Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease

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Green, A; Thompson, E; Stewart, G; Zeidler, M; McKenzie, J; MacLeod, M; Ironside, J; Will, R; Knight, R

2001-01-01

OBJECTIVES—The detection of the protein 14-3-3 in the CSF has been shown to be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD). Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and tau protein have also been reported to be increased in the CSF of patients with sporadic CJD. In 1996a variant of CJD (vCJD) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. This study reports and compares the findings of CSF brain specific protein analysis in 45 patients with vCJD and in 34 control patients.
METHODS—The CSF from 45 patients with vCJD and 34 controls were investigated for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoassays.
RESULTS—Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in CSF were significantly raised in patients with vCJD compared with controls. The positive predictive value of CSF 14-3-3 was 86% and the negative predictive value was 63%. These values are lower than those reported for sporadic CJD. An increased CSF tau had a positive predictive value of 93% and a negative predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau had a positive predictive value of 91% and a negative predictive value of 84%.
CONCLUSIONS—CSF protein 14-3-3 is not as useful a marker for vCJD as it is for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive marker of vCJD but as concentrations may be increased in many forms of non-CJD dementia, this may limit its usefulness as a diagnostic test.

 PMID:11385008

Constant Transmission Properties of Variant Creutzfeldt-Jakob Disease in 5 Countries

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Diack, Abigail B.; Ritchie, Diane; Bishop, Matthew; Pinion, Victoria; Brandel, Jean-Philippe; Haik, Stephane; Tagliavini, Fabrizio; Van Duijn, Cornelia; Belay, Ermias D.; Gambetti, Pierluigi; Schonberger, Lawrence B.; Piccardo, Pedro; Will, Robert G.

2012-01-01

Variant Creutzfeldt-Jakob disease (vCJD) has been reported in 12 countries. We hypothesized that a common strain of agent is responsible for all vCJD cases, regardless of geographic origin. To test this hypothesis, we inoculated strain-typing panels of wild-type mice with brain material from human vCJD case-patients from France, the Netherlands, Italy, and the United States. Mice were assessed for clinical disease, neuropathologic changes, and glycoform profile; results were compared with those for 2 reference vCJD cases from the United Kingdom. Transmission to mice occurred from each sample tested, and data were similar between non-UK and UK cases, with the exception of the ranking of mean clinical incubation times of mouse lines. These findings support the hypothesis that a single strain of infectious agent is responsible for all vCJD infections. However, differences in incubation times require further subpassage in mice to establish any true differences in strain properties between cases. PMID:23017202

Recent US Case of Variant Creutzfeldt-Jakob Disease-Global Implications.

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Maheshwari, Atul; Fischer, Michael; Gambetti, Pierluigi; Parker, Alicia; Ram, Aarthi; Soto, Claudio; Concha-Marambio, Luis; Cohen, Yvonne; Belay, Ermias D; Maddox, Ryan A; Mead, Simon; Goodman, Clay; Kass, Joseph S; Schonberger, Lawrence B; Hussein, Haitham M

2015-05-01

Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient's exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD.

Detection of prions in blood from patients with variant Creutzfeldt-Jakob disease.

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Concha-Marambio, Luis; Pritzkow, Sandra; Moda, Fabio; Tagliavini, Fabrizio; Ironside, James W; Schulz, Paul E; Soto, Claudio

2016-12-21

Human prion diseases are infectious and invariably fatal neurodegenerative diseases. They include sporadic Creutzfeldt-Jakob disease (sCJD), the most common form, and variant CJD (vCJD), which is caused by interspecies transmission of prions from cattle infected by bovine spongiform encephalopathy. Development of a biochemical assay for the sensitive, specific, early, and noninvasive detection of prions (PrP Sc ) in the blood of patients affected by prion disease is a top medical priority to increase the safety of the blood supply. vCJD has already been transmitted from human to human by blood transfusion, and the number of asymptomatic carriers of vCJD in the U.K. alone is estimated to be 1 in 2000 people. We used the protein misfolding cyclic amplification (PMCA) technique to analyze blood samples from 14 cases of vCJD and 153 controls, including patients affected by sCJD and other neurodegenerative or neurological disorders as well as healthy subjects. Our results showed that PrP Sc could be detected with 100% sensitivity and specificity in blood samples from vCJD patients. Detection was possible in any of the blood fractions analyzed and could be done with as little as a few microliters of sample volume. The PrP Sc concentration in blood was estimated to be ~0.5 pg/ml. Our findings suggest that PMCA may be useful for premortem noninvasive diagnosis of vCJD and to identify prion contamination of the blood supply. Further studies are needed to fully validate the technology. Copyright © 2016, American Association for the Advancement of Science.

Geographic exposure risk of variant Creutzfeldt-Jakob disease in US blood donors: a risk-ranking model to evaluate alternative donor-deferral policies.

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Yang, Hong; Huang, Yin; Gregori, Luisa; Asher, David M; Bui, Travis; Forshee, Richard A; Anderson, Steven A

2017-04-01

Variant Creutzfeldt-Jakob disease (vCJD) has been transmitted by blood transfusion (TTvCJD). The US Food and Drug Administration (FDA) recommends deferring blood donors who resided in or traveled to 30 European countries where they may have been exposed to bovine spongiform encephalopathy (BSE) through beef consumption. Those recommendations warrant re-evaluation, because new cases of BSE and vCJD have markedly abated. The FDA developed a risk-ranking model to calculate the geographic vCJD risk using country-specific case rates and person-years of exposure of US blood donors. We used the reported country vCJD case rates, when available, or imputed vCJD case rates from reported BSE and UK beef exports during the risk period. We estimated the risk reduction and donor loss should the deferral be restricted to a few high-risk countries. We also estimated additional risk reduction by leukocyte reduction (LR) of red blood cells (RBCs). The United Kingdom, Ireland, and France had the greatest vCJD risk, contributing approximately 95% of the total risk. The model estimated that deferring US donors who spent extended periods of time in these three countries, combined with currently voluntary LR (95% of RBC units), would reduce the vCJD risk by 89.3%, a reduction similar to that achieved under the current policy (89.8%). Limiting deferrals to exposure in these three countries would potentially allow donations from an additional 100,000 donors who are currently deferred. Our analysis suggests that a deferral option focusing on the three highest risk countries would achieve a level of blood safety similar to that achieved by the current policy. © 2016 AABB.

Human prion diseases in the United States.

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Robert C Holman

Full Text Available BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD, occurs worldwide. Variant CJD (vCJD, a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths. The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8% of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%; the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively. Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study.

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Balendra, Rubika; Uphill, James; Collinson, Claire; Druyeh, Ronald; Adamson, Gary; Hummerich, Holger; Zerr, Inga; Gambetti, Pierluigi; Collinge, John; Mead, Simon

2016-04-07

Human prion diseases are relentlessly progressive neurodegenerative disorders which include sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). Aside from variants of the prion protein gene (PRNP) replicated association at genome-wide levels of significance has proven elusive. A recent association study identified variants in or near to the PLCXD3 gene locus as strong disease risk factors in multiple human prion diseases. This study claimed the first non-PRNP locus to be highly significantly associated with prion disease in genomic studies. A sub-study of a genome-wide association study with imputation aiming to replicate the finding at PLCXD3 including 129 vCJD and 2500 sCJD samples. Whole exome sequencing to identify rare coding variants of PLCXD3. Imputation of relevant polymorphisms was accurate based on wet genotyping of a sample. We found no supportive evidence that PLCXD3 variants are associated with disease. The marked discordance in vCJD genotype frequencies between studies, despite extensive overlap in vCJD cases, and the finding of Hardy-Weinberg disequilibrium in the original study, suggests possible reasons for the discrepancies between studies.

Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

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Maxime Belondrade

Full Text Available The prevalence of variant Creutzfeldt-Jakob disease (vCJD in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA. This assay allowed the specific detection of minute quantities (10-8 brain dilution of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

The First Report of a Patient with Probable Variant Creutzfeldt-Jakob Disease in Turkey

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Demet Özbabalık Adapınar

2011-12-01

Full Text Available Variant Creutzfeldt-Jakob disease (vCJD was first reported in the UK in 1996. Here, we report the first Turkish case of vCJD. A 47-year-old man, who has never lived outside of Turkey and had had no transfusion, was admitted to the University Hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. The immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. Brain magnetic resonance imaging revealed high-signal lesions involving the bilateral caudate and lentiform nucleus on T2- and diffusion-weighted imaging. The patient developed akinetic mutism 10 months after disease onset. The clinical presentation and neuroimaging findings were compatible with the vCJD cases reported since 1996 and met the World Health Organization’s case definition for probable vCJD.

Phase I/II safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.

LENUS (Irish Health Repository)

Cahill, M R

2010-08-01

Variant Creutzfeldt-Jakob (vCJD) is a fatal transfusion transmissible prion infection. No test for vCJD in the donor population is currently available. Therefore, prion removal by filtration of red cell concentrate (RCC) is an attractive option for prevention.

Short TE quantitative proton magnetic resonance spectroscopy in variant Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Cordery, R.J.; Godbolt, A.; Rossor, M.N.; MacManus, D.; Waldman, A.D.

2006-01-01

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegerative disorder. Clinical diagnosis is difficult in the early stages as the disease often presents with non-specific psychiatric and neurological symptoms. To investigate the diagnostic potential of quantitative short TE in vivo MRS, and the nature and anatomical distribution of biochemical abnormalities in vCJD, localised single-voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions: thalami, caudate nuclei and frontal white matter. Metabolite concentrations and ratios from three patients with definite or probable vCJD were compared with eight normal age-matched controls. Abnormal signal on T2-weighted MRI was apparent in the pulvinar region in all vCJD patients; this region also showed greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N-acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate nuclei. The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination. (orig.)

Short TE quantitative proton magnetic resonance spectroscopy in variant Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Cordery, R.J.; Godbolt, A.; Rossor, M.N. [University College London, Dementia Research Group, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); MacManus, D. [University College London, NMR Research Unit, Department of Clinical Neurology,Institute of Neurology, London (United Kingdom); Waldman, A.D. [University College London, Dementia Research Group, Institute of Neurology, London (United Kingdom); Imperial College of Science, Technology and Medicine, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, London (United Kingdom); Charing Cross Hospital, Department of Imaging, London (United Kingdom); National Hospital for Neurology and Neurosurgery, Dementia Research Group, London (United Kingdom)

2006-08-15

Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegerative disorder. Clinical diagnosis is difficult in the early stages as the disease often presents with non-specific psychiatric and neurological symptoms. To investigate the diagnostic potential of quantitative short TE in vivo MRS, and the nature and anatomical distribution of biochemical abnormalities in vCJD, localised single-voxel spectra (TE/TR 30 ms/2,000 ms) were acquired from three brain regions: thalami, caudate nuclei and frontal white matter. Metabolite concentrations and ratios from three patients with definite or probable vCJD were compared with eight normal age-matched controls. Abnormal signal on T2-weighted MRI was apparent in the pulvinar region in all vCJD patients; this region also showed greatly increased myo-inositol [MI] (mean 2.5-fold, P=0.01) and decreased N-acetyl-aspartate (NAA; mean 2-fold, P=0.01). Two patients also showed increased [MI] (z=17, 11; one with decreased NAA, z=-12) in normal-appearing caudate nuclei. The magnitude of metabolite abnormalities in the thalami in moderately advanced vCJD suggests a potential role in earlier diagnosis. Short TE protocols allow the measurement of MI, which adds discriminant power to the MRS examination. (orig.)

Quantitative Risk Assessment of Bovine Spongiform Encephalopathy

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Tsutsui, Toshiyuki; Kasuga, Fumiko

Bovine spongiform encephalopathy (BSE) is a progressive neurological disease of cattle affecting the central nervous system and was first diagnosed in the United Kingdom (UK) in 1986 (Wells et al., 1987). This disease is one of the transmissible spongiform encephalopathy (TSE) which includes Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep. The causative agent of TSE is considered to be an abnormal form of prion protein. However, the details of its pathogenic mechanism have not been fully identified. Scrapie, which causes neurological symptoms in sheep and goats, has existed in the UK for 200 years (Hoinville, 1996) and spread across the rest of the world in the 1900s (Detwiler & Baylis, 2003). There has been no report so far that scrapie can be transmitted to humans. Initially, BSE was also considered as a disease affecting only animals. However, a variant type of Creutzfeldt-Jakob disease (vCJD) was first reported in the UK, and exposure to a BSE agent was suspected (Collinge, Sidle, Meads, Ironside, & Hill, 1996). vCJD is clinically and pathologically different from the sporadic type of CJD, and age at clinical onset of vCJD is younger than sporadic type (Will et al., 1996). Since the UK government announced the possible association between BSE and vCJD in 1996, BSE has become a huge public health concern all over the world. Of particular concern about vCJD, the fatal disease in younger age, distorted consumer confidence in beef safety, and as a result reduced beef consumption has been seen in many BSE-affected countries.

Psychiatric symptoms in patients with sporadic Creutzfeldt-Jakob disease in Germany.

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Krasnianski, Anna; Bohling, Geeske T; Harden, Markus; Zerr, Inga

2015-09-01

Psychiatric symptoms in sporadic Creutzfeldt-Jakob disease (sCJD) are still not sufficiently evaluated. To describe psychiatric symptoms in sCJD with respect to molecular subtype. Patients in this retrospective study were classified according to established diagnostic criteria. 248 sCJD patients with known molecular subtype were recruited from January 1993 to December 2004 and investigated. Psychiatric symptoms were defined according to Möller and colleagues and the AMDP system (Study Group for Methods and Documentation in Psychiatry) and were collected by direct examination by study physicians or extracted from medical documentation. Our data were compared with published data on variant CJD (vCJD). Psychiatric symptoms were common in sCJD patients (90%) and mostly found already at the disease onset (agitation in 64% of the patients, hallucinations in 45%, anxiety in 50%, depression in 37%). All psychiatric symptoms but illusions were found early in the disease course. Psychiatric symptoms in sCJD were less frequent than in vCJD. We provide the first detailed analysis of psychiatric symptoms in a large group of patients with sCJD with respect to differences concerning frequency and time point of occurrence of psychiatric symptoms between molecular subtypes. These data suggest that psychiatric symptoms occurring early in the disease course are common not only in vCJD but also in other CJD types. © Copyright 2015 Physicians Postgraduate Press, Inc.

Similarities of Variant Creutzfeldt-Jakob Disease Strain in Mother and Son in Spain to UK Reference Case.

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Diack, Abigail B; Boyle, Aileen; Ritchie, Diane; Plinston, Chris; Kisielewski, Dorothy; de Pedro-Cuesta, Jesús; Rábano, Alberto; Will, Robert G; Manson, Jean C

2017-09-01

We investigated transmission characteristics of variant Creutzfeldt-Jakob disease in a mother and son from Spain. Despite differences in patient age and disease manifestations, we found the same strain properties in these patients as in UK vCJD cases. A single strain of agent appears to be responsible for all vCJD cases to date.

Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease.

Science.gov (United States)

Fernández-Borges, Natalia; Espinosa, Juan Carlos; Marín-Moreno, Alba; Aguilar-Calvo, Patricia; Asante, Emmanuel A; Kitamoto, Tetsuyuki; Mohri, Shirou; Andréoletti, Olivier; Torres, Juan María

2017-09-01

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met 129 ) or valine (Val 129 ) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met 129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val 129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met 129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val 129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val 129 Hu-PrP-positive humans with the emergence of new strain features.

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

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Sanchez-Juan Pascual

2008-04-01

Full Text Available Abstract Background Variant Creutzfeldt-Jakob disease (vCJD originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571 previously examined in Alzheimer's disease (AD. Methods Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression. Results There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype. Conclusion This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.

MRI of Creutzfeldt-Jakob disease: Imaging features and recommended MRI protocol

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Collie, D.A.; Sellar, R.J.; Zeidler, M.; Colchester, A.C.F.; Knight, R.; Will, R.G

2001-09-01

Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease. Collie, D.A. et al. (2001)

MRI of Creutzfeldt-Jakob disease: Imaging features and recommended MRI protocol

International Nuclear Information System (INIS)

Collie, D.A.; Sellar, R.J.; Zeidler, M.; Colchester, A.C.F.; Knight, R.; Will, R.G.

2001-01-01

Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease. Collie, D.A. et al. (2001)

Insights into the management of emerging infections: regulating variant Creutzfeldt-Jakob disease transfusion risk in the UK and the US.

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Maya L Ponte

2006-10-01

products for possible vCJD contamination in the UK, contributed to a greater sense of urgency and a speedier implementation of regulations in that country. Third, while the results of scientific studies played a prominent role in the construction of regulations in both nations, this role was shaped by existing social and professional networks. In the UK, early focus on a European study implicating B-lymphocytes as the carrier of prion infectivity in blood led to the introduction of a policy that requires universal leukoreduction of blood components. In the US, early focus on an American study highlighting the ability of plasma to serve as a reservoir of prion infectivity led the FDA and its advisory panel to eschew similar measures.The results of this study yield three important theoretical insights that pertain to the global management of emerging infectious diseases. First, because the perception and management of disease may be shaped by previous experience with disease, especially catastrophic experience, there is always the possibility for over-management of some possible routes of transmission and relative neglect of others. Second, local specificities within a given nation may influence the temporality of decision making, which in turn may influence the choice of disease management policies. Third, a preference for science-based risk management among nations will not necessarily lead to homogeneous policies. This is because the exposure to and interpretation of scientific results depends on the existing social and professional networks within a given nation. Together, these theoretical insights provide a framework for analyzing and anticipating potential conflicts in the international management of emerging infectious diseases. In addition, this study illustrates the utility of qualitative methods in investigating research questions that are difficult to assess through quantitative means.

Insights into the management of emerging infections: regulating variant Creutzfeldt-Jakob disease transfusion risk in the UK and the US.

Science.gov (United States)

Ponte, Maya L

2006-10-01

vCJD contamination in the UK, contributed to a greater sense of urgency and a speedier implementation of regulations in that country. Third, while the results of scientific studies played a prominent role in the construction of regulations in both nations, this role was shaped by existing social and professional networks. In the UK, early focus on a European study implicating B-lymphocytes as the carrier of prion infectivity in blood led to the introduction of a policy that requires universal leukoreduction of blood components. In the US, early focus on an American study highlighting the ability of plasma to serve as a reservoir of prion infectivity led the FDA and its advisory panel to eschew similar measures. The results of this study yield three important theoretical insights that pertain to the global management of emerging infectious diseases. First, because the perception and management of disease may be shaped by previous experience with disease, especially catastrophic experience, there is always the possibility for over-management of some possible routes of transmission and relative neglect of others. Second, local specificities within a given nation may influence the temporality of decision making, which in turn may influence the choice of disease management policies. Third, a preference for science-based risk management among nations will not necessarily lead to homogeneous policies. This is because the exposure to and interpretation of scientific results depends on the existing social and professional networks within a given nation. Together, these theoretical insights provide a framework for analyzing and anticipating potential conflicts in the international management of emerging infectious diseases. In addition, this study illustrates the utility of qualitative methods in investigating research questions that are difficult to assess through quantitative means.

Radiological assessment of Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Tschampa, Henriette J.; Urbach, Horst [University of Bonn, Department of Radiology, Bonn (Germany); Zerr, Inga [University of Goettingen, National Reference Center for TSE Surveillance at the Department of Neurology, Goettingen (Germany)

2007-05-15

Creutzfeldt-Jakob disease is a rare fatal neurodegenerative disorder, characterized by rapidly progressive dementia and neurological signs. There is a need for early and accurate clinical diagnosis in order to exclude any treatable disorder. Additionally, it is of public interest to differentiate the sporadic form of the disease from the variant CJD type (vCJD), which is probably transmitted from cattle infected with bovine spongiform encephalopathy (BSE). High signal in the striatum on T2-weighted, FLAIR and diffusion weighted (DW) MRI as well as cortical high signal in FLAIR and DW MRI are the classical findings in sCJD. The ''pulvinar sign'', defined as high signal in the pulvinar thalami that is brighter than potential additional high signal in the basal ganglia, is considered pathognomonic for vCJD. (orig.)

Radiological assessment of Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Tschampa, Henriette J.; Urbach, Horst; Zerr, Inga

2007-01-01

Creutzfeldt-Jakob disease is a rare fatal neurodegenerative disorder, characterized by rapidly progressive dementia and neurological signs. There is a need for early and accurate clinical diagnosis in order to exclude any treatable disorder. Additionally, it is of public interest to differentiate the sporadic form of the disease from the variant CJD type (vCJD), which is probably transmitted from cattle infected with bovine spongiform encephalopathy (BSE). High signal in the striatum on T2-weighted, FLAIR and diffusion weighted (DW) MRI as well as cortical high signal in FLAIR and DW MRI are the classical findings in sCJD. The ''pulvinar sign'', defined as high signal in the pulvinar thalami that is brighter than potential additional high signal in the basal ganglia, is considered pathognomonic for vCJD. (orig.)

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

Science.gov (United States)

Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

2013-01-01

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

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Julie Nemecek

Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

Preclinical deposition of pathological prion protein in muscle of experimentally infected primates.

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Susanne Krasemann

Full Text Available Prion diseases are transmissible fatal neurodegenerative disorders affecting humans and animals. A central step in disease progression is the accumulation of a misfolded form (PrP(Sc of the host encoded prion protein (PrP(C in neuronal and non-neuronal tissues. The involvement of peripheral tissues in preclinical states increases the risk of accidental transmission. On the other hand, detection of PrP(Sc in non-neuronal easy-accessible compartments such as muscle may offer a novel diagnostic tool. Primate models have proven invaluable to investigate prion diseases. We have studied the deposition of PrP(Sc in muscle and central nervous system of rhesus monkeys challenged with sporadic Creutzfeldt-Jakob disease (sCJD, variant CJD (vCJD and bovine spongiform encephalopathy (BSE in preclinical and clinical stage using biochemical and morphological methods. Here, we show the preclinical presence of PrP(Sc in muscle and central nervous system of rhesus monkeys experimentally infected with vCJD.

The French surveillance network of Creutzfeldt-Jakob disease. Epidemiological data in France and worldwide.

Science.gov (United States)

Brandel, J-P; Peckeu, L; Haïk, S

2013-09-01

France, involved for a long time in the epidemiological surveillance of transmissible spongiform encephalopathy (TSE), created a national network of surveillance in 1991, because of the description of the first cases of Creutzfeldt-Jakob disease (CJD) linked to a treatment by growth hormone of human origin and the observation of cases of cats infected with the agent of the bovine spongiform encephalopathy in the United Kingdom (UK). The French surveillance network is integrated into the European network of surveillance since its creation in 1993. As in other countries, sporadic CJD is the most frequent form of TSE in France with an annual mortality rate of 1.44 per million. Genetic forms are most often associated with a mutation at codon 200. Among the cases of iatrogenic CJD, 13 cases of CJD after duramater grafts were observed and 119 related to treatment with growth hormone. France is the country worst affected in Europe and the world by this latter form, before the USA and UK. Since 1996, 27 cases of variant of CJD (vCJD) has been observed, making France the second country in the world most affected after the UK. No cases of transfusion-associated vCJD have been observed. Copyright © 2013. Published by Elsevier SAS.

Factors determining the potential for onward transmission of variant Creutzfeldt–Jakob disease via surgical instruments

Science.gov (United States)

Garske, Tini; Ward, Hester J.T; Clarke, Paul; Will, Robert G; Ghani, Azra C

2006-01-01

While the number of variant Creutzfeldt–Jakob disease (vCJD) cases continues to decline, concern has been raised that transmission could occur directly from one person to another through routes including the transfer of blood and shared use of surgical instruments. Here we firstly present data on the surgical procedures undertaken on vCJD patients prior to onset of clinical symptoms, which supports the hypothesis that cases via this route are possible. We then apply a mathematical framework to assess the potential for self-sustaining epidemics via surgical procedures. Data from hospital episode statistics on the rates of high- and medium-risk procedures in the UK were used to estimate model parameters, and sensitivity to other unknown parameters about surgically transmitted vCJD was assessed. Our results demonstrate that a key uncertainty determining the scale of an epidemic and whether it is self-sustaining is the number of times a single instrument is re-used, alongside the infectivity of contaminated instruments and the effectiveness of cleaning. A survey into the frequency of re-use of surgical instruments would help reduce these uncertainties. PMID:17015298

The Structural Stability of Wild-type Horse Prion Protein - Molecular Dynamics Studies

OpenAIRE

Zhang, Jiapu

2011-01-01

Prion diseases {\\it (e.g. Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD), Gerstmann-Str$\\ddot{\\text{a}}$ussler-Scheinker syndrome (GSS), Fatal Familial Insomnia (FFI) and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE or `mad-cow' disease) and chronic wasting disease (CWD) in cattles)} are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. However, by now there have not been some effective therapeutic approaches or med...

Plasminogen-based capture combined with amplification technology for the detection of PrP(TSE in the pre-clinical phase of infection.

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Christiane Segarra

Full Text Available BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD is a neurodegenerative infectious disorder, characterized by a prominent accumulation of pathological isoforms of the prion protein (PrP(TSE in the brain and lymphoid tissues. Since the publication in the United Kingdom of four apparent vCJD cases following transfusion of red blood cells and one apparent case following treatment with factor VIII, the presence of vCJD infectivity in the blood seems highly probable. For effective blood testing of vCJD individuals in the preclinical or clinical phase of infection, it is considered necessary that assays detect PrP(TSE concentrations in the femtomolar range. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a three-step assay that firstly captures PrP(TSE from infected blood using a plasminogen-coated magnetic-nanobead method prior to its serial amplification via protein misfolding cyclic amplification (PMCA and specific PrP(TSE detection by western blot. We achieved a PrP(TSE capture yield of 95% from scrapie-infected material. We demonstrated the possibility of detecting PrP(TSE in white blood cells, in buffy coat and in plasma isolated from the blood of scrapie-infected sheep collected at the pre-clinical stage of the disease. The test also allowed the detection of PrP(TSE in human plasma spiked with a 10(-8 dilution of vCJD-infected brain homogenate corresponding to the level of sensitivity (femtogram required for the detection of the PrP(TSE in asymptomatic carriers. The 100% specificity of the test was revealed using a blinded panel comprising 96 human plasma samples. CONCLUSION/SIGNIFICANCE: We have developed a sensitive and specific amplification assay allowing the detection of PrP(TSE in the plasma and buffy coat fractions of blood collected at the pre-clinical phase of the disease. This assay represents a good candidate as a confirmatory assay for the presence of PrP(TSE in blood of patients displaying positivity in large scale screening

A Low-Molecular-Weight Ferroxidase Is Increased in the CSF of sCJD Cases: CSF Ferroxidase and Transferrin as Diagnostic Biomarkers for sCJD

Science.gov (United States)

Haldar, Swati; Beveridge, ’Alim J.; Wong, Joseph; Singh, Ajay; Galimberti, Daniela; Borroni, Barbara; Zhu, Xiongwei; Blevins, Janis; Greenlee, Justin; Perry, George; Mukhopadhyay, Chinmay K.; Schmotzer, Christine

2013-01-01

Abstract Aims: Most biomarkers used for the premortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are surrogate in nature, and provide suboptimal sensitivity and specificity. Results: We report that CJD-associated brain iron dyshomeostasis is reflected in the cerebrospinal fluid (CSF), providing disease-specific diagnostic biomarkers. Analysis of 290 premortem CSF samples from confirmed cases of CJD, Alzheimer's disease, and other dementias (DMs), and 52 non-DM (ND) controls revealed a significant difference in ferroxidase (Frx) activity and transferrin (Tf) levels in sporadic Creutzfeldt-Jakob disease (sCJD) relative to other DM and ND controls. A combination of CSF Frx and Tf discriminated sCJD from other DMs with a sensitivity of 86.8%, specificity of 92.5%, accuracy of 88.9%, and area-under-the receiver-operating-characteristic (ROC) curve of 0.94. This combination provided a similar diagnostic accuracy in discriminating CJD from rapidly progressing cases who died within 6 months of sample collection. Surprisingly, ceruloplasmin and amyloid precursor protein, the major brain Frxs, displayed minimal activity in the CSF. Most of the Frx activity was concentrated in the <3-kDa fraction in normal and diseased CSF, and resisted heat and proteinase-K treatment. Innovation: (i) A combination of CSF Frx and Tf provides disease-specific premortem diagnostic biomarkers for sCJD. (ii) A novel, nonenzymatic, nonprotein Frx predominates in human CSF that is distinct from the currently known CSF Frxs. Conclusion: The underlying cause of iron imbalance is distinct in sCJD relative to other DMs associated with the brain iron imbalance. Thus, change in the CSF levels of iron-management proteins can provide disease-specific biomarkers and insight into the cause of iron imbalance in neurodegenerative conditions. Antioxid. Redox Signal. 19, 1662–1675. PMID:23379482

Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases

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Silvia Vanni

2018-01-01

Full Text Available Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively and in different genetic forms of prion diseases (gPrD in comparison to Alzheimer's disease (AD subjects and age-matched controls.Methods: Total RNA was obtained from the frontal cortex of vCJD (n = 20, iCJD (n = 11, sCJD (n = 23, gPrD (n = 30, and AD (n = 14 patients and age-matched controls (n = 30. RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis.Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level.Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue—together with specific molecular and conformational features of the pathological agent of the disease—seem to dictate the peculiar

Hemoglobin mRNA Changes in the Frontal Cortex of Patients with Neurodegenerative Diseases.

Science.gov (United States)

Vanni, Silvia; Zattoni, Marco; Moda, Fabio; Giaccone, Giorgio; Tagliavini, Fabrizio; Haïk, Stéphane; Deslys, Jean-Philippe; Zanusso, Gianluigi; Ironside, James W; Carmona, Margarita; Ferrer, Isidre; Kovacs, Gabor G; Legname, Giuseppe

2018-01-01

Background: Hemoglobin is the major protein found in erythrocytes, where it acts as an oxygen carrier molecule. In recent years, its expression has been reported also in neurons and glial cells, although its role in brain tissue remains still unknown. Altered hemoglobin expression has been associated with various neurodegenerative disorders. Here, we investigated hemoglobin mRNA levels in brains of patients affected by variant, iatrogenic, and sporadic forms of Creutzfeldt-Jakob disease (vCJD, iCJD, sCJD, respectively) and in different genetic forms of prion diseases (gPrD) in comparison to Alzheimer's disease (AD) subjects and age-matched controls. Methods: Total RNA was obtained from the frontal cortex of vCJD ( n = 20), iCJD ( n = 11), sCJD ( n = 23), gPrD ( n = 30), and AD ( n = 14) patients and age-matched controls ( n = 30). RT-qPCR was performed for hemoglobin transcripts HBB and HBA1/2 using four reference genes for normalization. In addition, expression analysis of the specific erythrocyte marker ALAS2 was performed in order to account for blood contamination of the tissue samples. Hba1/2 and Hbb protein expression was then investigated with immunofluorescence and confocal microscope analysis. Results: We observed a significant up-regulation of HBA1/2 in vCJD brains together with a significant down-regulation of HBB in iCJD. In addition, while in sporadic and genetic forms of prion disease hemoglobin transcripts did not shown any alterations, both chains display a strong down-regulation in AD brains. These results were confirmed also at a protein level. Conclusions: These data indicate distinct hemoglobin transcriptional responses depending on the specific alterations occurring in different neurodegenerative diseases. In particular, the initial site of misfolding event (central nervous system vs. peripheral tissue)-together with specific molecular and conformational features of the pathological agent of the disease-seem to dictate the peculiar hemoglobin

SCREENING FOR GENETIC CHANGES AND CODON 129 POLYMORPHISM IN PRNP GENE IN HEALTHY SLOVENIAN POPULATION AND SPORADIC CASES OF CREUTZFELDT-JAKOB DISEASE

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Sava Smerkolj

2004-11-01

Full Text Available Background. Prion protein has an important role in development of prion diseases, fatal neurodegenerative disorders. As the codon 129 genotype of the prion protein gene (PRNP is a known susceptibility factor for the diseases, we wanted to determine its distribution in healthy Slovenian population and also in cases of sporadic Creutzfeldt-Jakob disease (sCJD. Furthermore, we wanted to screen the whole gene in order to establish the presence of genetic changes.Methods. We screened 350 DNA samples of healthy blood donors and 12 DNA samples of patients deceased of sCJD. After the amplification and conformation analysis had been done, the gene was sequenced using an automatic sequencer.Results. Methionine homozygotes comprised 46.8% of healthy population, valine homozygotes 12.1% and heterozygotes 41.1%; out of 12 sCJD patients 10 were methionine homozygotes (83.3%, 1 was valine homozygote (8.3% and 1 was heterozygote (8.3%.Found SNPs were combination of codon 76 change (228C > T and codon 84 change (252T > C in a single sample of healthy population, combination of codon 68 change (204T > C and codon 76 change (228C > T in two samples of healthy population and codon 117 change (351A > G in a healthy population sample and in a valine homozygote patient.Conclusions. In comparison to the pooled Caucasian population is genotype M/M frequency slightly increased on account of decreased genotype M/V frequency in healthy Slovenian population, suggesting a little higher risk for acquiring a new variant of CJD (vCJD, because up to date all confirmed vCJD cases except one heterozygote were methionine homozygotes. Codon 129 genotype distribution in sCJD can be described as disease-specific. The absence of pathogenic mutations in sCJD patients confirms the non-familial, sporadic disease form.

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

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Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier [Clinica Universidad de Navarra, Nuclear Medicine Department, Pamplona (Spain); Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de [Clinica Universidad de Navarra, Neurology Department, Pamplona (Spain)

2015-09-15

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

International Nuclear Information System (INIS)

Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier; Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de

2015-01-01

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

Creutzfeldt-Jakob disease in Ireland: epidemiological aspects 1980-2002.

LENUS (Irish Health Repository)

Horan, Gail

2012-02-03

Surveillance for Creutzfeldt-Jakob disease (CJD) has been carried out in the Republic of Ireland since 1980. Initial surveillance was passive and based on consented autopsy confirmation of CJD in patients in whom there was a high index of clinical suspicion. Since 1999, an active surveillance programme involving formal notification of all suspect CJD cases has been in place. The annual mortality rate has increased from 0.34 cases\\/million in 1980 to 1.27 cases\\/million in 2001. In all, 29 cases have been pathologically confirmed: 1 had variant CJD (vCJD), 1 had iatrogenic human growth hormone-induced CJD and 1 had fatal insomnia. Sporadic CJD (sCJD) accounted for the remainder. This paper details the change in incidence over 22 years as the surveillance programme in Ireland got under way; the increased incidence is attributed to better case ascertainment, as has occurred in other countries where active surveillance programmes have been established.

Minimising the risk of prion transmission by contact tonometry.

Science.gov (United States)

Amin, S Z; Smith, L; Luthert, P J; Cheetham, M E; Buckley, R J

2003-11-01

The unknown prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the UK population has led to fears of horizontal transmission through routine medical procedures. The potential risk of transmission via contact tonometry was examined. The total amount of protein carried over by tonometer tips after applanation of patients was assessed. Tonometer tips had an inherent ability to carry proteinaceous material. There was a large variability in the load carried over between individual patients. Rinsing tonometer tips in water reduced protein carryover. Wiping the tonometer tips also reduced carriage, though less dramatically. There is a small theoretical risk of transmission of vCJD by contact tonometry through reuse, but this should be reduced if the prisms are washed and wiped. In the light of these findings a protocol for the management of reusable tonometer prisms is recommended.

68 ORIGINAL ARTICLE

African Journals Online (AJOL)

Dr Oboro VO

transmitted through blood transfusion. These include. Treponema pallidum,. Plasmodium sp., human T-lymphotrophic virus (HTLV), Babesia, Leishmania,. Trypanosoma cruzi, variant Creutzfeldt-Jacob. Disease (vCJD) agent, cytomegalovirus. (CMV)and Epstein Barr virus (EBV). Therefore, the need to render donated blood.

Decreased CSF transferrin in sCJD: a potential pre-mortem diagnostic test for prion disorders.

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Ajay Singh

2011-03-01

Full Text Available Sporadic Creutzfeldt-Jakob-disease (sCJD is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a 'new' biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the 'current' biomarker total-tau (T-tau. Levels of total-Tf (T-Tf, isoforms of Tf (Tf-1 and Tf-β2, and iron saturation of Tf were quantified in CSF collected 0.3-36 months before death (duration from 99 autopsy confirmed sCJD (CJD+ and 75 confirmed cases of dementia of non-CJD origin (CJD-. Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC analysis. Area under the ROC curve (AUC, sensitivity, specificity, positive and negative predictive values (PV, and likelihood ratios (LR of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893 and higher T-tau (11530 vs. 1266 values. AUC was 0.90 (95% confidence interval (CI, 0.85-0.94 for T-Tf, and 0.93 (95% CI, 0.89-0.97 for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ∼85%, T-Tf identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7, positive LR of 3.0 (95% CI, 2.1-4.5, negative LR of 0.2 (95% CI, 0.1-0.3, and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1, positive LR of 6.8 (95% CI, 3.5-13.1, negative LR of 0.2 (95% CI, 0.1-0.3, positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.

Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

Science.gov (United States)

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

Creutzfeldt-Jakob disease lookback study: 21 years of surveillance for transfusion transmission risk.

Science.gov (United States)

Crowder, Lauren A; Schonberger, Lawrence B; Dodd, Roger Y; Steele, Whitney R

2017-08-01

Transfusion transmission of human prion diseases has been observed for variant Creutzfeldt-Jakob disease (vCJD), but not for the classic forms of prion disease (CJD: sporadic, genetic, and iatrogenic). Although the presence of prions or misfolded prion proteins in blood has been documented in some patients with the most common form of CJD, sporadic CJD, no transfusion-transmitted cases of CJD have been recognized. Since 1995, the American Red Cross has conducted a lookback study of the recipients of blood products from donors who develop CJD to assess the risk of blood-borne CJD transmission in the United States. Blood donors subsequently diagnosed with confirmed or probable CJD were enrolled and the consignees were asked to identify the recipients of their blood products. These donors' transfusion recipients are traced annually with the National Death Index to see if they subsequently die of CJD. To date, 65 CJD donors have been enrolled along with 826 of their blood recipients. These recipients have contributed 3934 person-years of follow-up and no transfusion-transmitted cases of CJD have been recognized. From this study, as well as other epidemiologic studies, there is no evidence of CJD transfusion transmission; this risk remains theoretical. © 2017 AABB.

Reduction of prion infectivity in packed red blood cells

International Nuclear Information System (INIS)

Morales, Rodrigo; Buytaert-Hoefen, Kimberley A.; Gonzalez-Romero, Dennisse; Castilla, Joaquin; Hansen, Eric T.; Hlavinka, Dennis; Goodrich, Raymond P.; Soto, Claudio

2008-01-01

The link between a new variant form of Creutzfeldt-Jakob disease (vCJD) and the consumption of prion contaminated cattle meat as well as recent findings showing that vCJD can be transmitted by blood transfusion have raised public health concerns. Currently, a reliable test to identify prions in blood samples is not available. The purpose of this study was to evaluate the possibility to remove scrapie prion protein (PrP Sc ) and infectivity from red blood cell (RBC) suspensions by a simple washing procedure using a cell separation and washing device. The extent of prion removal was assessed by Western blot, PMCA and infectivity bioassays. Our results revealed a substantial removal of infectious prions (≥3 logs of infectivity) by all techniques used. These data suggest that a significant amount of infectivity present in RBC preparations can be removed by a simple washing procedure. This technology may lead to increased safety of blood products and reduce the risk of further propagation of prion diseases.

Detection and partial discrimination of atypical and classical bovine spongiform encephalopathies in cattle and primates using real-time quaking-induced conversion assay.

Science.gov (United States)

Levavasseur, Etienne; Biacabe, Anne-Gaëlle; Comoy, Emmanuel; Culeux, Audrey; Grznarova, Katarina; Privat, Nicolas; Simoneau, Steve; Flan, Benoit; Sazdovitch, Véronique; Seilhean, Danielle; Baron, Thierry; Haïk, Stéphane

2017-01-01

The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health. Recently, methods designed to amplify misfolded forms of PrP have emerged as promising tools to detect prion strains and to study their diversity. Here, we validated real-time quaking-induced conversion assay for the discrimination of atypical and classical BSE strains using a large series of bovine samples encompassing all the atypical BSE cases detected by the French Centre of Reference during 10 years of exhaustive active surveillance. We obtained a 100% sensitivity and specificity for atypical BSE detection. In addition, the assay was able to discriminate atypical and classical BSE in non-human primates, and also sporadic CJD and vCJD in humans. The RT-QuIC assay appears as a practical means for a reliable detection of atypical BSE strains in a homologous or heterologous PrP context.

The M129V polymorphism of codon 129 in the prion gene (PRNP) in the Danish population

DEFF Research Database (Denmark)

Dyrbye, Henrik; Broholm, Helle; Dziegiel, Morten Hanefeld

2008-01-01

Since variant Creutzfeldt-Jakob disease (vCJD) was described for the first time in 1995 and fears of an epidemic ensued, the assumed culprit the prion protein (PrP) and its precursor the prion-gene (PRNP) have been subjects to intense studies. Several polymorphisms in PRNP modify disease...

Novel mutation of the PRNP gene of a clinical CJD case

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Collinge John

2006-11-01

Full Text Available Abstract Background Transmissible spongiform encephalopathies (TSEs, a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrPC. The abnormal form of prion protein, PrPSc accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP, and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs. Case presentation A 70 year old woman was admitted to the hospital with severe confusion and inability to walk. Relatives recognized memory loss, gait and behavioral disturbances over a six month period prior to hospitalization. Neurological examination revealed Creutzfeldt-Jakob disease (CJD related symptoms such as incontinence, Babinski sign and myoclonus. EEG showed periodic sharp waves typical of sporadic CJD and cerebrospinal fluid analysis (CSF was positive for the presence of the 14-3-3-protein. As the disease progressed the patient developed akinetic mutism and died in the tenth month after onset of the disease symptoms. Unfortunately, no autopsy material was available. PRNP sequencing showed the occurrence of a point mutation on one allele at codon 193, which is altered from ACC, coding for a threonine, to ATC, encoding an isoleucine (T193I. Conclusion Here we report a novel mutation of the PRNP gene found in an elderly female patient resulting in heterozygosity for isoleucine and threonine at codon 193, in which normally homozygosity for threonine is expected (T193. The patient presented typical clinical symptoms of CJD. EEG findings and the presence of the 14-3-3 protein in the CSF, contributed to CJD diagnosis, allowing the classification of this case as a probable CJD according to the World Health Organization (WHO accepted criteria.

An alarming presentation of Creutzfeldt-Jakob disease following a self-inflicted gunshot wound to the head.

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Harnish, Carissa; Gross, Brian; Rittenhouse, Katelyn; Bupp, Katherine; Vellucci, Ashley; Anderson, Jeffrey; Riley, Deborah; Rogers, Frederick B

2015-05-01

Transmissible spongiform encephalopathies (TSE), also known as prion diseases, are characterized by rapid and fatal neurological decline. They not only detrimentally affect the patient, but also present additional challenges to healthcare systems due to the infectivity of the tissues and the difficulty of inactivating the prion. The most common TSE is Creutzfeldt-Jakob disease (CJD), which can occur after familial, spontaneous or acquired transmission. TSEs received more attention after the development of variant CJD (vCJD), also known as Mad Cow Disease, in the UK during the mid-1990s. Unlike familial or spontaneous CJD, this variant was connected to consumption of cattle contaminated with the prion disease, bovine spongiform encephalopathy.This development increased interest in the etiology of CJD and other TSEs and the risk it presents as an infectious disease. The following details the case of a 59-year-old male infected with CJD presented to our level II trauma center for treatment following a self-inflicted gunshot wound to the head. Copyright © 2014 Elsevier Ltd. All rights reserved.

CJD, Progress Report, 2010/2011, Summary of nuclear data activity by staff of the IPPE CJD

International Nuclear Information System (INIS)

Blokhin, A.I.; Demin, N.A.; Gay, E.V.; Ignatyuk, A.V.; Manokhin, V.N.; Mikhaylyukova, M.V.; Pronyaev, V.G.; Zolotarev, K.I.

2012-01-01

Since last NRDC-2011 meeting the compilation in the EXFOR and the work on fulfillment of meeting's Conclusions and Actions have been done in the center. But substantial part of CJD activity was related to the nuclear data evaluation. 1) Staff 2) EXFOR activity 3) NRDC2011 actions 4) Computer and software matters. WEB-site service 5) Nuclear data evaluation activity 6) Nuclear Data services 7) Journal YK 8) Publications 9) Acknowledgments

Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD)

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Gabizon, R.; Rosenmann, H.; Meiner, Z.; Kahana, I. (Hadassah Univ., Jerusalem (Israel)); Kahana, E. (Barzilai Medical Center, Ashkelon (Israel)); Shugart, Y.; Ott, J. (Columbia Univ., New York, NY (United States)); Prusiner, S.B. (Univ. of California, San Francisco, CA (United States))

1993-10-01

The inherited prion diseases are neurodegenerative disorders which are not only genetic but also transmissible. More than a dozen mutations in the prion protein gene that result in nonconservative amino acid substitutions segregate with the inherited prion diseases including familial Creutzfeldt-Jakob disease (CJD). In Israel, the incidence of CJD is about 1 case/10[sup 4] Libyan Jews. A Lys[sub 200] substitution segregates with CJD and is reported here to be genetically linked to CJD with a lod score of >4.8. Some healthy elderly Lys[sub 200] carriers > age 65 years were identified, suggesting the possibility of incomplete penetrance. In contrast, no linkage was found between the development of familial CJD and a polymorphism encoding either Met[sub 129] or Val[sub 129]. All Libyan Jewish CJD patients with the Lys[sub 200] mutation encode a Met[sub 129] on the mutant allele. Homozygosity for Met[sub 129] did not correlate with age at disease onset or the duration of illness. The frequency of the Met[sub 129] allele was higher in the affected pedigrees than in a control population of Libyan Jews. The frequency of the Met[sub 129] and Val[sub 129] alleles in the control Libyan population was similar to that found in the general Caucasian population. The identification of three Libyan Jews homozygous for the Lys[sub 200] mutation suggests frequent intrafamilial marriages, a custom documented by genealogical investigations. 26 refs., 3 figs., 6 tabs.

Heterozygous genotype at codon 129 correlates with prolonged disease course in Heidenhain variant sporadic CJD: case report.

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Townley, Ryan A; Dawson, Elliot T; Drubach, Daniel A

2018-02-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapid and fatal neurodegenerative disease defined by misfolded prion proteins accumulating in the brain. A minority of cases initially present with posterior cortical atrophy (PCA) phenotype, also known as Heidenhain variant or visual variant CJD. This case provides further evidence of sCJD presenting as PCA. The case also provides evidence for early DWI changes and cortical atrophy over 30 months before neurologic decline and subsequent death. The prolonged disease course correlates with prion protein codon 129 heterozygosity and coexistence of multiple prion strains.

Singled out?

Science.gov (United States)

Waller, Frank

2004-03-01

The increasing use of single use medical devices is being driven by a growing awareness of iatrogenic (from the Greek; caused by the doctor) and nosocomial infections. Public health perceptions relating to transmissible spongiform encephalopathies, specifically variant Creutzfeldt-Jakob disease (vCJD), the Human Immunodeficiency Virus (HIV) and Hepatitis B are high on the political agenda and a matter of concern to healthcare professionals.

Differential overexpression of SERPINA3 in human prion diseases.

