases occur only when ROS production is deregulated. One of the major sources of cellular ROS is Nicotinamide adenine dinucleotide phosphate oxidases (Noxes that are expressed in almost all cell types. Superoxide and hydrogen peroxide generated from them under various conditions act as signal transducers. Due to their immense importance in cellular physiology, various Nox inhibitors are now being developed as therapeutics. Another free radical of importance in cardiovascular system is nitric oxide (a reactive nitrogen species generated from nitric oxide synthase(s. It plays a critical role in cardiac function and its dysregulated generation along with superoxide leads to the formation of peroxynitrite a highly deleterious agent. Despite overwhelming evidences of association between increased level of ROS and cardiovascular diseases, antioxidant therapies using vitamins and omega 3 fatty acids have largely been unsuccessful till date. Also, there are major discrepancies between studies with laboratory animals and human trials. It thus appears that the biology of ROS is far complex than anticipated before. A comprehensive understanding of the redox biology of diseases is thus needed for developing targeted therapeutics.

  20. Aspirin Allergy Desensitization in Cerebrovascular Disease

    Science.gov (United States)

    Zuckerman, Scott L; Seder, David B; Tsujiura, Crystiana; Cushing, Deborah; Gallup, Holly; Mocco, J; Hanel, Richard A; Ecker, Robert D

    2014-01-01

    Summary Aspirin (ASA) is the mainstay of treatment in cerebrovascular and systemic vascular disease. ASA hypersensitivity can pose a challenge to achieving optimum medical management prior to and after neurointerventional treatment. Desensitization to ASA is well described in the allergy and cardiovascular literature, but there are no similar discussions specific to neurointervention. The purpose of our study was to describe our experience with ASA hypersensitivity management and review the relevant literature. Two cases of patients with symptomatic cerebrovascular disease requiring neurointervention who were successfully desensitized to their ASA hypersensitivity prior to treatment are described. The subsequent literature is reviewed. Several ASA desensitization protocols exist and have been proven to successfully treat ASA hypersensitivity and allow for ASA therapy to be safely initiated. We describe several previously published protocols. ASA desensitization is a safe and simple way to manage ASA hypersensitivity. We provide comprehensive management guidelines for the neurointerventionalist engaging in ASA desensitization. PMID:24556294

  1. Sex differences in disease-specific health status measures in patients with symptomatic peripheral artery disease: Data from the PORTRAIT study.

    Science.gov (United States)

    Roumia, Mazen; Aronow, Herbert D; Soukas, Peter; Gosch, Kensey; Smolderen, Kim G; Spertus, John A; Abbott, J Dawn

    2017-04-01

    Peripheral artery disease (PAD) is associated with poor health status (symptoms, functioning, quality of life (QOL)). Whether sex differences exist in PAD-specific health status is unknown. In patients presenting to a specialty clinic with new-onset or recent exacerbation of PAD, we examined sex differences as assessed by the Peripheral Artery Questionnaire (PAQ). The Patient-centered Outcomes Related to TReatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study is a multicenter, international prospective study of patients with new or worsening PAD symptoms. Baseline characteristics and mean PAQ scores were compared among women ( n=481) and men ( n=793) before they underwent treatment. The independent association of sex with health status was assessed with multivariable linear regression. As compared with men, women were less often Caucasian, married and employed, and more often lacking health insurance, living alone (36.2% vs 23.6%, pPAQ scores on all domains (physical functioning adjusted mean difference of -8.40, p<0.001; social functioning adjusted mean difference of -6.8, p<0.001; QOL adjusted mean difference of -6.7, p<0.001), although no differences were observed in treatment satisfaction (adjusted mean difference -0.20, p=0.904). Despite similar ABIs, women presenting with symptoms of PAD had poorer PAD-specific functioning as compared with men, impacting all major health status domains, independent of socio-economic and clinical characteristics.

  2. A novel Capsicum gene inhibits host-specific disease resistance to Phytophthora capsici.

    Science.gov (United States)

    Reeves, Gregory; Monroy-Barbosa, Ariadna; Bosland, Paul W

    2013-05-01

    A novel disease resistance inhibitor gene (inhibitor of P. capsici resistance [Ipcr]), found in the chile pepper (Capsicum annuum) variety 'New Mexico Capsicum Accession 10399' (NMCA10399), inhibits resistance to Phytophthora capsici but not to other species of Phytophthora. When a highly P. capsici-resistant variety was hybridized with NMCA10399, the resultant F1 populations, when screened, were completely susceptible to P. capsici for root rot and foliar blight disease syndromes, despite the dominance inheritance of P. capsici resistance in chile pepper. The F2 population displayed a 3:13 resistant-to-susceptible (R:S) ratio. The testcross population displayed a 1:1 R:S ratio, and a backcross population to NMCA10399 displayed complete susceptibility. These results demonstrate the presence of a single dominant inhibitor gene affecting P. capsici resistance in chile pepper. Moreover, when lines carrying the Ipcr gene were challenged against six Phytophthora spp., the nonhost resistance was not overcome. Therefore, the Ipcr gene is interfering with host-specific resistance but not the pathogen- or microbe-associated molecular pattern nonhost responses.

  3. Comprehensive evaluation of gene expression signatures in response to electroacupuncture stimulation at Zusanli (ST36) acupoint by transcriptomic analysis.

    Science.gov (United States)

    Wu, Jing-Shan; Lo, Hsin-Yi; Li, Chia-Cheng; Chen, Feng-Yuan; Hsiang, Chien-Yun; Ho, Tin-Yun

    2017-08-15

    Electroacupuncture (EA) has been applied to treat and prevent diseases for years. However, molecular events happened in both the acupunctured site and the internal organs after EA stimulation have not been clarified. Here we applied transcriptomic analysis to explore the gene expression signatures after EA stimulation. Mice were applied EA stimulation at ST36 for 15 min and nine tissues were collected three hours later for microarray analysis. We found that EA affected the expression of genes not only in the acupunctured site but also in the internal organs. EA commonly affected biological networks involved in cytoskeleton and cell adhesion, and also regulated unique process networks in specific organs, such as γ-aminobutyric acid-ergic neurotransmission in brain and inflammation process in lung. In addition, EA affected the expression of genes related to various diseases, such as neurodegenerative diseases in brain and obstructive pulmonary diseases in lung. This report applied, for the first time, a global comprehensive genome-wide approach to analyze the gene expression profiling of acupunctured site and internal organs after EA stimulation. The connection between gene expression signatures, biological processes, and diseases might provide a basis for prediction and explanation on the therapeutic potentials of acupuncture in organs.

  4. Disease-specific questionnaire for quality of life in patients with peripheral arterial occlusive disease in the stage of critical ischemia (FLeQKI) - methodical development of a specific measuring instrument and psychometric evaluation of its validity and reliability. Pt. 1

    International Nuclear Information System (INIS)

    Wohlgemuth, W.A.; Bohndorf, K.; Kirchhof, K.; Olbricht, W.; Klarmann, S.; Engelhardt, M.; Freitag, M.H.; Woelfle, K.

    2007-01-01

    Purpose: To develop a disease-specific measuring instrument for quality of life in German-speaking patients with peripheral arterial occlusive disease in the stage of critical ischemia and to test it in a prospective study for validity and reliability. Materials and methods: We developed a questionnaire compiling items representing subjective disease relevant health states. With 35 of these items, we designed the scales comorbidity (KO), physical pain (SZ), physical functioning (KF), physical state (KS), social functioning (SB), mental health (PB), and therapy-induced limitations (TE). Each item was to be valued as never, seldom, often or always. The scales were standardized with a control group of 40 individuals without peripheral arterial occlusive disease who were interviewed twice in an interval of 6 months using both the FLeQKI and the Medical Outcomes Study Group Short Form 36 (SF-36). Convergent and discriminative validity was determined in 65 consecutive in-patients with peripheral occlusive arterial disease in the stage of critical ischemia who were interviewed with FLeQKI and SF-36 prior to percutaneous transluminal angioplasty (PTA) or bypass operation and 1 month and 6 months after. The internal consistency and test-retest reliability of the FLeQKI were determined in the control group. For statistical analysis, Cronbach's α Test and Pearsons Product Moment Correlation were used. Results: The control group consisted of 21 men and 19 women with an age of 73.4 ± 7.8, and the treatment group was comprised of 35 men and 30 women with an age of 75.1 ± 7.0. In the treatment group, convergent validity reached high values in the scales SB, KF, PB, and SZ (r = 0.41 - 0.70). With their discriminative validity (r = -0.04 - 0.30), TE and KS were independent, specific dimensions of life quality. The control group showed good values for internal consistency (Cronbach's α = 0.54 - 0.93) and for test-retest reliability (r = 0.44 - 0.96). Conclusion: The FLeQKI is

  5. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  6. Enhancing L2 Reading Comprehension with Hypermedia Texts: Student Perceptions

    Science.gov (United States)

    Garrett-Rucks, Paula; Howles, Les; Lake, William M.