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Vanni, S; Moda, F; Zattoni, M; Bistaffa, E; De Cecco, E; Rossi, M; Giaccone, G; Tagliavini, F; Haïk, S; Deslys, J P; Zanusso, G; Ironside, J W; Ferrer, I; Kovacs, G G; Legname, G

2017-11-15

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.

R3-R4 deletion in the PRNP gene is associated with Creutzfeldt-Jakob disease (CJD)

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Cervenakova, L.; Brown, P.; Nagle, J. [and others

1994-09-01

There are conflicting reports on the association of deletions in the PRNP gene on chromosome 20 with CJD, a rapidly progressive fatal spongiform encephalopathy. We accumulated data suggesting that a deletion of R3-R4 type (parts of the third and fourth repeats are deleted from the area of four repeating 24 bp sequences in the 5{prime} region of the gene) is causing CJD. Screening of 129 unaffected control individuals demonstrated presence of a deletion of R2 type in four (1.55% of the studied chromosomes), but none of them had the R3-R4 type. Of 181 screened patients with spongiform encephalopathies, two had a deletion of R3-R4 type with no other mutations in the coding sequence. Both patients had a classical rapidly progressive dementing disease and diffuse spongiform degeneration, and both cases were apparently sporadic. The same R3-R4 type of deletion was detected in three additional neuropathologically confirmed spongiform encephalopathy patients, of which two had other known pathogenic mutations in the PRNP gene: at codon 178 on the methionine allele exhibiting the phenotype of fatal familial insomnia, and codon 200 causing CJD with severe dementia; the third was a patient with iatrogenic CJD who developed the disease after treatment with growth hormone extracted from cadaveric human pituitary glands. In all cases the deletion coincided with a variant sequence at position 129 coding for methionine.

High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions.

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Franceschini, Alessia; Baiardi, Simone; Hughson, Andrew G; McKenzie, Neil; Moda, Fabio; Rossi, Marcello; Capellari, Sabina; Green, Alison; Giaccone, Giorgio; Caughey, Byron; Parchi, Piero

2017-09-06

An early and accurate in vivo diagnosis of rapidly progressive dementia remains challenging, despite its critical importance for the outcome of treatable forms, and the formulation of prognosis. Real-Time Quaking-Induced Conversion (RT-QuIC) is an in vitro assay that, for the first time, specifically discriminates patients with prion disease. Here, using cerebrospinal fluid (CSF) samples from 239 patients with definite or probable prion disease and 100 patients with a definite alternative diagnosis, we compared the performance of the first (PQ-CSF) and second generation (IQ-CSF) RT-QuIC assays, and investigated the diagnostic value of IQ-CSF across the broad spectrum of human prions. Our results confirm the high sensitivity of IQ-CSF for detecting human prions with a sub-optimal sensitivity for the sporadic CJD subtypes MM2C and MM2T, and a low sensitivity limited to variant CJD, Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. While we found no difference in specificity between PQ-CSF and IQ-CSF, the latter showed a significant improvement in sensitivity, allowing prion detection in about 80% of PQ-CSF negative CJD samples. Our results strongly support the implementation of IQ-CSF in clinical practice. By rapidly confirming or excluding CJD with high accuracy the assay is expected to improve the outcome for patients and their enrollment in therapeutic trials.

Impact of the clinical context on the 14-3-3 test for the diagnosis of sporadic CJD

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Sierra-Moros Maríajosé

2006-07-01

Full Text Available Abstract Background The 14-3-3 test appears to be a valuable aid for the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD in selected populations. However, its usefulness in routine practice has been challenged. In this study, the influence of the clinical context on the performance of the 14-3-3 test for the diagnosis of sCJD is investigated through the analysis of a large prospective clinical series. Methods Six hundred seventy-two Spanish patients with clinically suspected sCJD were analyzed. Clinical classification at sample reception according to the World Health Organization's (WHO criteria (excluding the 14-3-3 test result was used to explore the influence of the clinical context on the pre-test probabilities, and positive (PPV and negative (NPV predictive values of the 14-3-3 test. Results Predictive values of the test varied greatly according to the initial clinical classification: PPV of 98.8%, 96.5% and 45.0%, and NPV of 26.1%, 66.6% and 100% for probable sCJDi (n = 115, possible sCJDi (n = 73 and non-sCJDi (n = 484 cases, respectively. According to multivariate and Bayesian analyses, these values represent an improvement of diagnostic certainty compared to clinical data alone. Conclusion In three different contexts of sCJD suspicion, the 14-3-3 assay provides useful information complementary to clinical and electroencephalographic (EEG data. The test is most useful supporting a clinical impression, whilst it may show deceptive when it is not in agreement with clinical data.

Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.

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Cali, Ignazio; Miller, Cathleen J; Parisi, Joseph E; Geschwind, Michael D; Gambetti, Pierluigi; Schonberger, Lawrence B

2015-06-25

The present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1). The index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1. Our study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.

Atypical Creutzfeldt-Jakob Disease Evolution after Electroconvulsive Therapy for Catatonic Depression

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Iria Grande

2011-01-01

Full Text Available We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI, diffusion changes, and electroencephalogram (EEG findings the case was reoriented to Creutzfeldt-Jakob disease (CJD. The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrPSc. On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.

The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD

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Jeong Byung-Hoon

2011-08-01

Full Text Available Abstract Background Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s modulating susceptibility to prion disease. Ribosomal protein SA (RPSA, also called 37 kDa laminin receptor precursor (LRP/67 kDa laminin receptor (LR, acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. Methods To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP analysis. Results We observed four single nucleotide polymorphisms (SNPs, including -8T>C (rs1803893 in the 5'-untranslated region (UTR of exon 2, 134-32C>T (rs3772138 in the intron, 519G>A (rs2269350 in the intron and 793+58C>T (rs2723 in the intron on the RPSA. The 519G>A (at codon 173 is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. Conclusion These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

Factors affecting the accuracy of urine-based biomarkers of BSE

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Ruddat Viola

2011-02-01

Full Text Available Abstract Background Transmissible spongiform encephalopathy diseases are untreatable, uniformly fatal degenerative syndromes of the central nervous system that can be transmitted both within as well as between species. The bovine spongiform encephalopathy (BSE epidemic and the emergence of a new human variant of Creutzfeldt-Jakob disease (vCJD, have profoundly influenced beef production processes as well as blood donation and surgical procedures. Simple, robust and cost effective diagnostic screening and surveillance tools are needed for both the preclinical and clinical stages of TSE disease in order to minimize both the economic costs and zoonotic risk of BSE and to further reduce the risk of secondary vCJD. Objective Urine is well suited as the matrix for an ante-mortem test for TSE diseases because it would permit non-invasive and repeated sampling. In this study urine samples collected from BSE infected and age matched control cattle were screened for the presence of individual proteins that exhibited disease specific changes in abundance in response to BSE infection that might form the basis of such an ante-mortem test. Results Two-dimensional differential gel electrophoresis (2D-DIGE was used to identify proteins exhibiting differential abundance in two sets of cattle. The known set consisted of BSE infected steers and age matched controls throughout the course of the disease. The blinded unknown set was composed of BSE infected and control samples of both genders, a wide range of ages and two different breeds. Multivariate analyses of individual protein abundance data generated classifiers comprised of the proteins best able to discriminate between the samples based on disease state, breed, age and gender. Conclusion Despite the presence of confounding factors, the disease specific changes in abundance exhibited by a panel of urine proteins permitted the creation of classifiers able to discriminate between control and infected cattle

Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

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Dasanu Constantin A

2010-11-01

Full Text Available Abstract Background Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" Methods Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study, and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. Results Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrPSc positive sheep (28 asymptomatic and 9 symptomatic, there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC. Conclusions Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1 that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2 that the amount of PrPSc in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.

[Basic research on BSE transmission to people].

Science.gov (United States)

Bodemer, W; Kaup, F J

2002-08-01

Prion diseases of animal and man belong to neurological diseases with amyloidal deposition of the respective proteins. As to prion disease, the cellular prionprotein is in its abnormal isoform(s) an essential component of prionprotein aggregates found in affected tissue. In contrast to all neurodegenerative diseases like Morbus Alzheimer or Huntington's disease, prion diseases are transmissible. Therefore, prion diseases were designated Transmissible Spongiform Encephalopathies (TSE). The diseases are well known since decades. Scrapie was first described around 1750, a BSE case was reported in the 1850, most likely a misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been described. Transmission of CJD i.e. Kuru had been suspected in the early 1950s and erronously classified as slow virus disease. The CJD transmission posed a problem to humans when transplants from CJD cases were used for treatment. Fortunately, these iatrogenic transmissions remained limited. But with the advent of BSE and appearance of variant CJD cases in the UK and some places in Europe scientists suspected that transmission from cattle to man could have happened. From animal models we know of successful transmission via several routes. Species barriers do not completely prevent transmission. Rather transmission barriers might exist controlling individual susceptibility against prions. Modes of transmission, susceptibility for transmission, identification of receptor molecules as well as molecular mechanisms of the transmission process are intensely investigated. Current knowledge let us to assume that inapparent stages of prion infection pretend a (not existing) species barrier. This inapparent infection preceeds overt disease and, thus, most re-search focuses on the development of highly sensitive assay systems for detection of minute amounts of pathological prionprotein in suspected cases. Inapparence also should warn us to underestimate BSE or human vCJD cases; at

Mad Cows and CJD A Physicist's View of Prion Brain Diseases

CERN Document Server

Morrison, Douglas Robert Ogston

1997-01-01

The research of Carleton Gajdusek on a stone-age tribe in Papua New Guinea, who suffered from a mysterious disease, kuru, spread by cannibalism, is described and short extracts from his films will be shown. Some deaths from kuru are still occuring after 45 years. This disease is believed to be caused by an entirely new mechanism, not a virus or bacteria, but by a small molecule known as a prion that occurs naturally in many living forms. The Prion Only hypothesis of Stan Prusiner is discussed critically. It has been calculated that 900,000 cows in Britain had the Mad Cow disease, BSE, but most were slaughtered before symptoms were recognised. This epidemic started with 10 cases in the first year, and finally 160,000 were officially classified as having BSE; it is now slowly dying out. The human epidemic, caused by a new version of Creutzfeldt-Jakob Disease, nvCJD, affects mainly young people, has just begun with 10 cases in the first year. The average incubation time may be about 14 years then death follows i...

Application of quantitative DTI metrics in sporadic CJD

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E. Caverzasi

2014-01-01

Full Text Available Diffusion Weighted Imaging is extremely important for the diagnosis of probable sporadic Jakob–Creutzfeldt disease, the most common human prion disease. Although visual assessment of DWI MRI is critical diagnostically, a more objective, quantifiable approach might more precisely identify the precise pattern of brain involvement. Furthermore, a quantitative, systematic tracking of MRI changes occurring over time might provide insights regarding the underlying histopathological mechanisms of human prion disease and provide information useful for clinical trials. The purposes of this study were: 1 to describe quantitatively the average cross-sectional pattern of reduced mean diffusivity, fractional anisotropy, atrophy and T1 relaxation in the gray matter (GM in sporadic Jakob–Creutzfeldt disease, 2 to study changes in mean diffusivity and atrophy over time and 3 to explore their relationship with clinical scales. Twenty-six sporadic Jakob–Creutzfeldt disease and nine control subjects had MRIs on the same scanner; seven sCJD subjects had a second scan after approximately two months. Cortical and subcortical gray matter regions were parcellated with Freesurfer. Average cortical thickness (or subcortical volume, T1-relaxiation and mean diffusivity from co-registered diffusion maps were calculated in each region for each subject. Quantitatively on cross-sectional analysis, certain brain regions were preferentially affected by reduced mean diffusivity (parietal, temporal lobes, posterior cingulate, thalamus and deep nuclei, but with relative sparing of the frontal and occipital lobes. Serial imaging, surprisingly showed that mean diffusivity did not have a linear or unidirectional reduction over time, but tended to decrease initially and then reverse and increase towards normalization. Furthermore, there was a strong correlation between worsening of patient clinical function (based on modified Barthel score and increasing mean diffusivity.

Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.

Science.gov (United States)

Wilson, Rona; Plinston, Chris; Hunter, Nora; Casalone, Cristina; Corona, Cristiano; Tagliavini, Fabrizio; Suardi, Silvia; Ruggerone, Margherita; Moda, Fabio; Graziano, Silvia; Sbriccoli, Marco; Cardone, Franco; Pocchiari, Maurizio; Ingrosso, Loredana; Baron, Thierry; Richt, Juergen; Andreoletti, Olivier; Simmons, Marion; Lockey, Richard; Manson, Jean C; Barron, Rona M

2012-07-01

The association between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health and raises the possibility that other ruminant TSEs may be transmissible to humans. In recent years, several novel TSEs in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. In this study, we inoculated two forms of atypical BSE (BASE and H-type BSE), a chronic wasting disease (CWD) isolate and seven isolates of atypical scrapie into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP). Upon challenge with these ruminant TSEs, gene-targeted Tg mice expressing human PrP did not show any signs of disease pathology. These data strongly suggest the presence of a substantial transmission barrier between these recently identified ruminant TSEs and humans.

Continues administration of Nano-PSO significantly increased survival of genetic CJD mice.

Science.gov (United States)

Binyamin, Orli; Keller, Guy; Frid, Kati; Larush, Liraz; Magdassi, Shlomo; Gabizon, Ruth

2017-12-01

We have shown previously that Nano-PSO, a nanodroplet formulation of pomegranate seed oil, delayed progression of neurodegeneration signs when administered for a designated period of time to TgMHu2ME199K mice, modeling for genetic prion disease. In the present work, we treated these mice with a self-emulsion formulation of Nano-PSO or a parallel Soybean oil formulation from their day of birth until a terminal disease stage. We found that long term Nano-PSO administration resulted in increased survival of TgMHu2ME199K lines by several months. Interestingly, initiation of treatment at day 1 had no clinical advantage over initiation at day 70, however cessation of treatment at 9months of age resulted in the rapid loss of the beneficial clinical effect. Pathological studies revealed that treatment with Nano-PSO resulted in the reduction of GAG accumulation and lipid oxidation, indicating a strong neuroprotective effect. Contrarily, the clinical effect of Nano-PSO did not correlate with reduction in the levels of disease related PrP, the main prion marker. We conclude that long term administration of Nano-PSO is safe and may be effective in the prevention/delay of onset of neurodegenerative conditions such as genetic CJD. Copyright © 2017. Published by Elsevier Inc.

CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

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Garcia Santos, J.M. [Servicio de Radiodiagnostico, HU Dr. Morales Meseguer, Murcia (Spain)]|[Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Lopez Corbalan, J.A. [Section of Neuroradiology, HU Virgen de la Arrixaca, Murcia (Spain); Martinez-Lage, J.F. [Service of Neurosurgery, HU Virgen de la Arrixaca, Murcia (Spain); Sicilis Guillen, J. [Service of Neurology, HU Virgen de la Arrixaca, Murcia (Spain)

1996-04-01

Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

CT and MRI in iatrogenic and sporadic Creutzfeldt-Jakob disease: as far as imaging perseives

International Nuclear Information System (INIS)

Garcia Santos, J.M.; Lopez Corbalan, J.A.; Martinez-Lage, J.F.; Sicilis Guillen, J.

1996-01-01

Creutzfeldt-Jakob Disease (CJD), an invariably fatal dementing illness, affects patients in middle and old age (sporadic form). However, the association of CJD with certain treatments (iatrogenic form) has been described in younger patients. The clinical onset of the two forms seems to differ; in the iatrogenic form a high frequency of the ataxic CJD variant has been reported. Nowadays, a definitive diagnosis of CJD is exclusively histological. We present five cases of CJD, one sporadic and the others iatrogenic, following dura mater grafts and analyse their CT and MRI features. CT typically demonstrates brain atrophy, generally progressive, but in sporadic CJD midfield MRI also showed abnormal signal, with predominant deep grey matter involvement. The use of narrow windows with proton-density sequences may reveal subtle cortical signal abnormalities not clearly visible with conventional windows. The early demonstration of these changes, in the appropriate clinical context, may suggest CJD and this supports the use of mid- or high magnetic fields in the diagnosis of CJD and other forms of dementia. In our cases of iatrogenic CJD, low-field MRI did not reveal more than the progressive atrophy displayed by CT, and raises the question on the one hand of possible differences, based on imaging, from the sporadic form, and on the other of the lack of sensitivity of low-field magnets to signal changes in CJD. (orig.)

Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE.

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Dongseob Tark

Full Text Available Bovine spongiform encephalopathy (BSE is a zoonotic transmissible spongiform encephalopathy (TSE thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD. Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

Transmission of sporadic Creutzfeldt-Jakob disease by blood transfusion: risk factor or possible biases.

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Puopolo, Maria; Ladogana, Anna; Vetrugno, Vito; Pocchiari, Maurizio

2011-07-01

The occurrence of transfusion transmissions of variant Creutzfeldt-Jakob disease (CJD) cases has reawakened attention to the possible similar risk posed by other forms of CJD. CJD with a definite or probable diagnosis (sporadic CJD, n = 741; genetic CJD, n = 175) and no-CJD patients with definite alternative diagnosis (n = 482) with available blood transfusion history were included in the study. The risk of exposure to blood transfusion occurring more than 10 years before disease onset and for some possible confounding factors was evaluated by calculating crude odds ratios (ORs). Variables with significant ORs in univariate analyses were included in multivariate logistic regression analyses. In the univariate model, blood transfusion occurring more than 10 years before clinical onset is 4.1-fold more frequent in sporadic CJD than in other neurologic disorders. This significance is lost when the 10-year lag time was not considered. Multivariate analyses show that the risk of developing sporadic CJD after transfusion increases (OR, 5.05) after adjusting for possible confounding factors. Analysis conducted on patients with genetic CJD did not reveal any significant risk factor associated with transfusion. This is the first case-control study showing a significant risk of transfusion occurring more than 10 years before clinical onset in sporadic CJD patients. It remains questionable whether the significance of these data is biologically plausible or the consequence of biases in the design of the study, but they counterbalance previous epidemiologic negative reports that might have overestimated the assessment of blood safety in sporadic CJD. © 2010 American Association of Blood Banks.

Combined Creutzfeldt-Jakob/ Alzheimer's Disease Cases are Important in Search for Microbes in Alzheimer's Disease.

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Bastian, Frank O

2017-01-01

The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD.

The price of the precautionary principle: cost-effectiveness of BSE intervention strategies in The Netherlands.

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Benedictus, A; Hogeveen, H; Berends, B R

2009-06-01

Since 1996, bovine spongiform encephalopathy (BSE) in cattle has been linked to a new variant of Creutzfeldt-Jakob disease (vCJD), a fatal brain disease in man. This paper assessed the cost-effectiveness of BSE control strategies instituted by the European Commission. In a Monte Carlo simulation model, a non-intervention baseline scenario was compared to three intervention strategies: removal of specified risk materials from slaughter animals, post-mortem testing for BSE and the culling of feed and age cohorts of BSE cases. The food risk in the baseline scenario ranged from 16.98 lost life years in 2002 to 2.69 lost life years in 2005. Removing specified risk materials removal practices, post-mortem testing and post-mortem testing plus cohort culling reduced this risk with 93%, 82.7% and 83.1%. The estimated cost-effectiveness of all BSE measures in The Netherlands ranged from 4.3 million euros per life year saved in 2002 to 17.7 million euros in 2005. It was discussed that the cost-effectiveness of BSE control strategies will further deviate from regular health economics thresholds as BSE prevalence and incidence declines.

The expanding universe of prion diseases.

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Watts, Joel C; Balachandran, Aru; Westaway, David

2006-03-01

Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C). Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE) the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases--including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and Nor98 of sheep--have been identified in the last ten years, and chronic wasting disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America. While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk) can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

Comparative evidence for a link between Peyer's patch development and susceptibility to transmissible spongiform encephalopathies

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Rhind Susan M

2006-01-01

Full Text Available Abstract Background Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE and variant CJD (vCJD, and the development of lymphoid tissue in the gut. Methods Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies for sheep, cattle and humans, we calculated the Spearman's rank correlation coefficient, rs, between available measures of Peyer's patch (PP development and the estimated risk of infection for an individual of the corresponding age. Results There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, rs = 0.913 (n = 19, P s = 0.933 (n = 19, P s = 0.693 (n = 94, P s = 0.384 (n = 46, P = 0.008. In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: rs = 0.360 (n = 46, P = 0.014. Conclusion Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

Case series of probable sporadic Creutzfeldt-Jakob disease from Eastern India

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Atanu Biswas

2013-01-01

Full Text Available Background: Creutzfeldt-Jakob disease is a rapidly progressive, fatal, transmissible neurodegenerative disorder caused by prion protein. It is still considered rare in countries like India. This is probably due to nonavailability of autopsy studies in majority of the center. The recent European diagnostic criterion for sporadic CJD (sCJD is useful for making an early diagnosis. Objective: To report a series of patients of probable sCJD from a neurology institute of eastern India. Materials and Methods: Patients of rapidly developing dementia fulfilling the diagnostic criteria for sCJD were included. All were investigated in detail to find out any possible treatable cause including electroencephalography (EEG, magnetic resonance imaging (MRI of brain, and cerebrospinal fluid analysis. Results: A total 10 patients of probable sCJD diagnosed using the European diagnostic criterion between December 2011 and January 2013. The clinical features are consistent with other reported series. While 60% of patients had the classical EEG findings, 100% had typical MRI features. Eight patients died within a mean duration of 4.56 months from the disease onset. Conclusions: The clinical features are similar to other reported series. Our observation raises question about the prevalence of this disease in India which needs more elaborate studies.

Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein.

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Sandberg, Malin K; Al-Doujaily, Huda; Sigurdson, Christina J; Glatzel, Markus; O'Malley, Catherine; Powell, Caroline; Asante, Emmanuel A; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2010-10-01

Chronic wasting disease (CWD) is a prion disease that affects free-ranging and captive cervids, including mule deer, white-tailed deer, Rocky Mountain elk and moose. CWD-infected cervids have been reported in 14 USA states, two Canadian provinces and in South Korea. The possibility of a zoonotic transmission of CWD prions via diet is of particular concern in North America where hunting of cervids is a popular sport. To investigate the potential public health risks posed by CWD prions, we have investigated whether intracerebral inoculation of brain and spinal cord from CWD-infected mule deer transmits prion infection to transgenic mice overexpressing human prion protein with methionine or valine at polymorphic residue 129. These transgenic mice have been utilized in extensive transmission studies of human and animal prion disease and are susceptible to BSE and vCJD prions, allowing comparison with CWD. Here, we show that these mice proved entirely resistant to infection with mule deer CWD prions arguing that the transmission barrier associated with this prion strain/host combination is greater than that observed with classical BSE prions. However, it is possible that CWD may be caused by multiple prion strains. Further studies will be required to evaluate the transmission properties of distinct cervid prion strains as they are characterized.

In vitro detection of prionemia in TSE-infected cervids and hamsters.

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Alan M Elder

Full Text Available Blood-borne transmission of infectious prions during the symptomatic and asymptomatic stages of disease occurs for both human and animal transmissible spongiform encephalopathies (TSEs. The geographical distribution of the cervid TSE, chronic wasting disease (CWD, continues to spread across North America and the prospective number of individuals harboring an asymptomatic infection of human variant Creutzfeldt-Jakob Disease (vCJD in the United Kingdom has been projected to be ~1 in 3000 residents. Thus, it is important to monitor cervid and human blood products to ensure herd health and human safety. Current methods for detecting blood-associated prions rely primarily upon bioassay in laboratory animals. While bioassay provides high sensitivity and specificity, it requires many months, animals, and it is costly. Here we report modification of the real time quaking-induced conversion (RT-QuIC assay to detect blood-borne prions in whole blood from prion-infected preclinical white-tailed deer, muntjac deer, and Syrian hamsters, attaining sensitivity of >90% while maintaining 100% specificity. Our results indicate that RT-QuIC methodology as modified can provide consistent and reliable detection of blood-borne prions in preclinical and symptomatic stages of two animal TSEs, offering promise for prionemia detection in other species, including humans.

Possible case of maternal transmission of feline spongiform encephalopathy in a captive cheetah.

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Anna Bencsik

Full Text Available Feline spongiform encephalopathy (FSE is considered to be related to bovine spongiform encephalopathy (BSE and has been reported in domestic cats as well as in captive wild cats including cheetahs, first in the United Kingdom (UK and then in other European countries. In France, several cases were described in cheetahs either imported from UK or born in France. Here we report details of two other FSE cases in captive cheetah including a 2(nd case of FSE in a cheetah born in France, most likely due to maternal transmission. Complete prion protein immunohistochemical study on both brains and peripheral organs showed the close likeness between the two cases. In addition, transmission studies to the TgOvPrP4 mouse line were also performed, for comparison with the transmission of cattle BSE. The TgOvPrP4 mouse brains infected with cattle BSE and cheetah FSE revealed similar vacuolar lesion profiles, PrP(d brain mapping with occurrence of typical florid plaques. Collectively, these data indicate that they harbor the same strain of agent as the cattle BSE agent. This new observation may have some impact on our knowledge of vertical transmission of BSE agent-linked TSEs such as in housecat FSE, or vCJD.

The expanding universe of prion diseases.

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2006-03-01

Full Text Available Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C. Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases-including human diseases variant Creutzfeldt-Jakob disease (vCJD and sporadic fatal insomnia (sFI, bovine amyloidotic spongiform encephalopathy (BASE, and Nor98 of sheep-have been identified in the last ten years, and chronic wasting disease (CWD of North American deer (Odocoileus Specis and Rocky Mountain elk (Cervus elaphus nelsoni is undergoing a dramatic spread across North America. While amplification (BSE and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

The expanding universe of prion diseases.

Directory of Open Access Journals (Sweden)

Joel C Watts

2006-03-01

Full Text Available Prions cause fatal and transmissible neurodegenerative disease. These etiological infectious agents are formed in greater part from a misfolded cell-surface protein called PrP(C. Several mammalian species are affected by the diseases, and in the case of "mad cow disease" (BSE the agent has a tropism for humans, with negative consequences for agribusiness and public health. Unfortunately, the known universe of prion diseases is expanding. At least four novel prion diseases--including human diseases variant Creutzfeldt-Jakob disease (vCJD and sporadic fatal insomnia (sFI, bovine amyloidotic spongiform encephalopathy (BASE, and Nor98 of sheep--have been identified in the last ten years, and chronic wasting disease (CWD of North American deer (Odocoileus Specis and Rocky Mountain elk (Cervus elaphus nelsoni is undergoing a dramatic spread across North America. While amplification (BSE and dissemination (CWD, commercial sourcing of cervids from the wild and movement of farmed elk can be attributed to human activity, the origins of emergent prion diseases cannot always be laid at the door of humankind. Instead, the continued appearance of new outbreaks in the form of "sporadic" disease may be an inevitable outcome in a situation where the replicating pathogen is host-encoded.

Creutzfeldt-Jakob Disease and Infection Control

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Lynn Johnston

2001-01-01

Full Text Available Over the past year, several situations have occurred in Canada in which patients who had recently undergone a surgical procedure were subsequently diagnosed with confirmed or suspected Creutzfeldt-Jakob disease (CJD. This raised concerns over contamination of surgical instruments: which instruments might have been contaminated from direct exposure to tissues; can instruments become cross-contaminated by exposure to other contaminated instruments; what assessment is necessary to determine cross-contamination; and what should be done with instruments that have been contaminated. Additionally, should there be a patient traceback in the face of potential but unproven exposure? Unfortunately, there are no easy answers to most of the above questions. Australia, the United Kingdom and the World Health Organization have developed guidelines for the infection control management of patients with CJD, as well as instruments and devices that come into contact with them and their tissues (1-3. Health Canada's draft CJD infection control guidelines, withdrawn from the Health Canada Web site until safety concerns regarding sodium hydroxide can be addressed, closely mirrored recommendations made in those documents. The Centers for Disease Control and Prevention guidelines for CJD are under revision. However, a recent American publication made recommendations on what procedures should be used for reprocessing items that have been in contact with the prion protein (PrP (4. These recommendations differ substantially from the draft Canadian guidelines. This article reviews current knowledge about CJD, and highlights some of the infection control concerns and controversies.

Comparative Study of Prions in Iatrogenic and Sporadic Creutzfeldt-Jakob Disease

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Xiao, Xiangzhu; Yuan, Jue; Qing, Liuting; Cali, Ignazio; Mikol, Jacqueline; Delisle, Marie-Bernadette; Uro-Coste, Emmanuelle; Zeng, Liang; Abouelsaad, Mai; Gazgalis, Dimitris; Martinez, Manuel Camacho; Wang, Gong-Xian; Brown, Paul; Ironside, James W.; Gambetti, Pierluigi; Kong, Qingzhong; Zou, Wen-Quan

2014-01-01

Differentiating iatrogenic Creutzfeldt-Jakob disease (iCJD) from sporadic CJD (sCJD) would be useful for the identification and prevention of human-to-human prion transmission. Currently, the diagnosis of iCJD depends on identification of a recognized source of contamination to which patients have been exposed, in addition to fulfilling basic requirements for the establishment of diagnosis of CJD. Attempts to identify differences in clinical manifestations, neuropathological changes and pathological prion protein (PrPSc) between iCJD and sCJD have been unsuccessful. In the present study, using a variety of more sophisticated methods including sucrose step gradient sedimentation, conformational stability immunoassay, protein misfolding cyclic amplification (PMCA), fragment-mapping, and transmission study, we show no significant differences in gel profiles, oligomeric state, conformational stability and infectivity of PrPSc between iCJD and sCJD. However, using PMCA, we find that convertibility and amplification efficiency of PrPSc is greater in iCJD than in sCJD in a polymorphism-dependent manner. Moreover, two protease-resistant PrP C-terminal fragments (termed PrP-CTF12/13) were detected in all 9 cases of sCJD but not in 6 of 8 cases of iCJD tested in this study. The use of fragment mapping- and PMCA-based assays thus provides a means to distinguish most cases of iCJD from sCJD. PMID:25419482

Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009.

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Peckeu, Laurene; Delasnerie-Lauprètre, Nicole; Brandel, Jean-Philippe; Salomon, Dominique; Sazdovitch, Véronique; Laplanche, Jean-Louis; Duyckaerts, Charles; Seilhean, Danielle; Haïk, Stéphane; Hauw, Jean-Jacques

2017-10-01

Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders. 14-3-3 detection was introduced into diagnostic criteria for CJD in 1998. Diagnostic accuracy decreased from 92% for the 1992-1997 period to 85% for the 1998-2009 period. This was associated with positive detections of 14-3-3 in cases with negative EEG and alternative diagnosis at autopsy. Potentially treatable diseases were found in 163 patients (10.5%). This study confirms the usefulness of the recent modification of diagnosis criteria by the addition of the results of CSF real-time quaking-induced conversion, a method based on prion seed-induced misfolding and aggregation of recombinant prion protein substrate that has proven to be a highly specific test for diagnosis of sporadic CJD.

Iatrogenic Creutzfeldt-Jakob disease with Amyloid-β pathology: an international study.

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Cali, Ignazio; Cohen, Mark L; Haїk, Stéphane; Parchi, Piero; Giaccone, Giorgio; Collins, Steven J; Kofskey, Diane; Wang, Han; McLean, Catriona A; Brandel, Jean-Philippe; Privat, Nicolas; Sazdovitch, Véronique; Duyckaerts, Charles; Kitamoto, Tetsuyuki; Belay, Ermias D; Maddox, Ryan A; Tagliavini, Fabrizio; Pocchiari, Maurizio; Leschek, Ellen; Appleby, Brian S; Safar, Jiri G; Schonberger, Lawrence B; Gambetti, Pierluigi

2018-01-08

The presence of pathology related to the deposition of amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation of growth hormone (GH) extracted from human cadaveric pituitary gland or use of cadaveric dura mater (DM) grafts.To investigate this phenomenon further, a cohort of 27 iCJD cases - 21 with adequate number of histopathological sections - originating from Australia, France, Italy, and the Unites States, were examined by immunohistochemistry, amyloid staining, and Western blot analysis of the scrapie prion protein (PrP Sc ), and compared with age-group matched cases of sporadic CJD (sCJD), Alzheimer disease (AD) or free of neurodegenerative diseases (non-ND).Cases of iCJD and sCJD shared similar profiles of proteinase K-resistant PrP Sc with the exception of iCJD harboring the "MMi" phenotype. Cerebral amyloid angiopathy (CAA), either associated with, or free of, Thioflavin S-positive amyloid core plaques (CP), was observed in 52% of 21 cases of iCJD, which comprised 37.5% and 61.5% of the cases of GH- and DM-iCJD, respectively. If only cases younger than 54 years were considered, Aβ pathology affected 41%, 2% and 0% of iCJD, sCJD and non-ND, respectively. Despite the patients' younger age CAA was more severe in iCJD than sCJD, while Aβ diffuse plaques, in absence of Aβ CP, populated one third of sCJD. Aβ pathology was by far most severe in AD. Tau pathology was scanty in iCJD and sCJD.In conclusion, (i) despite the divergences in the use of cadaveric GH and DM products, our cases combined with previous studies showed remarkably similar iCJD and Aβ phenotypes indicating that the occurrence of Aβ pathology in iCJD is a widespread phenomenon, (ii) CAA emerges as the hallmark of the Aβ phenotype in iCJD since it is observed in nearly 90% of all iCJD with Aβ pathology reported to date including ours, and it is shared by GH- and DM-iCJD, (iii) although the contributions to Aβ pathology of other

Update: Dura Mater Graft-Associated Creutzfeldt-Jakob Disease - Japan, 1975-2017.

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Ae, Ryusuke; Hamaguchi, Tsuyoshi; Nakamura, Yosikazu; Yamada, Masahito; Tsukamoto, Tadashi; Mizusawa, Hidehiro; Belay, Ermias D; Schonberger, Lawrence B

2018-03-09

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder that, according to the most well accepted hypothesis (1), is caused by replicating, transmissible, abnormal forms of a host-encoded prion protein (prions). Most CJD cases occur spontaneously (sporadic CJD) or are inherited (genetic CJD). Iatrogenic CJD can occur after exposure to prion-contaminated instruments or products in medical/surgical settings. Cadaveric dura mater graft-associated CJD (dCJD) accounts for a common form of iatrogenic CJD. This report summarizes the epidemiologic features of 154 cases of dCJD identified in Japan during 1975-2017; these cases account for >60% of dCJD cases reported worldwide (1,2). The unusually high prevalence of dCJD in Japan was first reported in 1997 (3). In 2008, a single brand of graft (Lyodura [B. Braun Melsungen AG, Melsungen, Germany]), frequently used as a patch in neurosurgical procedures, was identified as the probable vehicle of transmission (4). No international recall of the implicated Lyodura occurred, the product had a relatively long shelf life, and the grafts were used frequently in Japanese patients with non-life-threatening conditions (4,5). Since 2008, additional cases have been ascertained, reflecting the identification of previously missed cases and the occurrence of new cases with longer latency periods (interval from exposure to symptom onset) for dCJD (up to 30 years), underscoring the importance of maintaining surveillance for dCJD.

Subtype and regional regulation of prion biomarkers in sporadic Creutzfeldt-Jakob disease.

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Llorens, Franc; Zafar, Saima; Ansoleaga, Belén; Shafiq, Mohsin; Blanco, Rosi; Carmona, Marga; Grau-Rivera, Oriol; Nos, Carlos; Gelpí, Ellen; Del Río, José Antonio; Zerr, Inga; Ferrer, Isidre

2015-08-01

Creutzfeldt-Jakob disease (CJD) is a rapid progressive neurological disease leading to dementia and death. Prion biomarkers are altered in the cerebrospinal fluid (CSF) of CJD patients, but the pathogenic mechanisms underlying these alterations are still unknown. The present study examined prion biomarker levels in the brain and CSF of sporadic CJD (sCJD) cases and their correlation with neuropathological lesion profiles. The expression levels of 14-3-3, Tau, phospho-Tau and α-synuclein were measured in the CSF and brain of sCJD cases in a subtype- and region-specific manner. In addition, the activity of prion biomarker kinases, the expression levels of CJD hallmarks and the most frequent neuropathological sCJD findings were analysed. Prion biomarkers levels were increased in the CSF of sCJD patients; however, correlations between mRNA, total protein and their phosphorylated forms in brain were different. The observed downregulation of the main Tau kinase, GSK3, in sCJD brain samples may help to explain the differential phospho-Tau/Tau ratios between sCJD and other dementias in the CSF. Importantly, CSF biomarkers levels do not necessarily correlate with sCJD neuropathological findings. Present findings indicate that prion biomarkers levels in sCJD tissues and their release into the CSF are differentially regulated following specific modulated responses, and suggest a functional role for these proteins in sCJD pathogenesis. © 2014 British Neuropathological Society.

Diffusion tensor MRI: clinical applications

International Nuclear Information System (INIS)

Meli, Francisco; Romero, Carlos; Carpintiero, Silvina; Salvatico, Rosana; Lambre, Hector; Vila, Jose

2005-01-01

Purpose: To evaluate the usefulness of diffusion-tensor imaging (DTI) on different neurological diseases, and to know if this technique shows additional information than conventional Magnetic Resonance Imaging (MRI). Materials and method: Eight patients, with neurological diseases (five patients with brain tumors, one with multiple sclerosis (MS), one with variant Creutzfeldt-Jakob disease (vCJD) and the other with delayed CO intoxication were evaluated. A MR scanner of 1.5 T was used and conventional sequences and DTI with twenty-five directions were done. Quantitative maps were gotten, where the fractional anisotropy (FA) through regions of interest (ROIs) in specific anatomic area were quantified (i.e.: internal and external capsules, frontal and temporal bundles, corpus fibers). Results: In the patients with brain tumors, there was a decrease of FA on intra and peritumoral fibers. Some of them had a disruption in their pattern. In patients with MS and CO intoxication, partial interruption along white matter bundles was demonstrated. However, a 'mismatch' between the findings of FLAIR, Diffusion-weighted images (DWI) and DTI, in the case of CO intoxication, was seen. Conclusions: DTI gave more information compared to conventional sequences about ultrastructural brain tissue in almost all the diseases above mentioned. Therefore, there is a work in progress about DTI acquisition, to evaluate a new technique, called tractography. (author)

The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance.

LENUS (Irish Health Repository)

Keohane, C

2012-02-03

The transmissible spongiform encephalopathies or prion diseases represent a new group of diseases with unique clinical and neuropathological features, the transmission of which is both genetic and infectious. The responsible agent is unconventional and appears to be largely composed of a glycoprotein, the prion protein PrP. This is normally present on different cells. In prion diseases, it becomes converted to the pathogenic form PrPres which is resistant to proteinase and accumulates within the brain and this process is accompanied by the development of spongiform change, gliosis and neuronal loss. The human prion diseases include Kuru a progressive cerebellar degeneration with late dementia affecting Fore tribes in New-Guinea, now almost extinct, regarded as being related to cannibalism. Creutzfeldt-Jakob disease is the more frequent human prion disease. Its incidence is approximately one case per million per year. Four variants are now recognized: sporadic, familial, iatrogenic and the new variant. The latter represents a distinct clinico-pathological entity. It is now widely accepted that it is due to the same agent responsible for Bovine Spongiform Encephalopathy in cattle. Gerstmann-Straussler-Scheinker disease is a very rare inherited disorder due to a number of different mutations in the PRP gene, characterized by abundant deposits of plaque PrPres in the cerebral grey matter. Fatal familial insomnia is another inherited disorder due to a mutation at codon 178 of the PRP gene associated with methionine on codon 129 of the mutant allele. The main neuropathological change is neuronal loss in the thalamus with little or no spongiosis and usually no PrPres deposition. Following the emergence of new variant CJD in 1996, surveillance of all forms of prion diseases has been now been actively introduced in many European nations in order to determine the true incidence and geographic distribution of these rare disorders in humans.

Questioning the Questions

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Tienken, Christopher H.; Goldberg, Stephanie; DiRocco, Dominic

2010-01-01

Historical accounts of questioning used in the education process trace back to Socrates. One of the best examples of his use of questioning is found in Plato's "The Republic." Socrates used a series of strategic questions to help his student Glaucon come to understand the concept of justice. Socrates purposefully posed a series of…

Comparison Between Sporadic and Misdiagnosed Sporadic Creutzfeldt-Jakob Disease: A Report of Two Cases.

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Zhao, Xiongfei; Yu, Yingxin; Zhao, Zhiru; Xu, Jiaping

2015-06-01

Definite accurate diagnosis for Creutzfeldt-Jakob disease (CJD) depends on neuropathologic examination of brain biopsy or autopsy. However, transmissible nature makes the invasive examination dangerous. This study was set to determine that the clinical features are for the diagnosis of CJD through a comparison study. We compared clinical features of two cases with initial diagnosis of sporadic CJD. One case was finally diagnosed as definite sporadic CJD. According to World Health Organization diagnosis criteria, the other one, which had been diagnosed as probable sporadic CJD, was confirmed as limbic encephalitis after long-term follow-up. Compared with the case of definite sporadic CJD, the misdiagnosed case did not present typical electroencephalogram (EEG) and diffusion-weighted in magnetic resonance images (DWI) of CJD. However, cerebrospinal fluid in the misdiagnosed patient showed 14-3-3 protein positivity. The patient conditions improved after treatment. Through this case comparison, we conclude that EEG and DWI are necessary for accurate diagnosis of sporadic CJD. Further, long-term follow-up is crucial to diagnosis and treatment of CJD.

Association between the PRNP 1368 polymorphism and the occurrence of sporadic Creutzfeldt-Jakob disease

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Bratosiewicz-Wąsik, Jolanta; Smoleń-Dzirba, Joanna; Rozemuller, Annemieke J.; Jansen, Casper; Spliet, Wim; Jansen, Gerard H.; Wąsik, Tomasz J.; Liberski, Paweł P.

2012-01-01

Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. The etiology of sporadic form of CJD remains unsolved. In addition to the codon 129 polymorphism, polymorphisms in the non-coding region of PRNP are considered as important factors in sCJD development. To assess a possible association between PRNP 1368 SNP and sCJD, we compared the genotype, allele and haplotype frequencies of the 1368 SNP among 46 sCJD patients of Dutch origin with the respective frequencies in healthy controls. We detected a significant association between sCJD and 1368T/T genotype. A significant difference was also observed in 1368 alleles’ distribution. In the haplotype analysis, haplotype 1368C-129G was associated with decreased risk of sCJD in Dutch population. Our findings support the hypothesis that genetic variations in the regulatory region of the PRNP gene may influence the pathogenesis of sCJD. PMID:22895088

Cerebrospinal Fluid Biomarkers in the Diagnosis of Creutzfeldt-Jakob Disease in Slovak Patients: over 10-Year Period Review.

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Koscova, Silvia; Zakova Slivarichova, Dana; Tomeckova, Ivana; Melicherova, Katarina; Stelzer, Martin; Janakova, Alzbeta; Kosorinova, Dana; Belay, Girma; Mitrova, Eva

2017-10-01

Creutzfeldt-Jakob disease is a rare, but rapidly progressive, up to now untreatable and fatal neurodegenerative disorder. Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is difficult; however, it can be facilitated by suitable biomarkers. Aim of the present study is to compare levels of cerebrospinal fluid biomarkers (total tau protein, phosphorylated-tau protein, protein 14-3-3 and amyloid beta) in Slovak population of CJD suspect cases, retrospectively in over a 10-year period. One thousand three hundred sixty-four CSF samples from patients with suspect CJD, forming a homogenous group in terms of geographical as well as of equal transport conditions, storage and laboratory processing, were analysed. Definite diagnosis of Creutzfeldt-Jakob disease was confirmed in 101 patients with genetic form, and 60 patients with its sporadic form of the disease. Specificity of protein 14-3-3 and total tau in both forms CJD was similar (87 % for P14-3-3/85 % for total tau), sensitivity to P 14-3-3 and total tau was higher in sporadic Creutzfeldt-Jakob disease (sCJD) (90/95 %) than in genetic Creutzfeldt-Jakob disease (gCJD) (89/74 %). As expected, the total tau levels were significantly higher in CJD patients than in controls, but there was also significant difference between gCJD and sCJD (levels in gCJD were lower; p = 0.003). There was no significant difference in p-tau and Aβ 1-42 levels neither between both CJD forms nor between CJD patients and control group.

Prion disease. The characteristics and diagnostic points in Japan

International Nuclear Information System (INIS)

Sanjo, Nobuo; Mizusawa, Hidehiro

2010-01-01

Prion disease develops when normal prion proteins change into transmissible abnormal prion proteins and the converted proteins accumulate in the brain. The Japanese Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1,320 patients with prion diseases in the 10 years since 1999 (classified into 3 types: sporadic, 77.2%; hereditary, 16.7%; and environmentally acquired, 6.1%). Compared with patients in other countries, a relatively larger number of Japanese patients characteristically have dura mater graft-associated CJD and hereditary prion diseases. All the environmentally acquired cases, except 1 case of variant CJD, were acquired from dura grafts. Although most patients were diagnosed with a classical subtype of sporadic CJD (sCJD), whose features include rapidly progressing dementia, myoclonus, hyperintensity in the cerebral cortex and basal ganglia in diffusion-weighted magnetic resonance imaging, and periodic synchronous discharge in electroencephalography, the number of cases with atypical symptoms, such as MM2 (0.8%), MV2 (0.2%), VV1 (0%), and VV2 (0.2%) subtypes of sCJD cases, was not negligible. Appropriate diagnosis should be made based on clinical features, neuroradiological findings, cerebrospinal fluid (CSF) findings (14-3-3 and total tau proteins), and genetic analysis of polymorphisms. Hereditary prion diseases are classified into 3 major phenotypes: familial CJD (fCJD); Gerstmann-Straeussler-Scheinker disease (GSS), which mainly presents as spinocerebellar ataxia; and fatal familial insomnia. Many mutations of the prion protein gene have been identified, but V1801 (fCJD), P102L (GSS), and E200K (fCJD) mutations were the most common among the fCJD cases in Japan. Without a family history, genetic testing is necessary to distinguish even seemingly ''sporadic'' CJD from fCJD. Accurate diagnosis is important for clarification of the pathological process, prevention of secondary infection, and also psychological support. (author)

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

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Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

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Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D.

2003-01-01

AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153

Magnetic resonance spectroscopic abnormalities in sporadic and variant Creutzfeldt-Jakob disease

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Pandya, H.G.; Coley, S.C.; Wilkinson, I.D.; Griffiths, P.D

2003-02-01

AIM: To study the proton MR spectroscopic findings in Creutzfeldt-Jakob disease (CJD) (sporadic and variant). MATERIALS AND METHODS: MR imaging and proton MR spectra were acquired in two patients with sporadic CJD (biopsy proven) and one patient with variant CJD. RESULTS: The two patients with sporadic CJD demonstrated MR signal change within the basal ganglia and thalami and reduced N-acetylaspartate (NAA):creatine ratios. The patient with variant CJD showed characteristic signal change within the pulvinar of the thalami and a markedly reduced N-acetylaspartate:creatine ratio. CONCLUSION: All three patients with CJD demonstrated evidence of reduced N-acetylaspartate: creatine ratios on MR spectroscopy. These changes imply that neuronal loss and/or dysfunction is a consistent finding in established CJD. Pandya H. G., et al (2003) Clinical Radiology58, 148--153.

Seizures in E200K familial and sporadic Creutzfeldt-Jakob disease.

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Appel, S; Chapman, J; Cohen, O S; Rosenmann, H; Nitsan, Z; Blatt, I

2015-03-01

Although seizures (other than myoclonus) are frequently reported in Creutzfeldt-Jakob disease (CJD), their frequency, clinical manifestations, and effect on the disease course is unknown. To characterize the frequency of seizures in E200K familial and sporadic CJD, to describe its semiology, EEG and MRI findings. In this retrospective study, we reviewed all patients with CJD who were seen in the Sheba Medical Center between the years 2003-2012 and underwent clinical evaluation, genetic testing, EEG and MRI studies. The diagnosis of seizures was carried out based on documentation of episodes consistent with seizures or episode of unresponsiveness correlated with ictal activity in EEG. Sixty-four probable patients with CJD were included in the study, 57 (89%) with E200K familial (fCJD) and 7 (11%) with sporadic (sCJD). Seizures occurred in 8 patients: 3 of 7 (43%) in patients with sCJD compared to 5/57 (9%) in patients with E200K fCJD (P = 0.04, chi-square test). Two of E200K fCJD patients with seizures had other non-prion etiologies for seizures (brain metastasis, known history of temporal lobe epilepsy which started 44 years before the diagnosis of CJD). Seizures occurred late in the course of the disease with an average of 12 days between the onset of seizures and death. Seizures in E200K fCJD were infrequent and occurred late in the disease course. This difference suggests that E200K fCJD represents a separate subtype of the disease with distinct clinical characteristics. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sporadic Creutzfeldt-Jakob disease with focal findings: caveats to current diagnostic criteria

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Mader, Edward C.; El-Abassi, Rima; Villemarette-Pittman, Nicole R.; Santana-Gould, Lenay; Olejniczak, Piotr W.; England, John D.

2013-01-01

The clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is largely based on the 1998 World Health Organization diagnostic criteria. Unfortunately, rigid compliance with these criteria may result in failure to recognize sporadic CJD (sCJD), especially early in its course when focal findings predominate and traditional red flags are not yet present. A 61-year-old man presented with a 3-week history of epilepsia partialis continua (jerking of the left upper extremity) and a 2-week history of forgetfulness and left hemiparesis; left hemisensory neglect was also detected on admission. Repeated brain magnetic resonance imaging (MRI) showed areas of restricted diffusion in the cerebral cortex, initially on the right but later spreading to the left. Electroence-phalography (EEG) on hospital days 7, 10, and 14 showed right-sided periodic lateralized epileptiform discharges. On day 20, the EEG showed periodic sharp wave complexes leading to a diagnosis of probable sCJD and subsequently to definite sCJD with brain biopsy. Neurological decline was relatively fast with generalized myoclonus and akinetic mutism developing within 7 weeks from the onset of illness. CJD was not immediately recognized because of the patient's focal/lateralized manifestations. Focal/lateralized clinical, EEG, and MRI findings are not uncommon in sCJD and EEG/MRI results may not be diagnostic in the early stages of sCJD. Familiarity with these caveats and with the most current criteria for diagnosing probable sCJD (University of California San Francisco 2007, MRI-CJD Consortium 2009) will enhance the ability to recognize sCJD and implement early safety measures. PMID:23717780

The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients.

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Moore, Roger A; Head, Mark W; Ironside, James W; Ritchie, Diane L; Zanusso, Gianluigi; Choi, Young Pyo; Pyo Choi, Young; Priola, Suzette A

2016-02-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc). In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C) allotype to PrP(Sc) in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc) with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C) containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc) thus causing sCJD. By contrast, PrP(Sc) with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc) containing V at residue 129. In both types of CJD, the PrP(Sc) allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc) allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.

MM2-thalamic Creutzfeldt-Jakob disease: neuropathological, biochemical and transmission studies identify a distinctive prion strain.

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Moda, Fabio; Suardi, Silvia; Di Fede, Giuseppe; Indaco, Antonio; Limido, Lucia; Vimercati, Chiara; Ruggerone, Margherita; Campagnani, Ilaria; Langeveld, Jan; Terruzzi, Alessandro; Brambilla, Antonio; Zerbi, Pietro; Fociani, Paolo; Bishop, Matthew T; Will, Robert G; Manson, Jean C; Giaccone, Giorgio; Tagliavini, Fabrizio

2012-09-01

In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP(Sc) ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP(Sc) and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP(Sc) are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia. We observed two young patients with MM2-thalamic CJD. Main neuropathological features were diffuse, synaptic PrP immunoreactivity in the cerebral cortex and severe neuronal loss and gliosis in the thalamus and olivary nucleus. Western blot analysis showed the presence of type 2A PrP(Sc) . Challenge of transgenic mice expressing 129MM human PrP showed that MM2-thalamic sporadic CJD (sCJD) was able to transmit the disease, at variance with MM2-cortical sCJD. The affected mice showed deposition of type 2A PrP(Sc) , a scenario that is unprecedented in this mouse line. These data indicate that MM2-thalamic sCJD is caused by a prion strain distinct from the other sCJD subtypes including the MM2-cortical form. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.

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Kobayashi, Atsushi; Parchi, Piero; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

2016-06-01

As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases. © 2015 Japanese Society of Neuropathology.

VQABQ: Visual Question Answering by Basic Questions

KAUST Repository

Huang, Jia-Hong

2017-03-19

Taking an image and question as the input of our method, it can output the text-based answer of the query question about the given image, so called Visual Question Answering (VQA). There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the basic questions of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question. We formulate the basic questions generation problem as a LASSO optimization problem, and also propose a criterion about how to exploit these basic questions to help answer main question. Our method is evaluated on the challenging VQA dataset and yields state-of-the-art accuracy, 60.34% in open-ended task.

VQABQ: Visual Question Answering by Basic Questions

KAUST Repository

Huang, Jia-Hong; Alfadly, Modar; Ghanem, Bernard

2017-01-01

Taking an image and question as the input of our method, it can output the text-based answer of the query question about the given image, so called Visual Question Answering (VQA). There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the basic questions of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question. We formulate the basic questions generation problem as a LASSO optimization problem, and also propose a criterion about how to exploit these basic questions to help answer main question. Our method is evaluated on the challenging VQA dataset and yields state-of-the-art accuracy, 60.34% in open-ended task.

Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999–2008

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Hamaguchi, Tsuyoshi; Noguchi-Shinohara, Moeko; Nozaki, Ichiro; Nakamura, Yosikazu; Sato, Takeshi; Kitamoto, Tetsuyuki; Mizusawa, Hidehiro

2009-01-01

To elucidate the association between medical procedures and sporadic Creutzfeldt-Jakob disease (sCJD), we analyzed medical procedures (any surgical procedure, neurosurgery, ophthalmic surgery, and blood transfusion) for patients registered by the CJD Surveillance Committee in Japan during 1999–2008. We conducted an age-stratified case–control study with 753 sCJD patients and 210 controls and a study of patients who underwent neurosurgical or ophthalmic surgical procedures at the same hospital. Although the control group was relatively small, no evidence was found that prion disease was transmitted through the investigated medical procedures before onset of sCJD. After onset of sCJD, 4.5% of the sCJD patients underwent operations, including neurosurgical for 0.8% and ophthalmic for 1.9%; no special precautions against transmission of prion diseases were taken. Fortunately, we have not identified patients with prion disease attributed to these operations. Our findings indicate that surgical procedures or blood transfusion had little effect on the incidence of sCJD. PMID:19193271

Creutzfeldt-Jacob Disease: Two Case Reports

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Aysu Şen

2006-02-01

Full Text Available Creutzfeldt-Jakob Disease (CJD is characterised by subacute progressive dementia, cerebellar ataxia, myoclonic jerks together with pyramidal and extrapyramidal signs. It is a rare prion disease and definitive diagnosis can only be made by biopsy. It becomes progressively worse and the death is the rule. We presented two CJD cases because of their demonstrative characteristics. A 43 year-old female and a 52 year-old male patient was suspected to be CJD due to presence of subacute severe cognitive deterioration, neuropsychiatric disturbances, myoclonic jerks, ataxia, pyramidal and extrapyramidal signs and also periodic spike and wave complexes in EEG. Patients were lost in a short period of time because of the complications of disease process. Medical autopsy were done in both cases for definitive diagnosis and autopsy results displayed characteristic pathologic findings of CJD. Patients were diagnosed as definitive sporadic CJD according to Master’s, French and European criterias. CJD should be considered in patients with rapidly progressive dementia, that starts with various neuropsychiatric symptoms. Although seen very rare, CJD is a untreatable, fatal disease. Therefore we emphasize that, preventive precaution should be taken when a CJD diagnosis is suspected

UK Iatrogenic Creutzfeldt-Jakob disease: investigating human prion transmission across genotypic barriers using human tissue-based and molecular approaches.

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Ritchie, Diane L; Barria, Marcelo A; Peden, Alexander H; Yull, Helen M; Kirkpatrick, James; Adlard, Peter; Ironside, James W; Head, Mark W

2017-04-01

Creutzfeldt-Jakob disease (CJD) is the prototypic human prion disease that occurs most commonly in sporadic and genetic forms, but it is also transmissible and can be acquired through medical procedures, resulting in iatrogenic CJD (iCJD). The largest numbers of iCJD cases that have occurred worldwide have resulted from contaminated cadaveric pituitary-derived human growth hormone (hGH) and its use to treat primary and secondary growth hormone deficiency. We report a comprehensive, tissue-based and molecular genetic analysis of the largest series of UK hGH-iCJD cases reported to date, including in vitro kinetic molecular modelling of genotypic factors influencing prion transmission. The results show the interplay of prion strain and host genotype in governing the molecular, pathological and temporal characteristics of the UK hGH-iCJD epidemic and provide insights into the adaptive mechanisms involved when prions cross genotypic barriers. We conclude that all of the available evidence is consistent with the hypothesis that the UK hGH-iCJD epidemic resulted from transmission of the V2 human prion strain, which is associated with the second most common form of sporadic CJD.

Towards an age-dependent transmission model of acquired and sporadic Creutzfeldt-Jakob disease.

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de Pedro-Cuesta, Jesús; Mahillo-Fernandez, Ignacio; Calero, Miguel; Rábano, Alberto; Cruz, Mabel; Siden, Åke; Martínez-Martín, Pablo; Laursen, Henning; Ruiz-Tovar, María; Mølbak, Kåre

2014-01-01

Sporadic Creutzfeldt-Jakob disease (sCJD) might be transmitted by surgery. The purpose of this study was to investigate potential susceptibility to sCJD from surgery at juvenile age and in early adulthood. From Danish and Swedish national registries we identified 167 definite and probable sCJD cases with onset from 1987 through 2003, and 835 age-, sex- and residence-matched controls along with their surgical histories. Main, anatomically or etiologically classified surgical procedures followed by a ≥20-year lag were analyzed using logistic regression, and stratified by age at first-registered surgical discharge. The risk of having a diagnosis of CJD depended strongly on age at first surgery with odds ratio (OR) of 12.80 (95% CI 2.56-64.0) in patients <30 years, 3.04 (95% 1.26-7.33) in 30-39 years, and 1.75 (95% CI 0.89-3.45) in ≥40 years, for anatomically classified surgical procedures. Similar figures were obtained for etiologically classified surgical procedures. Risk of surgical-acquired sCJD depends on age at exposure; this pattern is similar to age-specific profiles reported for CJD accidentally transmitted by human pituitary-derived growth hormone and susceptibility curves for variant CJD estimated after adjustment for dietary exposure to bovine spongiform encephalopathy. There might be an age-at-exposure-related susceptibility to acquire all CJD forms, including sCJD from routine surgery.

Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease.

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Grau-Rivera, Oriol; Sánchez-Valle, Raquel; Saiz, Albert; Molinuevo, José Luis; Bernabé, Reyes; Munteis, Elvira; Pujadas, Francesc; Salvador, Antoni; Saura, Júlia; Ugarte, Antonio; Titulaer, Maarten; Dalmau, Josep; Graus, Francesc

2014-01-01

Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD. Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-d-aspartate (NMDA), and glycine (GlY) receptors. Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [δ/notch-like epidermal growth factor-related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs. A low, but

Questioning Questions: Elementary Teachers' Adaptations of Investigation Questions Across the Inquiry Continuum

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Biggers, Mandy

2018-02-01

Questioning is a central practice in science classrooms. However, not every question translates into a "good" science investigation. Questions that drive science investigations can be provided by many sources including the teacher, the curriculum, or the student. The variations in the source of investigation questions were explored in this study. A dataset of 120 elementary science classroom videos and associated lesson plans from 40 elementary teachers (K-5) across 21 elementary school campuses were scored on an instrument measuring the amount of teacher-direction or student-direction of the lessons' investigation questions. Results indicated that the investigation questions were overwhelmingly teacher directed in nature, with no opportunities for students to develop their own questions for investigation. This study has implications for researchers and practitioners alike, calling attention to the teacher-directed nature of investigation questions in existing science curriculum materials, and the need for teacher training in instructional strategies to adapt their existing curriculum materials across the continuum of teacher-directed and student-directed investigation questions. Teachers need strategies for adapting the teacher-directed questions provided in their existing curriculum materials in order to allow students the opportunity to engage in this essential scientific practice.

Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

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Simon, Stéphanie; Lugan, Séverine; Bilheude, Jean-Marc; Perret-Liaudet, Armand; Ironside, James W.; Haik, Stéphane; Basset-Leobon, Christelle; Lacroux, Caroline; Peoch', Katell; Streichenberger, Nathalie; Langeveld, Jan; Head, Mark W.; Grassi, Jacques; Hauw, Jean-Jacques; Schelcher, Francois; Delisle, Marie Bernadette; Andréoletti, Olivier

2008-01-01

Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability. PMID:18389084

Characteristics of Korean patients with suspected Creutzfeldt-Jakob disease with 14-3-3 protein in cerebrospinal fluid: Preliminary study of the Korean Creutzfeldt-Jakob disease active surveillance program.

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Lim, Jae-Sung; Kwon, Hyung-Min; Jang, Jae-Won; Ju, Young-Ran; Kim, SuYeon; Park, Young Ho; Park, So Young; Kim, SangYun

2015-01-01

Although Korea had a national surveillance system for Creutzfeldt-Jakob disease (CJD), it was mainly dependent on attending physician's reports. Thus, little prospective data about the epidemiology, characteristics, and final diagnoses of suspected patients were available. We have established a nationwide network for the active surveillance of patients with suspected CJD. When the requested cerebrospinal fluid (CSF) samples tested positive for 14-3-3 protein, we investigated the clinical characteristics of the corresponding patients and followed them until their final diagnoses were confirmed. A total of 218 samples were requested for CSF assays from May 2010 to August 2012, and 106 (48.6%) were positive for 14-3-3 protein. In 89 patients with complete clinical data, 38 (42.7%) were diagnosed with probable CJD and the estimated annual occurrence of CJD was 16.3 persons-per-year. The most common diagnoses of the remainder were central nervous system infection and any-cause encephalopathy. Non-CJD subjects showed worse initial consciousness levels than CJD patients. This preliminary study showed that the number of reported cases of CJD and the true positivity rates of CSF 14-3-3 protein assays were both low in Korea. An active surveillance system is urgently needed to provide the latest nationwide epidemiological data of CJD.

Identification of genomic differences between Campylobacter jejuni subsp. jejuni and C. jejuni subsp. doylei at the nap locus leads to the development of a C. jejuni subspeciation multiplex PCR method

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Heath Sekou

2007-02-01

Full Text Available Abstract Background The human bacterial pathogen Campylobacter jejuni contains two subspecies: C. jejuni subsp. jejuni (Cjj and C. jejuni subsp. doylei (Cjd. Although Cjd strains are isolated infrequently in many parts of the world, they are obtained primarily from human clinical samples and result in an unusual clinical symptomatology in that, in addition to gastroenteritis, they are associated often with bacteremia. In this study, we describe a novel multiplex PCR method, based on the nitrate reductase (nap locus, that can be used to unambiguously subspeciate C. jejuni isolates. Results Internal and flanking napA and napB primer sets were designed, based on existing C. jejuni and Campylobacter coli genome sequences to create two multiplex PCR primer sets, nap mpx1 and nap mpx2. Genomic DNA from 161 C. jejuni subsp. jejuni (Cjj and 27 C. jejuni subsp. doylei (Cjd strains were amplified with these multiplex primer sets. The Cjd strains could be distinguished clearly from the Cjj strains using either nap mpx1 or mpx2. In addition, combination of either nap multiplex method with an existing lpxA speciation multiplex method resulted in the unambiguous and simultaneous speciation and subspeciation of the thermophilic Campylobacters. The Cjd nap amplicons were also sequenced: all Cjd strains tested contained identical 2761 bp deletions in napA and several Cjd strains contained deletions in napB. Conclusion The nap multiplex PCR primer sets are robust and give a 100% discrimination of C. jejuni subspecies. The ability to rapidly subspeciate C. jejuni as well as speciate thermophilic Campylobacter species, most of which are pathogenic in humans, in a single amplification will be of value to clinical laboratories in strain identification and the determination of the environmental source of campylobacterioses caused by Cjd. Finally, the sequences of the Cjd napA and napB loci suggest that Cjd strains arose from a common ancestor, providing clues as to

Anesthetic management in patients suspected of Creutzfeldt-Jakob disease -A case report-.

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In, Chi Bum; Choi, Young Sil; Park, Eun Young; Chang, Dong Jin; Lee, Soo Kyung; Choi, Hyun; Moon, Hyun Soo

2011-09-01

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder in which accumulation of the pathogenic prion protein induces neuronal damage and results in distinct pathologic features. This abnormal prion is an infectious protein and resistant to methods of sterilization currently being used. Therefore, management of definite, or suspected CJD patients requires additional precautions. We report our experience of a patient who had undergone brain biopsy for suspected of CJD. The patient was confirmed to have sporadic CJD.

Diagnostic Accuracy of a Combined Analysis of Cerebrospinal Fluid t-PrP, t-tau, p-tau, and Aβ42 in the Differential Diagnosis of Creutzfeldt-Jakob Disease from Alzheimer's Disease with Emphasis on Atypical Disease Variants.

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Abu Rumeileh, Samir; Lattanzio, Francesca; Stanzani Maserati, Michelangelo; Rizzi, Romana; Capellari, Sabina; Parchi, Piero

2017-01-01

According to recent studies, the determination of cerebrospinal fluid (CSF) total tau (t-tau)/phosphorylated tau (p-tau) ratio and total prion protein (t-PrP) levels significantly improves the accuracy of the diagnosis of Alzheimer's disease (AD) in atypical cases with clinical or laboratory features mimicking Creutzfeldt-Jakob disease (CJD). However, this has neither been validated nor tested in series including atypical CJD variants. Furthermore, the added diagnostic value of amyloid-β (Aβ)42 remains unclear. To address these issues, we measured t-PrP, 14-3-3, t-tau, p-tau, and Aβ42 CSF levels in 45 typical and 44 atypical/rapidly progressive AD patients, 54 typical and 54 atypical CJD patients, and 33 controls. CJD patients showed significantly lower CSF t-PrP levels than controls and AD patients. Furthermore, atypical CJD was associated with lower t-PrP levels in comparison to typical CJD. T-tau, 14-3-3, or t-PrP alone yielded, respectively, 80.6, 63.0, and 73.0% sensitivity and 75.3, 92.1, and 75% specificity in distinguishing AD from CJD. On receiver operating characteristic (ROC) curve analyses of biomarker combinations, the (t-tau×Aβ42)/(p-tau×t-PrP) ratio achieved the best accuracy, with 98.1% sensitivity and 97.7% specificity overall, and 96.2% sensitivity and 95.5% specificity for the "atypical" disease groups. Our results show that the combined analysis of CSF t-PrP, t-tau, p-tau, and Aβ42 is clinically useful in the differential diagnosis between CJD and AD. Furthermore, the finding of reduced CSF t-PrP levels in CJD patients suggest that, likewise Aβ42 in AD, CSF t-PrP levels reflect the extent of PrPc conversion into abnormal PrP (PrPSc) and the burden of PrPSc deposition in CJD.

PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

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Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

2013-01-01

Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

Clinical radiological correlation in E200K familial Creutzfeldt-Jakob disease.

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Cohen, Oren S; Chapman, Joab; Korczyn, Amos D; Siaw, Oliver L; Warman-Alaluf, Naama; Nitsan, Zeev; Appel, Shmuel; Kahana, Esther; Rosenmann, Hanna; Hoffmann, Chen

2016-12-01

The use of diffusion MRI improved the accuracy of diagnosis in Creutzfeldt-Jakob disease (CJD) and expanded our knowledge of the changes occurring in the brain during the disease. The aim of this study was to test whether in patients with E200K familial CJD (fCJD) the clinical severity correlates with the disease burden as reflected by the extent of cortical involvement in DWI MRI. Consecutive fCJD patients were examined by a neurologist who performed several tests including the CJD neurological scale (CJD-NS), MiniMental status examination (MMSE), Frontal Assessment Battery (FAB), NIH Stroke Scale (NIHSS), and the expanded disability status scale (EDSS). A simultaneously acquired MRI was analyzed by measuring the extent of cortical involvement in the DWI axial sequence. Correlations were tested for using Pearson test. Fifty-two fCJD patients (35 males, mean age 59.4 ± 5.7 years) were recruited to the study. Significant negative correlation was found between the extent of cortical involvement and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between the MRI and the clinical disease severity scales CJD-NS and EDSS. The correlation between clinical scales of severity and cognitive dysfunction and the disease burden confirms the reliability of the CJD-NS scale. Further studies are warranted to examine whether MRI may serve not only for diagnosis but also as a biomarker for follow-up of disease progression and the efficacy of potential treatments.

Risk of transmission of sporadic Creutzfeldt-Jakob disease by surgical procedures: systematic reviews and quality of evidence.

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López, Fernando J García; Ruiz-Tovar, María; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; Calero, Miguel; de Pedro-Cuesta, Jesús

2017-10-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans. This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD. Firstly, we conducted systematic reviews and meta-analyses of case-control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments. Thirteen case-control studies met the inclusion criteria for the systematic review of case-control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case-control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments. The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.

Sporadic Creutzfeldt-Jakob Disease MM1+2C and MM1 are Identical in Transmission Properties.

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Kobayashi, Atsushi; Matsuura, Yuichi; Iwaki, Toru; Iwasaki, Yasushi; Yoshida, Mari; Takahashi, Hitoshi; Murayama, Shigeo; Takao, Masaki; Kato, Shinsuke; Yamada, Masahito; Mohri, Shirou; Kitamoto, Tetsuyuki

2016-01-01

The genotype (methionine, M or valine, V) at polymorphic codon 129 of the PRNP gene and the type (1 or 2) of abnormal prion protein in the brain are the major determinants of the clinicopathological features of sporadic Creutzfeldt-Jakob disease (CJD), thus providing molecular basis for classification of sporadic CJD, that is, MM1, MM2, MV1, MV2, VV1 or VV2. In addition to these "pure" cases, "mixed" cases presenting mixed neuropathological and biochemical features have also been recognized. The most frequently observed mixed form is the co-occurrence of MM1 and MM2, namely MM1+2. However, it has remained elusive whether MM1+2 could be a causative origin of dura mater graft-associated CJD (dCJD), one of the largest subgroups of iatrogenic CJD. To test this possibility, we performed transmission experiments of MM1+2 prions and a systematic neuropathological examination of dCJD patients in the present study. The transmission properties of the MM1+2 prions were identical to those of MM1 prions because MM2 prions lacked transmissibility. In addition, the neuropathological characteristics of MM2 were totally absent in dCJD patients examined. These results suggest that MM1+2 can be a causative origin of dCJD and causes neuropathological phenotype similar to that of MM1. © 2015 International Society of Neuropathology.

Questioning Questions: Elementary Teachers' Adaptations of Investigation Questions across the Inquiry Continuum

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Biggers, Mandy

2018-01-01

Questioning is a central practice in science classrooms. However, not every question translates into a "good" science investigation. Questions that drive science investigations can be provided by many sources including the teacher, the curriculum, or the student. The variations in the source of investigation questions were explored in…

Defining sporadic Creutzfeldt-Jakob disease strains and their transmission properties

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Bishop, Matthew T.; Will, Robert G.; Manson, Jean C.

2010-01-01

The biological determinants of the phenotypic variation in sporadic Creutzfeldt-Jakob disease (sCJD) are unknown. To categorize sCJD cases, the prion protein (PrP) codon 129 genotype and the biochemical characteristics of the disease-associated form of PrP (PrPSc) can be combined to form six subgroups (MM1, MM2, MV1, MV2, VV1, and VV2). This classification largely correlates with the known variation in the clinical and pathological features of sCJD, with the MM1 and MV1 cases representing the “classic” phenotype of sCJD. To address how this classification relates to different strains of sCJD we have inoculated each subgroup of sCJD to a panel of mice expressing different forms of the human PRNP gene (129MM, 129VV, and 129MV). We have established that all subtypes are transmissible to at least one genotype of mouse, and both agent and host factors determine transmission efficiency and the form of PrPSc deposited in the brain. Moreover, we have identified four distinct strains of sCJD using our in vivo strain typing panel. PMID:20547859

Rhetorical questions or rhetorical uses of questions?

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Špago Džemal

2016-12-01

Full Text Available This paper aims to explore whether some rhetorical questions contain certain linguistic elements or forms which would differentiate them from answer-eliciting and action-eliciting questions, and thereby hint at their rhetorical nature even outside the context. Namely, despite the fact that the same questions can be rhetorical in one context, and answer-eliciting in another, some of them are more likely to be associated with rhetorical or non-rhetorical use. The analysis is based on extensive data (over 1200 examples of rhetorical questions taken from 30 plays by two British and two American writers, and the results are expected to give an insight into whether we can talk about rhetorical questions or just a rhetorical use of questions.

Creutzfeldt-Jakob Disease

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... CJD diagnosed? Several tests can help diagnose CJD. Electroencephalography (EEG), which records the brain’s electrical pattern, can be ... to be accurate in about 90 percent of cases. The only way to confirm a ... can cure or control CJD, although studies of a variety of drugs are now in ...

Diffusion MR imaging in sporadic Creutzfeldt-Jakob disease

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Burcak Cakir Pekoz

2014-08-01

Full Text Available Creutzfeldt-Jakob disease (CJD is a rare dementing disease and is thought to caused by a prion. It is characterized by rapidly progressive dementia, ataxia, myoclonus, akinetic mutism and eventual death. Brain biopsy or autopsy is required for a definitive diagnosis of CJD. Diffusion-weighted imaging became an important tool for early diagnosis of CJD because of the high sensitivity. We present 59-year-old female patient diagnosed as sporadic CJD with typical MR imagings. [Cukurova Med J 2014; 39(4.000: 880-883

Brains with sporadic Creutzfeldt-Jakob disease and copathology showed a prolonged end-stage of disease.

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Miguelez-Rodriguez, Aitzol; Santos-Juanes, Jorge; Vicente-Etxenausia, Ikerne; Perez de Heredia-Goñi, Katty; Garcia, Beatriz; Quiros, Luis M; Lorente-Gea, Laura; Guerra-Merino, Isabel; Aguirre, Jose J; Fernandez-Vega, Ivan

2018-05-01

To investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD). Thirty consecutive cases of confirmed CJD during the period 2010-2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined. Copathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032). The existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases. © 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.

Creutzfeldt-Jakob Disease Presenting as Expressive Aphasia and Nonconvulsive Status Epilepticus

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Hafiz B. Mahboob

2018-01-01

Full Text Available Creutzfeldt-Jakob disease (CJD, the most common form of human prion diseases, is a fatal condition with a mortality rate reaching 85% within one year of clinical presentation. CJD is characterized by rapidly progressive neurological deterioration in combination with typical electroencephalography (EEG and magnetic resonance imaging (MRI findings and positive cerebrospinal spinal fluid (CSF analysis for 14-3-3 proteins. Unfortunately, CJD can have atypical clinical and radiological presentation in approximately 10% of cases, thus making the diagnosis often challenging. We report a rare clinical presentation of sporadic CJD (sCJD with combination of both expressive aphasia and nonconvulsive status epilepticus. This patient presented with slurred speech, confusion, myoclonus, headaches, and vertigo and succumbed to his disease within ten weeks of initial onset of his symptoms. He had a normal initial diagnostic workup, but subsequent workup initiated due to persistent clinical deterioration revealed CJD with typical MRI, EEG, and CSF findings. Other causes of rapidly progressive dementia and encephalopathy were ruled out. Though a rare condition, we recommend consideration of CJD on patients with expressive aphasia, progressive unexplained neurocognitive decline, and refractory epileptiform activity seen on EEG. Frequent reimaging (MRI, video EEGs and CSF examination might help diagnose this fatal condition earlier.

Creutzfeldt-Jakob disease: A great masquerade in neurology, a rare case report from South India

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Sivaprakash Varadan

2015-01-01

Full Text Available Creutzfeldt-Jakob disease (CJD is a rare, fatal neurodegenerative disease caused by an infectious protein called prion and is characterized by spongiform changes, neuronal loss, reactive astrocytic proliferation, and accumulation of pathologic cellular protein. Clinical presentation of CJD is characterized by rapidly progressive dementia, neurologic symptoms and visual impairment, and the development of akinetic mutism, which can mimic many neurological conditions. The diagnosis is based on clinical presentation, electroencephalogram, and typical cerebrospinal fluid and magnetic resonance imaging (MRI findings. Literature on the incidence and prevalence of CJD is lacking in South India. We report the case of a 57-year-old woman with progressive dementia and typical neurologic symptoms, myoclonic jerks, and MRI findings of CJD. This case highlights the need for a high index of suspicion to diagnose CJD.

Creutzfeldt-Jakob disease. What is the role of magnetic resonance tomography?; Creutzfeldt-Jakob-Krankheit. Welche Rolle spielt die MR-Tomographie?

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Kujat, C. [Inst. fuer Neuroradiologie der Univ. des Saarlandes, Homburg (Germany); Hagen, T. [Inst. fuer Neuroradiologie der Univ. des Saarlandes, Homburg (Germany); Feiden, W. [Abt. fuer Neuropathologie der Univ. des Saarlandes, Homburg (Germany)

1995-11-01

We report three patients with histologically confirmed CJD and confirm that MRI is a valuable tool for the diagnosis of this disease. (orig./MG) [Deutsch] Anhand der MRT-Ergebnisse von 3 Patienten mit histologisch gesicherter CJD und einer Literaturrecherche wird untersucht, ob die MRT einen Beitrag zur Diagnostik der CJD leisten kann. (orig./MG)

Creutzfeldt-Jakob disease: the value of MRI

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Urbach, H.; Tschampa, H.J.; Keller, E.; Schild, H.H.; Paus, S.

2001-01-01

To define the role of MRI in the diagnosis of Creutzfeldt-Jakob disease (CJD). Methods: 14 patients with suspected CJD were studied within 3 years. MRI findings were correlated with WHO established diagnostic criteria (clinical findings, EEG, CSF with 14-3-3 protein assay). Results: 12 patients had CJD. One patient each suffered from Hashimoto's encephalitis and ALS dementia complex, respectively. Nine of 12 CJD patients had increased signal intensity of the striatum (n = 8), pulvinar thalami (n = 5) and/or cerebellar and cerebral cortex (n = 3), respectively. Signal intensity was most pronounced on FLAIR sequences; six patients were studied with diffusion-weighted MRI and showed impaired diffusion in these areas. Both patients without CJD did not show the abovementioned signal changes (sensitivity 75%, specificity and positive predictive value 100%, respectively). Conclusion: If patients with suspected CJD are studied with FLAIR and diffusion-weighted sequences, this disorder can reliably be proven or ruled out. Typical MRI findings narrow down the differential diagnosis and should be included in the WHO diagnostic criteria. (orig.) [de

EEG Differences in Two Clinically Similar Rapid Dementias: Voltage-Gated Potassium Channel Complex-Associated Autoimmune Encephalitis and Creutzfeldt-Jakob Disease.

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Freund, Brin; Probasco, John C; Cervenka, Mackenzie C; Sutter, Raoul; Kaplan, Peter W

2018-05-01

Distinguishing treatable causes for rapidly progressive dementia from those that are incurable is vital. Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) are 2 such conditions with disparate outcomes and response to treatment. To determine the differences in electroencephalography between CJD and VGKC AE, we performed a retrospective review of medical records and examined clinical data, neuroimaging, and electroencephalographs performed in patients admitted for evaluation for rapidly progressive dementia diagnosed with CJD and VGKC AE at the Johns Hopkins Hospital and Bayview Medical Center between January 1, 2007 and December 31, 2015. More patients in the VGKC AE group had seizures (12/17) than those with CJD (3/14; P = .008). Serum sodium levels were lower in those with VGKC AE ( P = .001). Cerebrospinal fluid (CSF) white blood cell count was higher in VGKC AE ( P = .008). CSF protein 14-3-3 ( P = .018) was more commonly detected in CJD, and tau levels were higher in those with CJD ( P VGKC AE, and electroencephalography can aid in their diagnoses. Performing serial EEGs better delineates these conditions.

Can we share questions? Performance of questions from different question banks in a single medical school.

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Freeman, Adrian; Nicholls, Anthony; Ricketts, Chris; Coombes, Lee

2010-01-01

To use progress testing, a large bank of questions is required, particularly when planning to deliver tests over a long period of time. The questions need not only to be of good quality but also balanced in subject coverage across the curriculum to allow appropriate sampling. Hence as well as creating its own questions, an institution could share questions. Both methods allow ownership and structuring of the test appropriate to the educational requirements of the institution. Peninsula Medical School (PMS) has developed a mechanism to validate questions written in house. That mechanism can be adapted to utilise questions from an International question bank International Digital Electronic Access Library (IDEAL) and another UK-based question bank Universities Medical Assessment Partnership (UMAP). These questions have been used in our progress tests and analysed for relative performance. Data are presented to show that questions from differing sources can have comparable performance in a progress testing format. There are difficulties in transferring questions from one institution to another. These include problems of curricula and cultural differences. Whilst many of these difficulties exist, our experience suggests that it only requires a relatively small amount of work to adapt questions from external question banks for effective use. The longitudinal aspect of progress testing (albeit summatively) may allow more flexibility in question usage than single high stakes exams.

Genetic human prion disease modelled in PrP transgenic Drosophila.

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Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

2017-09-20

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

Inhibition of IL-1β Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease.

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Bertani, Ilaria; Iori, Valentina; Trusel, Massimo; Maroso, Mattia; Foray, Claudia; Mantovani, Susanna; Tonini, Raffaella; Vezzani, Annamaria; Chiesa, Roberto

2017-10-25

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice. Long-term potentiation (LTP) at the Schaffer collateral-commissural synapses in the CA1 area of ∼100-d-old Tg(CJD) mice was comparable to that of wild-type (WT) controls, but there was an inversion of metaplasticity, with increased GluN2B phosphorylation, which is indicative of enhanced NMDAR activation. Similar but less marked changes were seen in PrP KO mice. At ∼300 d of age, the magnitude of LTP increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal synaptic responsiveness. Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT controls to focal hippocampal seizures induced by kainic acid. IL-1β-positive astrocytes increased in the Tg(CJD) hippocampus, and blocking IL-1 receptor signaling restored normal synaptic responses and reduced seizure susceptibility. These results indicate that alterations in NMDA-dependent glutamatergic transmission in Tg(CJD) mice do not depend solely on PrP functional loss. Moreover, astrocytic IL-1β plays a role in the enhanced synaptic responsiveness and seizure susceptibility, suggesting that targeting IL-1β signaling may offer a novel symptomatic treatment for CJD. SIGNIFICANCE STATEMENT Dementia and myoclonic jerks develop in individuals with Creutzfeldt-Jakob disease (CJD), an incurable brain disorder caused by alterations in prion protein structure. These individuals are prone to seizures and have high

When is a research question not a research question?

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Mayo, Nancy E; Asano, Miho; Barbic, Skye Pamela

2013-06-01

Research is undertaken to answer important questions yet often the question is poorly expressed and lacks information on the population, the exposure or intervention, the comparison, and the outcome. An optimal research question sets out what the investigator wants to know, not what the investigator might do, nor what the results of the study might ultimately contribute. The purpose of this paper is to estimate the extent to which rehabilitation scientists optimally define their research questions. A cross-sectional survey of the rehabilitation research articles published during 2008. Two raters independently rated each question according to pre-specified criteria; a third rater adjudicated all discrepant ratings. The proportion of the 258 articles with a question formulated as methods or expected contribution and not as what knowledge was being sought was 65%; 30% of questions required reworking. The designs which most often had poorly formulated research questions were randomized trials, cross-sectional and measurement studies. Formulating the research question is not purely a semantic concern. When the question is poorly formulated, the design, analysis, sample size calculations, and presentation of results may not be optimal. The gap between research and clinical practice could be bridged by a clear, complete, and informative research question.

Creutzfeldt-Jakob disease in Venezuela a case report

Directory of Open Access Journals (Sweden)

Alejandro J. Caraballo H.

1991-06-01

Full Text Available A case of Creutzfeldt-Jakob disease (CJD in a 32 year old man is presented. The clinical picture included a rapid progressive dementia associated with ataxia, global aphasia, myoclonus and pyramidal signs, death ocurred after 13 months. The diagnosis of CJD was confirmed by CT and neuropathological studies. This is the first report of CJD occurring in Venezuela.

Questions and Questioning Techniques: A View of Indonesian Students’ Preferences

Directory of Open Access Journals (Sweden)

Debora Tri Ragawanti

2009-01-01

Full Text Available This study investigated students’ preference on teacher’s questions and questionings techniques and more importantly on how they could facilitate or impede their learning. The results on teacher’s questioning techniques showed that random nomination was more preferred than pre-arranged format nomination. In addition, techniques of nominating volunteering students and of giving wait-time were disliked by most student-respondents. As for types of question, the yes/no question was favored by most of the respondents. Different from the yes/no question, the number of respondents leaning forward to the analysis question, questions about fact of life, and questions to state opinion did not show a significant difference from the number of those leaning against the same questions.

Caregiver burden in atypical dementias: comparing frontotemporal dementia, Creutzfeldt-Jakob disease, and Alzheimer's disease.

Science.gov (United States)

Uflacker, Alice; Edmondson, Mary C; Onyike, Chiadi U; Appleby, Brian S

2016-02-01

Caregiver burden is a significant issue in the treatment of dementia and a known contributor to institutionalization of patients with dementia. Published data have documented increased caregiver burden in behavioral variant frontotemporal dementia (bvFTD) compared to Alzheimer's disease (AD). Another atypical dementia with high-perceived caregiver burden is sporadic Creutzfeldt-Jakob disease (sCJD), but no formal studies have assessed this perception. The aim of this study was to compare caregiver burden across atypical dementia etiologies. 76 adults with atypical dementia (young-onset AD [YOAD], bvFTD, language variant FTD [lvFTD], and sCJD) were administered an abbreviated version of the Zarit Burden Interview (ZBI), Neuropsychiatric Inventory (NPI-Q), and other assessment instruments during a five-year time period at Johns Hopkins Hospital (JHH). A Cox regression model examined differences between disease categories that impact mean ZBI scores. Mean ZBI scores were significantly different between dementia etiologies, with bvFTD and sCJD having the highest caregiver burden (p = 0.026). Mean NPI-Q caregiver distress scores were highest in bvFTD and sCJD (p = 0.002), with sCJD and bvFTD also having the highest number of endorsed symptom domains (p = 0.012). On regression analyses, an interactive variable combining final diagnosis category and NPI-Q total severity score demonstrated statistically significant differences in mean ZBI scores for sCJD and bvFTD. This study demonstrates that bvFTD and sCJD have increased levels of caregiver burden, NPI-Q caregiver distress, total severity scores, and number of endorsed symptom domains. These results suggest that higher caregiver burden in bvFTD and sCJD are disease specific and possibly related to neuropsychiatric symptoms.

Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein.

Science.gov (United States)

Grangeon, Lou; Paquet, Claire; Bombois, Stephanie; Quillard-Muraine, Muriel; Martinaud, Olivier; Bourre, Bertrand; Lefaucheur, Romain; Nicolas, Gaël; Dumurgier, Julien; Gerardin, Emmanuel; Jan, Mary; Laplanche, Jean-Louis; Peoc'h, Katell; Hugon, Jacques; Pasquier, Florence; Maltête, David; Hannequin, Didier; Wallon, David

2016-01-01

Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001). Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

Serum uric acid and lipid profiles in sporadic Creutzfeldt-Jakob disease.

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Chen, Shuai; He, Shuang; Shang, Jun-Kui; Ma, Ming-Ming; Xu, Chang-Shui; Shi, Xiao-Hong; Zhang, Jie-Wen

2016-02-01

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease affecting the central nervous system. Brain lipid homeostasis and oxidative stress seem to play an important role in the disease pathogenesis. But little was known whether serum lipids and uric acid (a natural antioxidant) levels changed in patients with prion disease. Here we retrospectively reviewed and compared the serum lipids and uric acid levels of 19 probable sporadic CJD patients and 26 healthy control subjects. We found that the serum uric acid levels in sporadic CJD patients were significantly lower than that in controls (P=0.01). Serum triglycerides, cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and apolipoprotein A1 (ApoA1) were similar in sporadic CJD patients and controls. However, LDL/HDL ratio was lower in sporadic CJD patients (P=0.003). The low serum uric acid and LDL/HDL ratio levels in sporadic CJD indicate that dysfunction in the lipid homeostasis and oxidative stress is associated with sporadic prion disease. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Brain Dopamine Transporter Binding and Glucose Metabolism in Progressive Supranuclear Palsy-Like Creutzfeldt-Jakob Disease

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Eero Rissanen

2014-01-01

Full Text Available Here, we present a patient with Creutzfeldt-Jakob disease (CJD who developed initial symptoms mimicking progressive supranuclear palsy (PSP. Before the development of typical CJD symptoms, functional imaging supported a diagnosis of PSP when [123I]-FP-CIT-SPECT showed a defect in striatal dopamine transporter binding, while [18F]-fluorodeoxyglucose PET showed cortical hypometabolism suggestive of Lewy body dementia. However, the postmortem neuropathological examination was indicative of CJD only, without tau protein or Lewy body findings. This case demonstrates that CJD should be taken into account in rapidly progressing atypical cases of parkinsonism, even when functional imaging supports a diagnosis of a movement disorder.

Creutzfeldt-Jakob disease and lyophilised dura mater grafts: report of two cases.

Science.gov (United States)

Esmonde, T; Lueck, C J; Symon, L; Duchen, L W; Will, R G

1993-01-01

Two further cases of Creutzfeldt-Jakob disease (CJD) in association with cadaveric dura mater grafts are described. The clinical features of all such reported cases resemble more closely those of sporadic CJD, in contrast with kuru and the cases of CJD which have arisen after therapy with human pituitary-derived growth hormone. This observation may reflect the route of inoculation of the agent. PMID:8410042

Question popularity analysis and prediction in community question answering services.

Science.gov (United States)

Liu, Ting; Zhang, Wei-Nan; Cao, Liujuan; Zhang, Yu

2014-01-01

With the blooming of online social media applications, Community Question Answering (CQA) services have become one of the most important online resources for information and knowledge seekers. A large number of high quality question and answer pairs have been accumulated, which allow users to not only share their knowledge with others, but also interact with each other. Accordingly, volumes of efforts have been taken to explore the questions and answers retrieval in CQA services so as to help users to finding the similar questions or the right answers. However, to our knowledge, less attention has been paid so far to question popularity in CQA. Question popularity can reflect the attention and interest of users. Hence, predicting question popularity can better capture the users' interest so as to improve the users' experience. Meanwhile, it can also promote the development of the community. In this paper, we investigate the problem of predicting question popularity in CQA. We first explore the factors that have impact on question popularity by employing statistical analysis. We then propose a supervised machine learning approach to model these factors for question popularity prediction. The experimental results show that our proposed approach can effectively distinguish the popular questions from unpopular ones in the Yahoo! Answers question and answer repository.

Robustness Analysis of Visual Question Answering Models by Basic Questions

KAUST Repository

Huang, Jia-Hong

2017-11-01

Visual Question Answering (VQA) models should have both high robustness and accuracy. Unfortunately, most of the current VQA research only focuses on accuracy because there is a lack of proper methods to measure the robustness of VQA models. There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the ranked basic questions, with similarity scores, of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question about the given image. We claim that a robust VQA model is one, whose performance is not changed much when related basic questions as also made available to it as input. We formulate the basic questions generation problem as a LASSO optimization, and also propose a large scale Basic Question Dataset (BQD) and Rscore (novel robustness measure), for analyzing the robustness of VQA models. We hope our BQD will be used as a benchmark for to evaluate the robustness of VQA models, so as to help the community build more robust and accurate VQA models.

Robustness Analysis of Visual Question Answering Models by Basic Questions

KAUST Repository

Huang, Jia-Hong

2017-01-01

Visual Question Answering (VQA) models should have both high robustness and accuracy. Unfortunately, most of the current VQA research only focuses on accuracy because there is a lack of proper methods to measure the robustness of VQA models. There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the ranked basic questions, with similarity scores, of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question about the given image. We claim that a robust VQA model is one, whose performance is not changed much when related basic questions as also made available to it as input. We formulate the basic questions generation problem as a LASSO optimization, and also propose a large scale Basic Question Dataset (BQD) and Rscore (novel robustness measure), for analyzing the robustness of VQA models. We hope our BQD will be used as a benchmark for to evaluate the robustness of VQA models, so as to help the community build more robust and accurate VQA models.

Two-Year-Old Children Differentiate Test Questions from Genuine Questions

Science.gov (United States)

Grosse, Gerlind; Tomasello, Michael

2012-01-01

Children are frequently confronted with so-called "test questions". While genuine questions are requests for missing information, test questions ask for information obviously already known to the questioner. In this study we explored whether two-year-old children respond differentially to one and the same question used as either a genuine question…

Nuclear questions; Le nucleaire en questions

Energy Technology Data Exchange (ETDEWEB)

Berg, Eugene

2012-02-15

Civilian and military nuclear questions fill a multitude of publications these days, especially after the Japanese tsunami and the Fukushima disaster. The author analyses some of them and highlights the links between civil and military nuclear industries, the realities of the nuclear cycle and related industrial questions before concluding on the controversial issue of weapons and their proliferation potential

Creutzfeldt-Jakob Disease with Mixed Transcortical Aphasia: Insights into Echolalia

OpenAIRE

McPherson, S. E.; Kuratani, J. D.; Cummings, J. L.; Shih, J.; Mischel, P. S.; Vinters, H. V.

1994-01-01

Aphasia is a common manifestation of Creutzfeldt-Jakob disease (CJD), and investigation of the linguistic disorders of CJD patients may provide insights into the neurobiological mechanisms of language and aphasia. We report an autopsy-confirmed case of CJD in which the presenting symptom was change in language abilities. The patient ultimately evidenced mixed transcortical aphasia (MTA) with echolalia. Disruption of frontal-subcortical circuits with environmental dependency accounts for the s...

Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease

OpenAIRE

Grau-Rivera, O.; Sánchez del Valle Díaz, Raquel; Saiz Hinajeros, Albert; Molinuevo, José L.; Bernabé, Reyes; Munteis, Elvira; Pujadas, Francesc; Salvador, Antoni; Saura, Júlia; Ugarte, Antonio; Titulaer, Maarten; Dalmau Obrador, Josep; Graus Ribas, Francesc

2014-01-01

IMPORTANCE Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. OBJECTIVE To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. DESIGN, SETTING, AND PARTICIPANTS A mixed ...

Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata-Possible Routes of Infection and Host Susceptibility.

Science.gov (United States)

Iacono, Diego; Ferrari, Sergio; Gelati, Matteo; Zanusso, Gianluigi; Mariotto, Sara; Monaco, Salvatore

2015-01-01

Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an "environmental exposure" might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a "triple match" hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.