    2015-01-01

    This study extends current research about L2 hypermedia texts by investigating the combined use of audiovisual features including: (a) Contextualized images, (b) rollover translations, (c) cultural information, (d) audio explanations and (e) comprehension check exercises. Specifically, student perceptions of hypermedia readings compared to…

  7. Using the Concept Attainment Strategy to Enhance Reading Comprehension

    Science.gov (United States)

    Boulware, Beverly J.; Crow, Mary Lynn

    2008-01-01

    The Concept Attainment Strategy is an instructional technique proposed by Jerome Bruner that targets the "big idea" or concept underlining concrete or abstract examples. This strategy focuses on the developing comprehension of words and ideas associated with a concept rather than on its name or what the concept is called. Specifically it develops…

  8. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  9. Screening for sequence-specific RNA-BPs by comprehensive UV crosslinking

    Directory of Open Access Journals (Sweden)

    Le Meuth-Metzinger Valerie

    2002-06-01

    Full Text Available Abstract Background Specific cis-elements and the associated trans-acting factors have been implicated in the post-transcriptional regulation of gene expression. In the era of genome wide analyses identifying novel trans-acting factors and cis-regulatory elements is a step towards understanding coordinated gene expression. UV-crosslink analysis is a standard method used to identify RNA-binding proteins. Uridine is traditionally used to radiolabel substrate RNAs, however, proteins binding to cis-elments particularly uridine poor will be weakly or not detected. We evaluate here the possibility of using UV-crosslinking with RNA substrates radiolabeled with each of the four ribonucleotides as an approach for screening for novel sequence specific RNA-binding proteins. Results The radiolabeled RNA substrates were derived from the 3'UTRs of the cloned Eg and c-mos Xenopus laevis maternal mRNAs. Specific, but not identical, uv-crosslinking signals were obtained, some of which corresponded to already identified proteins. A signal for a novel 90 kDa protein was observed with the c-mos 3'UTR radiolabeled with both CTP and GTP but not with UTP. The binding site of the 90 kDa RNA-binding protein was localised to a 59-nucleotide portion of the c-mos 3'UTR. Conclusion That the 90 kDa signal was detected with RNAs radiolabeled with CTP or GTP but not UTP illustrates the advantage of radiolabeling all four nucleotides in a UV-crosslink based screen. This method can be used for both long and short RNAs and does not require knowledge of the cis-acting sequence. It should be amenable to high throughput screening for RNA binding proteins.

  10. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Science.gov (United States)

    2014-01-01

    The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”). The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability). Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease. PMID:24877117

  11. Motor Training in Degenerative Spinocerebellar Disease: Ataxia-Specific Improvements by Intensive Physiotherapy and Exergames

    Directory of Open Access Journals (Sweden)

    Matthis Synofzik

    2014-01-01

    Full Text Available The cerebellum is essentially involved in movement control and plays a critical role in motor learning. It has remained controversial whether patients with degenerative cerebellar disease benefit from high-intensity coordinative training. Moreover, it remains unclear by which training methods and mechanisms these patients might improve their motor performance. Here, we review evidence from different high-intensity training studies in patients with degenerative spinocerebellar disease. These studies demonstrate that high-intensity coordinative training might lead to a significant benefit in patients with degenerative ataxia. This training might be based either on physiotherapy or on whole-body controlled videogames (“exergames”. The benefit shown in these studies is equal to regaining one or more years of natural disease progression. In addition, first case studies indicate that even subjects with advanced neurodegeneration might benefit from such training programs. For both types of training, the observed clinical improvements are paralleled by recoveries in ataxia-specific dysfunctions (e.g., multijoint coordination and dynamic stability. Importantly, for both types of training, the retention of the effects seems to depend on the frequency and continuity of training. Based on these studies, we here present preliminary recommendations for clinical practice, and articulate open questions that might guide future studies on neurorehabilitation in degenerative spinocerebellar disease.

  12. Effect of pneumococcal conjugate vaccination on serotype-specific carriage and invasive disease in England: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2011-04-01

    Full Text Available BACKGROUND: We investigated the effect of the 7-valent pneumococcal conjugate vaccine (PCV7 programme in England on serotype-specific carriage and invasive disease to help understand its role in serotype replacement and predict the impact of higher valency vaccines. METHODS AND FINDINGS: Nasopharyngeal swabs were taken from children <5 y old and family members (n=400 2 y after introduction of PCV7 into routine immunization programs. Proportions carrying Streptococcus pneumoniae and serotype distribution among carried isolates were compared with a similar population prior to PCV7 introduction. Serotype-specific case carrier ratios (CCRs were estimated using national data on invasive disease. In vaccinated children and their contacts vaccine-type (VT carriage decreased, but was offset by an increase in non-VT carriage, with no significant overall change in carriage prevalence, odds ratio 1.06 (95% confidence interval 0.76-1.49. The lower CCRs of the replacing serotypes resulted in a net reduction in invasive disease in children. The additional serotypes covered by higher valency vaccines had low carriage but high disease prevalence. Serotype 11C emerged as predominant in carriage but caused no invasive disease whereas 8, 12F, and 22F emerged in disease but had very low carriage prevalence. CONCLUSION: Because the additional serotypes included in PCV10/13 have high CCRs but low carriage prevalence, vaccinating against them is likely to significantly reduce invasive disease with less risk of serotype replacement. However, a few serotypes with high CCRs could mitigate the benefits of higher valency vaccines. Assessment of the effect of PCV on carriage as well as invasive disease should be part of enhanced surveillance activities for PCVs. Please see later in the article for the Editors' Summary.

  13. Understanding reading comprehension amongst Maltese speaking children.

    OpenAIRE

    Grech, Louisa.

    2011-01-01

    This thesis investigated reading comprehension levels amongst Maltese bilingual students. A total of 428 participants, aged between 8 and 13, from state schools across Malta, were tested and the results of five studies presented. The primary purpose underlying the research was to inform the development of assessment procedures that can be used in the identification of children who have specific difficulties in reading within the Maltese context. Initially, the suitability of reading comprehen...

  14. Physical therapy and occupational therapy in Parkinson's disease

    NARCIS (Netherlands)

    Radder, D.L.M.; Sturkenboom, I.H.W.M.; Nimwegen, M. van; Keus, S.H.; Bloem, B.R.; Vries, N.M. de

    2017-01-01

    Current medical management is only partially effective in controlling the symptoms of Parkinson's disease. As part of comprehensive multidisciplinary care, physical therapy and occupational therapy aim to support people with Parkinson's disease in dealing with the consequences of their disease in

  15. The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

    Science.gov (United States)

    Di Piazza, Ambra; Costanzo, Massimo; Scopelliti, Laura; Salvaggi, Francesco; Cupido, Francesco; Salerno, Sergio; Lo Casto, Antonio; Midiri, Massimo; Lo Re, Giuseppe; Lagalla, Roberto

    2017-01-01

    Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%–80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients. PMID:28706536

  16. Radiological aspects of Gaucher disease

    International Nuclear Information System (INIS)

    Katz, Robert; Booth, Tom; Hargunani, Rikin; Wylie, Peter; Holloway, Brian

    2011-01-01

    Advances in imaging and the development of commercially available enzyme therapy have significantly altered the traditional radiology of Gaucher disease. The cost of treatment and need for monitoring response to therapy have magnified the importance of imaging. There are no recent comprehensive reviews of the radiology of this relatively common lysosomal storage disease. This article describes the modern imaging, techniques and radiological manifestations of Gaucher disease. (orig.)

  17. Radiological aspects of Gaucher disease

    Energy Technology Data Exchange (ETDEWEB)

    Katz, Robert; Booth, Tom; Hargunani, Rikin; Wylie, Peter; Holloway, Brian [Royal Free Hospital, Radiology Department, London (United Kingdom)

    2011-12-15

    Advances in imaging and the development of commercially available enzyme therapy have significantly altered the traditional radiology of Gaucher disease. The cost of treatment and need for monitoring response to therapy have magnified the importance of imaging. There are no recent comprehensive reviews of the radiology of this relatively common lysosomal storage disease. This article describes the modern imaging, techniques and radiological manifestations of Gaucher disease. (orig.)

  18. Parkinson's Disease Videos

    Medline Plus

    Full Text Available ... CareMAP: Dealing with Dementia OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis CareMAP: Cambios en el ... to Know? Why Is Comprehensive Care or Team Approach Important? What Is the Relationship Between Depression and ...

  19. Cost-effectiveness of a disease-specific oral nutritional support for pressure ulcer healing.

    Science.gov (United States)

    Cereda, Emanuele; Klersy, Catherine; Andreola, Manuela; Pisati, Roberto; Schols, Jos M G A; Caccialanza, Riccardo; D'Andrea, Federico

    2017-02-01

    The Oligo Element Sore Trial has shown that supplementation with a disease-specific nutritional formula enriched with arginine, zinc, and antioxidants improves pressure ulcer (PU) healing in malnourished patients compared to an isocaloric-isonitrogenous support. However, the use of such a nutritional formula needs to be supported also by a cost-effectiveness evaluation. This economic evaluation - from a local healthcare system perspective - was conducted alongside a multicenter, randomized, controlled trial following a piggy-back approach. The primary efficacy endpoint was the percentage of change in PU area at 8 weeks. The cost analysis focused on: the difference in direct medical costs of local PU care between groups and incremental cost-effectiveness ratio (ICER) of nutritional therapy related to significant study endpoints (percentage of change in PU area and ≥40% reduction in PU area at 8 weeks). Although the experimental formula was more expensive (mean difference: 39.4 Euros; P costs of local PU care (difference, -74.3 Euros; P = 0.013). Therefore, given its efficacy it proved to be a cost-effective intervention. The robustness of these results was confirmed by the sensitivity analyses. The use of a disease-specific oral nutritional formula not only results in better healing of PUs, but also reduces the costs of local PU care from a local healthcare system perspective. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. Comparative study of the cytokine/chemokine response in children with differing disease severity in enterovirus 71-induced hand, foot, and mouth disease.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 infection can lead to a rapidly progressing, life-threatening, and severe neurological disease in young children, including the development of human hand, foot, and mouth disease (HFMD. This study aims to further characterize the specific immunological features in EV71-mediated HFMD patients presenting with differing degrees of disease severity. METHODOLOGY: Comprehensive cytokine and chemokine expression were broadly evaluated by cytokine antibody array in EV71-infected patients hospitalized for HFMD compared to Coxsackievirus A16-infected patients and age-matched healthy controls. More detailed analysis using Luminex-based cytokine bead array was performed in EV71-infected patients stratified into diverse clinic outcomes. Additionally, immune cell frequencies in peripheral blood and EV71-specific antibodies in plasma were also examined. PRINCIPAL FINDINGS: Expression of several cytokines and chemokines were significantly increased in plasma from EV71-infected patients compared to healthy controls, which further indicated that: (1 GM-CSF, MIP-1β, IL-2, IL-33, and IL-23 secretion was elevated in patients who rapidly developed disease and presented with uncomplicated neurological damage; (2 G-CSF and MCP-1 were distinguishably secreted in EV71 infected very severe patients presenting with acute respiratory failure; (3 IP-10, MCP-1, IL-6, IL-8, and G-CSF levels were much higher in cerebrospinal fluid than in plasma from patients with neurological damage; (4 FACS analysis revealed that the frequency of CD19(+HLADR(+ mature B cells dynamically changed over time during the course of hospitalization and was accompanied by dramatically increased EV71-specific antibodies. Our data provide a panoramic view of specific immune mediator and cellular immune responses of HFMD and may provide useful immunological profiles for monitoring the progress of EV71-induced fatal neurological symptoms with acute respiratory failure.