Regulation of human cerebrospinal fluid malate dehydrogenase 1 in sporadic Creutzfeldt-Jakob disease patients.

Science.gov (United States)

Schmitz, Matthias; Llorens, Franc; Pracht, Alexander; Thom, Tobias; Correia, Ângela; Zafar, Saima; Ferrer, Isidre; Zerr, Inga

2016-11-14

The identification of reliable diagnostic biomarkers in differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous two-dimensional proteomic study on cerebrospinal fluid (CSF) revealed an elevated level of an enzyme, mitochondrial malate dehydrogenase 1 (MDH1), in sporadic Creutzfeldt-Jakob disease (sCJD) patients. Here, we could demonstrate the expression of MDH1 in neurons as well as in the neuropil. Its levels are lower in sCJD brains than in control brains. An examination of CSF-MDH1 in sCJD patients by ELISA revealed a significant elevation of CSF-MDH1 levels in sCJD patients (independently from the PRNP codon 129 MV genotype or the prion protein scrapie (PrP Sc ) type) in comparison to controls. In combination with total tau (tau), CSF-MDH1 detection exhibited a high diagnostic accuracy for sCJD diagnosis with a sensitivity of 97.5% and a specificity of 95.6%. A correlation study of MDH1 level in CSF with other neurodegenerative marker proteins revealed a significant positive correlation between MDH1 concentration with tau, 14-3-3 and neuron specific enolase level. In conclusion, our study indicated the potential of MDH1 in combination with tau as an additional biomarker in sCJD improving diagnostic accuracy of tau markedly.

Can multiple-choice questions simulate free-response questions?

OpenAIRE

Lin, Shih-Yin; Singh, Chandralekha

2016-01-01

We discuss a study to evaluate the extent to which free-response questions could be approximated by multiple-choice equivalents. Two carefully designed research-based multiple-choice questions were transformed into a free-response format and administered on the final exam in a calculus-based introductory physics course. The original multiple-choice questions were administered in another similar introductory physics course on final exam. Findings suggest that carefully designed multiple-choice...

Four Questions

Science.gov (United States)

Hark-Weber, Amara G., Ed.

2013-01-01

The author is pleased to introduce a new section in "TAJ," Four Questions. The structure is simple: four questions are asked to teaching artists working in various media and locations. The questions are always the same, but because each teaching artist's approach is unique, their answers will provide an insight into particular methodologies that…

Phrasal Paraphrase Based Question Reformulation for Archived Question Retrieval.

Directory of Open Access Journals (Sweden)

Yu Zhang

Full Text Available Lexical gap in cQA search, resulted by the variability of languages, has been recognized as an important and widespread phenomenon. To address the problem, this paper presents a question reformulation scheme to enhance the question retrieval model by fully exploring the intelligence of paraphrase in phrase-level. It compensates for the existing paraphrasing research in a suitable granularity, which either falls into fine-grained lexical-level or coarse-grained sentence-level. Given a question in natural language, our scheme first detects the involved key-phrases by jointly integrating the corpus-dependent knowledge and question-aware cues. Next, it automatically extracts the paraphrases for each identified key-phrase utilizing multiple online translation engines, and then selects the most relevant reformulations from a large group of question rewrites, which is formed by full permutation and combination of the generated paraphrases. Extensive evaluations on a real world data set demonstrate that our model is able to characterize the complex questions and achieves promising performance as compared to the state-of-the-art methods.

[Perioperative considerations for performing a brain biopsy on a patient with subtype VV2 sporadic Creutzfeldt-Jakob disease].

Science.gov (United States)

Guerrero-Domínguez, R; Rubio-Romero, R; González-González, G; Jiménez, I

2015-04-01

Creutzfeldt-Jakob disease (CJD) is the most common transmissible spongiform encephalopathy. It is an infectious, progressive, degenerative neurological disorder, with a presumably long incubation period, but a rapid fatal course. CJD is transmitted by a proteinaceous infectious agent, or «prion». Because the prions are difficult to eradicate and are resistant to the currently used sterilization methods, special precautions must be taken with all surgical instruments. It is recommended the single-use equipment, destruction of contaminated equipment, decontamination of reusable instruments, use of protective clothing, and storing and quarantining surgical instruments. The single-use equipment and some tissues and body fluids from the patient with CJD are highly infectious and must be incinerated. We report a case of a patient who had undergone brain biopsy for suspected of CJD, being confirmed to have sporadic CJD. Specific preventive measures were taken to reduce the risk of transmission to healthcare workers. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

The Prion Protein Preference of Sporadic Creutzfeldt-Jakob Disease Subtypes*

Science.gov (United States)

Klemm, Helen M. J.; Welton, Jeremy M.; Masters, Colin L.; Klug, Genevieve M.; Boyd, Alison; Hill, Andrew F.; Collins, Steven J.; Lawson, Victoria A.

2012-01-01

Sporadic Creutzfeldt-Jakob disease (CJD) is the most prevalent manifestation of the transmissible spongiform encephalopathies or prion diseases affecting humans. The disease encompasses a spectrum of clinical phenotypes that have been correlated with molecular subtypes that are characterized by the molecular mass of the protease-resistant fragment of the disease-related conformation of the prion protein and a polymorphism at codon 129 of the gene encoding the prion protein. A cell-free assay of prion protein misfolding was used to investigate the ability of these sporadic CJD molecular subtypes to propagate using brain-derived sources of the cellular prion protein (PrPC). This study confirmed the presence of three distinct sporadic CJD molecular subtypes with PrPC substrate requirements that reflected their codon 129 associations in vivo. However, the ability of a sporadic CJD molecular subtype to use a specific PrPC substrate was not determined solely by codon 129 as the efficiency of prion propagation was also influenced by the composition of the brain tissue from which the PrPC substrate was sourced, thus indicating that nuances in PrPC or additional factors may determine sporadic CJD subtype. The results of this study will aid in the design of diagnostic assays that can detect prion disease across the diversity of sporadic CJD subtypes. PMID:22930754

Preserved regional cerebral blood flow in the occipital cortices, brainstem, and cerebellum of patients with V180I-129M genetic Creutzfeldt-Jakob disease in serial SPECT studies.

Science.gov (United States)

Hayashi, Yuichi; Yoshikura, Nobuaki; Takekoshi, Akira; Yamada, Megumi; Asano, Takahiko; Kimura, Akio; Satoh, Katsuya; Kitamoto, Tetsuyuki; Inuzuka, Takashi

2016-11-15

Creutzfeldt-Jakob disease (CJD) with a causative point mutation of valine to isoleucine at codon 180 (V180I) is one of the major types of genetic CJD (gCJD) in Japan. V180I gCJD is rarely accompanied by a family history, and its clinical characteristics include late-onset, long disease duration, and edematous cortical hyperintensity in diffusion, fluid attenuate inversion and T2-weighted MRI. We performed serial imaging with single-photon emission computed tomography (SPECT) and MRI in three V180I gCJD cases over long-term observation. All cases were characterized by progressive dementia, parkinsonism, and the absence of cerebellar signs or cortical visual dysfunction in their clinical courses. Moreover, during the end-stage, SPECT findings showed preserved regional cerebral blood flow (rCBF) in the occipital cortices, brainstem, and cerebellum. Similarly, no apparent atrophy or increased signal intensities were observed in MRI images of the occipital and cerebellar regions. In conclusion, we report a decrease in rCBF predominantly in the frontal and temporal cortices during the early-stage, which became more widespread as the disease progressed. Importantly, rCBF was preserved in the occipital cortices, brainstem, and cerebellar regions until the end-stage, which may be distinct to V180I gCJD cases. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuropsychological Symptoms in Sporadic Creutzfeldt-Jakob Disease Patients in Germany.

Science.gov (United States)

Krasnianski, Anna; Bohling, Geeske T; Heinemann, Uta; Varges, Daniela; Meissner, Bettina; Schulz-Schaeffer, Walter J; Reif, Andreas; Zerr, Inga

2017-01-01

The polymorphism at codon 129 of the prion protein gene (PRNP) and the PrPSc types 1 and 2 belong to a molecular classification of sporadic Creutzfeldt-Jakob disease (sCJD) that correlates well with the clinical and neuropathological phenotype of sCJD. The aim of the study was to perform the first detailed evaluation of neuropsychological deficits in a large group of definite sCJD patients with known molecular subtype. We analyzed neuropsychological symptoms in a cohort of 248 sCJD patients with known M129 V polymorphism of PRNP and prion protein type. Neuropsychological symptoms were very frequent in our patients (96%) and occurred as early as in the first third of the disease course. Besides amnesia and impaired attention (89% each), frontal lobe syndrome (75%), aphasia (63%), and apraxia (57%) were the most common neuropsychological deficits. There was no statistically significant difference with regard to frequency of neuropsychological symptoms between the subtypes. In MV2 and VV2 patients, the onset of neuropsychological symptoms was significantly later than in all other subtypes. We provide the first detailed analysis of neuropsychological symptoms in a large group of sCJD patients with known M129 V genotype and prion protein type. We suggest that the rate of progression of neuropsychological symptoms is subtype-specific. These data may improve the diagnosis in atypical sCJD subtypes.

Neuronal antibodies in patients with suspected or confirmed sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Rossi, Meghan; Mead, Simon; Collinge, John; Rudge, Peter; Vincent, Angela

2015-06-01

There have been reports of patients with antibodies to neuronal antigens misdiagnosed as sporadic Creutzfeldt-Jakob disease (sCJD). Conversely, low levels of antibodies to neuronal proteins have been reported in patients with sCJD. However, the frequency of misdiagnoses, or of antibodies in patients with subsequently confirmed sCJD, is not clear. We reviewed 256 consecutive cases of sCJD seen in the National Prion Clinic, of whom 150 had sera previously referred for selected antibody tests. Eighty-two available samples were retested for antibodies to N-methyl-d-aspartate receptor (NMDAR), the glycine receptor (GlyR), voltage-gated potassium channel (VGKC)-complex and the associated proteins, leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2). Four of the initial 150 sera referred were positive; two had antibodies to NMDAR, and two to the VGKC-complex, one of which was also positive for GlyR antibodies. Of the 82 sCJD sera retested, one had VGKC-complex antibodies confirming the previous result, two had CASPR2 and GlyR antibodies and one had CASPR2 and NMDAR antibodies; all antibodies were at low levels. Over the same period three patients with autoimmune encephalitis and high VGKC-complex antibodies were initially referred as sCJD. This study indicates that VGKC-complex/LGI1 antibodies. Low titres of neuronal antibodies occur only rarely in suspected patients with sCJD and when present should be interpreted with caution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Disease: H00061 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available se (GSD); Gerstmann-Straussler-Scheinker disease (GSSD); Fatal familial insomnia (FFI) Prion diseases, also ...einker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to

Antithyroideaantistof hos to patienter med subakut dementiel udvikling, ataksi og myoklonus

DEFF Research Database (Denmark)

Kondziella, Daniel; Hansen, Klaus; Gonzalez, Teresa

2012-01-01

Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus...... and positive antithyroid antibodies were given oral steroids. Whereas one progressively declined and had histopathologically proven CJD, the other made a complete recovery and was diagnosed with HE. Anti-thyroid antibodies can occur in CJD, but when present in a patient with subacute dementia, ataxia...

Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

Science.gov (United States)

Llorens, Franc; Kruse, Niels; Karch, André; Schmitz, Matthias; Zafar, Saima; Gotzmann, Nadine; Sun, Ting; Köchy, Silja; Knipper, Tobias; Cramm, Maria; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel P; Sánchez-Valle, Raquel; Fischer, Andre; Mollenhauer, Brit; Zerr, Inga

2018-03-01

The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

Differential diagnosis of Jakob-Creutzfeldt disease.

Science.gov (United States)

Paterson, Ross W; Torres-Chae, Charles C; Kuo, Amy L; Ando, Tim; Nguyen, Elizabeth A; Wong, Katherine; DeArmond, Stephen J; Haman, Aissa; Garcia, Paul; Johnson, David Y; Miller, Bruce L; Geschwind, Michael D

2012-12-01

To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Retrospective medical record review. A specialty referral center of a tertiary academic medical center. One hundred sixty-three serial patients over a 5.5-year period who ultimately had pathologically proven sCJD. The study used the subset of 97 patients for whom we had adequate medical records. Other diagnoses considered in the differential diagnosis and types of medical specialties assessing patients with sCJD. Ninety-seven subjects' records were used in the final analysis. The most common disease categories of misdiagnosis were neurodegenerative, autoimmune/paraneoplastic, infectious, and toxic/metabolic disorders. The most common individual misdiagnoses were viral encephalitis, paraneoplastic disorder, depression, vertigo, Alzheimer disease, stroke, unspecified dementia, central nervous system vasculitis, peripheral neuropathy, and Hashimoto encephalopathy. The physicians who most commonly made these misdiagnoses were primary care physicians and neurologists; in the 18% of patients who were diagnosed correctly at their first assessment, the diagnosis was almost always by a neurologist. The mean time from onset to diagnosis was 7.9 months, an average of two-thirds of the way through their disease course. Diagnosis of sCJD is quite delayed. When evaluating patients with rapidly progressive dementia with suspected neurodegenerative, autoimmune, infectious, or toxic/metabolic etiology, sCJD should also be included in the differential diagnosis, and appropriate diagnostic tests, such as diffusion brain magnetic resonance imaging, should be considered. Primary care physicians and neurologists need improved training in sCJD diagnosis.

Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

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Dirzius, Edgaras; Balnyte, Renata; Steibliene, Vesta; Gleizniene, Rymante; Gudinaviciene, Inga; Radziunas, Andrius; Petrikonis, Kestutis

2016-11-22

Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

Science.gov (United States)

Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

2016-12-01

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

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Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

2016-06-12

Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Fatal degenerative neurologic illnesses in men who participated in wild game feasts--Wisconsin, 2002.

Science.gov (United States)

2003-02-21

Creutzfeldt-Jakob disease (CJD) is a fatal neurologic disorder in humans. CJD is one of a group of conditions known as transmissible spongiform encephalopathies (TSEs), or prion diseases, that are believed to be caused by abnormally configured, host-encoded prion proteins that accumulate in the central nervous tissue. CJD has an annual incidence of approximately 1 case per million population in the United States and occurs in three forms: sporadic, genetically determined, and acquired by infection. In the latter form, the incubation period is measured typically in years. Recent evidence that prion infection can cross the species barrier between humans and cattle has raised increasing public health concerns about the possible transmission to humans of a TSE among deer and elk known as chronic wasting disease (CWD). During 1993-1999, three men who participated in wild game feasts in northern Wisconsin died of degenerative neurologic illnesses. This report documents the investigation of these deaths, which was initiated in August 2002 and which confirmed the death of only one person from CJD. Although no association between CWD and CJD was found, continued surveillance of both diseases remains important to assess the possible risk for CWD transmission to humans.

Progress report of CJD

International Nuclear Information System (INIS)

2002-01-01

This paper is the progress report of the Russian Nuclear Data Center at F.E.I., Obninsk. Evaluations have been made for dosimetry reactions and neutron reactions. Analysis of the spectra and the production cross sections were made. (a.n.)

Treating seizures in Creutzfeldt-Jakob disease.

Science.gov (United States)

Ng, Marcus C; Westover, M Brandon; Cole, Andrew J

2014-01-01

Seizures are known to occur in Creutzfeldt-Jakob disease (CJD). In the setting of a rapidly progressive condition with no effective therapy, determining appropriate treatment for seizures can be difficult if clinical morbidity is not obvious yet the electroencephalogram (EEG) demonstrates a worrisome pattern such as status epilepticus. Herein, we present the case of a 39-year-old man with CJD and electrographic seizures, discuss how this case challenges conventional definitions of seizures, and discuss a rational approach toward treatment. Coincidentally, our case is the first report of CJD in a patient with Stickler syndrome.

The association of neuroleptic sensitivity in Lewy body disease with a false positive clinical diagnosis of Creutzfeldt-Jakob disease

NARCIS (Netherlands)

Lemstra, A. W.; Schoenmaker, N.; Rozemuller-Kwakkel, A. J. M.; van Gool, W. A.

2006-01-01

BACKGROUND: Dementia with Lewy bodies (DLB) and Creutzfeldt-Jakob disease (CJD) share clinical features like cognitive decline, motor disturbances en psychiatric symptoms. Overlapping symptoms may cause physicians to mistake DLB for CJD. METHODS: Clinical data of 12 patients with autopsy-confirmed

Socratic Questioning-Guided Discovery

Directory of Open Access Journals (Sweden)

M. Hakan Türkçapar

2012-04-01

Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after eachstep. [JCBPR 2012; 1(1.000: 15-20

Genetics Home Reference: prion disease

Science.gov (United States)

... which have overlapping signs and symptoms, include familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal ... Sc . Sporadic forms of prion disease include sporadic Creutzfeldt-Jakob disease (sCJD), sporadic fatal insomnia (sFI), and variably protease- ...

MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

International Nuclear Information System (INIS)

Urbach, H.; Solymosi, L.; Klisch, J.; Brechtelsbauer, D.; Wolf, H.K.; Gass, S.

1998-01-01

To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.)

Diagnosing Sporadic Creutzfeldt-Jakob Disease in a Patient with a Suspected Status Epilepticus in the Intensive Care Unit

Directory of Open Access Journals (Sweden)

Harm J. van der Horn

2013-01-01

Full Text Available Objective. Several tests are available in the diagnostics of sporadic Creutzfeldt-Jakob disease (sCJD; however, none of these is conclusive. We review the values of these tests, from an intensive care unit (ICU perspective. Methods. Case report and review of the literature. Results. A 53-year-old woman initially presenting with psychiatric symptoms developed myoclonus and was admitted 1 month later to the ICU with a suspected nonconvulsive status epilepticus and respiratory insufficiency, probably due to extensive antiepileptic drug therapy. Typical MRI and EEG findings and a positive 14-3-3 protein led to the diagnosis of sCJD. All treatments were terminated, and autopsy confirmed sCJD. Conclusions. Clinical signs combined with MRI, EEG, and 14-3-3 and/or tau protein determination might be sufficient to diagnose or exclude sCJD and may therefore prevent the application of unnecessary diagnostic tests.

Beginning EFL Teachers' Beliefs about Quality Questions and Their Questioning Practices

Science.gov (United States)

Pham, Ly Ngoc Khanh; Hamid, M. Obaidul

2013-01-01

Motivated by the scarcity of research that examines the impact of teacher beliefs on their actual practices in Vietnam, this study investigated the relationship between teachers' beliefs about quality questions and their questioning behaviours in terms of questioning purposes, content focus, students' cognitive level, wording and syntax. Thirteen…

Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Llorens, Franc; Thüne, Katrin; Sikorska, Beata; Schmitz, Matthias; Tahir, Waqas; Fernández-Borges, Natalia; Cramm, Maria; Gotzmann, Nadine; Carmona, Margarita; Streichenberger, Nathalie; Michel, Uwe; Zafar, Saima; Schuetz, Anna-Lena; Rajput, Ashish; Andréoletti, Olivier; Bonn, Stefan; Fischer, Andre; Liberski, Pawel P; Torres, Juan Maria; Ferrer, Isidre; Zerr, Inga

2017-04-27

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP Sc ). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca 2+ ) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca 2+ responsive genes in sCJD brain tissue, accompanied by two Ca 2+ -dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrP Sc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca 2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention.

Repetitive Questioning II

Directory of Open Access Journals (Sweden)

R. C. Hamdy MD

2018-02-01

Full Text Available Repetitive questioning is a major problem for caregivers, particularly taxing if they are unable to recognize and understand the reasons why their loved one keeps asking the same question over and over again. Caregivers may be tempted to believe that the patient does not even try to remember the answer given or is just getting obnoxious. This is incorrect. Repetitive questioning is due to the underlying disease: The patient’s short term memory is impaired and he is unable to register, encode, retain and retrieve the answer. If he is concerned about a particular topic, he will keep asking the same question over and over again. To the patient each time she asks the question, it is as if she asked it for the first time. Just answering repetitive questioning by providing repeatedly the same answer is not sufficient. Caregivers should try to identify the underlying cause for this repetitive questioning. In an earlier case study, the patient was concerned about her and her family’s safety and kept asking whether the doors are locked. In this present case study, the patient does not know how to handle the awkward situation he finds himself in. He just does not know what to do. He is not able to adjust to the new unexpected situation. So he repeatedly wants to reassure himself that he is not intruding by asking the same question over and over again. We discuss how the patient’s son-in-law could have avoided this situation and averted the catastrophic ending.

Health professions and risk of sporadic Creutzfeldt- Jakob disease, 1965 to 2010

NARCIS (Netherlands)

E. Alcalde-Cabero; J. Almazán-Isla; J-P. Brandel (Jean-Philippe); M. Breithaupt; J. Catarino; S.J. Collins (Steven); J. Haybäck; R. Höftberger (Romana); E. Kahana; G.G. Kovacs (Gabor); A. Ladogana (Anna); E. Mitrová (Eva); A. Molesworth; Y. Nakamura; M. Pocchiari (Maurizio); M. Popovic; M. Ruiz-Tovar; A. Taratuto; C. van Duin; M. Yamada; R.G. Will (Robert); I. Zerr (Inga); J. de Pedro-Cuesta (Jesús)

2012-01-01

textabstractIn 2009, a pathologist with sporadic Creutzfeldt- Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network

The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

DEFF Research Database (Denmark)

Bahl, Justyna Maria Czarna; Heegaard, Niels Henrik Helweg; Falkenhorst, Gerhard

2009-01-01

) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE......Laboratory markers have a prominent place among the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and neuron-specific enolase (NSE) in cerebrospinal fluid (CSF...

Stereotypic Movements in Case of Sporadic Creutzfeldt-Jakob Disease: Possible Role of Anti-NMDA Receptor Antibodies

Directory of Open Access Journals (Sweden)

Michelle Molina

2012-12-01

Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD and anti-NMDA receptor antibody encephalitis (NMDAE can both produce a rapidly progressive dementia with resulting state of catatonia or akinetic mutism. Both are associated with movement disorders. In published case series, myoclonus appears to be the most frequent movement disorder in sCJD, while stereotypic, synchronized, one-cycle-per-second movements such as arm or leg elevation, jaw opening, grimacing, head turning, and eye deviation are seen in NMDAE. We report a case of a 59-year-old woman with rapidly worsening cognitive disturbance leading to a nearly catatonic state interrupted by stereotypic movements. sCJD was diagnosed via periodic sharp wave complexes on EEG as well as cerebrospinal fluid (CSF 14-3-3 and tau protein elevation. Characteristic movement disorder of NMDAE was present in absence of ovarian mass or CSF pleiocytosis. Given prior case reports of presence of anti-NMDA receptor antibodies in sCJD, we propose that the movement disorder in this case was caused by anti-NMDA receptor antibodies whose formation was secondary to neuronal damage from prion disease. It is important to consider sCJD even in cases that have some clinical features suggestive of NMDAE.

Comparison between Two Assessment Methods; Modified Essay Questions and Multiple Choice Questions

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Assadi S.N.* MD

2015-09-01

Full Text Available Aims Using the best assessment methods is an important factor in educational development of health students. Modified essay questions and multiple choice questions are two prevalent methods of assessing the students. The aim of this study was to compare two methods of modified essay questions and multiple choice questions in occupational health engineering and work laws courses. Materials & Methods This semi-experimental study was performed during 2013 to 2014 on occupational health students of Mashhad University of Medical Sciences. The class of occupational health and work laws course in 2013 was considered as group A and the class of 2014 as group B. Each group had 50 students.The group A students were assessed by modified essay questions method and the group B by multiple choice questions method.Data were analyzed in SPSS 16 software by paired T test and odd’s ratio. Findings The mean grade of occupational health and work laws course was 18.68±0.91 in group A (modified essay questions and was 18.78±0.86 in group B (multiple choice questions which was not significantly different (t=-0.41; p=0.684. The mean grade of chemical chapter (p<0.001 in occupational health engineering and harmful work law (p<0.001 and other (p=0.015 chapters in work laws were significantly different between two groups. Conclusion Modified essay questions and multiple choice questions methods have nearly the same student assessing value for the occupational health engineering and work laws course.

Formative student-authored question bank: perceptions, question quality and association with summative performance.

Science.gov (United States)

Walsh, Jason L; Harris, Benjamin H L; Denny, Paul; Smith, Phil

2018-02-01

There are few studies on the value of authoring questions as a study method, the quality of the questions produced by students and student perceptions of student-authored question banks. Here we evaluate PeerWise, a widely used and free online resource that allows students to author, answer and discuss multiple-choice questions. We introduced two undergraduate medical student cohorts to PeerWise (n=603). We looked at their patterns of PeerWise usage; identified associations between student engagement and summative exam performance; and used focus groups to assess student perceptions of the value of PeerWise for learning. We undertook item analysis to assess question difficulty and quality. Over two academic years, the two cohorts wrote 4671 questions, answered questions 606 658 times and posted 7735 comments. Question writing frequency correlated most strongly with summative performance (Spearman's rank: 0.24, p=<0.001). Student focus groups found that: (1) students valued curriculum specificity; and (2) students were concerned about student-authored question quality. Only two questions of the 300 'most-answered' questions analysed had an unacceptable discriminatory value (point-biserial correlation <0.2). Item analysis suggested acceptable question quality despite student concerns. Quantitative and qualitative methods indicated that PeerWise is a valuable study tool. © 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.

Nuclear questions

International Nuclear Information System (INIS)

Berg, Eugene

2012-01-01

Civilian and military nuclear questions fill a multitude of publications these days, especially after the Japanese tsunami and the Fukushima disaster. The author analyses some of them and highlights the links between civil and military nuclear industries, the realities of the nuclear cycle and related industrial questions before concluding on the controversial issue of weapons and their proliferation potential

Approaches to Exploring Category Information for Question Retrieval in Community Question-Answer Archives

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Cui, Bin

2012-01-01

, and it applies these approaches to existing question retrieval models, including a state-of-the-art question retrieval model. Experiments conducted on real CQA data demonstrate that the proposed techniques are effective and efficient and are capable of outperforming a variety of baseline methods significantly......Community Question Answering (CQA) is a popular type of service where users ask questions and where answers are obtained from other users or from historical question-answer pairs. CQA archives contain large volumes of questions organized into a hierarchy of categories. As an essential function...

Questioning ORACLE: An Assessment of ORACLE's Analysis of Teachers' Questions and [A Comment on "Questioning ORACLE"].

Science.gov (United States)

Scarth, John; And Others

1986-01-01

Analysis of teachers' questions, part of the ORACLE (Observation Research and Classroom Learning Evaluation) project research, is examined in detail. Scarth and Hammersley argue that the rules ORACLE uses for identifying different types of questions involve levels of ambiguity and inference that threaten reliability and validity of the study's…

A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk

NARCIS (Netherlands)

P. Sanchez-Juan (Pascual); M.T. Bishop (Matthew); G.G. Kovacs (Gabor); M. Calero (Miguel); Y.S. Aulchenko (Yurii); A. Ladogana (Anna); A. Boyd (Alison); V. Lewis (Victoria); C. Ponto (Claudia); Calero, O. (Olga); A. Poleggi (Anna); A. Carracedo (Angel); S.J. van der Lee (Sven); T. Ströbel (Thomas); F. Rivadeneira Ramirez (Fernando); A. Hofman (Albert); S. Haik; O. Combarros (Onofre); J. Berciano (José); A.G. Uitterlinden (André); S.J. Collins (Steven); H. Budka (Herbert); J-P. Brandel (Jean-Philippe); J.-L. Laplanche (Jean-Louis); M. Pocchiari (Maurizio); I. Zerr (Inga); R. Knight (Richard); R.G. Will (Robert); C.M. van Duijn (Cornelia)

2015-01-01

textabstractWe performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a

Description and analysis of 12 years of surveillance for Creutzfeldt-Jakob disease in Denmark, 1997 to 2008

DEFF Research Database (Denmark)

Gubbels, S; Bacci, S; Laursen, H

2012-01-01

those in other countries, has a multidisciplinary approach, which is labour-intensive and time-consuming but ensures the most complete set of information possible. With this approach we think that patients with variant CJD would have been detected had they occurred in Denmark. Certain aspects of CJD...

Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies.

NARCIS (Netherlands)

D.P.W.M. Wientjens (Dorothee); Z. Davanipour; K. Kondo; W.B. Matthews; R.G. Will (Robert); C.M. van Duijn (Cornelia); A. Hofman (Albert)

1996-01-01

textabstractTo review the evidence for risk factors of Creutzfeldt-Jakob disease (CJD), we pooled and reanalyzed the raw data of three case-control studies. The pooled data set comprised 178 patients and 333 control subjects. The strength of association between CJD and putative risk factors was

Curiosity Questions

Science.gov (United States)

Nelsen, Jane; DeLorenzo, Chip

2010-01-01

Have you ever found yourself lecturing a child, with the best of intentions, in an attempt to help him or her learn a lesson or process a situation in a manner that you feel will be productive? Curiosity questions, which the authors also call What and How questions, help children process an experience, event, or natural consequence so that they…

Sporadic Creutzfeldt–Jakob disease with cerebellar ataxia at onset in the UK

Science.gov (United States)

Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

2006-01-01

Objective To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods A retrospective review of autopsy‐proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)‐129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause. PMID:16835290

MRI in sporadic Creutzfeldt-Jakob disease: Correlation with clinical and neuropathological data

Energy Technology Data Exchange (ETDEWEB)

Urbach, H.; Solymosi, L. [Department of Neuroradiology, University of Wuerzburg (Germany); Klisch, J.; Brechtelsbauer, D. [Department of Neuroradiology, University of Bonn, Bonn (Germany); Wolf, H.K. [Department of Neuropathology, University of Bonn, Bonn (Germany); Gass, S. [Department of Neurology, University of Bonn, Bonn (Germany)

1998-02-01

To ascertain whether increased grey matter signal intensity on T2-weighted images in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the stage and severity of this disease, we correlated MRI findings in four of our own and previously reported patients with sporadic CJD with the clinical variants, neuropathological changes at autopsy, duration of the disease and survival time after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10 showed increased signal in the basal ganglia on T2-weighted images. One of seven patients with the Heidenhain variant had increased signal in the occipital cortex. Patients without increased grey matter signal intensity had a longer overall duration of CJD (P = 0.035). Although the interval between onset of neurological symptoms and MRI was not different, patients without increased grey matter signal also survived longer after MRI examination (P = 0.022). (orig.) With 5 figs., 2 tabs., 23 refs.

The Clinical Stages of Sporadic Creutzfeldt-Jakob Disease with Met/Met Genotype in Korean Patients.

Science.gov (United States)

Park, So Young; Wang, Min Jeong; Jang, Jae-Won; Park, Young Ho; Lim, Jae-Sung; Youn, Young Chul; Kim, Jungeun; Kim, SangYun

2016-01-01

Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis. © 2016 S. Karger AG, Basel.

Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.

Science.gov (United States)

Del Pilar-Morales, Esteban A; Cali, Ignazio; Chapas, Javier; Bertrán-Pasarell, Jorge; Puoti, Gianfranco; Gambetti, Pierluigi; Nobo, Ulises

2015-03-01

The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.

Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob disease.

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Bielewicz, Joanna; Szczepańska-Szerej, Anna; Ogórek, Magdalena; Dropko, Piotr; Wojtal, Katarzyna; Rejdak, Konrad

2018-03-04

We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis.

Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease.

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Galeno, Roberta; Di Bari, Michele Angelo; Nonno, Romolo; Cardone, Franco; Sbriccoli, Marco; Graziano, Silvia; Ingrosso, Loredana; Fiorini, Michele; Valanzano, Angelina; Pasini, Giulia; Poleggi, Anna; Vinci, Ramona; Ladogana, Anna; Puopolo, Maria; Monaco, Salvatore; Agrimi, Umberto; Zanusso, Gianluigi; Pocchiari, Maurizio

2017-06-01

In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrP TSE ) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrP TSE MV AG ), showing that PrP TSE MV AG is composed of multiple conformers with biochemical properties distinct from those of PrP TSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MV AG to bank voles and gene-targeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrP TSE deposition patterns, and PrP TSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MV AG IMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two different major conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combinations of pathological prion protein types with codon 129 genotypes results in the identification of 3 or 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding of the pathogenesis of the disease and of

Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

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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

A Genome Wide Association Study Links Glutamate Receptor Pathway to Sporadic Creutzfeldt-Jakob Disease Risk

Science.gov (United States)

Sanchez-Juan, Pascual; Bishop, Matthew T.; Kovacs, Gabor G.; Calero, Miguel; Aulchenko, Yurii S.; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J.; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G.; Collins, Steven J.; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S. G.; Will, Robert G.; van Duijn, Cornelia M.

2015-01-01

We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis. PMID:25918841

Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance

Science.gov (United States)

2013-01-01

Background There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance. Results We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset – potentially more contaminant - are taken into account. Data on hospital discharges and surgical procedures were obtained from Danish and Swedish national in-patient hospital registries for 167 sCJD cases, onset 1987–2003, and for 835 matched and 2,224 unmatched population controls. Surgery was allocated to different life-time periods as previously reported, and frequencies were compared using logistic regression analysis. In the year preceding clinical onset, persons with sCJD underwent a statistically significant higher number of minor surgical interventions (OR (95% CI): 17.50 (3.64-84.24)), transluminal endoscopies (OR: 2.73 (1.01–7.37)) and gastrointestinal operations (OR: 3.51 (1.21–10.19)) compared to matched controls. Surgical discharges clustered towards clinical onset. These differences increased during the clinical period, with statistically significant higher frequencies for both endoscopies and minor surgery (OR: 13.91 (5.87-32.95), and for main surgical procedures (OR: 2.10 (1.00-4.39)), particularly gastrointestinal surgery (OR: 6.00 (1.83-19.66)), and surgery contacting skeletal muscle. Comparisons with unmatched controls yielded similar results for neurosurgery in the clinical period (OR: 19.40 (2.22-168.34)). Conclusions These results suggest that some types of surgical procedures are associated with sCJD, after clinical onset or particularly just before onset. Selective planning of such surgery to minimize instrument/device contamination or quarantining might be feasible

Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease

NARCIS (Netherlands)

E.A. Croes (Esther); B.Z. Alizadeh (Behrooz); A.M. Bertoli Avella (Aida); T.A.M. Rademaker (Tessa); J. Vergeer-Drop (Jeannette); B. Dermaut (Bart); J.J. Houwing-Duistermaat (Jeanine); D.P.W.M. Wientjens (Dorothee); A. Hofman (Albert); C. van Broeckhoven (Christine); C.M. van Duijn (Cornelia)

2004-01-01

textabstractThe prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in

THE EXPLICIT COMPREHENSION-STRATEGY INSTRUCTION: QUESTION-ANSWER RELATIONSHIP VS SELF-QUESTIONING

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Lalu Thohir

2017-12-01

Full Text Available This study was aimed at examining and comparing the effectiveness of the Question-Answer Relationship (QAR and Self-Questioning (SQ strategies in improving the reading ability of the undergraduate students. This study was a quasi-experimental study in which two out of three classes of the third semester students at English department of Mataram University were selected randomly to receive either QAR strategy or SQ strategy instructions for ten weekly meetings. The findings of pre- and posttest with multiple-choice questions revealed that both comprehension strategies were effective in improving the undergraduate students‘ reading ability. The findings from the posttest with multiple-choice questions indicated the students who received SQ strategy instruction scored significantly higher than those students who received QAR strategy instruction. On the other hand, the students who received QAR strategy instruction scored slightly higher than those students who received SQ strategy instruction in the posttest with open-ended questions.

Evidence for varied aetiologies regulating the transmission of prion disease: implications for understanding the heritable basis of prion incubation times.

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Conrad O Iyegbe

2010-12-01

Full Text Available Transmissible Spongiform Encephalopathies (TSEs are a group of progressive fatal neurodegenerative disorders, triggered by abnormal folding of the endogenous prion protein molecule. The encoding gene is a major biological factor influencing the length of the asymptomatic period after infection. It remains unclear the extent to which the variation between quantitative trait loci (QTLs reported in mouse models is due to methodological differences between approaches or genuine differences between traits. With this in mind, our approach to identifying genetic factors has sought to extend the linkage mapping approach traditionally applied, to a series of additional traits, while minimising methodological variability between them. Our approach allows estimations of heritability to be derived, as well as predictions to be made about possible existence of genetic overlap between the various traits.Our data indicate a surprising degree of heritability (up to 60%. Correlations between traits are also identified. A series of QTLs on chromosomes 1, 2, 3, 4, 6, 11 and 18 accompany our heritability estimates. However, only a locus on chromosome 11 has a general effect across all 4 models explored.We have achieved some success in detecting novel and pre-existing QTLs associated with incubation time. However, aside from the general effects described, the model-specific nature of the broader host genetic architecture has also been brought into clearer focus. This suggests that genetic overlap can only partially account for the general heritability of incubation time when factors, such as the nature of the TSE agent and the route of administration are considered. This point is highly relevant to vCJD (a potential threat to public health where the route of primary importance is oral, while the QTLs being sought derive exclusively from studies of the ic route. Our results highlight the limitations of a single-model approach to QTL-mapping of TSEs.

Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

Science.gov (United States)

Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

2016-02-05

sporadic CJD upon homologous and heterologous transmission. The notion that the environment or matrix where replication is occurring is key to the selection and preferential amplification of prion substrain components raises new questions on the determinants of prion replication within and between species. These data also further interrogate on the interplay between animal and human prions.

Imaging and clinical characteristics of sporadic Creutzfeldt-Jakob disease

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HAN Shun-chang

2013-04-01

Full Text Available Five patients with sporadic Creutzfeldt-Jakob disease (sCJD presented rapidly progressive dementia which were subacute onset from 1 to 4 months. Among these cases, periodic synchronous discharge (PSD of electroencephalography (EEG was seen in 2 patients. Besides, 4 patients obtained positive results in cerebrospinal fluid (CSF analysis for 14-3-3 protein. The cranial MRI examination showed symmetrical or asymmetrical colored-ribbon-shaped high signals in cerebral cortex or basal ganglia by diffusion weighted imaging (DWI, suggesting that DWI had high sensitivity and specificity for the diagnosis of sCJD as a preferred method in the clinical examination of sCJD.

CT and MRI findings of Creutzfeldt-Jakob disease in the early stage. The usefulness of diffusion-weighted images

International Nuclear Information System (INIS)

Ukisu, Ryutaro; Kushihashi, Tamio; Gokan, Takehiko

2001-01-01

To detect subtle CT and MRI features of Creutzfeldt-Jacob disease (CJD) in the early stage is important to prevent a human-to-human transmission. This study included 10 patients of CJD who underwent CT and/or MRI in its early stage. CT, T1- and T2-weighted MRI, DWI, and FLAIR images were obtained in 10, 6, 4, and 2 patients respectively. On DWI, abnormal hyperintensities were observed in both cerebral cortex, and in basal ganglia in all patients. On FLAIR images, abnormal hyperintensies were observed in one patient. Detection of abnormal intensities may be possible in the early stage of CJD using MRI, particularly with DWI. (author)

CT and MRI findings of Creutzfeldt-Jakob disease in the early stage. The usefulness of diffusion-weighted images

Energy Technology Data Exchange (ETDEWEB)

Ukisu, Ryutaro; Kushihashi, Tamio; Gokan, Takehiko [Showa Univ., Tokyo (Japan). School of Medicine] [and others

2001-02-01

To detect subtle CT and MRI features of Creutzfeldt-Jacob disease (CJD) in the early stage is important to prevent a human-to-human transmission. This study included 10 patients of CJD who underwent CT and/or MRI in its early stage. CT, T1- and T2-weighted MRI, DWI, and FLAIR images were obtained in 10, 6, 4, and 2 patients respectively. On DWI, abnormal hyperintensities were observed in both cerebral cortex, and in basal ganglia in all patients. On FLAIR images, abnormal hyperintensies were observed in one patient. Detection of abnormal intensities may be possible in the early stage of CJD using MRI, particularly with DWI. (author)

MM2-Thalamic Creutzfeldt-Jacob Disease: Neuropathological, Biochemical and Transmission Studies Identify a Distinctive Prion Strain

NARCIS (Netherlands)

Moda, F.; Suardi, S.; Fede, Di G.; Indaco, A.; Limido, L.; Vimercati, C.; Ruggerone, M.; Campagnani, I.; Langeveld, J.P.M.; Terruzzi, A.; Brambilla, A.; Zerbi, P.; Fociani, P.; Bishop, T.; Will, G.W.; Manson, J.C.; Giaccone, G.; Tagliavini, F.

2012-01-01

In CreutzfeldtJakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrPSc) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD

Rapidly Progressive Corticobasal Degeneration Syndrome

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Ana Herrero Valverde

2011-08-01

Full Text Available Introduction: Corticobasal syndrome (CBS has a heterogeneous clinical presentation with no specific pathologic substratum. Its accurate diagnosis is a challenge for neurologists; in order to establish CBS definitively, postmortem confirmation is required. Some clinical and radiological features can help to distinguish it from other neurodegenerative conditions, such as Creutzfeldt-Jakob disease (CJD. Clinical Case: A 74-year-old woman presented with language impairment, difficulty in walking and poor attentiveness that had begun 10 days before. Other symptoms, such as asymmetrical extra-pyramidal dysfunction, limb dystonia and ‘alien limb’ phenomena, were established over the next 2 months, with rapid progression. Death occurred 3 months after symptom onset. Laboratory results were normal. Initially, imaging only showed restricted diffusion with bilateral parieto-occipital gyri involvement on DWI-MRI, with unspecific EEG changes. An autopsy was performed. Brain neuropathology confirmed sporadic CJD (sCJD. Conclusions: CBS is a heterogeneous clinical syndrome whose differential diagnosis is extensive. CJD can occasionally present with clinical characteristics resembling CBS. MRI detection of abnormalities in some sequences (FLAIR, DWI, as previously reported, has high diagnostic utility for sCJD diagnosis – especially in early stages – when other tests can still appear normal. Abnormalities on DWI sequencing may not correlate with neuropathological findings, suggesting a functional basis to explain the changes found.

Molecular pathogenesis of sporadic prion diseases in man

Science.gov (United States)

Safar, Jiri G.

2012-01-01

The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent’s efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation – intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins – are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare. PMID:22421210

Racial and ethnic differences in individuals with sporadic Creutzfeldt-jakob disease in the United States of America.

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Brian S Appleby

Full Text Available BACKGROUND: Little is known about racial and ethnic differences in individuals with sporadic Creutzfeldt-Jakob disease (sCJD. The authors sought to examine potential clinical, diagnostic, genetic, and neuropathological differences in sCJD patients of different races/ethnicities. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study of 116 definite and probable sCJD cases from Johns Hopkins and the Department of Veterans Affairs Healthcare Systems was conducted that examined differences in demographic, clinical, diagnostic, genetic, and neuropathological characteristics among racial/ethnic groups. Age at disease onset differed among racial/ethnic groups. Non-Hispanic Whites had a significantly older age at disease onset compared to the other groups (65 vs. 60, p = 0.036. Non-Whites were accurately diagnosed more rapidly than Whites (p = 0.008 and non-Hispanic Whites were more likely to have normal appearing basal ganglia on brain magnetic resonance imaging (MRI compared to minorities (p = 0.02. Whites were also more likely to undergo post-mortem evaluation compared to non-Whites (p = 0.02. CONCLUSIONS/SIGNIFICANCE: Racial/ethnic groups affected by sCJD demonstrated differences in age at disease onset, time to correct diagnosis, clinical presentation, and diagnostic test results. Whites were more likely to undergo autopsy compared to non-Whites. These results have implications in regards to case ascertainment, diagnosis, and surveillance of sCJD and possibly other human prion diseases.

Transgenic fatal familial insomnia mice indicate prion infectivity-independent mechanisms of pathogenesis and phenotypic expression of disease.

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Ihssane Bouybayoune

2015-04-01

Full Text Available Fatal familial insomnia (FFI and a genetic form of Creutzfeldt-Jakob disease (CJD178 are clinically different prion disorders linked to the D178N prion protein (PrP mutation. The disease phenotype is determined by the 129 M/V polymorphism on the mutant allele, which is thought to influence D178N PrP misfolding, leading to the formation of distinctive prion strains with specific neurotoxic properties. However, the mechanism by which misfolded variants of mutant PrP cause different diseases is not known. We generated transgenic (Tg mice expressing the mouse PrP homolog of the FFI mutation. These mice synthesize a misfolded form of mutant PrP in their brains and develop a neurological illness with severe sleep disruption, highly reminiscent of FFI and different from that of analogously generated Tg(CJD mice modeling CJD178. No prion infectivity was detectable in Tg(FFI and Tg(CJD brains by bioassay or protein misfolding cyclic amplification, indicating that mutant PrP has disease-encoding properties that do not depend on its ability to propagate its misfolded conformation. Tg(FFI and Tg(CJD neurons have different patterns of intracellular PrP accumulation associated with distinct morphological abnormalities of the endoplasmic reticulum and Golgi, suggesting that mutation-specific alterations of secretory transport may contribute to the disease phenotype.

Protease-sensitive conformers in broad spectrum of distinct PrPSc structures in sporadic Creutzfeldt-Jakob disease are indicator of progression rate.

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Chae Kim

2011-09-01

Full Text Available The origin, range, and structure of prions causing the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD, are largely unknown. To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD, we analyzed the conformational characteristics of protease-sensitive and protease-resistant fractions of the pathogenic prion protein (PrP(Sc using novel conformational methods derived from a conformation-dependent immunoassay (CDI. In 46 brains of patients homozygous for polymorphisms in the PRNP gene and exhibiting either Type 1 or Type 2 western blot pattern of the PrP(Sc, we identified an extensive array of PrP(Sc structures that differ in protease sensitivity, display of critical domains, and conformational stability. Surprisingly, in sCJD cases homozygous for methionine or valine at codon 129 of the PRNP gene, the concentration and stability of protease-sensitive conformers of PrP(Sc correlated with progression rate of the disease. These data indicate that sCJD brains exhibit a wide spectrum of PrP(Sc structural states, and accordingly argue for a broad spectrum of prion strains coding for different phenotypes. The link between disease duration, levels, and stability of protease-sensitive conformers of PrP(Sc suggests that these conformers play an important role in the pathogenesis of sCJD.

Asking Questions in Academia

DEFF Research Database (Denmark)

Hansen, Annette Skovsted

2014-01-01

Motivation for the activity In academia the most important skill is to ask academically relevant and sound questions. This is not easy and students need to practice asking questions orally and in writing before they write research papers.......Motivation for the activity In academia the most important skill is to ask academically relevant and sound questions. This is not easy and students need to practice asking questions orally and in writing before they write research papers....

The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease compared to Alzheimer's disease

DEFF Research Database (Denmark)

Bahl, J.M.; Heegaard, N.H.; Falkenhorst, G.

2009-01-01

) together with the prion protein gene genotype to discriminate patients with sCJD (n=21) from neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p-tau/t-tau ratio was the best single marker for sCJD with 90% specificity against neurological controls at 86% sensitivity whilst NSE...

Effects of a naturally occurring amino acid substitution in bovine PrP: a model for inherited prion disease in a natural host species

Science.gov (United States)

The most common hereditary prion disease is human Creutzfeldt-Jakob disease (CJD) associated with a mutation in the prion gene (PRNP) resulting in a glutamic acid to lysine substitution at position 200 (E200K) in the prion protein. Models of E200K CJD in transgenic mice have proven interesting but h...

MRI evidence of cerebellar and hippocampal involvement in Creutzfeldt-Jakob disease

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Poon, M.A. [Dept. of Neurology, Alfred Hospital, Victoria (Australia); Stuckey, S. [Dept. of Radiology, Alfred Hospital, Victoria (Australia); Storey, E. [Van Cleef Roet Centre for Nervous Diseases, Monash Univ., Victoria (Australia)

2001-09-01

We report a 51-year-old woman with the Brownell-Oppenheimer (cerebellar) variant of Creutzfeldt-Jakob disease (CJD). She had the typical findings of bilateral basal ganglion changes on MRI, as well as changes in the cerebellum and hippocampus. This case adds further information to the known imaging characteristics of CJD. (orig.)

MRI evidence of cerebellar and hippocampal involvement in Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Poon, M.A.; Stuckey, S.; Storey, E.

2001-01-01

We report a 51-year-old woman with the Brownell-Oppenheimer (cerebellar) variant of Creutzfeldt-Jakob disease (CJD). She had the typical findings of bilateral basal ganglion changes on MRI, as well as changes in the cerebellum and hippocampus. This case adds further information to the known imaging characteristics of CJD. (orig.)

Improving Student Question Classification

Science.gov (United States)

Heiner, Cecily; Zachary, Joseph L.

2009-01-01

Students in introductory programming classes often articulate their questions and information needs incompletely. Consequently, the automatic classification of student questions to provide automated tutorial responses is a challenging problem. This paper analyzes 411 questions from an introductory Java programming course by reducing the natural…

Guided Discovery with Socratic Questioning

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M. Hakan Türkçapar

2015-04-01

Full Text Available “The Socratic method” is a way of teaching philosophical thinking and knowledge by asking questions. It was first used by in ancient times by the Greek philosopher Socrates who taught his followers by asking questions; these conversations between them are known as “Socratic dialogues”. In this methodology, no new knowledge is taught to the individual; rather, the individual is guided to remember and rediscover what was formerly known through this process. The main method used in cognitive therapy is guided discovery. There are various methods of guided discovery in cognitive therapy. The form of verbal exchange between the therapist and client which is used during the process of cognitive behavioral therapy is known as “socratic questioning”. In this method the goal is to make the client rediscover, with a series of questions, a piece of knowledge which he could otherwise know but is not presently conscious of. The Socratic Questioning consists of several steps, including: identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly rediscovered information and questioning the old distorted belief, and reaching a new conclusion and applying it. Question types used during these procedures are: questions for collecting information, questions revealing meanings, questions revealing beliefs, questions about behaviours during similar past experiences, analytic questions and analytic synthesis questions. In order to make the patient feel understood, it is important to be empathetic and summarize the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues provided for each step. [JCBPR 2015; 4(1.000: 47-53

The sensitivity of auxiliary examinations in different stages of sporadic Creutzfeldt-Jakob disease

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Jiao-jiao JIANG

2017-06-01

Full Text Available Objective To analyze the sensitivity of auxiliary examinations in different periods of sporadic Creutzfeldt-Jakob disease (sCJD. Methods The clinical data of 53 sCJD patients were retrospectively analyzed including the different stages of skull diffusion-weighted magnetic resonance imaging (DWI, 24-hour ambulatory electroencephalogram (EEG, 18F-FDG PET/CT (PET-CT and cerebrospinal fluid 14-3-3 protein. When calculating the sensitivity of an auxiliary examination, the diagnostic criteria were defined by combining the specific clinical manifestations with two or more positive results of other auxiliary examinations. Results There were 24, 53 and 22 sCJD patients, respectively, met the criterion of early (E, middle (M and later (L stage of disease (some patients fit 2 or 3 stages. The sensitivity of DWI (E: 58.3%, M: 85.4%, L: 94.7%, EEG (E: 45.8%, M: 62.7%, L: 77.8%, 14-3-3 protein in cerebrospinal fluid (E: 11.1%, M: 52.9% and PET-CT (E: 80%, M: 100% increased gradually with disease progression. The sensitivity of PET-CT was higher than the other auxiliary examinations for E and M stages; no PET-CT was conducted in L stage. High signal regions mainly distributed in the cortex in E and M stages, but in L stage, no significant difference was found on the distribution of high signal regions between cortex and basal ganglia. Conclusions The sensitivities of the auxiliary examinations were different for sCJD patients in different stages. Reexaminations in different periods may improve the sensitivity for sCJD diagnosis. The sensitivity of PET-CT was high, and the combination of PET-CT and other auxiliary examinations may play a key role in the diagnosis of sCJD. DOI: 10.11855/j.issn.0577-7402.2017.05.15

Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings.

Science.gov (United States)

Baiardi, Simone; Capellari, Sabina; Ladogana, Anna; Strumia, Silvia; Santangelo, Mario; Pocchiari, Maurizio; Parchi, Piero

2016-01-01

The Heidenhain variant defines a peculiar clinical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by isolated visual disturbances at disease onset and reflecting the early targeting of prions to the occipital cortex. Molecular and histopathological typing, thus far performed in 23 cases, has linked the Heidenhain variant to the MM1 sCJD type. To contribute a comprehensive characterization of cases with the Heidenhain variant, we reviewed a series of 370 definite sCJD cases. Eighteen patients (4.9%) fulfilled the selection criteria. Fourteen of them belonging to sCJD types MM1 or MM1+2C had a short duration of isolated visual symptoms and overall clinical disease, a high prevalence of periodic sharp-wave complexes in EEG, and a marked increase of cerebrospinal fluid proteins t-tau and 14-3-3 levels. In contrast, three cases of the MM 2C or MM 2+1C types showed a longer duration of isolated visual symptoms and overall clinical disease, non-specific EEG findings, and cerebrospinal fluid concentration below threshold for the diagnosis of "probable" CJD of both 14-3-3 and t-tau. However, a brain DWI-MRI disclosed an occipital cortical hyperintensity in the majority of examined cases of both groups. While confirming the strong linkage with the methionine genotype at the polymorphic codon 129 of the prion protein gene, our results definitely establish that the Heidenhain variant can also be associated with the MM 2C sCJD type in addition to the more common MM1 type. Likewise, our results highlight the significant differences in clinical evolution and laboratory findings between cases according to the dominant PrPSc type (type 1 versus type 2).

Tau pathology in Creutzfeldt-Jakob disease revisited.

Science.gov (United States)

Kovacs, Gabor G; Rahimi, Jasmin; Ströbel, Thomas; Lutz, Mirjam I; Regelsberger, Günther; Streichenberger, Nathalie; Perret-Liaudet, Armand; Höftberger, Romana; Liberski, Pawel P; Budka, Herbert; Sikorska, Beata

2017-05-01

Creutzfeldt-Jakob disease (CJD) is a human prion disease with different etiologies. To determine the spectrum of tau pathologies in CJD, we assessed phospho-Tau (pTau) immunoreactivities in 75 sporadic CJD cases including an evaluation of the entorhinal cortex and six hippocampal subregions. Twelve cases (16%) showed only small tau-immunoreactive neuritic profiles. Fifty-two (69.3%) showed additional tau pathology in the medial temporal lobe compatible with primary age related tauopathy (PART). In 22/52 cases the lower pTau immunoreactivity load in the entorhinal cortex as compared to subiculum, dentate gyrus or CA4 region of the hippocampus was significantly different from the typical distribution of the Braak staging. A further 11 cases (14.7%) showed widespread tau pathologies compatible with features of primary tauopathies or the gray matter type of ageing-related tau astrogliopathy (ARTAG). Prominent gray matter ARTAG was also observed in two out of three additionally examined V203I genetic CJD cases. Analysis of cerebrospinal fluid revealed prominent increase of total tau protein in cases with widespread tau pathology, while pTau (T181) level was increased only in four. This correlated with immunohistochemical observations showing less pathology with anti-pTau T181 antibody when compared to anti-pTau S202/T205, T212/S214 and T231. The frequency of tau pathologies is not unusually high in sporadic CJD and does not precisely relate to PrP deposition. However, the pattern of hippocampal tau pathology often deviates from the stages of Braak. Currently applied examination of cerebrospinal fluid pTau (T181) level does not reliably reflect primary tauopathies, PART and ARTAG seen in CJD brains. © 2016 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Epistemology: 5 Questions

DEFF Research Database (Denmark)

Epistemology: 5 Questions is a collection of short interviews based on 5 questions presented to some of the most influential and prominent scholars in epistemology. We hear their views on epistemology with particular emphasis on the intersection between mainstream and formal approaches to the field...

Corticobasal syndrome due to sporadic Creutzfeldt-Jakob disease: a review and neuropsychological case report.

Science.gov (United States)

González, David Andrés; Soble, Jason R

2017-04-01

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disease with neuropsychological sequelae. This study highlighted a rare presentation of CJD (e.g. corticobasal syndrome [CBS]), reviewed updated diagnostic criteria and procedures for CJD (e.g. diffusion weighted imaging [DWI], real-time quaking-induced conversion [RT-QuIC]), and discussed differential diagnoses. Case report methodology focused on a 68-year-old, Hispanic, right-handed man with 11 years of education. He presented with a 1-2-month history of gait and motor difficulties (e.g. rigidity, myoclonus). After evaluation, a 'cortical ribboning' pattern on DWI and positive RT-QuIC was integrated with performance on neurobehavioral exam (i.e. alien limb phenomenon, unilateral ideomotor apraxia) and neuropsychological testing (i.e. frontal-parietal dysfunction pattern) to reach a diagnosis of sCJD-CBS. The patient expired 3 months after onset of symptoms. This literature review and case report highlighted the importance of staying abreast of developments in neurological literature and the added value of neuropsychology, when integrated with newer procedures, for confirming and excluding diagnostic considerations.

Codon 219 polymorphism of PRNP in healthy caucasians and Creutzfeldt-Jakob disease patients

Energy Technology Data Exchange (ETDEWEB)

Petraroli, R.; Pocchiari, M. [Instituto Superiore di Sanita, Rome (Italy)

1996-04-01

A number of point and insert mutations of the PrP gene (PRNP) have been linked to familial Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSS). Moreover, the methionine/valine homozygosity at the polymorphic codon 129 of PRNP may cause a predisposition to sporadic and iatrogenic CJD or may control the age at onset of familial cases carrying either the 144-bp insertion or codon 178, codon 198, and codon 210 pathogenic mutations in PRNP. In addition, the association of methionine or valine at codon 129 and the point mutation at codon 178 on the same allele seem to play an important role in determining either fatal familial insomnia or CJD. However, it is noteworthy that a relationship between codon 129 polymorphism and accelerated pathogenesis (early age at onset or shorter duration of the disease) has not been seen in familial CJD patients with codon 200 mutation or in GSS patients with codon 102 mutation, arguing that other, as yet unidentified, gene products or environmental factors, or both, may influence the clinical expression of these diseases. 17 refs.

Teacher's Questions in Reading Classes

Directory of Open Access Journals (Sweden)

Zuliati Rohmah

2002-01-01

Full Text Available Abstract: The present paper discusses an English teacher's questions in Reading classes at MAN Malang III. Types of questions, functions of teacher's questions, question levels and the strategies applied by the teacher were put as the research problems. Non-participant observa­tion was applied to collect the data with the researcher as the main in­strument aided by field-notes and a tape recorder. It was found that the distribution of the questions did not allow the students to talk longer and to think more analytically. Meanwhile, the strategies applied by the teacher helped the students to respond to the questions previously unanswered. The teacher is suggested to produce more open and refer­ential question as well as inference and evaluation questions as to give more chances for the students to think aloud more.

Bitemporal hypometabolism in Creutzfeldt-Jakob disease measured by positron emission tomography with [18F]-2-fluorodeoxyglucose

International Nuclear Information System (INIS)

Friedland, R.P.; Prusiner, S.B.; Jagust, W.J.; Budinger, T.F.; Davis, R.L.

1984-01-01

It is well established that Creutzfeldt-Jakob disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54-year-old man with autopsy confirmed CJD using [18F]-2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. Temporal lobe hypometabolism with hemispheric asymmetry was observed. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer disease (AD). The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the possibility that AD may be caused by a slow infectious prion

Creutzfeldt-Jakob disease with mixed transcortical aphasia: insights into echolalia.

Science.gov (United States)

McPherson, S E; Kuratani, J D; Cummings, J L; Shih, J; Mischel, P S; Vinters, H V

1994-01-01

Aphasia is a common manifestation of Creutzfeldt-Jakob disease (CJD), and investigation of the linguistic disorders of CJD patients may provide insights into the neurobiological mechanisms of language and aphasia. We report an autopsy-confirmed case of CJD in which the presenting symptom was change in language abilities. The patient ultimately evidenced mixed transcortical aphasia (MTA) with echolalia. Disruption of frontal-subcortical circuits with environmental dependency accounts for the symptoms in MTA, including intact repetition and echolalia. Observation in this patient and a review of the literature suggest that frontal-subcortical circuit dysfunction may contribute to the syndrome of echolalia. This hypothesis offers an alternative explanation to "isolation" of the speech area as the cause of MTA.

Bitemporal hypometabolism in Creutzfeldt-Jakob disease measured by positron emission tomography with (/sup 18/F)-2-fluorodeoxyglucose

Energy Technology Data Exchange (ETDEWEB)

Friedland, R.P.; Prusiner, S.B.; Jagust, W.J.; Budinger, T.F.; Davis, R.L.

1984-10-01

It is well established that Creutzfeldt-Jakob disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54-year-old man with autopsy confirmed CJD using (18F)-2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. Temporal lobe hypometabolism with hemispheric asymmetry was observed. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer disease (AD). The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the possibility that AD may be caused by a slow infectious prion.

The Priority of the Question: Focus Questions for Sustained Reasoning in Science

Science.gov (United States)

Lustick, David

2010-08-01

Science education standards place a high priority on promoting the skills and dispositions associated with inquiry at all levels of learning. Yet, the questions teachers employ to foster sustained reasoning are most likely borrowed from a textbook, lab manual, or worksheet. Such generic questions generated for a mass audience, lack authenticity and contextual cues that allow learners to immediately appreciate a question’s relevance. Teacher queries intended to motivate, guide, and foster learning through inquiry are known as focus questions. This theoretical article draws upon science education research to present a typology and conceptual framework intended to support science teacher educators as they identify, develop, and evaluate focus questions with their students.

Early detection of abnormal prion protein in genetic human prion diseases now possible using real-time QUIC assay.

Directory of Open Access Journals (Sweden)

Kazunori Sano

Full Text Available INTRODUCTION: The definitive diagnosis of genetic prion diseases (gPrD requires pathological confirmation. To date, diagnosis has relied upon the finding of the biomarkers 14-3-3 protein and total tau (t-tau protein in the cerebrospinal fluid (CSF, but many researchers have reported that these markers are not sufficiently elevated in gPrD, especially in Gerstmann-Sträussler-Scheinker syndrome (GSS. We recently developed a new in vitro amplification technology, designated "real-time quaking-induced conversion (RT-QUIC", to detect the abnormal form of prion protein in CSF from sporadic Creutzfeldt-Jakob disease (sCJD patients. In the present study, we aimed to investigate the presence of biomarkers and evaluate RT-QUIC assay in patients with gPrD, as the utility of RT-QUIC as a diagnostic tool in gPrD has yet to be determined. METHOD/PRINCIPAL FINDINGS: 56 CSF samples were obtained from gPrD patients, including 20 cases of GSS with P102L mutation, 12 cases of fatal familial insomnia (FFI; D178N, and 24 cases of genetic CJD (gCJD, comprising 22 cases with E200K mutation and 2 with V203I mutation. We subjected all CSF samples to RT-QUIC assay, analyzed 14-3-3 protein by Western blotting, and measured t-tau protein using an ELISA kit. The detection sensitivities of RT-QUIC were as follows: GSS (78%, FFI (100%, gCJD E200K (87%, and gCJD V203I (100%. On the other hand the detection sensitivities of biomarkers were considerably lower: GSS (11%, FFI (0%, gCJD E200K (73%, and gCJD V203I (67%. Thus, RT-QUIC had a much higher detection sensitivity compared with testing for biomarkers, especially in patients with GSS and FFI. CONCLUSION/SIGNIFICANCE: RT-QUIC assay is more sensitive than testing for biomarkers in gPrD patients. RT-QUIC method would thus be useful as a diagnostic tool when the patient or the patient's family does not agree to genetic testing, or to confirm the diagnosis in the presence of a positive result for genetic testing.

Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.

LENUS (Irish Health Repository)

Paquet, Claire

2009-02-01

The mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.

Secure amplify-and-forward untrusted relaying networks using cooperative jamming and zero-forcing cancelation

KAUST Repository

Park, Kihong

2015-12-03

In this paper, we investigate secure transmission in untrusted amplify-and-forward half-duplex relaying networks with the help of cooperative jamming at the destination (CJD). Under the assumption of full channel state information (CSI), conventional CJD using self-interference cancelation at the destination is efficient when the untrusted relay has no capability to suppress the jamming signal. However, if the source and destination are equipped with a single antenna and the only untrusted relay is equipped with N multiple antennas, it can remove the jamming signal from the received signal by linear filters and the full multiplexing gain of relaying cannot be achievable with the conventional CJD due to the saturation of the secrecy rate at the high transmit power regime. We propose in this paper new CJD scheme where neither destination nor relay can acquire CSI of relay-destination link. Our proposed scheme utilizes zero-forcing cancelation based on known jamming signals instead of self-interference subtraction, while the untrusted relay cannot suppress the jamming signals due to the lack of CSI. We show that the secrecy rate of the proposed scheme can enjoy a half of multiplexing gain in half-duplex relaying while that of conventional CJD is saturated at high transmit power for N ???2. The impact of channel estimation error at the destination is also investigated to show the robustness of the proposed scheme against strong estimation errors.

Asking a Great Question: A Librarian Teaches Questioning Skills to First-Year Medical Students.

Science.gov (United States)

Adams, Nancy E

2015-01-01

In a single one-hour session, first-year medical students were taught a framework for differentiating between lower-order questions that lead to knowledge of facts and higher-order questions that lead to integration of concepts and deeper learning, thereby preparing them for problem-based learning (PBL). Students generated lists of questions in response to an assertion prompt and categorized them according to Bloom's Taxonomy. These data were analyzed in addition to data from the course exam, which asked them to formulate a higher-level question in response to a prompt. Categorizing questions according to Bloom's Taxonomy was a more difficult task for students than was formulating higher-order questions. Students reported that the skills that they learned were used in subsequent PBL sessions to formulate higher-order learning objectives that integrated new and previously-learned concepts.

Efficient question answering with question decomposition and multiple answer streams

OpenAIRE

Hartrumpf, Sven; Glöckner, Ingo; Leveling, Johannes

2009-01-01

The German question answering (QA) system IRSAW (formerly: InSicht) participated in QA@CLEF for the fth time. IRSAW was introduced in 2007 by integrating the deep answer producer InSicht, several shallow answer producers, and a logical validator. InSicht builds on a deep QA approach: it transforms documents to semantic representations using a parser, draws inferences on semantic representations with rules, and matches semantic representations derived from questions and documents. InS...

CAT questions and answers

International Nuclear Information System (INIS)

1993-02-01

This document, prepared in February 1993, addresses the most common questions asked by APS Collaborative Access Teams (CATs). The answers represent the best judgment on the part of the APS at this time. In some cases, details are provided in separate documents to be supplied by the APS. Some of the answers are brief because details are not yet available. The questions are separated into five categories representing different aspects of CAT interactions with the APS: (1) Memorandum of Understanding (MOU), (2) CAT Beamline Review and Construction, (3) CAT Beamline Safety, (4) CAT Beamline Operations, and (5) Miscellaneous. The APS plans to generate similar documents as needed to both address new questions and clarify answers to present questions

Toward Question-Asking Machines: The Logic of Questions and the Inquiry Calculus

Science.gov (United States)

Knuth,Kevin H.

2005-01-01

For over a century, the study of logic has focused on the algebra of logical statements. This work, first performed by George Boole, has led to the development of modern computers, and was shown by Richard T. Cox to be the foundation of Bayesian inference. Meanwhile the logic of questions has been much neglected. For our computing machines to be truly intelligent, they need to be able to ask relevant questions. In this paper I will show how the Boolean lattice of logical statements gives rise to the free distributive lattice of questions thus defining their algebra. Furthermore, there exists a quantity analogous to probability, called relevance, which quantifies the degree to which one question answers another. I will show that relevance is not only a natural generalization of information theory, but also forms its foundation.

Sequential MRI in a case of Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Tribl, G.G.; Zeitlhofer, J.; Asenbaum, S.; Wessely, P.; Strasser, G.; Prayer, D.; Jarius, C.

2002-01-01

A 48-year-old man suddenly developed clinically and electroencephalographically nonspecific dementia. On MRI sequences, only diffusion-weighted images (DWI) of the cortex were unequivocally pathological. Obvious atrophy and basal ganglia signal changes appeared only 9 months after the onset. Brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). In rapidly progressive dementia, we recommend DWI for early diagnosis of CJD. (orig.)

Sequential MRI in a case of Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Tribl, G.G.; Zeitlhofer, J.; Asenbaum, S.; Wessely, P. [Universitaetsklinik fuer Neurologie, Allgemeines Krankenhaus Wien (Austria); Strasser, G.; Prayer, D. [Universitaetsklinik fuer Radiodiagnostik, Allgemeines Krankenhaus Wien (Austria); Jarius, C. [Klinisches Institut fuer Neurologie, Universitaet Wien (Austria)

2002-03-01

A 48-year-old man suddenly developed clinically and electroencephalographically nonspecific dementia. On MRI sequences, only diffusion-weighted images (DWI) of the cortex were unequivocally pathological. Obvious atrophy and basal ganglia signal changes appeared only 9 months after the onset. Brain biopsy confirmed Creutzfeldt-Jakob disease (CJD). In rapidly progressive dementia, we recommend DWI for early diagnosis of CJD. (orig.)

Creutzfeldt-Jakob Disease with Mixed Transcortical Aphasia: Insights into Echolalia

Directory of Open Access Journals (Sweden)

S. E. McPherson

1994-01-01

Full Text Available Aphasia is a common manifestation of Creutzfeldt-Jakob disease (CJD, and investigation of the linguistic disorders of CJD patients may provide insights into the neurobiological mechanisms of language and aphasia. We report an autopsy-confirmed case of CJD in which the presenting symptom was change in language abilities. The patient ultimately evidenced mixed transcortical aphasia (MTA with echolalia. Disruption of frontal-subcortical circuits with environmental dependency accounts for the symptoms in MTA, including intact repetition and echolalia. Observation in this patient and a review of the literature suggest that frontal-subcortical circuit dysfunction may contribute to the syndrome of echolalia. This hypothesis offers an alternative explanation to “isolation” of the speech area as the cause of MTA.

Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

2015-05-01

The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Asking the Right Questions

DEFF Research Database (Denmark)

Richter, Line

Based on fieldwork in Mali this paper discusses the role of anthropology (and the anthropologist) in a large public health research project on children's health. In the uncertainty and disquiet that comes with the battle to combat and avoid diseases in a setting where poverty and abysmal diseases......, is the ability to move beyond even the best hidden assumptions and question our own questions, thereby enabling us to ask the right questions....

Semantic annotation of consumer health questions.

Science.gov (United States)

Kilicoglu, Halil; Ben Abacha, Asma; Mrabet, Yassine; Shooshan, Sonya E; Rodriguez, Laritza; Masterton, Kate; Demner-Fushman, Dina

2018-02-06

Consumers increasingly use online resources for their health information needs. While current search engines can address these needs to some extent, they generally do not take into account that most health information needs are complex and can only fully be expressed in natural language. Consumer health question answering (QA) systems aim to fill this gap. A major challenge in developing consumer health QA systems is extracting relevant semantic content from the natural language questions (question understanding). To develop effective question understanding tools, question corpora semantically annotated for relevant question elements are needed. In this paper, we present a two-part consumer health question corpus annotated with several semantic categories: named entities, question triggers/types, question frames, and question topic. The first part (CHQA-email) consists of relatively long email requests received by the U.S. National Library of Medicine (NLM) customer service, while the second part (CHQA-web) consists of shorter questions posed to MedlinePlus search engine as queries. Each question has been annotated by two annotators. The annotation methodology is largely the same between the two parts of the corpus; however, we also explain and justify the differences between them. Additionally, we provide information about corpus characteristics, inter-annotator agreement, and our attempts to measure annotation confidence in the absence of adjudication of annotations. The resulting corpus consists of 2614 questions (CHQA-email: 1740, CHQA-web: 874). Problems are the most frequent named entities, while treatment and general information questions are the most common question types. Inter-annotator agreement was generally modest: question types and topics yielded highest agreement, while the agreement for more complex frame annotations was lower. Agreement in CHQA-web was consistently higher than that in CHQA-email. Pairwise inter-annotator agreement proved most

Bitemporal hypometabolism in Creutzfeldt-Jakob Disease measured by positron emission tomography with (F-18)2-fluorodeoxyglucose

International Nuclear Information System (INIS)

Friedland, R.P.; Budinger, T.F.; Prusiner, S.B.; Jagust, W.J.

1984-01-01

It is well established that Creutzfeldt-Jakob Disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54 year old male subject with autopsy confirmed CJD using (F-18)2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. An x-ray computed tomographic study of the brain performed 4 days prior to PET was normal. In the PET study the frontal to temporal cortex difference of activity densities was 30% on the left and 12% on the right, reflecting temporal hypometabolism. The left-right temporal cortex difference of activity density was 25%, documenting marked hemispheric asymmetry. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer's Disease (AD) and are distinctly different from PET-FDG finding in patients with other dementing illnesses or in healthy aged subjects. Recent work has demonstrated extensive biological similarities between CJD, scrapie and AD. The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the hypothesis that AD is caused by a slow infectious (prion-like) pathogen

Isolated visual symptoms at onset in sporadic Creutzfeldt-Jakob disease: the clinical phenotype of the “Heidenhain variant”

Science.gov (United States)

Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

2005-01-01

Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease (sCJD) is commonly understood to represent cases with early, prominent visual complaints. The term is clarified to represent those who present with isolated visual symptoms. This group may pose diagnostic difficulties and often present to ophthalmologists where they may undergo needless invasive procedures. Method: A retrospective review of 594 pathologically proved sCJD cases referred to the UK National CJD Surveillance Unit over a 15 year period to identify Heidenhain cases. Results: 22 cases had isolated visual symptoms at onset with a mean illness duration of 4 months. The mean age at disease onset was 67 years. Most displayed myoclonus, pyramidal signs, and a delay in the onset of dementia for some weeks. 17 (77%) were referred initially to ophthalmology. Two underwent cataract extraction before diagnosis. All tested cases were homozygous for methionine at codon 129 of the prion protein gene. Conclusions: This rare, but clinically distinct, group of patients with sCJD may cause diagnostic difficulties. Because ocular intervention carries with it the risk of onward transmission awareness of this condition among ophthalmologists is important. PMID:16170128

Value of diffusion-weighted MR imaging in the diagnosis of Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Xu Quangang; Wu Weiping; Huang Dehui; Zhang Jiatang; Lang Senyang; Pu Chuanqiang

2005-01-01

Objective: To assess the diagnosis value of diffusion- weighted imaging (DWI) in Creutzfeldt-Jakob disease (CJD). Methods: 8 cases of sporadic CJD who underwent MRI were reported. 4 cases were definite, 3 cases were probable and 1 case was possible. The sensitivity of DWI and conventional MRI were compared. Results: T 1 WI and T 2 WI revealed no abnormal signals except nonspecific diffuse brain atrophy in 4 cases, whereas DWI detected hyperintense abnormalities in all cases. 2 cases showed linear lesions only in the cerebral cortex, and 6 cases showed lesions in both the cerebral cortex and the striatum. The lesions were symmetric in 5 cases, but were asymmetric in the other 3 cases. Although fluid- attenuated inversion recovery (FLAIR) imaging also showed cortical hyperintensity in 1 case, the high signal changes were more evident and extensive on DWI. Conclusions: The hyperintense changes in the cerebral cortices and/or striata on DWI are considered characteristic of CJD. DWI is more sensitive than conventional MRI in depicting lesions of CJD and may be an essential tool for the early diagnosis of this disease. (authors)

Bitemporal hypometabolism in Creutzfeldt-Jakob Disease measured by positron emission tomography with (F-18)2-fluorodeoxyglucose

Energy Technology Data Exchange (ETDEWEB)

Friedland, R.P.; Budinger, T.F.; Prusiner, S.B.; Jagust, W.J.

1984-01-01

It is well established that Creutzfeldt-Jakob Disease (CJD) is caused by a slow infectious agent similar to the scrapie prion. However, the pathogenesis of this infection is poorly understood. Positron emission tomography (PET) was performed on a 54 year old male subject with autopsy confirmed CJD using (F-18)2-fluorodeoxyglucose (FDG) and the Donner 280-crystal tomograph. An x-ray computed tomographic study of the brain performed 4 days prior to PET was normal. In the PET study the frontal to temporal cortex difference of activity densities was 30% on the left and 12% on the right, reflecting temporal hypometabolism. The left-right temporal cortex difference of activity density was 25%, documenting marked hemispheric asymmetry. These findings are similar to those previously obtained in PET-FDG studies of patients with clinically defined Alzheimer's Disease (AD) and are distinctly different from PET-FDG finding in patients with other dementing illnesses or in healthy aged subjects. Recent work has demonstrated extensive biological similarities between CJD, scrapie and AD. The similarities in the regional metabolic alterations between CJD and AD provide additional evidence for the hypothesis that AD is caused by a slow infectious (prion-like) pathogen.

Live your questions now

OpenAIRE

Brownrigg, Jenny

2016-01-01

'Live Your Questions Now' is a case study for Cubitt Education's publication 'Aging in Public: creative practice in ageing and the public realm from across the UK', edited by Daniel Baker and published by Cubitt Gallery, Studios and Education, London in 2016. The publication was linked to Cubitt's programme 'Public Wisdom' (2011-2015). My case study is about 'Live your questions now', a group exhibition I curated in 2011 for Mackintosh Museum, The Glasgow School of Art. 'Live your questions n...

Creutzfeldt-Jakob Disease: Analysis of Four Cases

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Ali Al Balushi

2016-08-01

Full Text Available Background: Creutzfeldt-Jakob disease (CJD is a rare, rapidly progressive neurodegenerative disease that almost always results in death in under a year from onset of symptoms. Here, we report four cases of CJD with different clinical presentations diagnosed at our institution over two-year period. Cases: The first patient is an 82-year-old woman who presented with depression, cognitive decline and word-finding difficulty over 4 weeks. The patient deteriorated neurologically to akinetic mutism and death within 6 weeks of presentation. The second patient is a 54-year-old woman with liver cirrhosis who presented with confusion, ataxia and multiple falls over 4 weeks. She was treated initially for hepatic encephalopathy, but continued to progress to mutism, startle myoclonus and obtundation. Death occurred within 4 weeks of presentation. The third patient is a 58-year-old woman who presented with an 8-week history of confusion, urinary incontinence, Parkinsonism, ataxia and myoclonus. Death occurred within 2 months from presentation. The fourth patient is a 67-year-old man who presented with a 6-week history of headache, blurred vision, ataxia and personality change and progressed to confusion, myoclonus, akinetic mutism and obtundation. Death occurred within 3 weeks from presentation. Conclusion: These 4 cases highlight the varied possible clinical presentations of CJD and demonstrate the importance of considering CJD in patients with atypical presentations of rapidly progressive cognitive decline. To diagnose CJD, brain biopsy remains the gold standard. However, the presence of CSF protein 14-3-3, typical MRI findings and suggestive EEG abnormalities all support the diagnosis.

Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

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Cohen, O S; Kimiagar, I; Korczyn, A D; Nitsan, Z; Appel, S; Hoffmann, C; Rosenmann, H; Kahana, E; Chapman, J

2016-05-01

Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies. © 2016 EAN.

Role of the biomarkers for the diagnosis of Creutzfeldt-Jakob disease.

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Dulamea, A; Solomon, E

2016-01-01

Sporadic Creutzfeldt-Jakob disease (CJD) is a human prion disease, rapidly progressive and fatal, characterized by spongiform encephalopathy. The characteristic triad of signs - rapidly progressive dementia, myoclonus and periodic sharp wave complexes (PSWC) on electroencephalography (EEG) - usually appear in the late stages of the disease. The clinical diagnosis of CJD ante-mortem involves the exclusion of the rapidly progressive non-prionic dementias, the definitive diagnosis requiring brain tissue confirmation. Authors evaluated the methods of clinical diagnosis for sporadic CJD. This study retrospectively reviewed the medical records of patients diagnosed with probable sporadic CJD, based on brain magnetic resonance imaging (MRI), EEG, cerebrospinal fluid (CSF) analysis and extensive laboratory work-up. Four patients with a mean age of 67 years were included in our study. The mean duration from diagnosis until death was of 3.2 weeks. The clinical features of the disease at onset were atypical. In the final stage of the disease, all patients presented rapidly progressive dementia and myoclonus. High levels of 14-3-3 protein and tau protein and normal levels of amyloid β1-42 were found at CSF analysis, in all patients. PSWC on EEG were present in 3 out of 4 patients at different moments of the disease. MRI showed hyperintense lesions in brain cortex, caudate nucleus, and putamen on T2, FLAIR, and DWI. CJD may present various clinical features and, since brain biopsy is usually difficult to perform, a combination of biomarkers is useful in order to establish the diagnosis in the early phase of the disease.

Progressive Stroke-Like Symptoms in a Patient with Sporadic Creutzfeldt-Jakob Disease

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Jukka Lyytinen

2010-03-01

Full Text Available Sporadic Creutzfeldt-Jakob disease (sCJD is a rare neurodegenerative disorder in which accumulation of a pathogenic isoform of prion protein (PrPSc induces neuronal damage with distinct pathologic features. The prognosis of sCJD is devastating: rapid clinical decline is followed by death generally within months after onset of symptoms. The classic clinical manifestations of sCJD are rapidly progressing dementia, myoclonus, and ataxia. However, the spectrum of clinical features can vary considerably. We describe a definite, neuropathologically verified sCJD in a 67-year-old woman who initially presented with progressive stroke-like symptoms: left-sided hemiparesis and ataxia within a few days. The initial brain magnetic resonance imaging (MRI showed bilateral cortical hyperintensity on diffusion-weighted sequences (DWI resembling multiple ischemic lesions. Despite anticoagulation with low-molecular-weight heparin, the patient deteriorated rapidly, became dysphagic and bedridden with myoclonic jerks on her left side extremities correlating with intermittent high-amplitude epileptiform discharges on electroencephalography (EEG. Basal ganglia hyperintense signal changes in addition to cortical ribboning were seen in DWI images of a follow-up MRI. Repeated EEG recordings showed an evolution to periodic sharp wave complexes. Protein 14-3-3 was positive in her cerebrospinal fluid specimen, in addition to an abnormally high total tau level. In the terminal stage the patient was in an akinetic, mutistic state with deteriorating consciousness. She died 19 days after admission to the hospital. Neuropathologic investigation corroborated the clinical diagnosis of sCJD with spongiform degeneration and immunohistochemical demonstration of the deposition of pathologic PrPSc.

A Technique Socratic Questioning-Guided Discovery

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M. Hakan Türkçapar

2012-03-01

Full Text Available “Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during the process of cognitive behavioral therapy is known as Guided Discovery. In this method it is aimed to make the client notice the piece of knowledge which he could notice but is not aware with a series of questions. Socratic method or guided discovery consists of several steps which are: Identifying the problem by listening to the client and making reflections, finding alternatives by examining and evaluating, reidentification by using the newly found information and questioning the old distorted belief and reaching to a conclusion and applying it. Question types used during these procedures are, questions for gaining information, questions revealing the meanings, questions revealing the beliefs, questions about behaviours during the similar past experiences, analyse questions and analytic synthesis questions. In order to make the patient feel understood it is important to be empathetic and summarising the problem during the interview. In this text, steps of Socratic Questioning-Guided Discovery will be reviewed with sample dialogues after each step

Creutzfeldt-Jakob disease versus anti-LGI1 limbic encephalitis in a patient with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal electroencephalogram: a case report

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Sun L

2015-06-01

Full Text Available Li Sun, Jie Cao, Chang Liu, Yudan LvDepartment of Neurology, The First Hospital of JiLin University, ChangChun, People’s Republic of ChinaAbstract: Diagnosis of Creutzfeldt-Jakob disease (CJD is often challenging in elderly individuals, not only because of its variable clinical features but also because of nonspecific changes on the electroencephalogram (EEG in the early stages of the disease. Here we report on a patient who presented with progressive cognitive dysfunction, psychiatric symptoms, involuntary facio-brachio-crural movement, and an abnormal EEG. We provide a detailed analysis and differential diagnosis between anti-leucine-rich glioma inactivated 1 (LGI1 limbic encephalitis versus CJD, in the hope of providing a new understanding of CJD. A 65-year-old Chinese man presented with slowly progressive cognitive decline with psychiatric symptoms. On admission, he presented with facial grimacing and brief left upper limb dystonic posturing lasting 1–2 seconds, with hyponatremia that was difficult to rectify. Neurological examination showed increased muscle tension in the left limb but without pathological reflexes. His early EEG showed focal periodic wave complexes. Diffusion-weighted magnetic resonance imaging showed a suspected “lace sign” in the occipital cortex. His cerebrospinal fluid was negative for LGI1 antibodies and positive for 14-3-3 brain protein. Therefore, we made a presumptive diagnosis of CJD. At the following visit, a second EEG showed paroxysmal sharp wave complexes, but the patient had a poor prognosis. Atypical facio-brachio-crural movement and nonspecific EEG changes may occasionally be found in patients with CJD or anti-LGI1 encephalitis. Clinicians should not be dissuaded from a diagnosis of CJD where the EEG does not show paroxysmal sharp wave complexes in the early stages but abnormal facio-brachio-crural movement is present.Keywords: abnormal facio-brachio-crural movement, hyponatremia, Creutzfeldt

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

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Leitão, M J; Baldeiras, I; Almeida, M R; Ribeiro, M H; Santos, A C; Ribeiro, M; Tomás, J; Rocha, S; Santana, I; Oliveira, C R

2016-09-01

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

Frequent Questions on Recycling

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This is a list of frequent questions on recycling, broken down into five categories. These are answers to common questions that EPA has received from press and web inquiries. This list is located on the Reduce, Reuse, Recycle website.

Mathematical models for the diffusion magnetic resonance signal abnormality in patients with prion diseases

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Matteo Figini

2015-01-01

Full Text Available In clinical practice signal hyperintensity in the cortex and/or in the striatum on magnetic resonance (MR diffusion-weighted images (DWIs is a marker of sporadic Creutzfeldt–Jakob Disease (sCJD. MR diagnostic accuracy is greater than 90%, but the biophysical mechanisms underpinning the signal abnormality are unknown. The aim of this prospective study is to combine an advanced DWI protocol with new mathematical models of the microstructural changes occurring in prion disease patients to investigate the cause of MR signal alterations. This underpins the later development of more sensitive and specific image-based biomarkers. DWI data with a wide a range of echo times and diffusion weightings were acquired in 15 patients with suspected diagnosis of prion disease and in 4 healthy age-matched subjects. Clinical diagnosis of sCJD was made in nine patients, genetic CJD in one, rapidly progressive encephalopathy in three, and Gerstmann–Sträussler–Scheinker syndrome in two. Data were analysed with two bi-compartment models that represent different hypotheses about the histopathological alterations responsible for the DWI signal hyperintensity. A ROI-based analysis was performed in 13 grey matter areas located in affected and apparently unaffected regions from patients and healthy subjects. We provide for the first time non-invasive estimate of the restricted compartment radius, designed to reflect vacuole size, which is a key discriminator of sCJD subtypes. The estimated vacuole size in DWI hyperintense cortex was in the range between 3 and 10 µm that is compatible with neuropathology measurements. In DWI hyperintense grey matter of sCJD patients the two bi-compartment models outperform the classic mono-exponential ADC model. Both new models show that T2 relaxation times significantly increase, fast and slow diffusivities reduce, and the fraction of the compartment with slow/restricted diffusion increases compared to unaffected grey matter of

Strain-Specific Altered Regulatory Response of Rab7a and Tau in Creutzfeldt-Jakob Disease and Alzheimer's Disease.

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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

Examining the Impact of Question Surface Features on Students’ Answers to Constructed-Response Questions on Photosynthesis

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Weston, Michele; Haudek, Kevin C.; Prevost, Luanna; Urban-Lurain, Mark; Merrill, John

2015-01-01

One challenge in science education assessment is that students often focus on surface features of questions rather than the underlying scientific principles. We investigated how student written responses to constructed-response questions about photosynthesis vary based on two surface features of the question: the species of plant and the order of two question prompts. We asked four versions of the question with different combinations of the two plant species and order of prompts in an introductory cell biology course. We found that there was not a significant difference in the content of student responses to versions of the question stem with different species or order of prompts, using both computerized lexical analysis and expert scoring. We conducted 20 face-to-face interviews with students to further probe the effects of question wording on student responses. During the interviews, we found that students thought that the plant species was neither relevant nor confusing when answering the question. Students identified the prompts as both relevant and confusing. However, this confusion was not specific to a single version. PMID:25999312

Biology Question Generation from a Semantic Network

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Zhang, Lishan

Science instructors need questions for use in exams, homework assignments, class discussions, reviews, and other instructional activities. Textbooks never have enough questions, so instructors must find them from other sources or generate their own questions. In order to supply instructors with biology questions, a semantic network approach was developed for generating open response biology questions. The generated questions were compared to professional authorized questions. To boost students' learning experience, adaptive selection was built on the generated questions. Bayesian Knowledge Tracing was used as embedded assessment of the student's current competence so that a suitable question could be selected based on the student's previous performance. A between-subjects experiment with 42 participants was performed, where half of the participants studied with adaptive selected questions and the rest studied with mal-adaptive order of questions. Both groups significantly improved their test scores, and the participants in adaptive group registered larger learning gains than participants in the control group. To explore the possibility of generating rich instructional feedback for machine-generated questions, a question-paragraph mapping task was identified. Given a set of questions and a list of paragraphs for a textbook, the goal of the task was to map the related paragraphs to each question. An algorithm was developed whose performance was comparable to human annotators. A multiple-choice question with high quality distractors (incorrect answers) can be pedagogically valuable as well as being much easier to grade than open-response questions. Thus, an algorithm was developed to generate good distractors for multiple-choice questions. The machine-generated multiple-choice questions were compared to human-generated questions in terms of three measures: question difficulty, question discrimination and distractor usefulness. By recruiting 200 participants from

Questions for Music Education Research

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Jorgensen, Estelle R.

2008-01-01

In addressing the question-set "What questions do music education researchers need to address?", an illustrative list of juxtaposed descriptive and normative questions is sketched as follows: What are and should be the dimensions of music education? What are and should be the institutional agencies of music education? What are and should be the…

Dynamic Question Ordering in Online Surveys

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Early Kirstin

2017-09-01

Full Text Available Online surveys have the potential to support adaptive questions, where later questions depend on earlier responses. Past work has taken a rule-based approach, uniformly across all respondents. We envision a richer interpretation of adaptive questions, which we call Dynamic Question Ordering (DQO, where question order is personalized. Such an approach could increase engagement, and therefore response rate, as well as imputation quality. We present a DQO framework to improve survey completion and imputation. In the general survey-taking setting, we want to maximize survey completion, and so we focus on ordering questions to engage the respondent and collect hopefully all information, or at least the information that most characterizes the respondent, for accurate imputations. In another scenario, our goal is to provide a personalized prediction. Since it is possible to give reasonable predictions with only a subset of questions, we are not concerned with motivating users to answer all questions. Instead, we want to order questions to get information that reduces prediction uncertainty, while not being too burdensome. We illustrate this framework with two case studies, for the prediction and survey-taking settings. We also discuss DQO for national surveys and consider connections between our statistics-based question-ordering approach and cognitive survey methodology.

Repetitive Questioning Exasperates Caregivers

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R. C. Hamdy MD

2018-01-01

Full Text Available Repetitive questioning is due to an impaired episodic memory and is a frequent, often presenting, problem in patients with Alzheimer’s disease (amnestic type. It is due to the patients’ difficulties learning new information, retaining it, and recalling it, and is often aggravated by a poor attention span and easy distractibility. A number of factors may trigger and maintain repetitive questioning. Caregivers should try to identify and address these triggers. In the case discussion presented, it is due to the patient’s concerns about her and her family’s safety triggered by watching a particularly violent movie aired on TV. What went wrong in the patient/caregiver interaction and how it could have been avoided or averted are explored. Also reviewed are the impact of repetitive questioning, the challenges it raises for caregivers, and some effective intervention strategies that may be useful to diffuse the angst that caregivers experience with repetitive questioning.

The Question Complexity Rubric: Development and Application for a National Archive of Astro 101 Multiple-Choice Questions

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Cormier, Sebastien; Prather, E. E.; Brissenden, G.; Collaboration of Astronomy Teaching Scholars CATS

2011-01-01

For the last two years we have been developing an online national archive of multiple-choice questions for use in the Astro 101 classroom. These questions are intended to either supplement an instructor's implementation of Think-Pair-Share or be used for assessment purposes (i.e. exams and homework). In this talk we will describe the development, testing and implementation of the Question Complexity Rubric (QCR), which is designed to guide the ranking of questions in this archive based on their conceptual complexity. Using the QCR, a score is assigned to differentiate each question based on the cognitive steps necessary to comprehensively explain the reasoning pathway to the correct answer. The lowest QCR score is given to questions with a reasoning pathway requiring only declarative knowledge whereas the highest QCR score is given to questions that require multiple pathways of multi-step reasoning. When completed, the online question archive will provide users with the utility to 1) search for and download questions based on subject and average QCR score, 2) use the QCR to score questions, and 3) add their own questions to the archive. We will also discuss other potential applications of the QCR, such as how it informs our work in developing and testing of survey instruments by allowing us to calibrate the range of question complexity. This material is based upon work supported by the National Science Foundation under Grant No. 0715517, a CCLI Phase III Grant for the Collaboration of Astronomy Teaching Scholars (CATS). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

The Value Question in Metaphysics

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Kahane, Guy

2012-01-01

Much seems to be at stake in metaphysical questions about, for example, God, free will or morality. One thing that could be at stake is the value of the universe we inhabit—how good or bad it is. We can think of competing philosophical positions as describing possibilities, ways the world might turn out to be, and to which value can be assigned. When, for example, people hope that God exists, or fear that we do not possess free will, they express attitudes towards these possibilities, attitudes that presuppose answers to questions about their comparative value. My aim in this paper is to distinguish these evaluative questions from related questions with which they can be confused, to identify structural constraints on their proper pursuit, and to address objections to their very coherence. Answers to such evaluative questions offer one measure of the importance of philosophical disputes. PMID:23024399

The Value Question in Metaphysics.

Science.gov (United States)

Kahane, Guy

2012-07-01

Much seems to be at stake in metaphysical questions about, for example, God, free will or morality. One thing that could be at stake is the value of the universe we inhabit-how good or bad it is. We can think of competing philosophical positions as describing possibilities, ways the world might turn out to be, and to which value can be assigned. When, for example, people hope that God exists, or fear that we do not possess free will, they express attitudes towards these possibilities, attitudes that presuppose answers to questions about their comparative value. My aim in this paper is to distinguish these evaluative questions from related questions with which they can be confused, to identify structural constraints on their proper pursuit, and to address objections to their very coherence. Answers to such evaluative questions offer one measure of the importance of philosophical disputes.