  1. Comprehensive primary health care under neo-liberalism in Australia.

    Science.gov (United States)

    Baum, Fran; Freeman, Toby; Sanders, David; Labonté, Ronald; Lawless, Angela; Javanparast, Sara

    2016-11-01

    This paper applies a critical analysis of the impact of neo-liberal driven management reform to examine changes in Australian primary health care (PHC) services over five years. The implementation of comprehensive approaches to primary health care (PHC) in seven services: five state-managed and two non-government organisations (NGOs) was tracked from 2009 to 2014. Two questions are addressed: 1) How did the ability of Australian PHC services to implement comprehensive PHC change over the period 2009-2014? 2) To what extent is the ability of the PHC services to implement comprehensive PHC shaped by neo-liberal health sector reform processes? The study reports on detailed tracking and observations of the changes and in-depth interviews with 63 health service managers and practitioners, and regional and central health executives. The documented changes were: in the state-managed services (although not the NGOs) less comprehensive service coverage and more focus on clinical services and integration with hospitals and much less development activity including community development, advocacy, intersectoral collaboration and attention to the social determinants. These changes were found to be associated with practices typical of neo-liberal health sector reform: considerable uncertainty, more directive managerial control, budget reductions and competitive tendering and an emphasis on outputs rather than health outcomes. We conclude that a focus on clinical service provision, while highly compatible with neo-liberal reforms, will not on its own produce the shifts in population disease patterns that would be required to reduce demand for health services and promote health. Comprehensive PHC is much better suited to that task. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Synthetic oligonucleotide antigens modified with locked nucleic acids detect disease specific antibodies

    DEFF Research Database (Denmark)

    Samuelsen, Simone V; Solov'yov, Ilia A.; Balboni, Imelda M.

    2016-01-01

    New techniques to detect and quantify antibodies to nucleic acids would provide a significant advance over current methods, which often lack specificity. We investigate the potential of novel antigens containing locked nucleic acids (LNAs) as targets for antibodies. Particularly, employing...... molecular dynamics we predict optimal nucleotide composition for targeting DNA-binding antibodies. As a proof of concept, we address a problem of detecting anti-DNA antibodies that are characteristic of systemic lupus erythematosus, a chronic autoimmune disease with multiple manifestations. We test the best...... that the novel method is a promising tool to create antigens for research and point-of-care monitoring of anti-DNA antibodies....

  3. Neural bases of event knowledge and syntax integration in comprehension of complex sentences.

    Science.gov (United States)

    Malaia, Evie; Newman, Sharlene

    2015-01-01

    Comprehension of complex sentences is necessarily supported by both syntactic and semantic knowledge, but what linguistic factors trigger a readers' reliance on a specific system? This functional neuroimaging study orthogonally manipulated argument plausibility and verb event type to investigate cortical bases of the semantic effect on argument comprehension during reading. The data suggest that telic verbs facilitate online processing by means of consolidating the event schemas in episodic memory and by easing the computation of syntactico-thematic hierarchies in the left inferior frontal gyrus. The results demonstrate that syntax-semantics integration relies on trade-offs among a distributed network of regions for maximum comprehension efficiency.

  4. Keeping health facilities safe: one way of strengthening the interaction between disease-specific programmes and health systems.

    Science.gov (United States)

    Harries, Anthony D; Zachariah, Rony; Tayler-Smith, Katie; Schouten, Erik J; Chimbwandira, Frank; Van Damme, Wim; El-Sadr, Wafaa M

    2010-12-01

    The debate on the interaction between disease-specific programmes and health system strengthening in the last few years has intensified as experts seek to tease out common ground and find solutions and synergies to bridge the divide. Unfortunately, the debate continues to be largely academic and devoid of specificity, resulting in the issues being irrelevant to health care workers on the ground. Taking the theme 'What would entice HIV- and tuberculosis (TB)-programme managers to sit around the table on a Monday morning with health system experts', this viewpoint focuses on infection control and health facility safety as an important and highly relevant practical topic for both disease-specific programmes and health system strengthening. Our attentions, and the examples and lessons we draw on, are largely aimed at sub-Saharan Africa where the great burden of TB and HIV ⁄ AIDS resides, although the principles we outline would apply to other parts of the world as well. Health care infections, caused for example by poor hand hygiene, inadequate testing of donated blood, unsafe disposal of needles and syringes, poorly sterilized medical and surgical equipment and lack of adequate airborne infection control procedures, are responsible for a considerable burden of illness amongst patients and health care personnel, especially in resource-poor countries. Effective infection control in a district hospital requires that all the components of a health system function well: governance and stewardship, financing,infrastructure, procurement and supply chain management, human resources, health information systems, service delivery and finally supervision. We argue in this article that proper attention to infection control and an emphasis on safe health facilities is a concrete first step towards strengthening the interaction between disease-specific programmes and health systems where it really matters – for patients who are sick and for the health care workforce who provide

  5. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  6. Specific proof of various stages of Osler's disease of the brain via high field magnetic resonance tomography (1. 5 Tesla)

    Energy Technology Data Exchange (ETDEWEB)

    Billet, F.; Bluemm, R.G.; Beyer, H.K.

    1988-08-01

    MR is a sensitive noninvasive examination method for diagnosing parenchymatous cryptic arteriovenous malformations and sequels of cerebral haemorrhage. In a patient with recurring nosebleed and brain stem syndrome eleven so-called cryptic arteriovenous malformations or their haemorrhage sequels were diagnosed via magnetic resonance tomography. Basing on these specific findings, nosebleeding, and a positive family anamnesis, the findings could be classified as belonging to manifestations of Osler's disease (hereditary haemorrhagic telangiectasia). This rare disease is characterised by a triad of signs: telangiectasias, recurring bleeding, and heredity. In this article the specific MR image is compared with the CT pattern and the results are discussed against the background of literature on Osler's disease which is also known as Rendu-Osler-Weber disease.

  7. EFFICACY OF COMBINATION TREATMENT WITH ANTI_IGE PLUS SPECIFIC IMMUNOTHERAPY IN PATIENTS WITH ATOPIC DISEASES

    Directory of Open Access Journals (Sweden)

    N.I. Il'ina

    2008-01-01

    Full Text Available Allergen specific immunotherapy (ASIT is a very effective technique in treatment of many allergic diseases. It greatly improves the quality of life. There's a risk of adverse system reactions at the time of ASIT. Treatment with anti Ige antibodies (omalizumab, xolair allows decreasing the circulating Ige level and lessening an expression of high affinity fc_r1 receptors on the surface of basophiles and mast cells, inhibition of early and late phase of allergic inflammatory response. Combination of antibige therapy and ASIT can lead to decrease of risk of adverse system reactions.Key words: omalizumab, anti Ige antibodies, allergen specific immunotherapy.

  8. A four step model for the IL-6 amplifier, a regulator of chromic inflammations in tissue specific MHC class II-associated autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Masaaki eMurakami

    2011-06-01

    Full Text Available It is thought autoimmune diseases are caused by the breakdown of self-tolerance, which suggests the recognition of specific antigens by autoreactive CD4+ T cells contribute to the specificity of autoimmune diseases. In several cases, however, even for diseases associated with class II MHC alleles, the causative tissue-specific antigens recognized by memory/activated CD4+ T cells have not been established. Rheumatoid arthritis (RA and arthritis in F759 knock-in mouse line (F759 mice are such examples, even though evidences support a pathogenic role for CD4+ T cells in both diseases. We have recently shown local events such as microbleeding together with an accumulation of activated CD4+ T cells in a manner independent of tissue antigen-recognitions induces arthritis in the joints of F759 mice. For example, local microbleeding-mediated CCL20 expression induced such an accumulation, causing arthritis development via chronic activation of an IL-17A-dependent IL-6 signaling amplification loop in type 1 collagen+ cells that is triggered by CD4+ T cell-derived cytokine(s such as IL-17A, which leads to the synergistic activation of STAT3 and NFκB in non hematopoietic cells in the joint. We named this loop the IL-6-mediated inflammation amplifier, or IL-6 amplifier. Thus, certain class II MHC–associated, tissue-specific autoimmune diseases may be induced by local events that cause an antigen-independent accumulation of effector CD4+ T cells followed by the induction of the IL-6 amplifier in the affected tissue. To explain this hypothesis, we have proposed a Four Step Model for MHC class II associated autoimmune diseases. The interaction of four local events results in chronic activation of the IL-6 amplifier, leading to the manifestation of autoimmune diseases. Thus, we have concluded the IL-6 amplifier is a critical regulator of chromic inflammations in tissue specific MHC class II-associated autoimmune diseases.

  9. Cognitive Correlates of Listening Comprehension

    Science.gov (United States)

    Kim, Young-Suk; Phillips, Beth

    2014-01-01

    In an effort to understand cognitive foundations of oral language comprehension (i.e., listening comprehension), we examined how inhibitory control, theory of mind, and comprehension monitoring are uniquely related to listening comprehension over and above vocabulary and age. A total of 156 children in kindergarten and first grade from…

  10. [A comprehensive evaluation of intervention effects on workplace health promotion in a pharmaceutical company].