Diffusion-weighted imaging and magnetic resonance spectroscopy of sporadic Creutzfeldt-Jakob disease: correlation with clinical course

International Nuclear Information System (INIS)

Kim, Jae Hyoung; Choi, Byung Se; Jung, Cheolkyu; Chang, YoungHee; Kim, SangYun

2011-01-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease with variable clinical courses. The presence or absence of basal ganglia (BG) involvement has been reported to be associated with clinical course. We investigated the association of clinical course of sCJD with diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as well as BG involvement at early stage. DWI and single voxel proton MRS were performed in 14 patients with sCJD during the initial diagnostic workup. Apparent diffusion coefficient (ADC) and metabolites were measured in medial occipitoparietal cortices where large hyperintense DWI lesions were found in all patients. The presence or absence of BG involvement, ADC, N-acetylaspartate (NAA)/creatine (Cr) ratios, and choline (Cho)/Cr ratios were correlated with disease duration (i.e., the time from the symptom onset to death). The disease duration ranged from 2 to 31 months (median, 16). Hyperintense DWI lesions were observed bilaterally in both cortices and basal ganglia in eight patients and in cortices alone in six patients. Patients with BG involvement had shorter disease duration (median, 6.8 versus 20.5; p = 0.039) than those without and lower NAA/Cr ratios (median, 1.41 versus 2.03; p = 0.001). ADC and Cho/Cr ratios were not significantly different between the patients with BG involvement and those without. By multiple regression analysis, NAA/Cr ratios had the greatest correlation with the disease duration (p = 0.029). The disease duration of sCJD was variable. NAA/Cr ratios of the affected brain at the early stage of sCJD can be used as a useful parameter in predicting the clinical course. (orig.)

Diffusion-weighted imaging and magnetic resonance spectroscopy of sporadic Creutzfeldt-Jakob disease: correlation with clinical course

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Kim, Jae Hyoung; Choi, Byung Se; Jung, Cheolkyu [Seoul National University Bundang Hospital, Department of Radiology, Seoul National University College of Medicine, Seongnam-si (Korea, Republic of); Chang, YoungHee; Kim, SangYun [Seoul National University Bundang Hospital, Department of Neurology, Seoul National University College of Medicine, Seongnam-si (Korea, Republic of)

2011-12-15

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease with variable clinical courses. The presence or absence of basal ganglia (BG) involvement has been reported to be associated with clinical course. We investigated the association of clinical course of sCJD with diffusion-weighted imaging (DWI) and MR spectroscopy (MRS) as well as BG involvement at early stage. DWI and single voxel proton MRS were performed in 14 patients with sCJD during the initial diagnostic workup. Apparent diffusion coefficient (ADC) and metabolites were measured in medial occipitoparietal cortices where large hyperintense DWI lesions were found in all patients. The presence or absence of BG involvement, ADC, N-acetylaspartate (NAA)/creatine (Cr) ratios, and choline (Cho)/Cr ratios were correlated with disease duration (i.e., the time from the symptom onset to death). The disease duration ranged from 2 to 31 months (median, 16). Hyperintense DWI lesions were observed bilaterally in both cortices and basal ganglia in eight patients and in cortices alone in six patients. Patients with BG involvement had shorter disease duration (median, 6.8 versus 20.5; p = 0.039) than those without and lower NAA/Cr ratios (median, 1.41 versus 2.03; p = 0.001). ADC and Cho/Cr ratios were not significantly different between the patients with BG involvement and those without. By multiple regression analysis, NAA/Cr ratios had the greatest correlation with the disease duration (p = 0.029). The disease duration of sCJD was variable. NAA/Cr ratios of the affected brain at the early stage of sCJD can be used as a useful parameter in predicting the clinical course. (orig.)

CSF concentrations of cAMP and cGMP are lower in patients with Creutzfeldt-Jakob disease but not Parkinson's disease and amyotrophic lateral sclerosis.

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Patrick Oeckl

Full Text Available BACKGROUND: The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP and cyclic guanosine-3',5'-monophosphate (cGMP are important second messengers and are potential biomarkers for Parkinson's disease (PD, amyotrophic lateral sclerosis (ALS and Creutzfeldt-Jakob disease (CJD. METHODOLOGY/PRINCIPAL FINDINGS: Here, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS the cerebrospinal fluid (CSF concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15 had lower cAMP (-70% and cGMP (-55% concentrations in CSF compared with controls (n = 11. There was no difference in PD, PD dementia (PDD and ALS cases. Receiver operating characteristic (ROC curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC of 0.86 (cAMP and 0.85 (cGMP. We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92 and to 93% and 100% for the ratio tau/cAMP (AUC 0.99. CONCLUSIONS/SIGNIFICANCE: We conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

Voltage-Gated Potassium Channel Autoimmunity Mimicking Creutzfeldt-Jakob Disease

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Geschwind, Michael D.; Tan, K. Meng; Lennon, Vanda A.; Barajas, Ramon F.; Haman, Aissa; Klein, Christopher J.; Josephson, S. Andrew; Pittock, Sean J.

2009-01-01

Background Rapidly progressive dementia has a variety of causes, including Creutzfeldt-Jakob disease (CJD) and neuronal voltage-gated potassium channel (VGKC) autoantibody–associated encephalopathy. Objective To describe patients thought initially to have CJD but found subsequently to have immunotherapy-responsive VGKC autoimmunity. Design Observational, prospective case series. Setting Department of Neurology, Mayo Clinic, and the Memory and Aging Center, University of California, San Francisco. Patients A clinical serologic cohort of 15 patients referred for paraneoplastic autoantibody evaluation. Seven patients were evaluated clinically by at least one of us. Clinical information for the remaining patients was obtained by physician interview or medical record review. Main Outcome Measures Clinical features, magnetic resonance imaging abnormalities, electroencephalographic patterns, cerebrospinal fluid analyses, and responses to immunomodulatory therapy. Results All the patients presented subacutely with neurologic manifestations, including rapidly progressive dementia, myoclonus, extrapyramidal dysfunction, visual hallucinations, psychiatric disturbance, and seizures; most (60%) satisfied World Health Organization diagnostic criteria for CJD. Magnetic resonance imaging abnormalities included cerebral cortical diffusion-weighted imaging hyperintensities. Electroencephalographic abnormalities included diffuse slowing, frontal intermittent rhythmic delta activity, and focal epileptogenic activity but not periodic sharp wave complexes. Cerebrospinal fluid 14-3-3 protein or neuron-specific enolase levels were elevated in 5 of 8 patients. Hyponatremia was common (60%). Neoplasia was confirmed histologically in 5 patients (33%) and was suspected in another 5. Most patients’ conditions (92%) improved after immunomodulatory therapy. Conclusions Clinical, radiologic, electrophysiologic, and laboratory findings in VGKC autoantibody–associated encephalopathy may be

Legal Philosophy - Five Questions

DEFF Research Database (Denmark)

This collection gathers together a host of the most eminent contemporary legal philosophers, who writes about their take on legal philosophy, its fundamental questions and potential.......This collection gathers together a host of the most eminent contemporary legal philosophers, who writes about their take on legal philosophy, its fundamental questions and potential....

Positive, negative, and bipolar questions: The effect of question polarity on ratings of text readability

Directory of Open Access Journals (Sweden)

Naomi Kamoen

2013-12-01

Full Text Available For decades, survey researchers have known that respondents give different answers to attitude questions worded positively (X is good. Agree-Disagree, negatively (X is bad. Agree-Disagree or on a bipolar scale (X is bad-good. This makes survey answers hard to interpret, especially since findings on exactly how the answers are affected are conflicting. In the current paper, we present twelve studies in which the effect of question polarity was measured for a set of thirteen contrastive adjectives. In each study, the same adjectives were used so the generalizability of wording effects across studies could be examined for each word pair. Results show that for five of the word pairs an effect of question wording can be generalized. The direction of these effects are largely consistent: respondents generally give the same answers to positive and bipolar questions, but they are more likely to disagree with negative questions than to agree with positive questions or to choose the positive side of the bipolar scale. In other words, respondents express their opinions more positively when the question is worded negatively. Even though answers to the three wording alternatives sometimes differ, results also show that reliable answers can be obtained with all three wording alternatives. So, for survey practice, these results suggest that all three wording alternatives may be used for attitude measurement.

Diagnostic profiles of patients with late-onset Creutzfeldt-Jakob disease differ from those of younger Creutzfeldt-Jakob patients: a historical cohort study using data from the German National Reference Center.

Science.gov (United States)

Karch, André; Raddatz, Lena Maria; Ponto, Claudia; Hermann, Peter; Summers, David; Zerr, Inga

2014-05-01

In contrast to other neurodegenerative diseases, sporadic Creutzfeldt-Jakob disease (sCJD) is rarely diagnosed in patients older than 75 years. Data describing the characteristics of sCJD in the very old are rare and inconclusive. Therefore, a historical cohort study was designed to evaluate clinical, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) features of this group. Patients older than 75 years identified via the German surveillance program from 2001 to 2012 (n = 73) were compared to a random subsample of sCJD patients younger than 75 (n = 73) from the same time period using an historical cohort design. Older patients showed a faster disease progression represented by an earlier point of diagnosis and a shorter survival time (p disease, older patients presented slightly more often with dementia (p = 0.127) or dysarthria (p = 0.238), whereas disorders of the extrapyramidal (p = 0.056) and visual system (p = 0.015) were more common in the younger group. Atypical MRI profiles such as MRI lesions restricted to one hemisphere (p Creutzfeldt-Jakob disease cases in patients older than 75 years seems likely due to atypical clinical and radiological presentation. This might contribute to lower sCJD incidence rates in this age group.

Intracranial Procedures and Expected Frequency of Creutzfeldt-Jakob Disease.

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Abrams, Joseph Y; Maddox, Ryan A; Schonberger, Lawrence B; Belay, Ermias D

2016-01-01

To assess the frequency and characteristics of intracranial procedures (ICPs) performed and the number of U.S. residents living with a history of ICP. These data are used to calculate the expected annual number of sporadic Creutzfeldt-Jakob disease (CJD) cases among U.S. residents with a history of ICP. The Nationwide Inpatient Sample provided data on the frequency and types of ICPs, and data from the National Center for Health Statistics was used to produce age-adjusted mortality rates. A model was constructed, which estimated long-term survival and sporadic CJD rates among ICP patients based on procedure type and age. There were an estimated 2,070,488 ICPs in the United States from 1998 to 2007, an average of over 200,000 per year. There were an estimated 2,023,726 U.S. residents in 2013 with a history of ICP in the previous 30 years. In 2013, there was expected to be 4.1 sporadic CJD cases (95% CI 1-8) among people with a history of ICP in the past 30 years. The considerable proportion of U.S. residents living with a history of ICP is important information for retrospective assessments of CJD or any other suspected long-term outcome of ICPs. © 2015 S. Karger AG, Basel.

Thousand Questions

DEFF Research Database (Denmark)

2012-01-01

(perhaps as an expanded Turing test) on its listeners. These questions are extracted in real-time from Twitter with the keyword search of the ‘?’ symbol to create a spatio-temporal experience. The computerized voice the audience hears is a collective one, an entanglement of humans and non-humans......In this work the network asks “If I wrote you a love letter would you write back?” Like the love letters which appeared mysteriously on the noticeboards of Manchester University’s Computer Department in the 1950s, thousands of texts circulate as computational processes perform the questions......, that circulates across networks. If I wrote you a love letter would you write back? (and thousands of other questions’ ) (封不回的情書？千言萬語無人回 was commissioned by the Microwave International New Media Festival 2012....

Legacy question

International Nuclear Information System (INIS)

Healy, J.W.

1977-01-01

The legacy question discussed refers to the definition of appropriate actions in this generation to provide a world that will allow future generations to use the earth without excessive limitations caused by our use and disposal of potentially hazardous materials

An Online National Archive of Multiple-Choice Questions for Astro 101 and the Development of the Question Complexity Rubric

Science.gov (United States)

Cormier, S.; Prather, E.; Brissenden, G.

2011-09-01

We are developing a national archive of multiple-choice questions for use in the Astronomy 101 classroom. These questions are intended to supplement an instructor's implementation of Think-Pair-Share or for their assessment purposes (i.e., exams and homework). We are also developing the Question Complexity Rubric (QCR) to guide members of the Astro 101 teaching and learning community in assisting us with hierarchically ranking questions in this archive based on their conceptual complexity. Using the QCR, a score is assigned to differentiate each question based on the cognitive steps necessary to comprehensively explain the reasoning pathway to the correct answer. The lowest QCR score is given to questions with a reasoning pathway requiring only declarative knowledge. The highest QCR score is given to questions with a reasoning pathway that requires multiple connected cognitive steps. When completed, the online question archive will provide users with the utility to 1) use the QCR to score questions 2) search for and download questions based on topic and/or QCR score, and 3) add their own questions to the archive. Stop by our poster to test your skills at determining question complexity by trying out the QCR with our sample questions.

Difficult Questions of Difficult Questions: The Role of The Researcher and Transcription Styles

Science.gov (United States)

Henderson, Holly

2018-01-01

This paper refracts a comparison of three distinct transcription styles through questions of researcher reflexivity. It uses the data from a single question asked by the researcher in multiple interviews for a small empirical project. These data are transcribed in three ways, and the resulting transcripts are discussed in relation to the analysis…

Serial MR imaging in Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Uchino, A.; Hata, H.; Ohno, M. (Kyushu Rosai Hospital, Kitakyushu (Japan). Dept. of Radiology); Yoshinaga, M.; Shiokawa, O. (Kyushu Rosai Hospital, Kitakyushu (Japan). Stroke Care Unit)

1991-08-01

Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful. (orig.).

Serial MR imaging in Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Uchino, A.; Hata, H.; Ohno, M.; Yoshinaga, M.; Shiokawa, O.

1991-01-01

Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful. (orig.)

Let's talk nuclear energy in 30 questions; Parlons nucleaire en 30 questions

Energy Technology Data Exchange (ETDEWEB)

Reuss, Paul

2012-01-11

The Fukushima catastrophe of March 11, 2011 has called into question the share of nuclear energy in France and in foreign countries. Its replacement by renewable energy sources and the safety of nuclear power plants are in the center of today's debates. But what is the reality behind the mass of contradictory information that exists on this complex topic? This book moves the question out of the media noise and supplies objective and factual information with reliable figures about the nuclear industry by answering 30 key-questions. (J.S.)

Question, answer, compare: a cross-category comparison of answers on question and answer websites

Science.gov (United States)

Ocepek, Melissa G.; Westbrook, Lynn

2015-10-01

Online information seekers make heavy use of websites that accept their natural language questions. This study compared the three types of such websites: social question and answer (Q&A), digital reference services, and ask-an-expert services. Questions reflecting daily life, research, and crisis situations were posed to high use websites of all three types. The resulting answers' characteristics were analyzed in terms of speed, transparency, formality, and intimacy. The results indicate that social Q&A websites excel in speed, ask-an-expert websites in intimacy, and digital reference services in transparency and formality.

Examining the Impact of Question Surface Features on Students' Answers to Constructed-Response Questions on Photosynthesis

Science.gov (United States)

Weston, Michele; Haudek, Kevin C.; Prevost, Luanna; Urban-Lurain, Mark; Merrill, John

2015-01-01

One challenge in science education assessment is that students often focus on surface features of questions rather than the underlying scientific principles. We investigated how student written responses to constructed-response questions about photosynthesis vary based on two surface features of the question: the species of plant and the order of…

Generic Drugs: Questions and Answers

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... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

Comparison of Performance on Multiple-Choice Questions and Open-Ended Questions in an Introductory Astronomy Laboratory

Science.gov (United States)

Wooten, Michelle M.; Cool, Adrienne M.; Prather, Edward E.; Tanner, Kimberly D.

2014-01-01

When considering the variety of questions that can be used to measure students' learning, instructors may choose to use multiple-choice questions, which are easier to score than responses to open-ended questions. However, by design, analyses of multiple-choice responses cannot describe all of students' understanding. One method that can…

Questioning context: a set of interdisciplinary questions for investigating contextual factors affecting health decision making

Science.gov (United States)

Charise, Andrea; Witteman, Holly; Whyte, Sarah; Sutton, Erica J.; Bender, Jacqueline L.; Massimi, Michael; Stephens, Lindsay; Evans, Joshua; Logie, Carmen; Mirza, Raza M.; Elf, Marie

2011-01-01

Abstract Objective  To combine insights from multiple disciplines into a set of questions that can be used to investigate contextual factors affecting health decision making. Background  Decision‐making processes and outcomes may be shaped by a range of non‐medical or ‘contextual’ factors particular to an individual including social, economic, political, geographical and institutional conditions. Research concerning contextual factors occurs across many disciplines and theoretical domains, but few conceptual tools have attempted to integrate and translate this wide‐ranging research for health decision‐making purposes. Methods  To formulate this tool we employed an iterative, collaborative process of scenario development and question generation. Five hypothetical health decision‐making scenarios (preventative, screening, curative, supportive and palliative) were developed and used to generate a set of exploratory questions that aim to highlight potential contextual factors across a range of health decisions. Findings  We present an exploratory tool consisting of questions organized into four thematic domains – Bodies, Technologies, Place and Work (BTPW) – articulating wide‐ranging contextual factors relevant to health decision making. The BTPW tool encompasses health‐related scholarship and research from a range of disciplines pertinent to health decision making, and identifies concrete points of intersection between its four thematic domains. Examples of the practical application of the questions are also provided. Conclusions  These exploratory questions provide an interdisciplinary toolkit for identifying the complex contextual factors affecting decision making. The set of questions comprised by the BTPW tool may be applied wholly or partially in the context of clinical practice, policy development and health‐related research. PMID:21029277

Creutzfeldt-Jakob disease: the value of MRI; Creutzfeldt-Jakob-Krankheit: Stellenwert der MRT

Energy Technology Data Exchange (ETDEWEB)

Urbach, H.; Tschampa, H.J.; Keller, E.; Schild, H.H. [Radiologische Klinik, Neuroradiologie, Rheinische Friedrich-Wilhelms-Univ. Bonn (Germany); Paus, S. [Neurologische Klinik, Rheinische Friedrich-Wilhelms-Univ. Bonn (Germany)

2001-06-01

To define the role of MRI in the diagnosis of Creutzfeldt-Jakob disease (CJD). Methods: 14 patients with suspected CJD were studied within 3 years. MRI findings were correlated with WHO established diagnostic criteria (clinical findings, EEG, CSF with 14-3-3 protein assay). Results: 12 patients had CJD. One patient each suffered from Hashimoto's encephalitis and ALS dementia complex, respectively. Nine of 12 CJD patients had increased signal intensity of the striatum (n = 8), pulvinar thalami (n = 5) and/or cerebellar and cerebral cortex (n = 3), respectively. Signal intensity was most pronounced on FLAIR sequences; six patients were studied with diffusion-weighted MRI and showed impaired diffusion in these areas. Both patients without CJD did not show the abovementioned signal changes (sensitivity 75%, specificity and positive predictive value 100%, respectively). Conclusion: If patients with suspected CJD are studied with FLAIR and diffusion-weighted sequences, this disorder can reliably be proven or ruled out. Typical MRI findings narrow down the differential diagnosis and should be included in the WHO diagnostic criteria. (orig.) [German] Bestimmung des Stellenwerts der MRT in der Diagnostik der Creutzfeldt-Jakob-Krankheit (CJK). Methoden: Analyse der MRTs von 14 innerhalb von drei Jahren mit Verdacht auf CJK zugewiesenen Patienten. Korrelation der MRTs mit den entsprechend den WHO-Diagnosekriterien etablierten Untersuchungsverfahren (Klinik, EEG, Liquor mit 14-3-3 Protein-Nachweis). Ergebnisse: 12 Patienten hatten eine CJK, jeweils ein Patient hatte eine Hashimoto-Enzephalitis bzw. einen ALS-Demenz-Komplex. Bei 9 der 12 CJK-Patienten fanden sich beidseits Signalerhoehungen des Striatum (n = 8), des Pulvinar thalami (n = 5) und/oder des Kleinhirn- bzw. Grosshirnkortex (n = 3). Die Signalerhoehungen waren am deutlichsten auf FLAIR-Aufnahmen erkennbar; 6 mit diffusionsgewichteter MRT untersuchte Patienten wiesen eine eingeschraenkte Diffusion dieser Areale

Multitracer study with positron emission tomography in Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Engler, Henry; Lundberg, Per Olov; Ekbom, Karl; Nennesmo, Inger; Nilsson, Anna; Bergstroem, Mats; Hartvig, Per; Laangstroem, Bengt; Tsukada, Hideo

2003-01-01

During the period February 1997 to April 2000, 15 patients with clinical symptoms of Creutzfeldt-Jakob disease (CJD) were referred to Uppsala University PET Centre. Positron emission tomography (PET) was performed to detect characteristic signs of the disease, e.g. neuronal death and/or astrocytosis in the brain. The examinations were performed in one session starting with oxygen-15 labelled water scan to measure regional cerebral blood flow, followed by imaging with the monoamine oxidase B inhibitor N-[ 11 C-methyl]-L-deuterodeprenyl (DED) to assess astrocytosis in the brain and finally imaging with fluorine-18 2-fluorodeoxyglucose (FDG) to assess regional cerebral glucose metabolism (rCMR glu ). Nine of the patients fulfilled the clinical criteria of probable CJD. In eight of them, FDG and DED imaging revealed, in comparison with normal controls, a typical pattern characterized by a pronounced regional decrease ( 2SD) in DED binding, indicating astrocytosis. These changes were most pronounced in the cerebellum and the frontal, occipital and parietal cortices, whereas the pons, the thalamus and the putamen were less affected and the temporal cortex appeared unaffected. The cerebral blood flow showed a pattern similar to that observed with FDG. In the ninth patient, analysis with DED was not possible. The diagnosis of definite CJD according to international consensus criteria was confirmed in six of these patients. In one patient with probable CJD, protease-resistant prion protein (PrPres) could not be demonstrated. In two patients with probable CJD, autopsy was not allowed. Computed tomography and magnetic resonance imaging, performed in four and seven of these nine patients respectively, showed unspecific, mainly atrophic changes. In six other patients, the PET examinations gave a different pattern. In three of them, high rCMR glu was noticed in parts of the brain, particularly in the temporal lobes and basal ganglia, which could suggest encephalitis. One of the

Annotating Logical Forms for EHR Questions.

Science.gov (United States)

Roberts, Kirk; Demner-Fushman, Dina

2016-05-01

This paper discusses the creation of a semantically annotated corpus of questions about patient data in electronic health records (EHRs). The goal is to provide the training data necessary for semantic parsers to automatically convert EHR questions into a structured query. A layered annotation strategy is used which mirrors a typical natural language processing (NLP) pipeline. First, questions are syntactically analyzed to identify multi-part questions. Second, medical concepts are recognized and normalized to a clinical ontology. Finally, logical forms are created using a lambda calculus representation. We use a corpus of 446 questions asking for patient-specific information. From these, 468 specific questions are found containing 259 unique medical concepts and requiring 53 unique predicates to represent the logical forms. We further present detailed characteristics of the corpus, including inter-annotator agreement results, and describe the challenges automatic NLP systems will face on this task.

Generating ethnographic research questions

DEFF Research Database (Denmark)

Friberg, Torbjörn

2015-01-01

? By drawing on the conceptual history of anthropology, the aim of this article is to generate ethnographic-oriented research questions concerned with higher education. The first part of the article provides an ethnographic background, while the second part focuses on Paul Willis's reasoning on ethnographic......As part of recent complex transformations, it seems that higher educational organisations are being forced to reorganise, standardise and streamline in order to survive in the new political and economic context. How are ethnographers in general going to approach these contemporary phenomena...... imagination, as a prerequisite for generating alternative research questions. The third part makes explicit anthropologist Maurice Godelier's theoretical imagination, carving out some specific theoretical parts which may be used in the generating process. The conclusion then suggests a number of questions...

Differential diagnosis of Jakob-Creutzfeldt disease

OpenAIRE

Paterson, RW; Torres-Chae, CC; Kuo, AL; Ando, T; Nguyen, EA; Wong, K; DeArmond, SJ; Haman, A; Garcia, P; Johnson, DY; Miller, BL; Geschwind, MD

2012-01-01

Objectives: To identify the misdiagnoses of patients with sporadic Jakob-Creutzfeldt disease (sCJD) during the course of their disease and determine which medical specialties saw patients with sCJD prior to the correct diagnosis being made and at what point in the disease course a correct diagnosis was made. Design: Retrospective medical record review. Setting: A specialty referral center of a tertiary academic medical center. Participants: One hundred sixty-three serial patients over a 5.5-y...

Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease

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Baker, Christopher A.; Manuelidis, Laura

2003-01-01

Previous studies in Creutzfeldt-Jakob disease (CJD) have shown that myeloid cells in the periphery as well as derivative microglial cells in the brain are infectious. Microglia can show an activated phenotype before prion protein (PrP) pathology is detectable in brain, and isolated infectious microglia contain very little PrP. To find whether a set of inflammatory genes are significantly induced or suppressed with infection, we analyzed RNA from isolated microglia with relevant cDNA arrays, and identified 30 transcripts not previously examined in any transmissible spongiform encephalopathy. This CJD expression profile contrasted with that of uninfected microglia exposed to prototypic inflammatory stimuli such as lipopolysaccharide and IFN-, as well as PrP amyloid. These findings underscore inflammatory pathways evoked by the infectious agent in brain. Transcript profiles unique for CJD microglia and other myeloid cells provide opportunities for more sensitive preclinical diagnoses of infectious and noninfectious neurodegenerative diseases.

Development of a dot blot assay with antibodies to recombinant “core” 14-3-3 protein: Evaluation of its usefulness in diagnosis of Creutzfeldt–Jakob disease

Directory of Open Access Journals (Sweden)

Sarada Subramanian

2016-01-01

Full Text Available Background and Purpose: Definitive diagnosis of Creutzfeldt–Jakob disease (CJD requires demonstration of infective prion protein (PrPSc in brain tissues by immunohistochemistry or immunoblot, making antemortem diagnosis of CJD difficult. The World Health Organization (WHO recommends detection of 14-3-3 protein in cerebrospinal fluid (CSF in cases of dementia, with clinical correlation, as a useful diagnostic marker for CJD, obviating the need for brain biopsy.This facility is currently available in only a few specialized centers in the West and no commercial kit is available for clinical diagnostic use in India. Hence the objective of this study was to develop an in-house sensitive assay for quantitation of 14-3-3 protein and to evaluate its diagnostic potential to detect 14-3-3 proteins in CSF as a biomarker in suspected cases of CJD. Materials and Methods: A minigene expressing the “core” 14-3-3 protein was synthesized by overlapping polymerase chain reaction (PCR and the recombinant protein was produced by employing a bacterial expression system. Polyclonal antibodies raised in rabbit against the purified recombinant protein were used for developing a dot blot assay with avidin-biotin technology for signal amplification and quantitation of 14-3-3 protein in CSF. Results: The results in the present study suggest the diagnostic potential of the dot blot method with about 10-fold difference (P< 0.001 in the CSF levels of 14-3-3 protein between the CJD cases (N= 50 and disease controls (N= 70. The receiver operating characteristic (ROC analysis of the results suggested an optimal cutoff value of 2 ng/mL. Conclusions: We have developed an indigenous, economical, and sensitive dot blot method for the quantitation of 14-3-3 protein in CSF.

Instance-Based Question Answering

Science.gov (United States)

2006-12-01

cluster-based query expan- sion, learning answering strategies, machine learning in NLP To my wife Monica Abstract During recent years, question...process is typically tedious and involves expertise in crafting and implement- ing these models (e.g. rule-based), utilizing NLP resources, and...questions. For languages that use capitalization (e.g. not Chinese or Arabic ) for named entities, IBQA can make use of NE classing (e.g. “Bob Marley

Protein Electrochemistry: Questions and Answers.

Science.gov (United States)

Fourmond, V; Léger, C

This chapter presents the fundamentals of electrochemistry in the context of protein electrochemistry. We discuss redox proteins and enzymes that are not photoactive. Of course, the principles described herein also apply to photobioelectrochemistry, as discussed in later chapters of this book. Depending on which experiment is considered, electron transfer between proteins and electrodes can be either direct or mediated, and achieved in a variety of configurations: with the protein and/or the mediator free to diffuse in solution, immobilized in a thick, hydrated film, or adsorbed as a sub-monolayer on the electrode. The experiments can be performed with the goal to study the protein or to use it. Here emphasis is on mechanistic studies, which are easier in the configuration where the protein is adsorbed and electron transfer is direct, but we also explain the interpretation of signals obtained when diffusion processes affect the response.This chapter is organized as a series of responses to questions. Questions 1-5 are related to the basics of electrochemistry: what does "potential" or "current" mean, what does an electrochemical set-up look like? Questions 6-9 are related to the distinction between adsorbed and diffusive redox species. The answers to questions 10-13 explain the interpretation of slow and fast scan voltammetry with redox proteins. Questions 14-19 deal with catalytic electrochemistry, when the protein studied is actually an enzyme. Questions 20, 21 and 22 are general.

IMS Learning Design Frequently Asked Questions

NARCIS (Netherlands)

Tattersall, Colin; Manderveld, Jocelyn; Hummel, Hans; Sloep, Peter; Koper, Rob; De Vries, Fred

2004-01-01

This list of frequently asked questions was composed on the basis of questions asked of the Educational Technology Expertise Centrum. The questions addessed are: Where can I find the IMS Learning Design Specification? What is meant by the phrase “Learning Design”? What is the IMS LD Specification

Effect of two types of control questions and two question formats on the outcomes of polygraph examinations.

Science.gov (United States)

Horvath, Frank; Palmatier, John J

2008-07-01

Two major variations of polygraph "Control Question" testing, the Zone Comparison (ZoC) and the Modified General Question Test (MGQT) were evaluated. Within each, the type of control question, Exclusive or "time bar" (e.g., "Before you were 21, did you ever...") and Nonexclusive or "no time bar" (e.g., "Did you ever....?") was manipulated in a mock theft scenario, with 80 male and 40 female subjects randomly assigned to be either innocent or guilty. Polygraphic data collected by experienced field examiners were numerically scored by an evaluator blind to all aspects of the study. Decision accuracy was not related to the type of procedure (ZoC/MGQT) used or the subject's sex. Accuracy was significantly related to the type of control question [chi(2) (2) = 11.46, p = 0.003; tau c = 0.29]. Nonexclusive control questions produced greater accuracy than Exclusive control questions on both innocent and guilty subjects. These results and subjects' self-reports support the general "theory" on which control question (CQ) testing is based. The need for better empirical support of accepted dogma and current field practices is strongly indicated by these findings.

Questioning As a Pedagogical Tool for Eliciting Student Generated Questions During the Teaching of Acid-base Equilibria

Directory of Open Access Journals (Sweden)

Ayoade Ejiwale Okanlawon

2012-04-01

Full Text Available Traditionally, teachers simply taught problem-solving by explaining the worked-out examples taken from textbooks and students were expected to listen quietly, copy the solution to the problem, and then work independently at their desks. But a large body of research notes that guiding students to develop a solution pathway with questioning is more effective than simply explaining the sequence of steps to solve the problem. Students involved in question- and-answer sessions are more attentive than those who listen passively to teacher explanations and they are more likely to generate questions. The questions students ask during a lesson perform a number of important functions, including providing the teacher with valuable information about students’ understanding and misunderstanding, fostering self-regulation, inviting classroom discussions and aiding comprehension of contents presented. The skill of posing questions during classroom instruction is often under-valued and under taught in today’s classrooms. To encourage students to ask quality and thought provoking questions related to the contents taught, explicit instruction is required. This paper, therefore, qualitatively reports factors that foster student generated questions during the problem-solving instruction involving acid-base titration problem.

Sporadic Creutzfeldt-Jakob Disease (sCJD)

Centers for Disease Control (CDC) Podcasts

In this podcast, Dr. Lynne Sehulster discusses Creutzfeldt-Jakob disease, a rare neurodegenerative disease. This disease is caused by a pathological accumulation in the brain of an abnormal protein known as prions.

Sporadic Creutzfeldt-Jakob Disease (sCJD)

Centers for Disease Control (CDC) Podcasts

2009-02-03

In this podcast, Dr. Lynne Sehulster discusses Creutzfeldt-Jakob disease, a rare neurodegenerative disease. This disease is caused by a pathological accumulation in the brain of an abnormal protein known as prions.  Created: 2/3/2009 by Emerging Infectious Diseases.   Date Released: 2/3/2009.

Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Gmitterová, K; Heinemann, U; Krasnianski, A; Gawinecka, J; Zerr, I

2016-06-01

Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes. The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined. Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P disease duration and clinical stage influenced the test sensitivity in all proteins. Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known. © 2016 EAN.

Atypical presentation of probable Creutzfeldt-Jakob disease associated with anti-Zic4 antibody: Literature review of neuronal antibodies in Creutzfeldt-Jakob disease.

Science.gov (United States)

Salazar, Richard

2018-05-01

Sporadic Creutzfeldt-Jakob disease is a prion disease characterized by rapidly progressive dementia, ataxia and myoclonus. Atypical phenotype masquerading as stroke, movement disorders or autoimmune encephalitis have been described. Here, I report a probable case of sCJD with an atypical presentation associated with anti-Zic4 antibody and review the literature of neuronal antibodies in CJD. A 70 year-old gentleman is admitted with a 2-month history of recurrent stroke-like symptoms associated with behavioral disturbances, gait ataxia and rapidly progressive dementia. His initial examination demonstrated akinetic mutism, diffuse rigidity, dysautononia, and Cheyne-Stokes respiration. Over the following weeks his condition progressed to profound coma. A comprehensive infectious, metabolic, inflammatory and autoimmune work-up yielded negative results. Empiric immunosuppressive therapy ensued. He expired three months after symptoms onset. Autopsy was not performed. After his demise, prion tests came back abnormal for elevated 14-3-3 protein, total tau and positive RTQuIC. Later on, anti-Zic4 antibodies were found in serum. This case underscores the importance of a high index of suspicion for CJD even in case of atypical features or the concurrence of neuronal antibodies. Further larger prospective studies on the prevalence of these neuronal antibodies in CJD and the contribution of these autoantibodies to disease pathophysiology are necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

[Autoimmune Associated Encephalitis and Dementia].

Science.gov (United States)

Watanabe, Osamu

2016-04-01

Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.

The Question Concerning Thinking

DEFF Research Database (Denmark)

Riis, Søren

2008-01-01

Martin Heidegger's thought-provoking essay "The Question Concerning Technology" (1977a) placed technology at the heart of philosophy. Heidegger tried to show that the essence of technology provokes humans to think about the world in a very dangerous way. Yet if we follow Heidegger's analysis...... of technology, what role does that ascribe to philosophy? To be able to understand the programmatic scope of Heidegger's question ‘concerning' technology, we need to see it as inseparable from his famous thesis about the end of philosophy (1977c) and what he considers to be the ideal kind of thinking. However......, by doing so, we will in the end realize two important things. First, that Heidegger's declaration of the end of philosophy in fact also means the end of anything we can meaningfully call thinking. Second, that Heidegger's own thinking is completely different from his own ideal of thinking. Our question...

Creutzfeldt jakob disease

International Nuclear Information System (INIS)

Haider, E.; Raja, S.; Wali, W.; Tariq, M.

2013-01-01

A case of 50 years of age, male with sporadic Creutzfeldt Jakob Disease (sCJD) is reported. Patient had dementia, behavioural abnormalities, unsteady gait and myoclonic jerks. Magnetic resonance imaging (MRI) brain T2 weighted and Fluid Attenuated Inverse Recovery (FLAIR) images showed abnormally increased signal intensity in caudate nucleus and putamen. Scalp electroencephalogram (EEG) revealed periodic synchronous biphasic sharp wave complexes. On the basis of history, clinical findings, typical MRI brain and EEG changes, diagnosis of sporadic CJD was made. (author)

Control of bovine spongiform encephalopathy by genetic engineering: possible approaches and regulatory considerations

International Nuclear Information System (INIS)

Gavora, J.S.; Kochhar, H.P.S.; Gifford, G.A.

2005-01-01

Transmissible spongiform encephalopathies (TSE) include bovine spongiform encephalopathy (BSE), scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans. A new CJD variant (nvCJD) is believed to be related to consumption of meat from BSE cattle. In TSE individuals, prion proteins (PrP) with approximately 250 amino acids convert to the pathogenic prion PrP Sc , leading to a dysfunction of the central neural system. Research elsewhere with mice has indicated a possible genetic engineering approach to the introduction of BSE resistance: individuals with amino acid substitutions at positions 167 or 218, inoculated with a pathogenic prion protein, did not support PrP Sc replication. This raises the possibility of producing prion-resistant cattle with a single PrP amino acid substitution. Since prion-resistant animals might still harbour acquired prion infectivity, regulatory assessment of the engineered animals would need to ascertain that such possible 'carriers' do not result in a threat to animal and human health. (author)

Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene

Energy Technology Data Exchange (ETDEWEB)

Goldfarb, L.G.; Brown, P.; McCombie, W.R.; Gibbs, C.J. Jr.; Gajdusek, D.C. (National Inst. of Health, Bethesda, MD (United States)); Goldgaber, D. (State Univ. of New York, Stony Brook (United States)); Swergold, G.D. (National Inst. of Health, Bethesda, MD (United States)); Wills, P.R. (Univ. of Auckland (New Zealand)); Cervenakova, L. (Inst. of Preventive and Clinical Medicine, Bratislava (Czechoslovakia)); Baron, H. (Searle Pharmaceuticals, Paris (France))

1991-12-01

The PRNP gene, encoding the amyloid precursor protein that is centrally involved in Creutzfeldt-Jakob disease (CJD), has an unstable region of five variant tandem octapeptide coding repeats between codons 51 and 91. The authors screened a total of 535 individuals for the presence of extra repeats in this region, including patients with sporadic and familial forms of spongiform encephalopathy, members of their families, other neurological and non-neurological patients, and normal controls. They identified three CJD families (in each of which the proband's disease was neuropathologically confirmed and experimentally transmitted to primates) that were heterozygous for alleles with 10, 12, or 13 repeats, some of which had wobble nucleotide substitutions. They also found one individual with 9 repeats and no nucleotide substitutions who had no evidence of neurological disease. These observations, together with data on published British patients with 11 and 14 repeats, strongly suggest that the occurrence of 10 or more octapeptide repeats in the encoded amyloid precursor protein predisposes to CJD.

MRI manifestation for the diagnosis of sporadic Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Xue Yonggang; Qi Ji; Xia Shuang

2007-01-01

Objective: To study the MRI features of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: Three patients with clinically diagnosed sCJD underwent MR study, including SE T 1 WI, FSE T 2 WI, and DWI sequences. The MR imaging features were analyzed. Results: The lesions were not definite either in SE T 1 WI or in FSE T 2 WI, but were prominent in DWI. Abnormal hyperintensive signal appeared in the cerebral cortex, with the frontal, parietal, and occipital lobes being the mostly involved region. The subcortical white matter was normal. The bilateral caudate nuclei and thalami could also be involved. The abnormal signal could be either symmetrical or asymmetrical. There was diffuse atrophy of the brain parenchyma in the late phase of disease, especially in the cortex. Conclusion: With the application of MR study, especially the DWI, combined with its characteristic clinical manifestation, the diagnosis of sCJD can be made definitely. (authors)

The Heidenhain variant of Creutzfeldt-Jakob disease and concomitant tau pathology: A case report.

Science.gov (United States)

Ehler, Edvard; Pipka, Michael; Meleková, Alena; Mandysová, Petra; Johanidesová, Silvie; Matěj, Radoslav; Rusina, Robert

The Heidenhain form of Creutzfeldt-Jakob disease (CJD) is a rare CJD variant with predominantly visual symptoms in the early stages. Clinical manifestations of metamorphopsia, hemianopia and Balint's syndrome correlate with the involvement of the posterior cortical regions. A 71-year old healthy and very active man was admitted because of impaired visual acuity, hemianopia, and gait disturbance progressing over one week. MRI found typical cortical hyperintensities in the occipital regions while rhythm slowing and sharp waves were seen in the occipital regions on EEG. Protein 14-3-3 was detected in the cerebrospinal fluid. Postmortem neuropathology revealed typical histopathological changes consistent with CJD. Moreover, we found deposits of phosphorylated tau protein in the limbic regions that met the criteria for primary age-related tauopathy (PART); representing an additional and interesting finding in our case. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

CSF tau correlates with the degree of cortical involvement in E200K familial Creutzfeldt-Jakob disease.

Science.gov (United States)

Cohen, Oren S; Chapman, Joab; Korczyn, Amos D; Siaw, Oliver L; Warman-Alaluf, Naama; Nitsan, Zeev; Appel, Shmuel; Kahana, Esther; Rosenmann, Hanna; Hoffmann, Chen

2016-11-10

Cerebrospinal fluid (CSF) tau was found to correlate with disease severity and cognitive status in E200K familial Creutzfeldt-Jakob disease (fCJD) patients. The objective of the present study was to test whether tau levels in the CSF also correlate with the disease burden as reflected by the degree of cortical involvement in DWI MRI. Forty-four consecutive E200K fCJD patients (25 males, mean age 58.6±7.5, range 48-75 years) were recruited to the study and had a CSF tau examination as well as measurements of the extent of the cortical involvement in the DWI axial MRI. Correlation was tested using Pearson test. A significant correlation (r=0.617 pdisease burden reinforce the notion that tau can be used as a biomarker reflecting the extent of disease in patients with E200K fCJD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of performance on multiple-choice questions and open-ended questions in an introductory astronomy laboratory

OpenAIRE

Michelle M. Wooten; Adrienne M. Cool; Edward E. Prather; Kimberly D. Tanner

2014-01-01

When considering the variety of questions that can be used to measure students’ learning, instructors may choose to use multiple-choice questions, which are easier to score than responses to open-ended questions. However, by design, analyses of multiple-choice responses cannot describe all of students’ understanding. One method that can be used to learn more about students’ learning is the analysis of the open-ended responses students’ provide when explaining their multiple-choice response. I...

Diagnostic accuracy of cerebrospinal fluid protein markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-year prospective study

Science.gov (United States)

2011-01-01

Background To better characterize the value of cerebrospinal fluid (CSF) proteins as diagnostic markers in a clinical population of subacute encephalopathy patients with relatively low prevalence of sporadic Creutzfeldt-Jakob disease (sCJD), we studied the diagnostic accuracies of several such markers (14-3-3, tau and S100B) in 1000 prospectively and sequentially recruited Canadian patients with clinically suspected sCJD. Methods The study included 127 patients with autopsy-confirmed sCJD (prevalence = 12.7%) and 873 with probable non-CJD diagnoses. Standard statistical measures of diagnostic accuracy were employed, including sensitivity (Se), specificity (Sp), predictive values (PVs), likelihood ratios (LRs), and Receiver Operating Characteristic (ROC) analysis. Results At optimal cutoff thresholds (empirically selected for 14-3-3, assayed by immunoblot; 976 pg/mL for tau and 2.5 ng/mL for S100B, both assayed by ELISA), Se and Sp respectively were 0.88 (95% CI, 0.81-0.93) and 0.72 (0.69-0.75) for 14-3-3; 0.91 (0.84-0.95) and 0.88 (0.85-0.90) for tau; and 0.87 (0.80-0.92) and 0.87 (0.84-0.89) for S100B. The observed differences in Sp between 14-3-3 and either of the other 2 markers were statistically significant. Positive LRs were 3.1 (2.8-3.6) for 14-3-3; 7.4 (6.9-7.8) for tau; and 6.6 (6.1-7.1) for S100B. Negative LRs were 0.16 (0.10-0.26) for 14-3-3; 0.10 (0.06-0.20) for tau; and 0.15 (0.09-0.20) for S100B. Estimates of areas under ROC curves were 0.947 (0.931-0.961) for tau and 0.908 (0.888-0.926) for S100B. Use of interval LRs (iLRs) significantly enhanced accuracy for patient subsets [e.g., 41/120 (34.2%) of tested sCJD patients displayed tau levels > 10,000 pg/mL, with an iLR of 56.4 (22.8-140.0)], as did combining tau and S100B [e.g., for tau > 976 pg/mL and S100B > 2.5 ng/mL, positive LR = 18.0 (12.9-25.0) and negative LR = 0.02 (0.01-0.09)]. Conclusions CSF 14-3-3, tau and S100B proteins are useful diagnostic markers of sCJD even in a low

Questioning the Patient, Questioning Hippocrates: Rufus of Ephesus and the Pursuit of Knowledge.

Science.gov (United States)

Letts, Melinda

2016-01-01

Rufus of Ephesus' short treatise, Quaestiones Medicinales, the only ancient medical work that takes as its topic the dialogue between doctor and patient, has usually been seen as a procedural practical handbook serving an essentially operational purpose. In this paper I argue that the treatise, with its insistent message that doctors cannot properly understand and treat illnesses unless they supplement their own knowledge by questioning patients, and its remarkable appreciation of the singularity of each patient's experience, shows itself to be no mere handbook but a work addressing the place of questioning in the clinical encounter. I illustrate some of the differences between Rufus' conceptualisation of the relevance and use of questioning and that which can be seen in the theoretical and descriptive writings of Galen and in the Hippocratic corpus, and show how apparent resonances with some of the preoccupations of modern Western healthcare can be used judiciously to elucidate the significance of those differences.

Antithyroideaantistof hos to patienter med subakut dementiel udvikling, ataksi og myoklonus

DEFF Research Database (Denmark)

Kondziella, Daniel; Hansen, Klaus; Gonzalez, Teresa

2012-01-01

Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus and posit......Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus...

EEG–EMG polygraphic study of dystonia and myoclonus in a case of Creutzfeldt–Jakob disease

Directory of Open Access Journals (Sweden)

Takao Hashimoto

2015-01-01

Full Text Available We report on a patient with sporadic Creutzfeldt–Jakob disease (CJD who showed dystonia, periodic myoclonus, and periodic sharp wave complexes (PSWCs on EEG. The EEG–EMG polygraphic study revealed that dystonia appeared without relation to periodic myoclonus and PSWCs and that dystonia EMGs were strongly suppressed after periodic myoclonus EMGs. These findings suggest that dystonia has a pathogenesis different from that of periodic myoclonus and PSWCs, but dystonia and periodic myoclonus may be generated through the sensorimotor cortex in CJD.

Structured Attentions for Visual Question Answering

OpenAIRE

Zhu, Chen; Zhao, Yanpeng; Huang, Shuaiyi; Tu, Kewei; Ma, Yi

2017-01-01

Visual attention, which assigns weights to image regions according to their relevance to a question, is considered as an indispensable part by most Visual Question Answering models. Although the questions may involve complex relations among multiple regions, few attention models can effectively encode such cross-region relations. In this paper, we demonstrate the importance of encoding such relations by showing the limited effective receptive field of ResNet on two datasets, and propose to mo...

A Technique Socratic Questioning-Guided Discovery

OpenAIRE

M. Hakan Türkçapar; A. Emre Sargýn

2012-01-01

“Socratic Method” is a way of teaching philosophical thinking and knowledge by asking questions which was used by antique period greek philosopher Socrates. Socrates was teaching knowledge to his followers by asking questions and the conversation between them was named “Socratic Dialogues”. In this meaning, no novel knowledge is taught to the individual but only what is formerly known is reminded and rediscovered. The form of socratic questioning which is used during t...

Traveling questions

DEFF Research Database (Denmark)

Hoeyer, Klaus

2016-01-01

In this paper, I argue that uncertainty and nonknowledge, and not just research results, can be important vehicles of translation through which genetic research participation comes to affect the lives of research participants. Based on interviews with participants in a genetic research project, I....... Research questions, and not just results, may serve as a generative form of knowledge that can travel as fast as any answer....

Cosmetic Procedure Questions

Science.gov (United States)

... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Cosmetic Procedure Questions Want to look younger? Start ...

QUESTION ANSWERING SYSTEM DAN PENERAPANNYA PADA ALKITAB

Directory of Open Access Journals (Sweden)

Gunawan Gunawan

2006-01-01

Full Text Available Question answering system is a system that allows user to state his or her information need in the form of natural language question, and return short text excerpts or even phrases as an answer. The availability of a wide and various information source and improvements in the techniques of natural language processing, information extraction (wrapper, and information retrieval give a big effect on the development of question answering system, from just answering questions in a specific domain by consulting to structured information source such as database, and like in this research, answering any questions based on information stored in an unstructured text collection. A general architecture of question answering system based on text consists of six processing stages, i.e. question analysis, document collection preprocessing, candidate document selection, candidate document analysis, answer extraction, and response generation. Application of question answering system like AnswerBus, Mulder, and Webclopedia that are developed with its own characteristics has similar processing steps as in the general architecture. Answers returned by a question answering system need to be evaluated for performance measure. This research completed with a simple question answering system application using english Bible in World English Bible (WEB version as the source of information to answer some questions. Because specific domain is selected: Bible, questions that can be posed by user could ask about information in the Bible itself only. Question is also limited to three types of answers that can be supported by the application: person (who, location (where, and date (when. Abstract in Bahasa Indonesia : Question answering system (QA system adalah sistem yang mengijinkan user menyatakan kebutuhan informasinya dalam bentuk natural language question (pertanyaan dalam bahasa alami, dan mengembalikan kutipan teks singkat atau bahkan frase sebagai jawaban. Ketersediaan

Multitracer study with positron emission tomography in Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Engler, Henry [Uppsala University PET Centre, Uppsala University Hospital, SE 751 85 Uppsala (Sweden); Department of Neurology, Uppsala University Hospital, Uppsala (Sweden); Lundberg, Per Olov [Department of Neurology, Uppsala University Hospital, Uppsala (Sweden); Ekbom, Karl [Department of Neurology, Huddinge University Hospital, Stockholm (Sweden); Nennesmo, Inger [Department of Pathology, Huddinge University Hospital, Stockholm (Sweden); Nilsson, Anna; Bergstroem, Mats; Hartvig, Per; Laangstroem, Bengt [Uppsala University PET Centre, Uppsala University Hospital, SE 751 85 Uppsala (Sweden); Tsukada, Hideo [Hamamatsu Photonics K.K.Central Research Lab, Hamakita City (Japan)

2003-01-01

During the period February 1997 to April 2000, 15 patients with clinical symptoms of Creutzfeldt-Jakob disease (CJD) were referred to Uppsala University PET Centre. Positron emission tomography (PET) was performed to detect characteristic signs of the disease, e.g. neuronal death and/or astrocytosis in the brain. The examinations were performed in one session starting with oxygen-15 labelled water scan to measure regional cerebral blood flow, followed by imaging with the monoamine oxidase B inhibitor N-[{sup 11}C-methyl]-L-deuterodeprenyl (DED) to assess astrocytosis in the brain and finally imaging with fluorine-18 2-fluorodeoxyglucose (FDG) to assess regional cerebral glucose metabolism (rCMR{sub glu}). Nine of the patients fulfilled the clinical criteria of probable CJD. In eight of them, FDG and DED imaging revealed, in comparison with normal controls, a typical pattern characterized by a pronounced regional decrease (<2SD) in glucose brain metabolism, indicative of neuronal dysfunction; this was accompanied by a similar increase (>2SD) in DED binding, indicating astrocytosis. These changes were most pronounced in the cerebellum and the frontal, occipital and parietal cortices, whereas the pons, the thalamus and the putamen were less affected and the temporal cortex appeared unaffected. The cerebral blood flow showed a pattern similar to that observed with FDG. In the ninth patient, analysis with DED was not possible. The diagnosis of definite CJD according to international consensus criteria was confirmed in six of these patients. In one patient with probable CJD, protease-resistant prion protein (PrPres) could not be demonstrated. In two patients with probable CJD, autopsy was not allowed. Computed tomography and magnetic resonance imaging, performed in four and seven of these nine patients respectively, showed unspecific, mainly atrophic changes. In six other patients, the PET examinations gave a different pattern. In three of them, high rCMR{sub glu} was

Evolution of Diffusion-Weighted Magnetic Resonance Imaging Signal Abnormality in Sporadic Creutzfeldt-Jakob Disease, With Histopathological Correlation.

Science.gov (United States)

Eisenmenger, Laura; Porter, Marie-Claire; Carswell, Christopher J; Thompson, Andrew; Mead, Simon; Rudge, Peter; Collinge, John; Brandner, Sebastian; Jäger, Hans R; Hyare, Harpreet

2016-01-01

Prion diseases represent the archetype of brain diseases caused by protein misfolding, with the most common subtype being sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia. Diffusion-weighted imaging (DWI) has emerged as the most sensitive magnetic resonance imaging (MRI) sequence for the diagnosis of sCJD, but few studies have assessed the evolution of MRI signal as the disease progresses. To assess the natural history of the MRI signal abnormalities on DWI in sCJD to improve our understanding of the pathogenesis and to investigate the potential of DWI as a biomarker of disease progression, with histopathological correlation. Gray matter involvement on DWI was assessed among 37 patients with sCJD in 26 cortical and 5 subcortical subdivisions per hemisphere using a semiquantitative scoring system of 0 to 2 at baseline and follow-up. A total brain score was calculated as the summed scores in the individual regions. In 7 patients, serial mean diffusivity measurements were obtained. Age at baseline MRI, disease duration, atrophy, codon 129 methionine valine polymorphism, Medical Research Council Rating Scale score, and histopathological findings were documented. The study setting was the National Prion Clinic, London, England. All participants had a probable or definite diagnosis of sCJD and had at least 2 MRI studies performed during the course of their illness. The study dates were October 1, 2008 to April 1, 2012. The dates of our analysis were January 19 to April 20, 2012. Correlation of regional and total brain scores with disease duration. Among the 37 patients with sCJD in this study there was a significant increase in the number of regions demonstrating signal abnormality during the study period, with 59 of 62 regions showing increased signal intensity (SI) at follow-up, most substantially in the caudate and putamen (P disease duration (r = 0.47, P = .003 at baseline and r = 0.35, P = .03 at follow-up), and the left

[Human transmissible subacute spongiform encephalopathy].

Science.gov (United States)

Dormont, D

1994-05-01

Human transmissible spongiform encephalopathies (TSE) are rare chronic subacute degenerative diseases of the central nervous system (CNS) which include Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Sträussler-Scheinker syndrome (GSS), and Fatal Familial Insomnia (FFI). CJD can be either inherited or sporadic. All these diseases are always fatal. Neuropathological features are mainly constituted of neuronal vacuolisation, neuronal death, gliosis with hyperastrocytosis; plaques might be evidenced in kuru and GSS. Neither inflammatory syndrome nor demyelination is detectable. No virus like structure could be identified reproducibly. Human TSE are transmissible to non human primates and rodents. Iatrogenic CJD have been described after tissue grafting (cornea, dura mater), neurosurgery, electrophysiology investigation, and treatment with pituitary derived gonadotrophins and growth hormone. Molecular biochemistry of the CNS investigation revealed that a host encoded protein, the prion protein (PrP), accumulates proportionally to the infectious titer: this abnormality is the only detectable hallmark in TSE. Infectious fractions contain no detectable specific nucleic acid, and are mainly constituted of PrP under an isoform which resists to proteinase K digestion (PrP-res). The PrP gene (PRNP) is located on chromosome 20 in humans. Several mutations of this gene have been described in all inherited TSE (CJD, GSS, and IFF). No treatment is available today. Agents inducing TSE (TSA) are not known: several authors claim that TSA are only constituted of PrP-res; others support the hypothesis of a conventional agent with a specific genetic information.

Genetic and Transcriptomic Profiles of Inflammation in Neurodegenerative Diseases: Alzheimer, Parkinson, Creutzfeldt-Jakob and Tauopathies.

Science.gov (United States)

López González, Irene; Garcia-Esparcia, Paula; Llorens, Franc; Ferrer, Isidre

2016-02-04

Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer's disease (AD) and sporadic Parkinson's disease (sPD). Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2, Pick's disease (PiD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD-tau). The studies have disclosed variable gene regulation which is: (1) disease-dependent in the frontal cortex area 8 in AD, sPD, sCJD MM1 and VV2, PiD, PSP and FTLD-tau; (2) region-dependent as seen when comparing the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 (FC) in AD; the substantia nigra, putamen, FC, and angular gyrus in PD, as well as the FC and cerebellum in sCJD; (3) genotype-dependent as seen considering sCJD MM1 and VV2; and (4) stage-dependent as seen in AD at different stages of disease progression. These observations show that regulation of inflammation is much more complicated and diverse than currently understood, and that new therapeutic approaches must be designed in order to selectively act on specific targets in particular diseases and at different time points of disease progression.

Redefining periodic patterns on electroencephalograms of patients with sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Shin, Jung-Won; Yim, Byeongsoo; Oh, Seung Hun; Kim, Nam Keun; Lee, Sang Kun; Kim, Ok-Joon

2017-05-01

We aimed to redefine various periodic patterns (PPs) observed on electroencephalography (EEG) in patients with sporadic Creutzfeldt-Jakob disease (sCJD) using the American Clinical Neurophysiology Society's (ACNS) Criteria. We analyzed EEG data of 23 patients with sCJD were admitted to two university hospitals between August 2005 and September 2015. We classified PPs on EEG data into three types: irregular periodic discharges (PDs) with superimposed rhythmic activities, appearing at a median of 8weeks after onset (w.a.o.); rhythmic sharp-and-wave, at a median of 11w.a.o.; and PDs with biphasic or triphasic morphology, at a median of 17w.a.o. Of 16 patients presenting with PPs, 14 had widespread lesions in both cortical and subcortical areas with clinical stage III at admission, and shorter time intervals for admission to hospital from disease onset than patients without PPs (Patients with PP, 11.6±12.2weeks; without PP, 18.2±8.3weeks; p=0.033). PPs largely presented as three types at different stages of disease progression, and patients who had PPs had more wide spread lesions and rapid disease progression. Our redefinition of PPs demonstrated on EEG using the ACNS criteria may contribute to further understanding of the pathological mechanisms of sCJD, and PPs might be a predictive factor of a rapid sCJD progression. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Genetic and Transcriptomic Profiles of Inflammation in Neurodegenerative Diseases: Alzheimer, Parkinson, Creutzfeldt-Jakob and Tauopathies

Directory of Open Access Journals (Sweden)

Irene López González

2016-02-01

Full Text Available Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer’s disease (AD and sporadic Parkinson’s disease (sPD. Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD subtypes MM1 and VV2, Pick’s disease (PiD, progressive supranuclear palsy (PSP and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD-tau. The studies have disclosed variable gene regulation which is: (1 disease-dependent in the frontal cortex area 8 in AD, sPD, sCJD MM1 and VV2, PiD, PSP and FTLD-tau; (2 region-dependent as seen when comparing the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 (FC in AD; the substantia nigra, putamen, FC, and angular gyrus in PD, as well as the FC and cerebellum in sCJD; (3 genotype-dependent as seen considering sCJD MM1 and VV2; and (4 stage-dependent as seen in AD at different stages of disease progression. These observations show that regulation of inflammation is much more complicated and diverse than currently understood, and that new therapeutic approaches must be designed in order to selectively act on specific targets in particular diseases and at different time points of disease progression.

Frequently Asked Questions about Bunion Surgery

Science.gov (United States)

... A | Print | Share Frequently Asked Questions About Bunion Surgery Here are some frequently asked questions (FAQs) and ... best for you. 5. How can I avoid surgery? Sometimes observation of the bunion is all that ...

Finding Question-Answer Pairs from Online Forums

DEFF Research Database (Denmark)

Cong, Gao; Wang, Long; Lin, Chin-Yew

2008-01-01

Online forums contain a huge amount of valuable user generated content. In this paper we address the problem of extracting question-answer pairs from forums. Question-answer pairs extracted from forums can be used to help Question Answering services (e.g. Yahoo! Answers) among other applications...

How to…write a good research question

NARCIS (Netherlands)

Mattick, Karen; Johnston, Jenny; de la Croix, Anne

This paper, on writing research questions, is the first in a series that aims to support novice researchers within clinical education, particularly those undertaking their first qualitative study. Put simply, a research question is a question that a research project sets out to answer. Most research

The Socratic Method and Levels of Questioning.

Science.gov (United States)

Watson, Karilee

1980-01-01

Determines if instruction in the Socratic method would increase higher level questioning during peer teaching experiences in teacher education programs. Raters, using the higher order questioning strategy, evaluated 14 students. A significant increase in higher level questions being asked suggests the Socratic Method may be useful. (Author)

Question Answering for Dutch : Simple does it

NARCIS (Netherlands)

Hoekstra, A.H.; Hiemstra, Djoerd; van der Vet, P.E.; Huibers, Theo W.C.; Schobbens, Pierre-Yves; Vanhoof, Wim; Schwanen, Gabriel

2006-01-01

When people pose questions in natural language to search for information on the web, the role of question answering (QA) systems becomes important. In this paper the QAsystem simpleQA, capable of answering Dutch questions on which the answer is a person or a location, is described. The system's

"I didn't write the questions!" - Negotiating telephone-survey questions on birth timing

Directory of Open Access Journals (Sweden)

Marian May

2008-06-01

Full Text Available This paper examines interviewer-respondent interaction in the collection of demographic data. Conversation analysis (CA makes transparent the interaction between an interviewer and 25 respondents on a question about pregnancy and birth timing in an Australian telephone survey, Negotiating the Life Course. The analysis focuses on the troubles that occur and the work interviewers do to fit respondents' answers to the survey researcher's categories. Interviewers are shown to act as mediators in difficult interaction, with responses often distorted by question format, the imperative of achieving an allowed response, and the need to keep the respondent in the survey.

Designing effective questions for classroom response system teaching

Science.gov (United States)

Beatty, Ian D.; Gerace, William J.; Leonard, William J.; Dufresne, Robert J.

2006-01-01

Classroom response systems can be powerful tools for teaching physics. Their efficacy depends strongly on the quality of the questions. Creating effective questions is difficult and differs from creating exam and homework problems. Each classroom response system question should have an explicit pedagogic purpose consisting of a content goal, a process goal, and a metacognitive goal. Questions can be designed to fulfill their purpose through four complementary mechanisms: directing students' attention, stimulating specific cognitive processes, communicating information to the instructor and students via classroom response system-tabulated answer counts, and facilitating the articulation and confrontation of ideas. We identify several tactics that are useful for designing potent questions and present four "makeovers" to show how these tactics can be used to convert traditional physics questions into more powerful questions for a classroom response system.

30 CFR 250.1200 - Question index table.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Question index table. 250.1200 Section 250.1200 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR... Security § 250.1200 Question index table. The table in this section lists questions concerning Oil and Gas...

Questions and dependency in intuitionistic logic

NARCIS (Netherlands)

Ciardelli, Ivano; Iemhoff, Rosalie; Yang, Fan

2017-01-01

In recent years, the logic of questions and dependencies has been investigated in the closely related frameworks of inquisitive logic and dependence logic. These investigations have assumed classical logic as the background logic of statements, and added formulas expressing questions and

Questions and Answers About Nuclear Power Plants.

Science.gov (United States)

Environmental Protection Agency, Washington, DC.

This pamphlet is designed to answer many of the questions that have arisen about nuclear power plants and the environment. It is organized into a question and answer format, with the questions taken from those most often asked by the public. Topics include regulation of nuclear power sources, potential dangers to people's health, whether nuclear…

Conducting systematic reviews of intervention questions I: Writing the review protocol, formulating the question and searching the literature.

Science.gov (United States)

O'Connor, A M; Anderson, K M; Goodell, C K; Sargeant, J M

2014-06-01

This article is the fourth of six articles addressing systematic reviews in animal agriculture and veterinary medicine. Previous articles in the series have introduced systematic reviews, discussed study designs and hierarchies of evidence, and provided details on conducting randomized controlled trials, a common design for use in systematic reviews. This article describes development of a review protocol and the first two steps in a systematic review: formulating a review question, and searching the literature for relevant research. The emphasis is on systematic reviews of questions related to interventions. The review protocol is developed prior to conducting the review and specifies the plan for the conduct of the review, identifies the roles and responsibilities of the review team and provides structured definitions related to the review question. For intervention questions, the review question should be defined by the PICO components: population, intervention, comparison and outcome(s). The literature search is designed to identify all potentially relevant original research that may address the question. Search terms related to some or all of the PICO components are entered into literature databases, and searches for unpublished literature also are conducted. All steps of the literature search are documented to provide transparent reporting of the process. © 2014 Blackwell Verlag GmbH.

How do 5-year-olds understand questions?

DEFF Research Database (Denmark)

Sauerland, Uli; Grohmann, Kleanthes; Teresa Guasti, Maria

2016-01-01

developing children across 19 European countries, 18 different languages, and 7 language (sub-)families. The study investigated the effects of two factors on question formation: (a) whether the question contains a simple interrogative word like ‘who’ or a complex one like ‘which princess’, and (b) whether......The comprehension of constituent questions is an important topic for language acquisition research and for applications in the diagnosis of language impairment. This article presents the results of a study investigating the comprehension of different types of questions by 5-year-old, typically...... the question word was related to the sentential subject or object position of the verb. The findings show that there is considerable variation among languages, but the two factors mentioned consistently affect children’s performance. The cross-linguistic variation shows that three linguistic factors facilitate...

Environmental Ethics: Questions for Adult Education.

Science.gov (United States)

Parker, Jenneth

1993-01-01

Presents a series of questions through which adult educators can explore controversial questions of environmental values and moral behavior in their programs. The subjects include geography, local history, natural history, economics, politics, business, labor education, world affairs, literature, women's studies, psychology, and courses for the…

From Question Answering to Visual Exploration

Energy Technology Data Exchange (ETDEWEB)

McColgin, Dave W.; Gregory, Michelle L.; Hetzler, Elizabeth G.; Turner, Alan E.

2006-08-11

Research in Question Answering has focused on the quality of information retrieval or extraction using the metrics of precision and recall to judge success; these metrics drive toward finding the specific best answer(s) and are best supportive of a lookup type of search. These do not address the opportunity that users? natural language questions present for exploratory interactions. In this paper, we present an integrated Question Answering environment that combines a visual analytics tool for unstructured text and a state-of-the-art query expansion tool designed to compliment the cognitive processes associated with an information analysts work flow. Analysts are seldom looking for factoid answers to simple questions; their information needs are much more complex in that they may be interested in patterns of answers over time, conflicting information, and even related non-answer data may be critical to learning about a problem or reaching prudent conclusions. In our visual analytics tool, questions result in a comprehensive answer space that allows users to explore the variety within the answers and spot related information in the rest of the data. The exploratory nature of the dialog between the user and this system requires tailored evaluation methods that better address the evolving user goals and counter cognitive biases inherent to exploratory search tasks.

N-isopropyl I-123 p-iodoamphetamine (IMP) brain SPECT in dementia

International Nuclear Information System (INIS)

Momose, Toshimitsu; Kosaka, Noboru; Nishikawa, Junichi; Yoshikawa, Kohki; Ohtake, Tohru; Watanabe, Toshiaki; Iwata, Makoto; Shimizu, Teruo; Iio, Masahiro

1988-01-01

Six patients of Alzheimer's disease (AD), two patients of Pick disease (PD) and two patients of Creutzfeldt-Jakob disease (CJD) were studied with N-Isopropyl I-123 p-Iodoamphetamine (IMP) with SPECT. The pattern of IMP uptake in these demented groups were compared with that in five agematched normal controls and correlated with MRI and XCT. In all AD cases, SPECT revealed focal reduction of IMP uptake in frontal (6/6), parietal (6/6) and temporal (6/6) cortex, although MRI and XCT were normal. In both PD case, SPECT showed focal reduction of IMP uptake in frontal (1/2) and temporal (2/2) cortex with moderate labor atrophy on MRI and XCT. In both CJD case, SPECT showed diffuse reduction of IMP uptake in cerebral cortex in spite of no abnormality on MRI and XCT. These findings suggest that SPECT can detect earlier diseased process of AD and CJD than MRI or XCT and that SPECT may be helpful for the differential diagnosis of non-vascular dementia. (author)

N-isopropyl I-123 p-iodoamphetamine (IMP) brain SPECT in dementia

Energy Technology Data Exchange (ETDEWEB)

Momose, Toshimitsu; Kosaka, Noboru; Nishikawa, Junichi; Yoshikawa, Kohki; Ohtake, Tohru; Watanabe, Toshiaki; Iwata, Makoto; Shimizu, Teruo; Iio, Masahiro

1988-12-01

Six patients of Alzheimer's disease (AD), two patients of Pick disease (PD) and two patients of Creutzfeldt-Jakob disease (CJD) were studied with N-Isopropyl I-123 p-Iodoamphetamine (IMP) with SPECT. The pattern of IMP uptake in these demented groups were compared with that in five agematched normal controls and correlated with MRI and XCT. In all AD cases, SPECT revealed focal reduction of IMP uptake in frontal (6/6), parietal (6/6) and temporal (6/6) cortex, although MRI and XCT were normal. In both PD case, SPECT showed focal reduction of IMP uptake in frontal (1/2) and temporal (2/2) cortex with moderate labor atrophy on MRI and XCT. In both CJD case, SPECT showed diffuse reduction of IMP uptake in cerebral cortex in spite of no abnormality on MRI and XCT. These findings suggest that SPECT can detect earlier diseased process of AD and CJD than MRI or XCT and that SPECT may be helpful for the differential diagnosis of non-vascular dementia.

N-isopropyl I-123 p-iodoamphetamine brain scintigraphy with SPECT in Creutzfeldt-Jakob disease

Energy Technology Data Exchange (ETDEWEB)

Momose, Toshimitsu; Kosaka, Noboru; Nishikawa, Junichi; Ohtake, Tohru; Watanabe, Toshiaki; Yoshikawa, Kohki; Iio, Masahiro

1988-10-01

Two patients of clinically diagnosed Creutzfeldt-Jakob disease (CJD) were examined with N-Isopropyl I-123 p-Iodoamphetamine (IMP) SPECT, MRI and XCT. Both patient has myoclonus and severe conscious disturbance with periodic synchronized discharge (PSD) on EEG. SPECT images were obtained using GE400AC/T. Regional IMP uptake was determined by calculating the ratio of each cortical regional to cerebellar IMP uptake (cortico-cerebellar ratio: CCR) and compared with that of five normal controls. In both case, CCR was remarkably decreased in all cortical areas, although XCT or MRI shows no abnormality except slight cortical atrophy. It suggests that metabolic and functional changes proceed morphological abnormality seen on XCT or MRI. In one case of CJD, serial studies of SPECT and XCT were performed after three months of interval. CCR in second study was higher than in first study, while XCT revealed remarkable brain atrophy including cerebrum, pons and cerebellum. It can be interpreted as regional differences of disease process. In conclusion, I-123 IMP-SPECT is useful for the earlier detection of lesions in CJD.

Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease.

Science.gov (United States)

Podlesniy, Petar; Llorens, Franc; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel; Zerr, Inga; Trullas, Ramon

2016-05-01

Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown. CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia. Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t-tau, p-tau, and 14-3-3 protein levels in CSF. Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD. Copyright © 2015 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

N-isopropyl I-123 p-iodoamphetamine brain scintigraphy with SPECT in Creutzfeldt-Jakob disease

International Nuclear Information System (INIS)

Momose, Toshimitsu; Kosaka, Noboru; Nishikawa, Junichi; Ohtake, Tohru; Watanabe, Toshiaki; Yoshikawa, Kohki; Iio, Masahiro

1988-01-01

Two patients of clinically diagnosed Creutzfeldt-Jakob disease (CJD) were examined with N-Isopropyl I-123 p-Iodoamphetamine (IMP) SPECT, MRI and XCT. Both patient has myoclonus and severe conscious disturbance with periodic synchronized discharge (PSD) on EEG. SPECT images were obtained using GE400AC/T. Regional IMP uptake was determined by calculating the ratio of each cortical regional to cerebellar IMP uptake [cortico-cerebellar ratio: CCR] and compared with that of five normal controls. In both case, CCR was remarkably decreased in all cortical areas, although XCT or MRI shows no abnormality except slight cortical atrophy. It suggests that metabolic and functional changes proceed morphological abnormality seen on XCT or MRI. In one case of CJD, serial studies of SPECT and XCT were performed after three months of interval. CCR in second study was higher than in first study, while XCT revealed remarkable brain atrophy including cerebrum, pons and cerebellum. It can be interpreted as regional differences of disease process. In conclusion, I-123 IMP-SPECT is useful for the earlier detection of lesions in CJD. (author)

'Any questions?'--Clinicians' usage of invitations to ask questions (IAQs) in outpatient plastic surgery consultations.

Science.gov (United States)

Bristowe, Katherine; Patrick, Peter L

2014-12-01

To explore use of 'Invitations to Ask Questions' (IAQs) by plastic surgeons in outpatient consultations, and consider how type of IAQ impacts on patients' responses to, and recollection of, IAQs. Descriptive study: 63 patients were audio recorded in consultation with 5 plastic surgeons, and completed a brief questionnaire immediately after the consultation. Consultation transcripts were analyzed using inductive qualitative methods of Discourse Analysis and compared with questionnaire findings. A taxonomy of IAQs was developed, including three types of IAQ (Overt, Covert, and Borderline). Overt IAQs were rarely identified, and almost all IAQs occurred in the closing stages of the consultation. However, when an overt IAQ was used, patients always recollected being asked if they had any questions after the consultation. Patients are rarely explicitly offered the opportunity to ask questions. When this does occur, it is often in the closing stages of the consultation. Clinicians should openly encourage patients to ask questions frequently throughout the consultation, and be mindful that subtle differences in construction of these utterances may impact upon interpretation. Clear communication, of message and intention, is essential in clinical encounters to minimize misunderstanding, misinterpretation, or missed opportunities for patients to raise concerns. Copyright © 2014. Published by Elsevier Ireland Ltd.

Probability of climatic change. Identification of key questions

International Nuclear Information System (INIS)

Fransen, W.

1995-01-01

Addressing the question what the probability is of an anthropogenically induced change in the climate, leads to a number of other, underlying questions. These questions, which deal with the characteristics of climate, of climatic change, and of probabilistic statements on climatic change, should be addressed first. The long-term objective of the underlying study, i.e. a quantitative assessment of the risks and opportunities of the predicted climatic change, sets the context against which of those questions should be answered. In addition, this context induces extra questions, i.e. about the characteristics of risk

Question-answer sequences in survey interviews

NARCIS (Netherlands)

Dijkstra, W.; Ongena, Y.P.

2006-01-01

Interaction analysis was used to analyze a total of 14,265 question-answer sequences of (Q-A Sequences) 80 questions that originated from two face-to-face and three telephone surveys. The analysis was directed towards the causes and effects of particular interactional problems. Our results showed

Question Word in the Mandarin Language

Directory of Open Access Journals (Sweden)

Xu Yunyu

2016-12-01

Full Text Available In an interrogative sentence in Mandarin language, a question word can be placed in the beginning, middle or end of a sentence. Because of the different nation and culture, when a foreign student learns Mandarin, they find it difficult to understand the question words and the position of the question words in that language. Because of that, the writer proposes to explain such problems. This research aims to find out what are the types of question words in Mandarin, and also to explain the function and usage of question words in the Mandarin interrogative sentence. An interrogative sentence is a very important sentence. In Mandarin, the following question words: 谁(shuí “Who”，在哪里(zài nǎli “where”, 在哪儿(zài nǎ’er “where”，为什么(wèi shénme “why”, 怎么(zěnme “why”，多少（duō shǎo） “how many”，多久(duō jiǔ “how long”，什么时候 (shénme shíhòu “when”，什么(shénme “what”，做什么(zuò shénme “why”，干 什么(gàn shénme “why”，干嘛(gànma “why” and so on are used to ask “who”, “where”, “what”, “how much”, “when”, “what time”, and “why”. Those words have different functions and usage. Each sentence has a certain structure and word order. A question word can be placed in the beginning, middle, or end of a sentence. When the place is changed, there is a possibility of miscommunication.   DOI: https://doi.org/10.24071/llt.2013.160106

Academic Oversight: Asking Questions, Building Bridges

Science.gov (United States)

Wilson, E. B.

2011-01-01

The best way for trustees to fully understand and fulfill their responsibility to ensure that their institution is providing quality education and meeting academic goals is by asking appropriate questions. Collaboration among trustees, faculty members, and administrators is essential to framing questions from a strategic perspective. Just the act…

37 CFR 354.2 - Novel questions.

Science.gov (United States)

2010-07-01

... of law, referral to the Register of Copyrights by the Copyright Royalty Judges is mandatory. A “novel... discretionary referral of material questions of copyright law to the Register of Copyrights by the Copyright... Copyrights in resolving material questions of substantive law is binding upon the Copyright Royalty Judges...

Robustness Analysis of Visual QA Models by Basic Questions

KAUST Repository

Huang, Jia-Hong

2017-09-14

Visual Question Answering (VQA) models should have both high robustness and accuracy. Unfortunately, most of the current VQA research only focuses on accuracy because there is a lack of proper methods to measure the robustness of VQA models. There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the ranked basic questions, with similarity scores, of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question about the given image. We claim that a robust VQA model is one, whose performance is not changed much when related basic questions as also made available to it as input. We formulate the basic questions generation problem as a LASSO optimization, and also propose a large scale Basic Question Dataset (BQD) and Rscore (novel robustness measure), for analyzing the robustness of VQA models. We hope our BQD will be used as a benchmark for to evaluate the robustness of VQA models, so as to help the community build more robust and accurate VQA models.

Robustness Analysis of Visual QA Models by Basic Questions

KAUST Repository

Huang, Jia-Hong; Alfadly, Modar; Ghanem, Bernard

2017-01-01

Visual Question Answering (VQA) models should have both high robustness and accuracy. Unfortunately, most of the current VQA research only focuses on accuracy because there is a lack of proper methods to measure the robustness of VQA models. There are two main modules in our algorithm. Given a natural language question about an image, the first module takes the question as input and then outputs the ranked basic questions, with similarity scores, of the main given question. The second module takes the main question, image and these basic questions as input and then outputs the text-based answer of the main question about the given image. We claim that a robust VQA model is one, whose performance is not changed much when related basic questions as also made available to it as input. We formulate the basic questions generation problem as a LASSO optimization, and also propose a large scale Basic Question Dataset (BQD) and Rscore (novel robustness measure), for analyzing the robustness of VQA models. We hope our BQD will be used as a benchmark for to evaluate the robustness of VQA models, so as to help the community build more robust and accurate VQA models.

"Wh"-Questions in the English Language

Science.gov (United States)

Mowarin, Macaulay

2011-01-01

This paper analyzes "wh"-questions in the English Language based mainly on Chomsky's Minimalist Programme of transformational grammar as the theoretical model. The four main objectives of this paper are as follows: first, it undertakes a cross linguistic typological analysis of "wh"-questions and it then discusses the derivation of…

Three Key Questions on Measuring Learning

Science.gov (United States)

McTighe, Jay

2018-01-01

The author examines three essential questions on educational assessment: What really matters in a contemporary education? How should we assess those things that matter? How might our assessments enhance learning that matters, not just measure it? In answering these question, he argues that schools need a broader collection of measures, with a…

The acquisition of wh-questions in Russian

Directory of Open Access Journals (Sweden)

Nina Rojina

2005-02-01

Full Text Available In this paper, I study the acquisition of wh-questions in Russian by one Russian-speaking child from an early stage of syntactic development. For my analysis, I follow Plunkett (1992:73 in adopting a weak version of the Continuity Hypothesis where all the principles of UG are available from the outset of the acquisition process, but the structure of the functional template must be built up before parameter setting can begin. I adopt this hypothesis due to its compatibility with my finding that in the acquisition of Russian wh-questions, the functional projection CP appears at a later stage of syntactic development than other functional projections. Following Plunkett, I assume that in the beginning, the landing site for the wh-word is [Spec,TP] and later, for the valuation of other features (such as finiteness, the child is forced to acquire another functional projection (CP in order to create a landing site for the wh-word. The analysis shows that the first wh-questions acquired by the child are wh-complement questions. The child starts to produce subject wh-questions when the CP projection is acquired, and by the age of 2;4.14, the child’s structure of wh-questions is close to that of adult speech.

Semi-automated categorization of open-ended questions

Directory of Open Access Journals (Sweden)

Matthias Schonlau

2016-08-01

Full Text Available Text data from open-ended questions in surveys are difficult to analyze and are frequently ignored. Yet open-ended questions are important because they do not constrain respondents’ answer choices. Where open-ended questions are necessary, sometimes multiple human coders hand-code answers into one of several categories. At the same time, computer scientists have made impressive advances in text mining that may allow automation of such coding. Automated algorithms do not achieve an overall accuracy high enough to entirely replace humans. We categorize open-ended questions soliciting narrative responses using text mining for easy-to-categorize answers and humans for the remainder using expected accuracies to guide the choice of the threshold delineating between “easy” and “hard”. Employing multinomial boosting avoids the common practice of converting machine learning “confidence scores” into pseudo-probabilities. This approach is illustrated with examples from open-ended questions related to respondents’ advice to a patient in a hypothetical dilemma, a follow-up probe related to respondents’ perception of disclosure/privacy risk, and from a question on reasons for quitting smoking from a follow-up survey from the Ontario Smoker’s Helpline. Targeting 80% combined accuracy, we found that 54%-80% of the data could be categorized automatically in research surveys.

Creutzfeldt-Jakob disease

Directory of Open Access Journals (Sweden)

LIU Jian-rong

2013-01-01

Full Text Available Creutzfeldt-Jakob disease (CJD is a degenerative central nervous system (CNS disease caused by infection of prion protein (PrP, with clinical features including short course, rapid development and 100% mortality. This article aims to discuss the pathogenesis, histopathological features, clinical manifestations, electroencephalogram (EEG findings, imaging data and treatment progress of this disease based on literature review. Cerebrospinal fluid 14-3-3 protein detection, EEG and MRI are three important methods to make an early diagnosis on patients with suspected CJD, such as elderly patients with rapidly progressive dementia (RPD and young patients with mental symptoms involving multiple systems (MS.

Two questions about surrogacy and exploitation.

Science.gov (United States)

Wertheimer, Alan

1992-01-01

In this article I will consider two related questions about surrogacy and exploitation: (1) Is surrogacy exploitative? (2) If surrogacy is exploitative, what is the moral force of this exploitation? Briefly stated, I shall argue that whether surrogacy is exploitative depends on whether exploitation must be harmful to the exploited party or whether (as I think) there can be mutually advantageous exploitation. It also depends on some facts about surrogacy about which we have little reliable evidence and on our philosophical view on what counts as a harm to the surrogate. Our answer to the second question will turn in part on the account of exploitation we invoke in answering the first question and in part on the way in which we resolve some other questions about the justification of state interference. I shall suggest, however, that if surrogacy is a form of voluntary and mutually advantageous exploitation, then there is a strong presumption that surrogacy contracts should be permitted and even enforceable, although that presumption may be overridden on other grounds.

KEMAMPUAN MAHASISWA DALAM MEMBUAT COMPREHENSION QUESTIONS

Directory of Open Access Journals (Sweden)

Pudiyono Pudiyono

2016-10-01

Full Text Available The aims of the research were to find out (a the level of the students’ ability in making comprehension questions, (b the students’ map of problems in making comprehension questions. The population of the research was all students joining Reading 4 academic year 2016, totaling to 30 students, while the sample was taken from all students. The result of data analysis showed that the average ability of the students, with score more than 70 reached 66.66%. In details, only 4 of the samples (13.33% got no wrong answers or an A. Those who got good achievement (B, considered as majority, amounted to 16 students (53.33%. The participants achieving enough grades (C reached 7 students or 23.33%. The last level achieved in this research was D with the number reaching 3 (10%. The map of problems laid on their inability in identifying between yes/no and WH questions, inverted sentence, choosing the right auxiliary and verbs and their spelling ability. Keyword: comprehension, questions, inversion, problem map, ability

Transforming classroom questioning using emerging technology.

Science.gov (United States)

Mahon, Paul; Lyng, Colette; Crotty, Yvonne; Farren, Margaret

2018-04-12

Classroom questioning is a common teaching and learning strategy in postgraduate nurse education. Technologies such as audience response systems (ARS) may offer advantage over traditional approaches to classroom questioning. However, despite being available since the 1960s, ARSs are still considered novel in many postgraduate nurse education classroom settings. This article aims to explicate the attitudes of postgraduate nursing students in an Irish academic teaching hospital towards classroom questioning (CQ) and the use of ARSs as an alternative to traditional CQ techniques. The results of this small-scale study demonstrate that ARSs have a role to play in CQ in the postgraduate setting, being regarded by students as beneficial to learning, psychological safety and classroom interaction.

Comparison of integrated testlet and constructed-response question formats

Directory of Open Access Journals (Sweden)

Aaron D. Slepkov

2014-09-01

Full Text Available Constructed-response (CR questions are a mainstay of introductory physics textbooks and exams. However, because of the time, cost, and scoring reliability constraints associated with this format, CR questions are being increasingly replaced by multiple-choice (MC questions in formal exams. The integrated testlet (IT is a recently developed question structure designed to provide a proxy of the pedagogical advantages of CR questions while procedurally functioning as set of MC questions. ITs utilize an answer-until-correct response format that provides immediate confirmatory or corrective feedback, and they thus allow not only for the granting of partial credit in cases of initially incorrect reasoning, but, furthermore, the ability to build cumulative question structures. Here, we report on a study that directly compares the functionality of ITs and CR questions in introductory physics exams. To do this, CR questions were converted to concept-equivalent ITs, and both sets of questions were deployed in midterm and final exams. We find that both question types provide adequate discrimination between stronger and weaker students, with CR questions discriminating slightly better than the ITs. There is some indication that any difference in discriminatory power may result from the baseline score for guessing that is inherent in MC testing. Meanwhile, an analysis of interrater scoring of the CR questions raises serious concerns about the reliability of the granting of partial credit when this traditional assessment technique is used in a realistic (but nonoptimized setting. Furthermore, we show evidence that partial credit is granted in a valid manner in the ITs. Thus, together with consideration of the vastly reduced costs of administering IT-based examinations compared to CR-based examinations, our findings indicate that ITs are viable replacements for CR questions in formal examinations where it is desirable both to assess concept integration and to

Interviewers' question rewording: not always a bad thing

NARCIS (Netherlands)

Haan, Marieke; Ongena, Yfke; Huiskes, Mike

2013-01-01

Although correct question reading is a fundamental assumption of standardized interviewing, in surveys, interviewers will not always read all questions exactly as worded. In this study the deviations in question reading by interviewers were analyzed. In addition, we studied if these deviations were

Probability and Statistics: 5 Questions

DEFF Research Database (Denmark)

Probability and Statistics: 5 Questions is a collection of short interviews based on 5 questions presented to some of the most influential and prominent scholars in probability and statistics. We hear their views on the fields, aims, scopes, the future direction of research and how their work fits...... in these respects. Interviews with Nick Bingham, Luc Bovens, Terrence L. Fine, Haim Gaifman, Donald Gillies, James Hawthorne, Carl Hoefer, James M. Joyce, Joseph B. Kadane Isaac Levi, D.H. Mellor, Patrick Suppes, Jan von Plato, Carl Wagner, Sandy Zabell...

Accuracy of questions related to allergic contact dermatitis.

Science.gov (United States)

Fleming, C J; Burden, A D; Forsyth, A

2000-12-01

The ability of a physician to select individuals likely to benefit from patch testing depends on his or her ability to interpret responses to enquiries related to contact allergy. The significance of such responses to questions of nickel, fragrance and colophon allergy is unclear. The specificity, sensitivity and predictive value of questions relating to nickel, fragrance and colophony allergy were determined. A total of 258 patients attending for routine patch testing were questioned about skin reactions to nickel, fragrances and Elastoplast (Smith and Nephew Healthcare, Hull, England). All subjects were then patch tested to nickel, fragrance mix, and colophony. Responses to questions were compared with patch test results. The sensitivity of questions relating to nickel, fragrance, and colophony was 82%, 49%, and 71%, respectively. The specificity of the same questions was 77%, 79%, and 90%; the positive predictive value was 54%, 46% and 29%, respectively. After adjustment to include clinical relevance, the sensitivity of nickel questions rose to 100%. These data permit greater understanding of the role of patient history in selection of patients for patch testing. Copyright 2000 by W.B. Saunders Company

Children's Question Asking and Curiosity: A Training Study

Science.gov (United States)

Jirout, Jamie; Klahr, David

2011-01-01

A primary instructional objective of most early science programs is to foster children's scientific curiosity and question-asking skills (Jirout & Klahr, 2011). However, little is known about the relationship between curiosity, question-asking behavior, and general inquiry skills. While curiosity and question asking are invariably mentioned in…

D-linking or set-restriction? Processing Which-questions in Dutch

NARCIS (Netherlands)

Donkers, Jantien; Hoeks, John C. J.; Stowe, Laurie A.

2013-01-01

Research on Wh-questions suggests that Which questions are harder to process than Who questions (e.g., Who/Which athlete won the competition?). According to the Discourse (D)-linking Hypothesis, Which-questions differ from Who-questions in that Which questions need a link to a preceding discourse,

Questioning care at the end of life.

Science.gov (United States)

Ruopp, Patricia; Good, Mary-Jo Delvecchio; Lakoma, Matthew; Gadmer, Nina M; Arnold, Robert M; Block, Susan D

2005-06-01

The goal of the larger study was to explore physicians' emotional responses to the death of their patients; this study analyzed a subset of physician transcripts to elucidate the construct of questioning care, which emerged from the larger study. To analyzes how physicians question care-expressing concern, unease, or uncertainty about treatment decisions and practices, errors, or adverse events-as they attend dying patients. Retrospective interview study of physicians caring for randomly selected deaths on the medical service of a major academic teaching hospital, using qualitative and quantitative measures. SETTING, SUBJECTS: 188 attendings, residents, and interns on the internal medical services of two academic medical centers were part of the larger study. A subsample of 75 physician narratives was selected for qualitative data analysis for this study. Qualitative measures included open-ended questions eliciting physicians' stories of the most recent and a most emotionally powerful patient death they have experienced. Grounded theory was used to analyze physician narratives. Quantitative instruments measured physician attitudes toward end-of-life care and responses to the most recent and most emotional patient death. Physicians question care more frequently in most emotional deaths (42%) than in most recent deaths (34%). Physicians question communication with patients and families and within medical teams, medical judgment and technique, standards of practice, and high-risk treatments, often assigning responsibility for medical management they perceive as inappropriate, futile, overly aggressive, or mistakes in judgment and technique. Responsibility ranges from the distal (the culture of medicine) to the proximal (personal). Frustration, guilt, and anger are more frequently expressed in these narratives when care is questioned. A typology of questioning care emerged from these physicians' narratives that parallels and reflects recent and classic research on

Question-asking behavior as a form of cognitive activity

Directory of Open Access Journals (Sweden)

Elvira A. Baranova

2017-03-01

Full Text Available Children’s questions are an indicator of active cognitive perception of reality. Questions but not answers are relevant in revealing a child’s mental life, consciousness and thinking. The lack of question-asking skills can hinder learning, searching and exploration in children. To determine in 7- and 8-year-old school children the common and variable peculiarities of designing a search process for necessary information concerning an unknown object by volitionally formulated questions, as well as the dynamics of the questioning process throughout a school year. The study was based on an experimental methodology, codenamed Guess what there is in the box, and was conducted in four schools in Cheboksary. The sample comprised 158 primary school first-graders who took part in a confirmatory experiment twice, once in September and once in May. The research showed that 96.3% of the questions asked were search questions. Only 30% of the first-graders initiated their searching activities of their own will without having to resort to the given search algorithm, while 70% did not begin asking questions without outside stimulation. The analysis of the dynamics of children’s question-asking behavior exhibited a tendency to decrease in a number of questions asked over the course of the school year. Primary school children need psychological and pedagogical scaffolding aimed at developing a question-asking behavior as a form of cognitive activity to achieve a possible age potential in development.

A questions-based investigation of consumer mental-health information

Science.gov (United States)

Kart, Joyce Brothers

2015-01-01

Despite the wealth of mental-health information available online to consumers, research has shown that the mental-health information needs of consumers are not being met. This study contributes to that research by soliciting consumer questions directly, categorizing them, analyzing their form, and assessing the extent to which they can be answered from a trusted and vetted source of online information, namely the website of the US National Institute of Mental Health (NIMH). As an alternative to surveys and analyses of online activity, this study shows how consumer questions provide new insight into what consumers do not know and how they express their information needs. The study crowdsourced 100 consumer questions through Amazon Inc.’s Mechanical Turk. Categorization of the questions shows broad agreement with earlier studies in terms of the content of consumer questions. It also suggests that consumers’ grasp of mental health issues may be low compared to other health topics. The majority of the questions (74%) were simple in form, with the remainder being multi-part, multifaceted or narrative. Even simple-form questions could, however, have complex interpretations. Fifty four questions were submitted to the search box at the NIMH website. For 32 questions, no answer could be found in the top one to three documents returned. Inadequacies in the search and retrieval technology deployed at websites account for some of the failure to find answers. The nature of consumer questions in mental health also plays a role. A question that has a false presupposition is less likely to have an answer in trusted and vetted sources of information. Consumer questions are also expressed with a degree of specificity that makes the retrieval of relevant information difficult. The significance of this study is that it shows what an analysis of consumer mental-health questions can tell us about consumer information needs and it provides new insight into the difficulties facing

The role of teacher questions in the chemistry classroom

DEFF Research Database (Denmark)

Dohrn, Sofie Weiss; Dohn, Niels Bonderup

2018-01-01

, the students become highly accomplished in recalling facts but have difficulties when higher order thinking is required. The findings suggest that an interactive classroom can be created by using many engaging teacher questions. The six different categories of questions promote the students' learning process......The purpose of this study was to investigate how a chemistry teacher's questions influence the classroom discourse. It presents a fine-grained analysis of the rich variety of one teacher's questions and the roles they play in an upper secondary chemistry classroom. The study identifies six...... different functions for the teacher's questions: Student Knowledge, Request, Monologic Discourse, Clarification, Relations and Interaction of Contexts. Overall, these questions create a safe and interactive learning environment. However, the questions are predominantly closed in form. As a result...

QUESTION FORMATION OF BAHASA INDONESIA AS A SECOND LANGUAGE

Directory of Open Access Journals (Sweden)

zulfa Sakhiyya

2013-07-01

Full Text Available Abstract: This article aims to implement Processability Theory (PT to Bahasa Indonesia or Indonesian language and to identify developmental stages for question formation in the setting of Bahasa Indonesia as a second language (ISL. PT provides a theoretical framework in making predictions about the course of language development, in this case the question formation acquisition. This study proposes developmental stages of question formation in ISL setting by contrasting the lexical functional grammar of Indonesian question as compared to ESL question formation. Four stages of ISL question formation were proposed. The proposed stages serve as the basis for data analysis and to show its plausibility.

On the placement of practice questions during study.