    Science.gov (United States)

    Li, Shuang; Li, Tao; Li, Jian-guo; Chen, Li; Ren, Jun; Li, Chao-lin

    2012-02-01

    To evaluate the comprehensive workplace health promotion intervention effect in a pharmaceutical company. The evaluation was conducted by using questionnaires, access to information, on-site surveys, satisfaction surveys and interviews. After the intervention, the awareness rate of the staff on "Occupational Disease Prevention Law", occupational disease prevention measures, the definition of hypertension, HIV transmission and high blood pressure, coronary heart disease preventive measures, have been raised from 72.4%, 13.8%, 67.5%, 45.8%, 51.7% to 97.8%, 19.9%, 82.3%, 94.7%, 53.1% respectively. The lifestyle of the staff has been improved, the improvement rate of smoking, drinking, having breakfast 4 times a week and above are 98.5%, 70.2% and 30.6% separately. Out of the 47 evaluation indicators, 41 meet the requirements, 5 basically meet the requirements. After implementing workplace health promotion activities, the level of occupational safety and health management of the pharmaceutical company has been enhanced, the physical and mental health of the staff have been promoted. The WHP comprehensive interventions are feasible and effective.

  11. Advances in Diagnosis of Respiratory Diseases of Small Ruminants

    Directory of Open Access Journals (Sweden)

    Sandip Chakraborty

    2014-01-01

    Full Text Available Irrespective of aetiology, infectious respiratory diseases of sheep and goats contribute to 5.6 percent of the total diseases of small ruminants. These infectious respiratory disorders are divided into two groups: the diseases of upper respiratory tract, namely, nasal myiasis and enzootic nasal tumors, and diseases of lower respiratory tract, namely, peste des petits ruminants (PPR, parainfluenza, Pasteurellosis, Ovine progressive pneumonia, mycoplasmosis, caprine arthritis encephalitis virus, caseous lymphadenitis, verminous pneumonia, and many others. Depending upon aetiology, many of them are acute and fatal in nature. Early, rapid, and specific diagnosis of such diseases holds great importance to reduce the losses. The advanced enzyme-linked immunosorbent assays (ELISAs for the detection of antigen as well as antibodies directly from the samples and molecular diagnostic assays along with microsatellites comprehensively assist in diagnosis as well as treatment and epidemiological studies. The present review discusses the advancements made in the diagnosis of common infectious respiratory diseases of sheep and goats. It would update the knowledge and help in adapting and implementing appropriate, timely, and confirmatory diagnostic procedures. Moreover, it would assist in designing appropriate prevention protocols and devising suitable control strategies to overcome respiratory diseases and alleviate the economic losses.

  12. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  13. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks

    Science.gov (United States)

    Glicksberg, Benjamin S.; Li, Li; Badgeley, Marcus A.; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D.; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L.; Hoffman, Gabriel E.; Dan Li, Shuyu; Schadt, Eric E.; Patel, Chirag J.; Chen, Rong; Dudley, Joel T.

    2016-01-01

    Motivation: Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). Results: We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key ‘hub’ diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. Contacts: rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307606

  14. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease.

    Science.gov (United States)

    McEachern, Kerry Anne; Fung, John; Komarnitsky, Svetlana; Siegel, Craig S; Chuang, Wei-Lien; Hutto, Elizabeth; Shayman, James A; Grabowski, Gregory A; Aerts, Johannes M F G; Cheng, Seng H; Copeland, Diane P; Marshall, John

    2007-07-01

    An approach to treating Gaucher disease is substrate inhibition therapy which seeks to abate the aberrant lysosomal accumulation of glucosylceramide. We have identified a novel inhibitor of glucosylceramide synthase (Genz-112638) and assessed its activity in a murine model of Gaucher disease (D409V/null). Biochemical characterization of Genz-112638 showed good potency (IC(50) approximately 24nM) and specificity against the target enzyme. Mice that received drug prior to significant accumulation of substrate (10 weeks of age) showed reduced levels of glucosylceramide and number of Gaucher cells in the spleen, lung and liver when compared to age-matched control animals. Treatment of older mice that already displayed significant amounts of tissue glucosylceramide (7 months old) resulted in arrest of further accumulation of the substrate and appearance of additional Gaucher cells in affected organs. These data indicate that substrate inhibition therapy with Genz-112638 represents a viable alternate approach to enzyme therapy to treat the visceral pathology in Gaucher disease.

  15. Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts.

    Science.gov (United States)

    Porfirio, Berardino; Paganini, Marco; Mazzanti, Benedetta; Bagnoli, Silvia; Bucciantini, Sandra; Ghelli, Elena; Nacmias, Benedetta; Putignano, Anna Laura; Rombolà, Giovanni; Saccardi, Riccardo; Lombardini, Letizia; Di Lorenzo, Nicola; Vannelli, Gabriella B; Gallina, Pasquale

    2015-01-01

    Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

  16. Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases

    Science.gov (United States)

    Gesheva, Vera; Szekeres, Zsuzsanna; Mihaylova, Nikolina; Dimitrova, Iliyana; Nikolova, Maria; Erdei, Anna; Prechl, Jozsef

    2012-01-01

    Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis. PMID:23075110

  17. Comprehensive national energy strategy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-01

    This Comprehensive National Energy Strategy sets forth a set of five common sense goals for national energy policy: (1) improve the efficiency of the energy system, (2) ensure against energy disruptions, (3) promote energy production and use in ways that respect health and environmental values, (4) expand future energy choices, and (5) cooperate internationally on global issues. These goals are further elaborated by a series of objectives and strategies to illustrate how the goals will be achieved. Taken together, the goals, objectives, and strategies form a blueprint for the specific programs, projects, initiatives, investments, and other actions that will be developed and undertaken by the Federal Government, with significant emphasis on the importance of the scientific and technological advancements that will allow implementation of this Comprehensive National Energy Strategy. Moreover, the statutory requirement of regular submissions of national energy policy plans ensures that this framework can be modified to reflect evolving conditions, such as better knowledge of our surroundings, changes in energy markets, and advances in technology. This Strategy, then, should be thought of as a living document. Finally, this plan benefited from the comments and suggestions of numerous individuals and organizations, both inside and outside of government. The Summary of Public Comments, located at the end of this document, describes the public participation process and summarizes the comments that were received. 8 figs.

  18. iSmaRT: a toolkit for a comprehensive analysis of small RNA-Seq data.

    Science.gov (United States)

    Panero, Riccardo; Rinaldi, Antonio; Memoli, Domenico; Nassa, Giovanni; Ravo, Maria; Rizzo, Francesca; Tarallo, Roberta; Milanesi, Luciano; Weisz, Alessandro; Giurato, Giorgio

    2017-03-15

    The interest in investigating the biological roles of small non-coding RNAs (sncRNAs) is increasing, due to the pleiotropic effects of these molecules exert in many biological contexts. While several methods and tools are available to study microRNAs (miRNAs), only few focus on novel classes of sncRNAs, in particular PIWI-interacting RNAs (piRNAs). To overcome these limitations, we implemented iSmaRT ( i ntegrative Sm all R NA T ool-kit), an automated pipeline to analyze smallRNA-Seq data. iSmaRT is a collection of bioinformatics tools and own algorithms, interconnected through a Graphical User Interface (GUI). In addition to performing comprehensive analyses on miRNAs, it implements specific computational modules to analyze piRNAs, predicting novel ones and identifying their RNA targets. A smallRNA-Seq dataset generated from brain samples of Huntington's Disease patients was used here to illustrate iSmaRT performances, demonstrating how the pipeline can provide, in a rapid and user friendly way, a comprehensive analysis of different classes of sncRNAs. iSmaRT is freely available on the web at ftp://labmedmolge-1.unisa.it (User: iSmart - Password: password). aweisz@unisa.it or ggiurato@unisa.it. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. Disease-specific structural changes in thalamus and dentatorubrothalamic tract in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Surova, Yulia; Hall, Sara; Widner, Haakan [Lund University, Department of Clinical Sciences, Lund (Sweden); Skaane University Hospital, Department of Neurology, Lund (Sweden); Nilsson, Markus [Lund University, Lund University Bioimaging Center, Lund (Sweden); Laett, Jimmy [Skaane University Hospital, Center for Medical Imaging and Physiology, Lund (Sweden); Lampinen, Bjoern [Lund University, Department of Medical Radiation Physics, Lund (Sweden); Lindberg, Olof [Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Nilsson, Christer [Skaane University Hospital, Department of Neurology, Lund (Sweden); Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Westen, Danielle van [Lund University, Department of Clinical Sciences, Lund (Sweden); Skaane University Hospital, Center for Medical Imaging and Physiology, Lund (Sweden); Hansson, Oskar [Malmoe, Lund University, Department of Clinical Sciences, Malmoe (Sweden); Skaane University Hospital, Memory Clinic, Lund (Sweden)

    2015-11-15

    The aim of this study is to identify disease-specific changes of the thalamus, basal ganglia, pons, and midbrain in patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD), and multiple system atrophy with predominant parkinsonism (MSA-P) using diffusion tensor imaging and volumetric analysis. MRI diffusion and volumetric data were acquired in a derivation of 30 controls and 8 patients with PSP and a validation cohort comprised of controls (n = 21) and patients with PSP (n = 27), PD (n = 10), and MSA-P (n = 11). Analysis was performed using regions of interest (ROI), tract-based spatial statistic (TBSS), and tractography and results compared between diagnostic groups. In the derivation cohort, we observed increased mean diffusivity (MD) in the thalamus, superior cerebellar peduncle, and the midbrain in PSP compared to controls. Furthermore, volumetric analysis showed reduced thalamic volumes in PSP. In the validation cohort, the observations of increased MD were replicated by ROI-based analysis and in the thalamus by TBSS-based analysis. Such differences were not found for patients with PD in any of the cohorts. Tractography of the dentatorubrothalamic tract (DRTT) showed increased MD in PSP patients from both cohorts compared to controls and in the validation cohort in PSP compared to PD and MSA patients. Increased MD in the thalamus and along the DRTT correlated with disease stage and motor function in PSP. Patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. These changes are associated with disease stage and impaired motor function. (orig.)

  20. Disease-specific structural changes in thalamus and dentatorubrothalamic tract in progressive supranuclear palsy

    International Nuclear Information System (INIS)

    Surova, Yulia; Hall, Sara; Widner, Haakan; Nilsson, Markus; Laett, Jimmy; Lampinen, Bjoern; Lindberg, Olof; Nilsson, Christer; Westen, Danielle van; Hansson, Oskar

    2015-01-01

    The aim of this study is to identify disease-specific changes of the thalamus, basal ganglia, pons, and midbrain in patients with progressive supranuclear palsy (PSP), Parkinson's disease (PD), and multiple system atrophy with predominant parkinsonism (MSA-P) using diffusion tensor imaging and volumetric analysis. MRI diffusion and volumetric data were acquired in a derivation of 30 controls and 8 patients with PSP and a validation cohort comprised of controls (n = 21) and patients with PSP (n = 27), PD (n = 10), and MSA-P (n = 11). Analysis was performed using regions of interest (ROI), tract-based spatial statistic (TBSS), and tractography and results compared between diagnostic groups. In the derivation cohort, we observed increased mean diffusivity (MD) in the thalamus, superior cerebellar peduncle, and the midbrain in PSP compared to controls. Furthermore, volumetric analysis showed reduced thalamic volumes in PSP. In the validation cohort, the observations of increased MD were replicated by ROI-based analysis and in the thalamus by TBSS-based analysis. Such differences were not found for patients with PD in any of the cohorts. Tractography of the dentatorubrothalamic tract (DRTT) showed increased MD in PSP patients from both cohorts compared to controls and in the validation cohort in PSP compared to PD and MSA patients. Increased MD in the thalamus and along the DRTT correlated with disease stage and motor function in PSP. Patients with PSP, but not PD or MSA-P, exhibit signs of structural abnormalities in the thalamus and in the DRTT. These changes are associated with disease stage and impaired motor function. (orig.)

  1. Socioeconomic inequalities in cause-specific mortality after disability retirement due to different diseases.

    Science.gov (United States)

    Polvinen, A; Laaksonen, M; Gould, R; Lahelma, E; Leinonen, T; Martikainen, P

    2015-03-01

    Socioeconomic inequalities in both disability retirement and mortality are large. The aim of this study was to examine socioeconomic differences in cause-specific mortality after disability retirement due to different diseases. We used administrative register data from various sources linked together by Statistics Finland and included an 11% sample of the Finnish population between the years 1987 and 2007. The data also include an 80% oversample of the deceased during the follow-up. The study included men and women aged 30-64 years at baseline and those who turned 30 during the follow-up. We used Cox regression analysis to examine socioeconomic differences in mortality after disability retirement. Socioeconomic differences in mortality after disability retirement were smaller than in the population in general. However, manual workers had a higher risk of mortality than upper non-manual employees after disability retirement due to mental disorders and cardiovascular diseases, and among men also diseases of the nervous system. After all-cause disability retirement, manual workers ran a higher risk of cardiovascular and alcohol-related death. However, among men who retired due to mental disorders or cardiovascular diseases, differences in social class were found for all causes of death examined. For women, an opposite socioeconomic gradient in mortality after disability retirement from neoplasms was found. Conclusions: The disability retirement process leads to smaller socioeconomic differences in mortality compared with those generally found in the population. This suggests that the disability retirement system is likely to accurately identify chronic health problems with regard to socioeconomic status. © 2014 the Nordic Societies of Public Health.

  2. A comprehensive approach to benefit-risk assessment in drug development

    DEFF Research Database (Denmark)

    Sarac, Sinan B; Rasmussen, Christian H; Rasmussen, Morten A.

    2012-01-01

    Major regulatory agencies, for example, FDA and EMA, have started to request comprehensive benefit-risk analyses of pharmaceutical products prior to approval or labelling expansion. The purpose of this study is to develop a generally applicable and reliable data-driven benefit-risk assessment......) discussion and formulation of an overall conclusion. To reduce the impact of subjective judgements, scores are assigned to each criterion on the basis of objective information (data) wherever possible. The proposed benefit-risk evaluation approach offers comprehensive, data-driven assessments that can...... method, where two or more drugs/doses can be compared. Our aim is to formulate an approach that is simple to apply, allows direct comparison of different types of risks and benefits, and is tailored for application in different disease areas both during clinical development and in the marketing approval...

  3. Developing injectable immunoglobulins to treat cognitive impairment in Alzheimer's disease.

    Science.gov (United States)

    Steinitz, Michael

    2008-05-01

    Alzheimer's disease is a devastating disorder, clinically characterized by a comprehensive cognitive decline. The novel strategy of anti-amyloid-beta immunotherapy has been suggested following encouraging results obtained in murine models of Alzheimer's disease, in non-human primates, and in small-scale clinical trials. To examine the choice between active or passive anti-amyloid-beta immunization and the choice of the molecule to which the immune machinery should be targeted, which are central issues in future immune therapy of Alzheimer's disease. Research into the new area of Alzheimer's disease immune therapy is primarily based on in vivo and in vitro studies of murine models of Alzheimer's disease. The studies are hence limited to defined genetic deficiencies. In humans, infusion of anti-amyloid-beta antibodies is considered a safer approach than active anti-amyloid-beta vaccination. Alzheimer's-disease-protective anti-amyloid-beta monoclonal antibodies should target specific epitopes within the amyloid beta(1 42) peptide, avoiding possibly harmful binding to the ubiquitous normal amyloid precursor protein. Since Alzheimer's disease immunotherapy requires repeated infusion of antibodies over a prolonged period of time, Alzheimer's disease patients will tolerate such antibodies provided the latter are exclusively of human origin. Human monoclonal antibodies that correspond to ubiquitous anti-amyloid-beta, present in all healthy humans, might bear important protective characteristics.

  4. Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

    Science.gov (United States)

    Taylor, Kimberly E.; Remmers, Elaine F.; Lee, Annette T.; Ortmann, Ward A.; Plenge, Robert M.; Tian, Chao; Chung, Sharon A.; Nititham, Joanne; Hom, Geoffrey; Kao, Amy H.; Demirci, F. Yesim; Kamboh, M. Ilyas; Petri, Michelle; Manzi, Susan; Kastner, Daniel L.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy W.; Criswell, Lindsey A.

    2008-01-01

    Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease. PMID

  5. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Kimberly E Taylor

    2008-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398 and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r(2 = 0.94 to 0.99 were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10(-16. This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19, nephritis (MAF = 34.3%, OR = 1.80, p<10(-11, and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13. An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10(-4 in the homogeneous subset of subjects. In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease.

  6. When all children comprehend: increasing the external validity of narrative comprehension development research

    Science.gov (United States)

    Burris, Silas E.; Brown, Danielle D.

    2014-01-01

    Narratives, also called stories, can be found in conversations, children's play interactions, reading material, and television programs. From infancy to adulthood, narrative comprehension processes interpret events and inform our understanding of physical and social environments. These processes have been extensively studied to ascertain the multifaceted nature of narrative comprehension. From this research we know that three overlapping processes (i.e., knowledge integration, goal structure understanding, and causal inference generation) proposed by the constructionist paradigm are necessary for narrative comprehension, narrative comprehension has a predictive relationship with children's later reading performance, and comprehension processes are generalizable to other contexts. Much of the previous research has emphasized internal and predictive validity; thus, limiting the generalizability of previous findings. We are concerned these limitations may be excluding underrepresented populations from benefits and implications identified by early comprehension processes research. This review identifies gaps in extant literature regarding external validity and argues for increased emphasis on externally valid research. We highlight limited research on narrative comprehension processes in children from low-income and minority populations, and argue for changes in comprehension assessments. Specifically, we argue both on- and off-line assessments should be used across various narrative types (e.g., picture books, televised narratives) with traditionally underserved and underrepresented populations. We propose increasing the generalizability of narrative comprehension processes research can inform persistent reading achievement gaps, and have practical implications for how children learn from narratives. PMID:24659973

  7. When All Children Comprehend: Increasing the External Validity of Narrative Comprehension Development Research

    Directory of Open Access Journals (Sweden)

    Silas E. Burris

    2014-03-01

    Full Text Available Narratives, also called stories, can be found in conversations, children’s play interactions, reading material, and television programs. From infancy to adulthood, narrative comprehension processes interpret events and inform our understanding of physical and social environments. These processes have been extensively studied to ascertain the multifaceted nature of narrative comprehension. From this research we know that three overlapping processes (i.e., knowledge integration, goal structure understanding, and causal inference generation proposed by the constructionist paradigm are necessary for narrative comprehension, narrative comprehension has a predictive relationship with children’s later reading performance, and comprehension processes are generalizable to other contexts. Much of the previous research has emphasized internal and predictive validity; thus, limiting the generalizability of previous findings. We are concerned these limitations may be excluding underrepresented populations from benefits and implications identified by early comprehension processes research. This review identifies gaps in extant literature regarding external validity and argues for increased emphasis on externally valid research. We highlight limited research on narrative comprehension processes in children from low-income and minority populations, and argue for changes in comprehension assessments. Specifically, we argue both on- and off-line assessments should be used across various narrative types (e.g., picture books, televised narratives with traditionally underserved and underrepresented populations. We propose increasing the generalizability narrative comprehension processes research can inform persistent reading achievement gaps, and have practical implications for how children learn from narratives.

  8. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  9. Association between Smokefree Legislation and Hospitalizations for Cardiac, Cerebrovascular and Respiratory Diseases: A Meta-Analysis

    Science.gov (United States)

    Tan, Crystal E.; Glantz, Stanton A.

    2012-01-01

    Background Secondhand smoke causes cardiovascular and respiratory disease. Smokefree legislation is associated with a lower risk of hospitalization and death from these diseases. Methods and Results Random effects meta-analysis was conducted by law comprehensiveness to determine the relationship between smokefree legislation and hospital admission or death from cardiac, cerebrovascular, and respiratory diseases. Studies were identified using a systematic search for studies published before November 30, 2011 using Science Citation Index, Google Scholar, PubMed, and Embase and references in identified papers. Change in hospital admissions (or deaths) in the presence of a smokefree law, duration of follow-up, and law comprehensiveness (workplaces only; workplaces and restaurants; or workplaces, restaurants, and bars) were recorded. Forty-five studies of 33 smokefree laws with median follow-up of 24 months (range 2–57 months) were included. Comprehensive smokefree legislation was associated with significantly lower rates of hospital admissions (or deaths) for all 4 diagnostic groups: coronary events (RR .848, 95% CI .816–.881), other heart disease (RR .610, 95% CI .440–.847), cerebrovascular accidents (RR .840, 95% CI .753–.936), and respiratory disease (RR .760, 95% CI .682–.846). The difference in risk following comprehensive smokefree laws does not change with longer follow-up. More comprehensive laws were associated with larger changes in risk. Conclusions Smokefree legislation was associated with a lower risk of smoking-related cardiac, cerebrovascular, and respiratory diseases, with more comprehensive laws associated with greater changes in risk. PMID:23109514

  10. Immersive Data Comprehension: Visualizing Uncertainty in Measurable Models

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    Pere eBrunet

    2015-09-01

    Full Text Available Recent advances in 3D scanning technologies have opened new possibilities in a broad range of applications includingcultural heritage, medicine, civil engineering and urban planning. Virtual Reality systems can provide new tools toprofessionals that want to understand acquired 3D models. In this paper, we review the concept of data comprehension with an emphasis on visualization and inspection tools on immersive setups. We claim that in most application fields, data comprehension requires model measurements which in turn should be based on the explicit visualization of uncertainty. As 3D digital representations are not faithful, information on their fidelity at local level should be included in the model itself as uncertainty bounds. We propose the concept of Measurable 3D Models as digital models that explicitly encode local uncertainty bounds related to their quality. We claim that professionals and experts can strongly benefit from immersive interaction through new specific, fidelity-aware measurement tools which can facilitate 3D data comprehension. Since noise and processing errors are ubiquitous in acquired datasets, we discuss the estimation, representation and visualization of data uncertainty. We show that, based on typical user requirements in Cultural Heritage and other domains, application-oriented measuring tools in 3D models must consider uncertainty and local error bounds. We also discuss the requirements of immersive interaction tools for the comprehension of huge 3D and nD datasets acquired from real objects.

  11. KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility

    Science.gov (United States)

    Ragazzo, Michele; Manzo, Laura; Costanza, Gaetana; Bowes, John; Hüffmeier, Ulrike; Potenza, Saverio; Sangiuolo, Federica; Reis, André; Barton, Anne; Novelli, Giuseppe; Orlandi, Augusto; Giardina, Emiliano

    2017-01-01

    To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis. PMID:29221136

  12. Bid specifications and bid evaluations

    International Nuclear Information System (INIS)

    Zijl, N.A. van

    1977-01-01

    Bid specifications are in view of the size of these projects important and comprehensive documents. The basic content and set up of the specifications are discussed such as: 1) Bid invitation letter, 2) instruction to bidders, 3) draft contract (terms and conditions), 4) technical specifications, 5) side data and information. - The evaluations of bids for nuclear power stations is due to the complexity of such bids a difficult undertaking. Evaluation methods and approaches which can be applied for such bid evaluations are discussed as well as the preparations which are required for carrying out such evaluations. (orig.) [de

  13. Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

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    Alies van Lier

    Full Text Available Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands.The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961 and influenza (8670 DALYs/year; 95% UI: 8468-8874, which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be

  14. Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011

    Science.gov (United States)

    Bouwknegt, Martijn; Kretzschmar, Mirjam E.; Mangen, Marie-Josée J.; Wallinga, Jacco; de Melker, Hester E.

    2016-01-01

    Background Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. Methods and Findings The average annual disease burden was computed for the period 2007–2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911–9961) and influenza (8670 DALYs/year; 95% UI: 8468–8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five

  15. Disease Burden of 32 Infectious Diseases in the Netherlands, 2007-2011.

    Science.gov (United States)

    van Lier, Alies; McDonald, Scott A; Bouwknegt, Martijn; Kretzschmar, Mirjam E; Havelaar, Arie H; Mangen, Marie-Josée J; Wallinga, Jacco; de Melker, Hester E

    2016-01-01

    Infectious disease burden estimates provided by a composite health measure give a balanced view of the true impact of a disease on a population, allowing the relative impact of diseases that differ in severity and mortality to be monitored over time. This article presents the first national disease burden estimates for a comprehensive set of 32 infectious diseases in the Netherlands. The average annual disease burden was computed for the period 2007-2011 for selected infectious diseases in the Netherlands using the disability-adjusted life years (DALY) measure. The pathogen- and incidence-based approach was adopted to quantify the burden due to both morbidity and premature mortality associated with all short and long-term consequences of infection. Natural history models, disease progression probabilities, disability weights, and other parameters were adapted from previous research. Annual incidence was obtained from statutory notification and other surveillance systems, which was corrected for under-ascertainment and under-reporting. The highest average annual disease burden was estimated for invasive pneumococcal disease (9444 DALYs/year; 95% uncertainty interval [UI]: 8911-9961) and influenza (8670 DALYs/year; 95% UI: 8468-8874), which represents 16% and 15% of the total burden of all 32 diseases, respectively. The remaining 30 diseases ranked by number of DALYs/year from high to low were: HIV infection, legionellosis, toxoplasmosis, chlamydia, campylobacteriosis, pertussis, tuberculosis, hepatitis C infection, Q fever, norovirus infection, salmonellosis, gonorrhoea, invasive meningococcal disease, hepatitis B infection, invasive Haemophilus influenzae infection, shigellosis, listeriosis, giardiasis, hepatitis A infection, infection with STEC O157, measles, cryptosporidiosis, syphilis, rabies, variant Creutzfeldt-Jakob disease, tetanus, mumps, rubella, diphtheria, and poliomyelitis. The very low burden for the latter five diseases can be attributed to the

  16. Comparative analyses of population-scale phenomic data in electronic medical records reveal race-specific disease networks.

    Science.gov (United States)

    Glicksberg, Benjamin S; Li, Li; Badgeley, Marcus A; Shameer, Khader; Kosoy, Roman; Beckmann, Noam D; Pho, Nam; Hakenberg, Jörg; Ma, Meng; Ayers, Kristin L; Hoffman, Gabriel E; Dan Li, Shuyu; Schadt, Eric E; Patel, Chirag J; Chen, Rong; Dudley, Joel T

    2016-06-15

    Underrepresentation of racial groups represents an important challenge and major gap in phenomics research. Most of the current human phenomics research is based primarily on European populations; hence it is an important challenge to expand it to consider other population groups. One approach is to utilize data from EMR databases that contain patient data from diverse demographics and ancestries. The implications of this racial underrepresentation of data can be profound regarding effects on the healthcare delivery and actionability. To the best of our knowledge, our work is the first attempt to perform comparative, population-scale analyses of disease networks across three different populations, namely Caucasian (EA), African American (AA) and Hispanic/Latino (HL). We compared susceptibility profiles and temporal connectivity patterns for 1988 diseases and 37 282 disease pairs represented in a clinical population of 1 025 573 patients. Accordingly, we revealed appreciable differences in disease susceptibility, temporal patterns, network structure and underlying disease connections between EA, AA and HL populations. We found 2158 significantly comorbid diseases for the EA cohort, 3265 for AA and 672 for HL. We further outlined key disease pair associations unique to each population as well as categorical enrichments of these pairs. Finally, we identified 51 key 'hub' diseases that are the focal points in the race-centric networks and of particular clinical importance. Incorporating race-specific disease comorbidity patterns will produce a more accurate and complete picture of the disease landscape overall and could support more precise understanding of disease relationships and patient management towards improved clinical outcomes. rong.chen@mssm.edu or joel.dudley@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  17. Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

    Science.gov (United States)

    Fan, Bo; Hu, Bin; Yuan, Qingmin; Wen, Shuang; Liu, Tianqing; Bai, Shanshan; Qi, Xiaofeng; Wang, Xin; Yang, Deyong; Sun, Xiuzhen; Song, Xishuang

    2017-07-01

    Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC

  18. The Relationship of Error Rate and Comprehension in Second and Third Grade Oral Reading Fluency.

    Science.gov (United States)

    Abbott, Mary; Wills, Howard; Miller, Angela; Kaufman, Journ

    2012-01-01

    This study explored the relationships of oral reading speed and error rate on comprehension with second and third grade students with identified reading risk. The study included 920 2nd graders and 974 3rd graders. Participants were assessed using Dynamic Indicators of Basic Early Literacy Skills (DIBELS) and the Woodcock Reading Mastery Test (WRMT) Passage Comprehension subtest. Results from this study further illuminate the significant relationships between error rate, oral reading fluency, and reading comprehension performance, and grade-specific guidelines for appropriate error rate levels. Low oral reading fluency and high error rates predict the level of passage comprehension performance. For second grade students below benchmark, a fall assessment error rate of 28% predicts that student comprehension performance will be below average. For third grade students below benchmark, the fall assessment cut point is 14%. Instructional implications of the findings are discussed.

  19. 'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

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    Nathali Kaushansky

    Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

  20. Quotient-Comprehension Chains

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    Kenta Cho

    2015-11-01

    Full Text Available Quotients and comprehension are fundamental mathematical constructions that can be described via adjunctions in categorical logic. This paper reveals that quotients and comprehension are related to measurement, not only in quantum logic, but also in probabilistic and classical logic. This relation is presented by a long series of examples, some of them easy, and some also highly non-trivial (esp. for von Neumann algebras. We have not yet identified a unifying theory. Nevertheless, the paper contributes towards such a theory by introducing the new quotient-and-comprehension perspective on measurement instruments, and by describing the examples on which such a theory should be built.

  1. Therapeutic potential of flavonoids in inflammatory bowel disease: A comprehensive review.

    Science.gov (United States)

    Salaritabar, Ali; Darvishi, Behrad; Hadjiakhoondi, Farzaneh; Manayi, Azadeh; Sureda, Antoni; Nabavi, Seyed Fazel; Fitzpatrick, Leo R; Nabavi, Seyed Mohammad; Bishayee, Anupam

    2017-07-28

    The inflammatory process plays a central role in the development and progression of numerous pathological situations, such as inflammatory bowel disease (IBD), autoimmune and neurodegenerative diseases, metabolic syndrome, and cardiovascular disorders. IBDs involve inflammation of the gastrointestinal area and mainly comprise Crohn's disease (CD) and ulcerative colitis (UC). Both pathological situations usually involve recurring or bloody diarrhea, pain, fatigue and weight loss. There is at present no pharmacological cure for CD or UC. However, surgery may be curative for UC patients. The prescribed treatment aims to ameliorate the symptoms and prevent and/or delay new painful episodes. Flavonoid compounds are a large family of hydroxylated polyphenolic molecules abundant in plants, including vegetables and fruits which are the major dietary sources of these compounds for humans, together with wine and tea. Flavonoids are becoming very popular because they have many health-promoting and disease-preventive effects. Most interest has been directed towards the antioxidant activity of flavonoids, evidencing a remarkable free-radical scavenging capacity. However, accumulating evidence suggests that flavonoids have many other biological properties, including anti-inflammatory, antiviral, anticancer, and neuroprotective activities through different mechanisms of action. The present review analyzes the available data about the different types of flavonoids and their potential effectiveness as adjuvant therapy of IBDs.

  2. Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform.

    Science.gov (United States)

    Scheiblhofer, Sandra; Machado, Yoan; Feinle, Andrea; Thalhamer, Josef; Hüsing, Nicola; Weiss, Richard

    2016-12-01

    Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.

  3. Role of strain imaging in right heart disease: a comprehensive review.

    Science.gov (United States)

    Kannan, Arun; Poongkunran, Chithra; Jayaraj, Mahendran; Janardhanan, Rajesh

    2014-10-01

    Advances in the imaging techniques of the heart have fueled the interest in understanding of right heart pathology. Recently, speckle tracking echocardiography has shown to aid in understanding various right heart diseases and better management. Its role is well established in diagnosing right heart failure, pulmonary artery hypertension, arrhythmogenic right ventricular dysplasia and congenital heart disease. We review the basic mechanics of speckle tracking and analyze its role in various right heart conditions.

  4. Assessing behavioural changes in ALS: cross-validation of ALS-specific measures.

    Science.gov (United States)

    Pinto-Grau, Marta; Costello, Emmet; O'Connor, Sarah; Elamin, Marwa; Burke, Tom; Heverin, Mark; Pender, Niall; Hardiman, Orla

    2017-07-01

    The Beaumont Behavioural Inventory (BBI) is a behavioural proxy report for the assessment of behavioural changes in ALS. This tool has been validated against the FrSBe, a non-ALS-specific behavioural assessment, and further comparison of the BBI against a disease-specific tool was considered. This study cross-validates the BBI against the ALS-FTD-Q. Sixty ALS patients, 8% also meeting criteria for FTD, were recruited. All patients were evaluated using the BBI and the ALS-FTD-Q, completed by a carer. Correlational analysis was performed to assess construct validity. Precision, sensitivity, specificity, and overall accuracy of the BBI when compared to the ALS-FTD-Q, were obtained. The mean score of the whole sample on the BBI was 11.45 ± 13.06. ALS-FTD patients scored significantly higher than non-demented ALS patients (31.6 ± 14.64, 9.62 ± 11.38; p ALS-FTD-Q was observed (r = 0.807, p ALS-FTD-Q. Good construct validity has been further confirmed when the BBI is compared to an ALS-specific tool. Furthermore, the BBI is a more comprehensive behavioural assessment for ALS, as it measures the whole behavioural spectrum in this condition.

  5. Associations of specific psychiatric disorders with isolated focal dystonia, and monogenic and idiopathic Parkinson's disease.

    Science.gov (United States)

    Steinlechner, Susanne; Hagenah, Johann; Rumpf, Hans-Jürgen; Meyer, Christian; John, Ulrich; Bäumer, Tobias; Brüggemann, Norbert; Kasten, Meike; Münchau, Alexander; Klein, Christine; Lencer, Rebekka

    2017-06-01

    Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075). Our results indicate an odds ratio (OR) of 2.6 [confidence interval (CI) 1.7-4.0] for general axis I disorders in IFD, an OR of 2.5 (CI 1.4-4.7) in monogenic PD, and an OR of 1.4 (CI 0.8-2.6) in idiopathic PD. More specifically, the monogenic PD group showed the highest ORs for affective disorders including depression (OR = 4.9), bipolar disorder (OR = 17.4), and hypomanic episodes (OR = 17.0), whereas IFD expressed the highest rates of anxiety disorders (OR = 3.3). Psychotic symptoms were only observed in the PD groups but not in IFD. Our findings underline the notion that psychiatric disorders are part of the phenotypic spectrum of movement disorders. Moreover, they suggest that IFD, monogenic PD, and idiopathic PD are associated with specific psychiatric disorders indicating disturbances in a different neural circuitry for sensorimotor control.

  6. On the importance of listening comprehension.

    Science.gov (United States)

    Hogan, Tiffany P; Adlof, Suzanne M; Alonzo, Crystle N

    2014-06-01

    The simple view of reading highlights the importance of two primary components which account for individual differences in reading comprehension across development: word recognition (i.e., decoding) and listening comprehension. While assessments and interventions for decoding have been the focus of pedagogy in the past several decades, the importance of listening comprehension has received less attention. This paper reviews evidence showing that listening comprehension becomes the dominating influence on reading comprehension starting even in the elementary grades. It also highlights a growing number of children who fail to develop adequate reading comprehension skills, primarily due to deficient listening comprehension skills (i.e., poor comprehenders). Finally we discuss key language influences on listening comprehension for consideration during assessment and treatment of reading disabilities.

  7. Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries. METHODS: The data from 57 Chinese sCJD patients were retrospectively analyzed, including demographic data, clinical manifestations, laboratory examinations, electroencephalograms (EEGs, diffusion-weighted imaging (DWI scans, positron emission tomography (PET scans, and pathological results. RESULT: The disease was pathologically confirmed in 11 patients. 39 cases were diagnosed as probable sCJD, and 7 were possible. Of the total cases, 33 were male, and 24 were female. The onset age ranged from 36 to 75 years (mean: 55.5, median: 57. Disease onset before the age of 60 occurred in 57.9% of patients. The disease duration from onset to death ranged 5-22 months (mean: 11.6, median: 11, and 51.9% of patients died 7 to 12 months after disease onset. The majority of patients presented with sub-acute onset with progressive dementia. 3 of the 9 patients who took 14-3-3 protein analysis had positive results (33.3%. The sensitivity of EEG was 79.6% (43/54. For DWI and PET examinations, the sensitivities were 94% (47/50 and 94.1% (16/17, respectively. In seven patients who did not show typical hyper-intensities on the first DWI examination, abnormalities of hypo-metabolism in the cerebral cortex were clearly detected by PET. In 13 out of the 17 patients, PET detected extra abnormal regions in addition to the hyper-intense areas observed in DWI. CONCLUSION: This is the first study to indicate that Chinese sCJD patients have a much earlier onset age and a longer disease duration than other populations, which is most likely related to racial differences. The longer disease duration may also be a probable characteristic of Asian populations. PET had high sensitivity for the

  8. Nanoimaging in cardiovascular diseases: Current state of the art

    Directory of Open Access Journals (Sweden)

    Suryyani Deb

    2015-01-01

    Full Text Available Nanotechnology has been integrated into healthcare system in terms of diagnosis as well as therapy. The massive impact of imaging nanotechnology has a deeper intervention in cardiology i.e. as contrast agents , to target vulnerable plaques with site specificity and in a theranostic approach to treat these plaques, stem cell delivery in necrotic myocardium, etc. Thus cardiovascular nanoimaging is not limited to simple diagnosis but also can help real time tracking during therapy as well as surgery. The present review provides a comprehensive description of the molecular imaging techniques for cardiovascular diseases with the help of nanotechnology and the potential clinical implications of nanotechnology for future applications.

  9. Follow-up study on reading comprehension in Down's syndrome: the role of reading skills and listening comprehension.

    Science.gov (United States)

    Roch, Maja; Florit, Elena; Levorato, Chiara

    2011-01-01

    According to the 'Simple View of Reading', reading comprehension requires some abilities such as reading skill and listening comprehension. Individuals with Down's syndrome show relative strengths in reading skills, mainly in word recognition, where they attain a reading age of about 7-8 years. Compared with word recognition, their reading comprehension is usually delayed by at least 6 months. Poor reading comprehension is paralleled by weak listening comprehension. It is claimed that poor listening comprehension might constrain the development of reading comprehension and, therefore, be a cause for the asynchrony between reading skills and reading comprehension. A follow-up study was carried out in order to analyse the improvements in reading skills, listening and reading text comprehension, and to support the hypothesis of a causal relationship between listening and reading comprehension. Ten children and adolescents with Down's syndrome, aged between 11 years 3 months and 19 years 10 months, were assessed twice over a one-year period as to their reading skills, listening and reading text comprehension. Three main findings emerged: (1) reading skills, on the one hand, and comprehension (both listening and reading), on the other hand, are independent; (2) reading comprehension development is determined mainly by listening comprehension, which in the present study proved to be very poor; and (3) an improvement after a one-year period, even though limited, occurred for all examined abilities except for listening comprehension. The results are discussed in the light of the theoretical framework of the 'Simple View of Reading' and of their relevance for practical and educational issues. © 2011 Royal College of Speech & Language Therapists.

  10. Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility.

    Science.gov (United States)

    Lesch, M F; Horrey, W J; Wogalter, M S; Powell, W R

    2011-10-01

    Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory.

  11. Case report of Lewy body disease mimicking Creutzfeldt-Jakob disease in a 44-year-old man.

    Science.gov (United States)

    Saint-Aubert, Laure; Pariente, Jérémie; Dumas, Herve; Payoux, Pierre; Brandel, Jean-Philippe; Puel, Michèle; Vital, Anne; Guedj, Eric; Lesage, Suzanne; Peoc'h, Katell; Brefel Courbon, Christine; Ory Magne, Fabienne

    2016-07-30

    Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease. We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations. Creutzfeldt-Jakob disease was first suspected in this patient with no previous medical history, who developed acute and rapid cognitive impairment, L-dopa-non-responsive parkinsonism, and delusion. Positive 14-3-3 protein was initially detected in cerebrospinal fluid and until the late stages of the disease. Severe atrophy with no diffusion hypersignal was found on structural MRI as well as an extensive hypometabolism on (18)F-FDG-PET, in comparison to age-matched healthy volunteers. Genetic investigation found no alpha-synuclein gene mutation. The patient died within 5 years, and post-mortem examination found numerous Lewy bodies and Lewy neurites consistent with pure Lewy body disease. This comprehensively described case illustrates that dementia with Lewy bodies can occur in young patients with atypical clinical presentation. Biochemistry and neuroimaging investigations can sometimes be insufficient to allow accurate diagnostic. More specific markers to support such diagnosis are needed.

  12. Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences.

    Science.gov (United States)

    Galson, Jacob D; Trück, Johannes; Fowler, Anna; Clutterbuck, Elizabeth A; Münz, Márton; Cerundolo, Vincenzo; Reinhard, Claudia; van der Most, Robbert; Pollard, Andrew J; Lunter, Gerton; Kelly, Dominic F

    2015-12-01

    Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.

  13. The Effect of Note Taking vs. Summarizing Strategy on Iranian EFL Learners’ Listening Comprehension

    OpenAIRE

    Mehri Khavazi; Mandana Yousefi; Naeemeh Kharaghani

    2018-01-01

    This study, specifically, investigated the effect of note taking and summarizing strategies on Iranian EFL learners’ listening comprehension. The study aimed at investigating the effects of note taking and summarizing on listening comprehension of Iranian EFL learners. The participants of the study included 75 female language learners in Bojnord who were homogenized in terms of language proficiency. They were divided into two experimental and onecontrol groups. ANCOVA test was used to analyze...

  14. Strain-Specific Altered Regulatory Response of Rab7a and Tau in Creutzfeldt-Jakob Disease and Alzheimer's Disease.

    Science.gov (United States)

    Zafar, Saima; Younas, Neelam; Correia, Susana; Shafiq, Mohsin; Tahir, Waqas; Schmitz, Matthias; Ferrer, Isidre; Andréoletti, Olivier; Zerr, Inga

    2017-01-01

    There is an increasing demand for the understanding of pathophysiology on neurodegeneration diseases at early stages. Changes in endocytic machinery and the cytoskeleton-associated response are the first alterations observed in Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease AD brain. In this study, we performed a targeted search for endocytic pathway proteins in the different regions of the brain. We found late endosome marker Rab7a which was significantly upregulated in the frontal cortex region in the rapid progressive CJD form (MM1) and rapid progressive AD (rpAD) forms. However, Rab9 expression was significantly downregulated only in CJD-MM1 brain frontal cortex region. In the cerebellum, Rab7a expression showed significant upregulation in both subtype MM1 and VV2 CJD forms, in contrast to Rab9 which showed significant downregulation in both subtype MM1 and VV2 CJD forms at terminal stage of the disease. To check regulatory response at pre-symptomatic stage of the disease, we checked the regulatory interactive response of Rab7a, Rab9, and known biomarkers PrP C and tau forms in frontal cortex at pre-symptomatic stage of the disease in tg340 mice expressing about fourfold of human PrP-M129 with PrP-null background that had been inoculated with human sCJD MM1 brain tissue homogenates (sCJD MM1 mice). In addition, we analyzed 5XFAD mice, exhibiting five mutations in the APP and presenilin genes related to familial Alzheimer's disease (FAD), to validate specific regulatory response of Rab7a, Rab9, tau, and phosphorylated form of tau by immunostaining 5XFAD mice in comparison with the wild-type age-matched mice brain. The cortical region of 5XFAD mice brain showed accumulated form of Rab7a in puncta that co-label for p-Tau, indicating colocalization by using confocal laser-scanning microscopy and was confirmed by using reverse co-immunoprecipitation. Furthermore, synthetic RNA (siRNA) against the Rab7a gene decreased expression of Rab7a protein, in cortical

  15. Patients with Revision Modern Megaprostheses of the Distal Femur Have Improved Disease-Specific and Health-Related Outcomes Compared to Those with Primary Replacements.

    Science.gov (United States)

    Heyberger, Clémence; Auberger, Guillaume; Babinet, Antoine; Anract, Philippe; Biau, David J

    2017-12-21

    We asked whether there would be any difference between primary and revision modern cemented fixed hinge megaprosthesis of the distal femur in function and activity-related outcomes following treatment of a bone tumor. An identical custom-made fixed hinge cemented megaprosthesis with a hydroxyapatite collar was used in all cases. The main outcomes were joint-specific function, disease-specific activity, and health-related quality of life. Implant survival was also evaluated. Patients in the revision group performed slightly better than patients in the primary group on disease-specific (Toronto Extremity Salvage Score, p  = 0.033; Musculoskeletal Tumor Society, p  = 0.072) and health-related outcomes (Short Form 36 [SF-36] physical component, p  = 0.085; SF-36 mental component, p  = 0.069) but not on joint-specific outcomes (Knee Society Score, p  = 0.94). The cumulative probabilities of revision for any reason were 14.5% (7-25%) at 5 years with no statistically significant difference between primary and revision procedures ( p  = 0.77). In conclusion, patients undergoing a revision have similar joint-specific functional outcome but improved disease-specific and health-related outcomes. Implant survival are similar between groups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  16. The natural history of gastro-esophageal reflux disease: a comprehensive review.

    Science.gov (United States)

    Savarino, E; de Bortoli, N; De Cassan, C; Della Coletta, M; Bartolo, O; Furnari, M; Ottonello, A; Marabotto, E; Bodini, G; Savarino, V

    2017-02-01

    Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus. © 2016 International Society for Diseases of the Esophagus.

  17. Explaining Variance in Comprehension for Students in a High-Poverty Setting

    Science.gov (United States)

    Conradi, Kristin; Amendum, Steven J.; Liebfreund, Meghan D.

    2016-01-01

    This study examined the contributions of decoding, language, spelling, and motivation to the reading comprehension of elementary school readers in a high-poverty setting. Specifically, the research questions addressed whether and how the influences of word reading efficiency, semantic knowledge, reading self-concept, and spelling on reading…

  18. Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review.

    Science.gov (United States)

    Mozaffarian, Dariush

    2016-01-12

    Suboptimal nutrition is a leading cause of poor health. Nutrition and policy science have advanced rapidly, creating confusion yet also providing powerful opportunities to reduce the adverse health and economic impacts of poor diets. This review considers the history, new evidence, controversies, and corresponding lessons for modern dietary and policy priorities for cardiovascular diseases, obesity, and diabetes mellitus. Major identified themes include the importance of evaluating the full diversity of diet-related risk pathways, not only blood lipids or obesity; focusing on foods and overall diet patterns, rather than single isolated nutrients; recognizing the complex influences of different foods on long-term weight regulation, rather than simply counting calories; and characterizing and implementing evidence-based strategies, including policy approaches, for lifestyle change. Evidence-informed dietary priorities include increased fruits, nonstarchy vegetables, nuts, legumes, fish, vegetable oils, yogurt, and minimally processed whole grains; and fewer red meats, processed (eg, sodium-preserved) meats, and foods rich in refined grains, starch, added sugars, salt, and trans fat. More investigation is needed on the cardiometabolic effects of phenolics, dairy fat, probiotics, fermentation, coffee, tea, cocoa, eggs, specific vegetable and tropical oils, vitamin D, individual fatty acids, and diet-microbiome interactions. Little evidence to date supports the cardiometabolic relevance of other popular priorities: eg, local, organic, grass-fed, farmed/wild, or non-genetically modified. Evidence-based personalized nutrition appears to depend more on nongenetic characteristics (eg, physical activity, abdominal adiposity, gender, socioeconomic status, culture) than genetic factors. Food choices must be strongly supported by clinical behavior change efforts, health systems reforms, novel technologies, and robust policy strategies targeting economic incentives, schools and

  19. Overlapping neural circuitry for narrative comprehension and proficient reading in children and adolescents.

    Science.gov (United States)

    Horowitz-Kraus, Tzipi; Vannest, Jennifer J; Holland, Scott K

    2013-11-01

    Narrative comprehension is a perinatal linguistic ability which is more intuitive than reading activity. Whether there are specific shared brain regions for narrative comprehension and reading that are tuned to reading proficiency, even before reading is acquired, is the question of the current study. We acquired fMRI data during a narrative comprehension task at two age points, when children are age 5-7 (K-2nd grade) and later when the same children were age 11 (5th-7th grade). We then examined correlations between this fMRI data and reading and reading comprehension scores from the same children at age 11. We found that greater frontal and supramarginal gyrus (BA 40) activation in narrative comprehension at the age of 5-7 years old was associated with better word reading and reading comprehension scores at the age of 11. A shift towards temporal and occipital activation was found when correlating their narrative comprehension functional data at age 11, with reading scores at the same age point. We suggest that increased reliance on executive functions and auditory-visual networks when listening to stories before reading is acquired, facilitates reading proficiency in older age and may be a biomarker for future reading ability. Children, who rely on use of imagination/visualization as well as auditory processing for narrative comprehension when they reach age 11, also show greater reading abilities. Understanding concordant neural pathways supporting auditory narrative and reading comprehension might be guide for development of effective tools for reading intervention programs. Published by Elsevier Ltd.

  20. Simultaneous measurements of auto-immune and infectious disease specific antibodies using a high throughput multiplexing tool.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Considering importance of ganglioside antibodies as biomarkers in various immune-mediated neuropathies and neurological disorders, we developed a high throughput multiplexing tool for the assessment of gangliosides-specific antibodies based on Biolpex/Luminex platform. In this report, we demonstrate that the ganglioside high throughput multiplexing tool is robust, highly specific and demonstrating ∼100-fold higher concentration sensitivity for IgG detection than ELISA. In addition to the ganglioside-coated array, the high throughput multiplexing tool contains beads coated with influenza hemagglutinins derived from H1N1 A/Brisbane/59/07 and H1N1 A/California/07/09 strains. Influenza beads provided an added advantage of simultaneous detection of ganglioside- and influenza-specific antibodies, a capacity important for the assay of both infectious antigen-specific and autoimmune antibodies following vaccination or disease. Taken together, these results support the potential adoption of the ganglioside high throughput multiplexing tool for measuring ganglioside antibodies in various neuropathic and neurological disorders.