Science.gov (United States)

Weinstein, Yana; Nunes, Ludmila D; Karpicke, Jeffrey D

2016-03-01

Retrieval practice improves retention of information on later tests. A question remains: When should retrieval occur during learning-interspersed throughout study or at the end of each study period? In a lab experiment, an online experiment, and a classroom study, we aimed to determine the ideal placement (interspersed vs. at-the-end) of retrieval practice questions. In the lab experiment, 64 subjects viewed slides about APA style and answered short-answer practice questions about the content or restudied the slides (restudy condition). The practice questions either appeared 1 every 1-2 slides (interspersed condition), or all at the end of the presentation (at-the-end condition). One week later, subjects returned and answered the same questions on a final test. In the online experiment, 175 subjects completed the same procedure. In the classroom study, 62 undergraduate students took quizzes as part of class lectures. Short-answer practice questions appeared either throughout the lectures (interspersed condition) or at the end of the lectures (at-the-end condition). Nineteen days after the last quiz, students were given a surprise final test. Results from the 3 experiments converge in demonstrating an advantage for interspersing practice questions on the initial tests, but an absence of this advantage on the final test. (c) 2016 APA, all rights reserved).

Radiation protection in questions and answers

International Nuclear Information System (INIS)

Ewen, K.; Hoppe, G.

1976-01-01

An easily surveyable catalogue of questions is presented which is to make it easier for medical personnel to get acquainted with the basic knowledge according to the X-ray Ordinance and to acquire the expert knowledge in radiation protection. The catalogue is arranged according to different subjects. There are several alternative answers to every question. The right answer is given in the solution index (annex). (HP) [de

The implications of nonauthentic questions in Galatians | Verster ...

African Journals Online (AJOL)

A new classification of non-authentic questions is helpful in understanding the way in which Paul uses persuasion in Galatians. Paul uses many non-authentic questions, and the implications thereof are evident in the type of question used. The way in which he violates the maxims identified by Grice also entails certain ...

Questions about elastic waves

CERN Document Server

Engelbrecht, Jüri

2015-01-01

This book addresses the modelling of mechanical waves by asking the right questions about them and trying to find suitable answers. The questions follow the analytical sequence from elementary understandings to complicated cases, following a step-by-step path towards increased knowledge. The focus is on waves in elastic solids, although some examples also concern non-conservative cases for the sake of completeness. Special attention is paid to the understanding of the influence of microstructure, nonlinearity and internal variables in continua. With the help of many mathematical models for describing waves, physical phenomena concerning wave dispersion, nonlinear effects, emergence of solitary waves, scales and hierarchies of waves as well as the governing physical parameters are analysed. Also, the energy balance in waves and non-conservative models with energy influx are discussed. Finally, all answers are interwoven into the canvas of complexity.

Some of the unanswered questions in finance

Directory of Open Access Journals (Sweden)

Đurić Dragana M.

2006-01-01

Full Text Available A very dynamic development of finance in the last 50 years is inter alia probably due to experiments and innovations in this field. Previously theoretical base could not explain and predict movements especially in volatile times. "The new finance" appeared 50 years ago (portfolio theory CAPM, the efficient market theory, M&M theorem and made substantial progress in understanding movements in globalized and internationalized financial markets. However, many questions remain open. The author tries to put emphasis on some of these questions, perfectly aware that these are not the only ones. Unresolved questions are related to company's aims, project's risks, degree of portfolio optimization, importance of liquidity, dividend policy, as well as factors that determine M&A. As the "new finance" is not able to predict and explain volatile movements, a question that should be posed is whether it is appropriate to add some non-economic factors as the behaviorist theory suggests. Although the behaviorist theory is an important part of "new finance", it is unfortunately the only theory able to explain movements in volatile times. In conclusion, many questions still remain unanswered and wait for appropriate theoretical explanations.

Rabies: Questions and Answers

Science.gov (United States)

Rabies: Questions and Answers Information about the disease and vaccines What causes rabies? Rabies is caused by a virus. The virus invades ... nervous system and disrupts its functioning. How does rabies spread? The rabies virus is transmitted in the ...

Categorization of questions posed before and after inquiry-based learning

Directory of Open Access Journals (Sweden)

Sandra Milena García González

2014-07-01

Full Text Available Posing research questions is the central ability of the scientific thought. This article examines the ability of sixth grade children to pose researchable questions before and after a three months’ work on a didactic sequence based on the inquiry school model. According to their purpose, the questions asked by children, after reading a text, were classified into researchable questions -susceptible to be empirically explored-, questions about a cause, and questions on a piece of data. The results show that the amount and the type of questions the students were able to pose during the intervention changed, from most of questions on data or information, to most of researchable questions, subsequently, the importance of designing teaching approaches to foster this ability was proved.

Questioning Strategies of Literature Teachers among Grade 8 Filipino Students

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Magdalena M. Ocbian

2015-11-01

Full Text Available Questioning is a useful and relevant tool to facilitate classroom discussion in a literature class. This study identified the levels of questions teachers use in their literature class, determined the different question strategies they utilized and proposed activities to enhance the questioning strategies of literature teachers. Video analysis was the main instrument used. These videos were provided during the conduct of class observations by the researchers. There were eight respondents in the study selected through total enumeration. They are teachers from Gubat Cluster of secondary schools of Sorsogon Province. To identify the levels of questions and questioning strategies, question tally form and percentage were used. Results revealed that knowledge was the most used level of questions followed by comprehension, application, analysis, synthesis and evaluation. The most used question technique is the participation, followed by proving, sequencing, wait time, balance and student questions. It was recommended that literature teachers vary their level of questions when discussing literary pieces. They may utilize different question techniques to develop critical thinking skills of their students. The use of the proposed activities may enhance the questioning strategies of literature teachers. Likewise, school heads and program supervisors may utilize video analysis technique as a mode for classroom observation.

Children's Exhaustive Readings of Questions

Science.gov (United States)

Cremers, Alexandre; Tieu, Lyn; Chemla, Emmanuel

2017-01-01

Questions, just like plain declarative sentences, can give rise to multiple interpretations. As discussed by Spector & Egré (2015), among others, questions embedded under know are ambiguous between "weakly exhaustive" (WE), "intermediate exhaustive" (IE), and "strongly exhaustive" (SE) interpretations (for…

A new method for the characterization of strain-specific conformational stability of protease-sensitive and protease-resistant PrPSc.

Directory of Open Access Journals (Sweden)

Laura Pirisinu

Full Text Available Although proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrP(Sc, a disease-associated isoform of the host-encoded cellular protein (PrP(C. Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrP(Sc. However, PrP(Sc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrP(Sc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrP(C and PrP(Sc by means of differential centrifugation. The conformational solubility and stability assay (CSSA was then developed by measuring PrP(Sc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl](1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl](1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M, followed by sheep scrapie (2.2 M and by MM2 sCJD (1.6 M. In order to test the ability of CSSA to characterise protease-sensitive PrP(Sc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrP(Sc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrP(Sc conformational stabilities of protease-resistant and protease-sensitive PrP(Sc and that it is a valuable tool

Sample Focus Group Questions for Girls in STEM

Energy Technology Data Exchange (ETDEWEB)

Coronado, Elizabeth Phillips [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2018-02-13

These are sample questions for focus groups to be conducted as part of qualitative data collection for Year 2- Year 6 of Girls in STEM. You may use any of the questions from the list during the two sessions during the school year, as long as those questions are not repeated in both Baseline and follow-up sessions.

Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease.

Science.gov (United States)

Givaty, Gili; Maggio, Nicola; Cohen, Oren S; Blatt, Ilan; Chapman, Joab

2016-10-01

In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease. © 2016 European Sleep Research Society.

Age at Death of Creutzfeldt-Jakob disease in subsequent family generation carrying the E200K mutation of the prion protein gene.

Directory of Open Access Journals (Sweden)

Maurizio Pocchiari

Full Text Available The E200K mutation of the prion protein gene (PRNP is the most frequent amino acid substitution in genetic Creutzfeldt-Jakob disease and is the only one responsible for the appearance of clustered cases in the world. In the Israel and Slovakian clusters, age of disease onset was reduced in successive generations but the absence of a clear molecular basis raised the possibility that this event was an observational bias. The aim of the present study was to investigate possible selection biases or confounding factors related to anticipation in E200K CJD patients belonging to a cluster in Southern Italy.Clinical and demographical data of 41 parent-offspring pairs from 19 pedigrees of the Italian cluster of E200K patients were collected. Age at death of parents was compared with age at death of E200K CJD offspring. Subgroup analyses were performed for controlling possible selection biases, confounding factors, or both.The mean age at death/last follow-up of the parent generation was 71.4 years while that of CJD offspring was 59.3 years with an estimated anticipation of 12.1 years. When the same analysis was performed including only parents with CJD or carrying the E200K mutation (n = 26, the difference between offspring and parents increased to 14.8 years.These results show that early age at death occurs in offspring of families carrying the E200K PRNP mutation and that this event is not linked to observational biases. Although molecular or environmental bases for this occurrence remain unsettled, this information is important for improving the accuracy of information to give to mutated carriers.

Specific clinical signs and symptoms are predictive of clinical course in sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Nakatani, E; Kanatani, Y; Kaneda, H; Nagai, Y; Teramukai, S; Nishimura, T; Zhou, B; Kojima, S; Kono, H; Fukushima, M; Kitamoto, T; Mizusawa, H

2016-09-01

Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

The kinds of questions asked by novice teachers in learning mathematics

Science.gov (United States)

Zahra, L.; Kusmayadi, T. A.; Usodo, B.

2018-05-01

This study describes the kinds of questions asked by novice teachers during mathematics learning process in senior high school. This study used descriptive analysis. The subjects of this study were two novice teachers who teach mathematics in 10th grade. The result showed that the frequently asked questions by novice teachers based on the objective were compliance questions, rethorical questions and sometimes prompting questions and probing questions. The frequently questions asked by novice teacher based on the cognitive process dimension of Revised Bloom’s Taxonomy were questions of remembering, questions of understanding, questions of applying, questions of analyzing and questions of evaluating. The novice teachers asked the routine questions which had same thinking level. The question with the highest level of thinking did not asked by the novice teachers.

Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy.

Science.gov (United States)

Manix, Marc; Kalakoti, Piyush; Henry, Miriam; Thakur, Jai; Menger, Richard; Guthikonda, Bharat; Nanda, Anil

2015-11-01

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis-the gold standard for definitive diagnosis is considered to be histopathological confirmation-but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Imaging studies, electroencephalography, and biomarkers are used in conjunction with the clinical picture to try to make the diagnosis of CJD without brain tissue samples, and all of these are reviewed in this article. The current diagnostic criteria are limited; test sensitivity and specificity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. The authors review CJD, discuss the role of brain biopsy in this patient population, provide a diagnostic pathway for the patient presenting with rapidly progressive dementia, and propose newer diagnostic criteria.

Small protease sensitive oligomers of PrPSc in distinct human prions determine conversion rate of PrP(C.

Directory of Open Access Journals (Sweden)

Chae Kim

Full Text Available The mammalian prions replicate by converting cellular prion protein (PrP(C into pathogenic conformational isoform (PrP(Sc. Variations in prions, which cause different disease phenotypes, are referred to as strains. The mechanism of high-fidelity replication of prion strains in the absence of nucleic acid remains unsolved. We investigated the impact of different conformational characteristics of PrP(Sc on conversion of PrP(C in vitro using PrP(Sc seeds from the most frequent human prion disease worldwide, the Creutzfeldt-Jakob disease (sCJD. The conversion potency of a broad spectrum of distinct sCJD prions was governed by the level, conformation, and stability of small oligomers of the protease-sensitive (s PrP(Sc. The smallest most potent prions present in sCJD brains were composed only of∼20 monomers of PrP(Sc. The tight correlation between conversion potency of small oligomers of human sPrP(Sc observed in vitro and duration of the disease suggests that sPrP(Sc conformers are an important determinant of prion strain characteristics that control the progression rate of the disease.

Questions and Answers about Sex (For Parents)

Science.gov (United States)

... español Preguntas y respuestas sobre sexo Answering their kids' questions about sex is a responsibility that many parents dread. Otherwise ... avoided. Parents can help foster healthy feelings about sex if they answer kids' questions in an age-appropriate way. When do ...

Question presentation methods for paired-associate learning

NARCIS (Netherlands)

Engel, F.L.; Geerings, M.P.W.

1988-01-01

Four different methods of question presentation, in interactive computeraided learning of Dutch-English word pairs are evaluated experimentally. These methods are: 1) the 'open-question method', 2) the 'multiple-choice method', 3) the 'sequential method' and 4) the 'true/ false method'. When

[Two simple questions to diagnose post-stroke depression].

Science.gov (United States)

Nolte, C H; Müller-Nordhorn, J; Jungehülsing, G J; Rossnagel, K; Reich, A; Roll, S; Laumeier, I; Beerfelde, D; Willich, S N; Villringer, A

2006-05-01

Many patients develop a depression after having suffered a stroke. Such a Post-Stroke Depression (PSD) impairs rehabilitation and quality of life. PSD is underdiagnosed in spite of available treatment. Several questionnaires have been created to diagnose a PSD. But questionnaires have been considered cumbersome and time-consuming. The aim of this study was to find out whether two simple, standardised questions will identify those stroke patients, who have developed a PSD. The two case-finding questions and the Beck Depression Inventory (BDI) were sent to patients of the Berlin Acute Stroke Study (BASS) four years after their stroke. Incomplete questionnaires were complemented via mail or telephone. Severity of depression was assessed by means of BDI. Out of 211 patients, 199 responded to the questionnaire (94 %). 193 questionnaires were complete (97 %). Forty-two patients affirmed both case-finding questions (22 %). Compared to patients, who did not affirm both questions, these patients had a higher BDI score (19 +/- 8 vs. 7 +/- 5; p two questions were 89 % and 90 %, respectively. The positive and negative predictive value were 60 % and 98 % respectively. The number of confirmed questions (0, 1, 2) correlated well with the BDI score (r (2) = 0.67, p Two standardized questions can identify patients with PSD for further diagnostic evaluation and therapy. Diagnosis of PSD might be facilitated by using them as screening instrument.

America in Perspective: Yesterday's Questions and Today's Students.

Science.gov (United States)

Danzer, Gerald A.

In 1780, a prize was established in France for the best answer to the question; "Was the discovery of America a blessing or a curse to mankind?" This question and its only response from an individual living in America, constitute the basis of a high school history class unit. The background of the question and the content are developed,…

On safety goals and related questions

International Nuclear Information System (INIS)

Kaplan, S.

1985-01-01

The question of what safety goals should be established for nuclear power plants has been receiving a great deal of urgent attention and debate recently, both by those responsible for reactor licensing and by others interested in establishing a quantitative measure of reactor safety. The same question, phrased alternately in the forms: ''What is acceptable risk?'' and ''How safe is safe enough?,'' has been debated extensively for quite a long time. The purpose of the present paper, therefore, is to show that the above questions, taken at face value, exist within an unworkable context, which the authors shall call the Old Regulatory Context (ORC), and that within this context lead to several absurdities. They shall argue that this context needs to be replaced by another context, which they call the Decision Theory Context (DTC), and which the authors discuss here

Rapidly aggravated Creutzfeldt-Jacob disease: autopsy-proven case

Energy Technology Data Exchange (ETDEWEB)

Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun [Seoul Veterans Hospital, Seoul (Korea, Republic of)

2005-11-15

Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images.

Rapidly aggravated Creutzfeldt-Jacob disease: autopsy-proven case

International Nuclear Information System (INIS)

Park, Seung Hyun; Kang, Hyun Koo; Yu, Hyeon; Lee, Sang Chun

2005-01-01

Creutzfeldt-Jakob disease (DJD) is one of the transmissible spongiform encephalopathies, which is mediated by what has been known as 'prion'. It is a rare and fatal progressive neurodegenerative disease that affects the middle and old aged. There are a number of subtypes of CJD, one of which is the sporadic type characterized by rapidly progressing clinical symptoms, including progressive dementia, myoclonic jerk, and pyramidal or extrapyramidal syndrome. Patients usually end up dying within 1 to 2 years of contacting the disease. We report an autopsy-proven case of sporadic CJD with clinical symptoms that progressed within several days, along with dramatic changes on diffusion weighted magnetic resonance images

Fifty important research questions in microbial ecology.

Science.gov (United States)

Antwis, Rachael E; Griffiths, Sarah M; Harrison, Xavier A; Aranega-Bou, Paz; Arce, Andres; Bettridge, Aimee S; Brailsford, Francesca L; de Menezes, Alexandre; Devaynes, Andrew; Forbes, Kristian M; Fry, Ellen L; Goodhead, Ian; Haskell, Erin; Heys, Chloe; James, Chloe; Johnston, Sarah R; Lewis, Gillian R; Lewis, Zenobia; Macey, Michael C; McCarthy, Alan; McDonald, James E; Mejia-Florez, Nasmille L; O'Brien, David; Orland, Chloé; Pautasso, Marco; Reid, William D K; Robinson, Heather A; Wilson, Kenneth; Sutherland, William J

2017-05-01

Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host-microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Questions and answers on nuclear energy

International Nuclear Information System (INIS)

1989-04-01

Leading questions about nuclear power are posed. These include questions about how much extra radioactivity in the environments is due to the nuclear industry, the risk of a nuclear accident, radioactive wastes, nuclear power as a solution to the greenhouse effect, alternative energy sources, and the economics of nuclear power. The answers are presented from the view point of the authors, members of Greenpeace. A glossary, notes and references are included. (UK)

Power dynamics and questioning in elementary science lessons

Science.gov (United States)

Reinsvold, Lori Ann

Discourse interactions between a teacher and students in an inquiry-based fourth-grade science classroom were analyzed to investigate how power dynamics and questioning strategies within elementary science lessons help support students in building their science understanding. Five inquiry-based classroom sessions were observed; verbal interactions were audio- and video-recorded. Research data consisted of observation transcripts, teacher interviews, student work, and instructional materials. Analyses were conducted on the frequencies of utterances, participation roles, power categories, and questioning categories. Results revealed that when students used more frequent power, (a) no significant differences were noted between frequencies of teacher and student talk, (b) the teacher posed more questions than did the students, and (c) students explained what they knew and asked questions to clarify their understanding. When the teacher used more frequent power, she asked questions to provide students opportunities to negotiate investigative processes and explain what they knew and how they knew it. Evidence of student understanding of the science concepts was found in how students used subject matter to discuss what they knew and how they knew it. Pre-service and in-service teachers should be encouraged to consider how their use of power and questioning strategies can engage students to reflect on how they build understanding of science concepts. Teachers can use Professional Learning Communities to reflect on how their practice engages students. Future research should be employed to observe classrooms across an entire school year to determine how power and questioning dynamics flow among students and teachers and change over time. Research can also be used to understand the influence of gender and culture on power and questioning dynamics in classroom settings.

The social question revisited

DEFF Research Database (Denmark)

Kenneth, Petersson; Olsson, Ulf; Krejsler, John B.

2015-01-01

The focus of this chapter is the re-installation of the social question as a historical practice. The purpose is to investigate how historic figures return and are applied in contemporary political discourses, more precisely in the context of education, education policy and teacher education...

Michaelis' hundred Questions and the Royal Instructions

DEFF Research Database (Denmark)

Friis, Ib

2017-01-01

Michaelis' 100 questions for the expedition is a remarkable document. It provides insight into the sources and methods of biblical research anno 1762, at the same time as highlighting the challenges the members of the expedition faced. As the scholarly foundation of the expedition, the questions ...

Michaelis' Hundred Questions and the Royal Instruction

DEFF Research Database (Denmark)

Friis, Ib

2015-01-01

Michaelis' 100 questions for the expedition is a remarkable document. It provides insight into the sources and methods of biblical research anno 1762, at the same time as highlighting the challenges the members of the expedition faced. As the scholarly foundation of the expedition, the questions ...

asking questions for higher order thinking in visual literacy

African Journals Online (AJOL)

Numerous factors such as socio-economic back- ground of .... questions should comprise 40% low-order questions (Knowledge), 40% middle-order questions ... The data obtained from the class participants comprise details of a two-step tea-.

The ecological crisis: a question of justice

International Nuclear Information System (INIS)

Kempf, H.

2010-01-01

The question of ecology has become a major issue for international relations in the next half-century. But it poses new problems of worldwide justice more than questions of power politics, and its solution will always be a reflection of internal social issues in the countries concerned. (author)

Open-ended questions in sensory testing practice

NARCIS (Netherlands)

Piqueras Fiszman, B.

2015-01-01

Why use open-ended questions? This chapter provides an up-to-date overview on the use of open-ended questions in novel rapid sensory methodologies and the potential applications in which they could provide unique benefits. Next, the step-by-step process is described (from task performance to

Questioning Danish Cartoon Images

DEFF Research Database (Denmark)

Bojsen, Heidi

2007-01-01

Danes today when it is considered demeaning and racist in most other countries. The conclusion does emphatically not plead in favour of law enforced limitations of the freedom of expression, but does question the prevalent "freedom of ignorance" concerning black identities which means...

Quantum theory from questions

Energy Technology Data Exchange (ETDEWEB)

Hoehn, Philipp [Institute for Quantum Optics and Quantum Information, Austrian Academy of Sciences, Vienna (Austria); Wever, Christopher [Institute for Theoretical Particle Physics, Karlsruhe (Germany)

2016-07-01

In contrast to relativity, quantum theory has evaded a commonly accepted apprehension, in part because of the lack of physical statements that fully characterize it. In an attempt to remedy the situation, we summarize a novel reconstruction of the explicit formalism of quantum theory (for arbitrarily many qubits) from elementary rules on an observer's information acquisition. Our approach is purely operational: we consider an observer O interrogating a system S with binary questions and define S's state as O's ''catalogue of knowledge'' about S; no ontic assumptions are necessary. From the rules, one can derive, among other things, the state spaces, the unitary group, the von Neumann evolution and show that the binary questions correspond to Pauli operators. The reconstruction also offers new structural insights in the form of novel informational charges and informational complementarity relations which define the state spaces and the unitary group. This reconstruction permits a new perspective on quantum theory.

Promoting Self-Questioning through Picture Book Illustrations

Science.gov (United States)

Lohfink, Gayla

2013-01-01

This teaching tip manuscript demonstrates how picture book illustrations can be used as an inquiry tool that facilitates one's connecting of visual investigations in a picture to the process of generating self-questions. Techniques suggested to promote self-questioning are (1) introducing young readers to an interactive picture book read aloud…

The science and art of asking questions in cognitive therapy.

Science.gov (United States)

James, Ian Andrew; Morse, Rachel; Howarth, Alan

2010-01-01

Questions underpin all aspects of therapeutic assessment and intervention and are a vital component of the clinical process. Over recent years frameworks have started to be applied to obtain a greater understanding of questioning formats and processes. This paper examines the use of questions in cognitive therapy (CT). An overview of the main types of questions identified in the literature is presented. In addition, we examine a range of client and therapist characteristics that may impact on the questioning process. Asking questions in therapy is a complex, yet under-taught, skill. This paper provides a set of frameworks to assist in identifying helpful and unhelpful questioning skills. Thus the article has implications for further training and research.

Interviewer Effects on a Network-Size Filter Question

Directory of Open Access Journals (Sweden)

Josten Michael

2016-06-01

Full Text Available There is evidence that survey interviewers may be tempted to manipulate answers to filter questions in a way that minimizes the number of follow-up questions. This becomes relevant when ego-centered network data are collected. The reported network size has a huge impact on interview duration if multiple questions on each alter are triggered. We analyze interviewer effects on a network-size question in the mixed-mode survey “Panel Study ‘Labour Market and Social Security’” (PASS, where interviewers could skip up to 15 follow-up questions by generating small networks. Applying multilevel models, we find almost no interviewer effects in CATI mode, where interviewers are paid by the hour and frequently supervised. In CAPI, however, where interviewers are paid by case and no close supervision is possible, we find strong interviewer effects on network size. As the area-specific network size is known from telephone mode, where allocation to interviewers is random, interviewer and area effects can be separated. Furthermore, a difference-in-difference analysis reveals the negative effect of introducing the follow-up questions in Wave 3 on CAPI network size. Attempting to explain interviewer effects we neither find significant main effects of experience within a wave, nor significantly different slopes between interviewers.

Postsecondary Education Issues: Visible Questions. Invisible Answers.

Science.gov (United States)

Western Interstate Commission for Higher Education, Boulder, CO. National Center for Higher Education Management Systems.

With some justification, the inability to answer most of the important questions in higher education is due to the lack of necessary information. But careful examination of our many faceted questions suggests that more information may not be the only answer. The National Center for Higher Education Management Systems (NCHEMS) has found other…

A statistical analysis of student questions in a cell biology laboratory.

Science.gov (United States)

Keeling, Elena L; Polacek, Kelly M; Ingram, Ella L

2009-01-01

Asking questions is an essential component of the practice of science, but question-asking skills are often underemphasized in science education. In this study, we examined questions written by students as they prepared for laboratory exercises in a senior-level cell biology class. Our goals were to discover 1) what types of questions students asked about laboratory activities, 2) whether the types or quality of questions changed over time, and 3) whether the quality of questions or degree of improvement was related to academic performance. We found a majority of questions were about laboratory outcomes or seeking additional descriptive information about organisms or processes to be studied. Few questions earned the highest possible ranking, which required demonstration of extended thought, integration of information, and/or hypotheses and future experiments, although a majority of students asked such a question at least once. We found no correlation between types of student questions or improvement in questions and final grades. Only a small improvement in overall question quality was seen despite considerable practice at writing questions about science. Our results suggest that improving students' ability to generate higher-order questions may require specific pedagogical intervention.

Phenomenology of the innovative question when based on wonderment

DEFF Research Database (Denmark)

Herholdt-Lomholdt, Sine Maria; Hansen, Finn Thorbjørn

This paper questions, how we, from a phenomenological point of view, can describe and understand the phenomenology of innovative questions and processes of questioning when based in a wonderdriven approach to innovation and entrepreneurship. Approach: In our research we take on a phenomenological...

Children’s questions as a base of teaching

Directory of Open Access Journals (Sweden)

Pavlović Branka S.

2003-01-01

Full Text Available The paper considers interrelationships between children’s questions and teaching and learning in the light of experimental studies on the role and aim of children’s questions in Nature and Society teaching in the third grade of primary school. The experiment comprising two parallel groups was carried out on the sample of 150 respondents from two primary schools in Šabac during the second term of the academic year 2002/2003. The present paper involves a portion of the results obtained for the type of questions children asked during teaching process as classified by independent observers; average distribution of some types of questions; qualitative analysis of discussions conducted with children after two classes where identical teaching content was presented in groups E and K; qualitative analysis of two interviews conducted with teachers after those classes in groups E and K; observers’ general impression of classes in groups E and K. The results showed that teaching based on children’s questions encourages children’s proactive attitude towards learning and leads to its higher cognitive efficiency and that children express a high degree of satisfaction by participating in thus organized work during classes and preference of atmosphere present in the classroom during such classes compared to the atmosphere during classes managed in a traditional way. Communication between children and between teacher and children is less formal, more relaxed and dynamic, which all produces motivational effects on children makes them more engaged in learning during teaching whose base is in their questions and not in teaching managed by teacher’s questions.

Training IBM Watson using Automatically Generated Question-Answer Pairs

OpenAIRE

Lee, Jangho; Kim, Gyuwan; Yoo, Jaeyoon; Jung, Changwoo; Kim, Minseok; Yoon, Sungroh

2016-01-01

IBM Watson is a cognitive computing system capable of question answering in natural languages. It is believed that IBM Watson can understand large corpora and answer relevant questions more effectively than any other question-answering system currently available. To unleash the full power of Watson, however, we need to train its instance with a large number of well-prepared question-answer pairs. Obviously, manually generating such pairs in a large quantity is prohibitively time consuming and...

Reply & Supply: Efficient crowdsourcing when workers do more than answer questions.

Science.gov (United States)

McAndrew, Thomas C; Guseva, Elizaveta A; Bagrow, James P

2017-01-01

Crowdsourcing works by distributing many small tasks to large numbers of workers, yet the true potential of crowdsourcing lies in workers doing more than performing simple tasks-they can apply their experience and creativity to provide new and unexpected information to the crowdsourcer. One such case is when workers not only answer a crowdsourcer's questions but also contribute new questions for subsequent crowd analysis, leading to a growing set of questions. This growth creates an inherent bias for early questions since a question introduced earlier by a worker can be answered by more subsequent workers than a question introduced later. Here we study how to perform efficient crowdsourcing with such growing question sets. By modeling question sets as networks of interrelated questions, we introduce algorithms to help curtail the growth bias by efficiently distributing workers between exploring new questions and addressing current questions. Experiments and simulations demonstrate that these algorithms can efficiently explore an unbounded set of questions without losing confidence in crowd answers.

Augmenting Fellow Education Through Spaced Multiple-Choice Questions.

Science.gov (United States)

Barsoumian, Alice E; Yun, Heather C

2018-01-01

The San Antonio Uniformed Services Health Education Consortium Infectious Disease Fellowship program historically included a monthly short-answer and multiple-choice quiz. The intent was to ensure medical knowledge in relevant content areas that may not be addressed through clinical rotations, such as operationally relevant infectious disease. After completion, it was discussed in a small group with faculty. Over time, faculty noted increasing dissatisfaction with the activity. Spaced interval education is useful in retention of medical knowledge and skills by medical students and residents. Its use in infectious disease fellow education has not been described. To improve the quiz experience, we assessed the introduction of spaced education curriculum in our program. A pre-intervention survey was distributed to assess the monthly quiz with Likert scale and open-ended questions. A multiple-choice question spaced education curriculum was created using the Qstream(R) platform in 2011. Faculty development on question writing was conducted. Two questions were delivered every 2 d. Incorrectly and correctly answered questions were repeated after 7 and 13 d, respectively. Questions needed to be answered correctly twice to be retired. Fellow satisfaction was assessed at semi-annual fellowship reviews over 5 yr and by a one-time repeat survey. Pre-intervention survey of six fellows indicated dissatisfaction with the time commitment of the monthly quiz (median Likert score of 2, mean 6.5 h to complete), neutral in perceived utility, but satisfaction with knowledge retention (Likert score 4). Eighteen fellows over 5 yr participated in the spaced education curriculum. Three quizzes with 20, 39, and 48 questions were designed. Seventeen percentage of questions addressed operationally relevant topics. Fifty-nine percentage of questions were answered correctly on first attempt, improving to 93% correct answer rate at the end of the analysis. Questions were attempted 2,999 times

Globalisation and blood safety.

Science.gov (United States)

Farrugia, Albert

2009-05-01

Globalisation may be viewed as the growing interdependence of countries worldwide through the increasing volume and variety of cross-border transactions in goods and services, and also through the more rapid and widespread diffusion of technology. Globalisation is not just an economic phenomenon, although it is frequently described as such, but includes commerce, disease and travel, and immigration, and as such it affects blood safety and supply in various ways. The relatively short travel times offered by modern aviation can result in the rapid spread of blood-borne pathogens before measures to counteract transmission can be put in place; this would have happened with SARS if the basic life cycle of the SARS virus included an asymptomatic viraemia. This risk can be amplified by ecological factors which effect the spread of these pathogens once they are transferred to a naïve ecosystem, as happened with West Nile Virus (WNV) in North America. The rationalization and contraction of the plasma products industry may be viewed as one aspect of globalisation imposed by the remorseless inevitability of the market; the effect of this development on the safety and supply of products has yet to be seen, but the oversight and assurance of a shrinking number of players will present particular challenges. Similarly, the monopolization of technology, through patent enforcement which puts access beyond the reach of developing countries, can have an effect on blood safety. The challenges presented to blood safety by globalisation are heightening the tensions between the traditional focus on the product safety - zero risk paradigm and the need to view the delivery of safe blood as an integrated process. As an illustration of this tension, donor deferral measures imposed by globalisation-induced risks such as vCJD and WNV have resulted in the loss of the safest and most committed portion of the blood donor population in many Western countries, leading to an increased risk to

Importance of questionnaire context for a physical activity question.

Science.gov (United States)

Jørgensen, M E; Sørensen, M R; Ekholm, O; Rasmussen, N K

2013-10-01

Adequate information about physical activity habits is essential for surveillance, implementing, and evaluating public health initiatives in this area. Previous studies have shown that question order and differences in wording result in systematic differences in people's responses to questionnaires; however, this has never been shown for physical activity questions. The aim was to study the influence of different formulations and question order on self-report physical activity in a population-based health interview survey. Four samples of each 1000 adults were drawn at random from the National Person Register. A new question about physical activity was included with minor differences in formulations in samples 1-3. Furthermore, the question in sample 2 was included in sample 4 but was placed in the end of the questionnaire. The mean time spent on moderate physical activity varied between the four samples from 57 to 100 min/day. Question order was associated with the reported number of minutes spent on moderate-intensity physical activity and with prevalence of meeting the recommendation, whereas physical inactivity was associated with the differences in formulation of the question. Questionnaire context influences the way people respond to questions about physical activity significantly and should be tested systematically in validation studies of physical activity questionnaires. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk Factor Analysis and the Youth Question

Science.gov (United States)

France, Alan

2008-01-01

This paper is concerned with exploring how in late modernity the "youth question" is being addressed by public policy and what impact this is having on understandings of childhood and youth. Historically the youth question has been shaped by adult anxieties over youth delinquency and their problems of social integration. In late modernity, this is…

Visual question answering using hierarchical dynamic memory networks

Science.gov (United States)

Shang, Jiayu; Li, Shiren; Duan, Zhikui; Huang, Junwei

2018-04-01

Visual Question Answering (VQA) is one of the most popular research fields in machine learning which aims to let the computer learn to answer natural language questions with images. In this paper, we propose a new method called hierarchical dynamic memory networks (HDMN), which takes both question attention and visual attention into consideration impressed by Co-Attention method, which is the best (or among the best) algorithm for now. Additionally, we use bi-directional LSTMs, which have a better capability to remain more information from the question and image, to replace the old unit so that we can capture information from both past and future sentences to be used. Then we rebuild the hierarchical architecture for not only question attention but also visual attention. What's more, we accelerate the algorithm via a new technic called Batch Normalization which helps the network converge more quickly than other algorithms. The experimental result shows that our model improves the state of the art on the large COCO-QA dataset, compared with other methods.

Chapter 9: Questions from CNEN specific exams

Energy Technology Data Exchange (ETDEWEB)

NONE

2018-04-01

The following are real questions from CNEN specific exams for obtaining the certification of RSO for gamma irradiators. These are questions that require essay answers, that are interpretative ones and therefore that may accept more than one interpretation, therefore more than one answer. For this reason, suggestions of answers will be presented in the second part of this chapter.

Chapter 9: Questions from CNEN specific exams

International Nuclear Information System (INIS)

2018-01-01

The following are real questions from CNEN specific exams for obtaining the certification of RSO for gamma irradiators. These are questions that require essay answers, that are interpretative ones and therefore that may accept more than one interpretation, therefore more than one answer. For this reason, suggestions of answers will be presented in the second part of this chapter

It's worth the wait: optimizing questioning methods for effective intraoperative teaching.

Science.gov (United States)

Barrett, Meredith; Magas, Christopher P; Gruppen, Larry D; Dedhia, Priya H; Sandhu, Gurjit

2017-07-01

The use of questioning to engage learners is critical to furthering resident education intraoperatively. Previous studies have demonstrated that higher level questioning and optimal wait times (>3 s) result in learner responses reflective of higher cognition and retention. Given the importance of intraoperative learning, we investigated question delivery in the operating room. A total of 12 laparoscopic cholecystectomies were observed and recorded. All questions were transcribed and classified using Bloom's Taxonomy, a framework associated with hierarchical levels of learning outcomes. Wait time between question end and response was recorded. Six faculty attendings and seven house officers at our institution were observed. A total of 133 questions were recorded with an average number of questions per case of 11.2. The majority of questions 112 out of 133 (84%) were classified as Bloom's levels 1-3, with only 6% of questions of the highest level. The wait time before the resident answered the question averaged 1.75 s, with attendings interceding after 2.50 s. Question complexity and wait time did not vary based on resident postgraduate year level suggesting limited tailoring of question to learner. Intraoperative questioning is not aligned with higher level thinking. The majority of questions were Bloom's level 3 or below, limiting the complexity of answer formulation. Most responses were given within 2 s, hindering opportunity to pursue higher-order thinking. This suggests including higher level questions and tailoring questions to learner level may improve retention and maximize gains. In addition, with attendings answering 20% of their own questions, increasing their wait time offers another area for teaching development. © 2017 Royal Australasian College of Surgeons.

Comparison of Integrated Testlet and Constructed-Response Question Formats

Science.gov (United States)

Slepkov, Aaron D.; Shiell, Ralph C.

2014-01-01

Constructed-response (CR) questions are a mainstay of introductory physics textbooks and exams. However, because of the time, cost, and scoring reliability constraints associated with this format, CR questions are being increasingly replaced by multiple-choice (MC) questions in formal exams. The integrated testlet (IT) is a recently developed…

Intention-to-treat. What is the question?

Directory of Open Access Journals (Sweden)

Feinman Richard D

2009-01-01

Full Text Available Abstract It has become commonplace for Randomized Controlled Trials (RCTs to be analyzed according to Intention-to-Treat (ITT principles in which data from all subjects are used regardless of the subjects' adherence to protocol. While ITT analyses can provide useful information in some cases, they do not answer the question that motivates many RCTs, namely, whether the treatments differ in efficacy. ITT tends to reduce information by combining two questions, whether the intervention is effective and whether, as implemented, it has good compliance. Because these questions may be separate there is a risk of misuse. Two examples are presented that demonstrate this potential for abuse: a study on the effectiveness of vitamin E in reducing cardiovascular risk and comparisons of low fat and low carbohydrate diets. In the first case, a treatment that is demonstrably effective is described as without merit. In the second, ITT describes as the same, two diets that actually have different outcomes. These misuses of ITT are not atypical and are not technical problems in statistics but have real consequences for scientific principles and health recommendations. ITT analyses may answer the question of what happens when treatments are recommended but are inappropriate where separate information on adherence and performance is available. It is proposed that results of RCTs, or any experimental study, be reported, not in terms of the analyses that were performed, but rather in terms of the questions that the analyses can answer properly.

Explicit Knowledge-based Reasoning for Visual Question Answering

OpenAIRE

Wang, Peng; Wu, Qi; Shen, Chunhua; Hengel, Anton van den; Dick, Anthony

2015-01-01

We describe a method for visual question answering which is capable of reasoning about contents of an image on the basis of information extracted from a large-scale knowledge base. The method not only answers natural language questions using concepts not contained in the image, but can provide an explanation of the reasoning by which it developed its answer. The method is capable of answering far more complex questions than the predominant long short-term memory-based approach, and outperform...

Doença de Creutzfeldt-Jakob: a propósito de um caso com comprometimento medular Creutzfeldt-Jakob disease: case report with spinal cord involvement

Directory of Open Access Journals (Sweden)

Marlos Fábio Alves de Azevedo

2001-12-01

Full Text Available A doença de Creutzfeldt-Jakob (DCJ é a encefalopatia espongiforme subaguda transmissível mais frequente nos seres humanos. Aproximadamente 85% dos casos pertencem à forma esporádica da doença. Os outros 15% consistem na forma genética e iatrogênica. Relatamos o caso de uma paciente com a forma esporádica da doença de Creutzfeldt-Jakob, com comprometimento medular e apresentação clínica caracterizada por síndrome demencial e cerebelar, miofasciculação com arreflexia difusa e crises convulsivas do tipo tônico-clônico generalizada. É rara a associação das duas últimas manifestações clínicas. O caso foi considerado como provável DCJ até confirmação por autópsia e imunohistoquímica. Concluímos que se deve sempre pensar na DCJ em pacientes que apresentam demência rapidamente progressiva e, na ausência de sinais piramidais ou extrapiramidais, pensar em acometimento periférico e/ou medular.Creutzfeldt-Jakob disease (CJD is the most common subacute transmissible spongiform encephalopathy. Approximately 85% of the cases are sporadic. The remaining 15% consist of genetic and iatrogenic forms. We report a sporadic form of CJD with spinal cord involvement and a clinical manifestation characterized by dementia and cerebellar syndrome, myofasciculation with absent reflexes and seizures. The two last manifestations are rare. The clinical hypothesis was probable CJD which was confirmed with autopsy and immunohistochemistry. We conclude that CJD should always be suspected when rapidly progressive dementia occurs and the absence of pyramidal or extrapyramidal signs suggest a spinal cord and/or peripheral nerve involvement.

Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.

Science.gov (United States)

Foutz, Aaron; Appleby, Brian S; Hamlin, Clive; Liu, Xiaoqin; Yang, Sheng; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Fausett, Cameron; Wang, Han; Gambetti, Pierluigi; Zhang, Shulin; Hughson, Andrew; Tatsuoka, Curtis; Schonberger, Lawrence B; Cohen, Mark L; Caughey, Byron; Safar, Jiri G

2017-01-01

Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion seeding activity with second-generation real-time quaking-induced conversion (RT-QuIC). The objective of this study was to investigate the diagnostic performance of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases. We performed CSF RT-QuIC testing in 2,141 patients who had rapidly progressive neurological disorders, determined diagnostic sensitivity and specificity in 272 cases that were autopsied, and evaluated the impact of mutations and polymorphisms in the PRNP gene, and type 1 or type 2 human prions on diagnostic performance. The 98.5% diagnostic specificity and 92% sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100% specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1-2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC patterns, whereas genetic prion diseases revealed distinct profiles for each PRNP gene mutation. The diagnostic performance of the improved CSF RT-QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and tau proteins, and together with PRNP gene sequencing the test allows the major prion subtypes to be differentiated in vivo. This differentiation facilitates prediction of the clinicopathological phenotype and duration of the disease-two important considerations for envisioned therapeutic interventions. ANN NEUROL 2017;81:79-92. © 2016 American Neurological Association.

Questioning the Universe concepts in physics

CERN Document Server

Sadoff, Ahren

2008-01-01

UNITS AND POWERS OF TEN PHYSICS AND ITS METHODOLOGY  What Is Physics? Methodology The First Scientist Why Do You Believe? Back to the Questions How Do We Answer theQuestions? The Need to BeQuantitative Theories Models AestheticJudgments  MOTION Relating the Variables of Motion Graphs of One-Dimensional Motion Constant Speed Constant Acceleration Two-Dimensional Motion FORCES The Fundamental Forces A Specific Force Law: Newtonian Gravity Weight How Does Force Affect Motion? Newton's SecondLaw Newton, the Apple, and the Moon Combining Two Laws The Mass of the Earth Newton's Firs

The Role of Teacher Questions in the Chemistry Classroom

Science.gov (United States)

Dohrn, Sofie Weiss; Dohn, Niels Bonderup

2018-01-01

The purpose of this study was to investigate how a chemistry teacher's questions influence the classroom discourse. It presents a fine-grained analysis of the rich variety of one teacher's questions and the roles they play in an upper secondary chemistry classroom. The study identifies six different functions for the teacher's questions:…

Interview Questions with Bentham Scientific

Science.gov (United States)

Mather, John C.

2013-01-01

John Mather answers questions for an interview for the Bentham Science Newsletter. He covers topics ranging from his childhood, his professional career and his thoughts on research, technology and today's scientists and engineers.

Ontologies and adaptivity in dialogue for question answering

CERN Document Server

Sonntag, D

2010-01-01

Question answering (QA) has become one of the fastest growing topics in computational linguistics and information access. To advance research in the area of dialogue-based question answering, we propose a combination of methods from different scientific fields (i.e., Information Retrieval, Dialogue Systems, Semantic Web, and Machine Learning). This book sheds light on adaptable dialogue-based question answering. We demonstrate the technical and computational feasibility of the proposed ideas, the introspective methods in particular, by beginning with an extensive introduction to the dialogical

Long-term preclinical magnetic resonance imaging alterations in sporadic Creutzfeldt-Jakob disease.

Science.gov (United States)

Zanusso, Gianluigi; Camporese, Giulia; Ferrari, Sergio; Santelli, Luca; Bongianni, Matilde; Fiorini, Michele; Monaco, Salvatore; Manara, Renzo; Cagnin, Annachiara

2016-10-01

An asymptomatic 74-year-old woman, on follow-up for a carotid body tumor, showed magnetic resonance imaging (MRI) focal restricted diffusion confined to the left temporal and occipital cortices. Thirteen months later, diffusion-weighted images revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the patient developed gait instability and cognitive decline rapidly evolving to severe dementia and death within 3 months. Prion protein gene sequence, molecular, and neuropathological studies confirmed the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629-632. © 2016 American Neurological Association.

Human growth hormone-related latrogenic Creutzfeldt-Jakob disease: Search for a genetic susceptibility by analysis of the PRNP coding region

Energy Technology Data Exchange (ETDEWEB)

Jaegly, A.; Boussin, F.; Deslys, J.P. [CEA/CRSSA/DSV/DPTE, Fontenay-aux-Roses (France)] [and others

1995-05-20

The human PRNP gene encoding PrP is located on chromosome 20 and consists of two exons and a single intron. The open reading frame is entirely fitted into the second exon. Genetic studies indicate that all of the familial and several sporadic forms of TSSEs are associated with mutations in the PRNP 759-bp coding region. Moreover, homozygosity at codon 129, a locus harboring a polymorphism among the general population, was proposed as a genetic susceptibility marker for both sporadic and iatrogenic CJD. To assess whether additional genetic predisposition markers exist in the PRNP gene, the authors sequenced the PRNP coding region of 17 of the 32 French patients who developed a hGH-related CJD.

Fostering Effective Studying and Study Planning with Study Questions

Science.gov (United States)

Wilhelm, Pascal; Pieters, Jules M.

2007-01-01

In a course on biological psychology and neuropsychology, study questions were provided that also appeared as test questions in the course exam. This method was introduced to support students in active processing and reproduction of the study texts, and study planning. Data were gathered to test the hypothesis that study question use would be…

Climate Leadership Awards Frequent Questions

Science.gov (United States)

Provides answers to frequently asked questions regarding the Climate Leadership Awards, sponsored by EPA's Center for Corporate Climate Leadership with co-sponsorship from the Center for Climate and Energy Solutions and The Climate Registry.

Question Inventory on Tobacco (QIT)

Data.gov (United States)

U.S. Department of Health & Human Services — 1965, 1966, 1970, 1974-2017. Centers for Disease Control and Prevention (CDC). Office on Smoking and Health (OSH). Tobacco-Related Survey Questions. The QIT is a...

The use of categorization information in language models for question retrieval

DEFF Research Database (Denmark)

Cao, Xin; Cong, Gao; Cui, Bin

2009-01-01

Community Question Answering (CQA) has emerged as a popular type of service meeting a wide range of information needs. Such services enable users to ask and answer questions and to access existing question-answer pairs. CQA archives contain very large volumes of valuable user-generated content...... and have become important information resources on the Web. To make the body of knowledge accumulated in CQA archives accessible, effective and efficient question search is required. Question search in a CQA archive aims to retrieve historical questions that are relevant to new questions posed by users...

Key Questions in Marine Megafauna Movement Ecology

KAUST Repository

Hays, Graeme C.; Ferreira, Luciana C.; Sequeira, Ana M.M.; Meekan, Mark G.; Duarte, Carlos M.; Bailey, Helen; Bailleul, Fred; Bowen, W. Don; Caley, M. Julian; Costa, Daniel P.; Eguí luz, Victor M.; Fossette, Sabrina; Friedlaender, Ari S.; Gales, Nick; Gleiss, Adrian C.; Gunn, John; Harcourt, Rob; Hazen, Elliott L.; Heithaus, Michael R.; Heupel, Michelle; Holland, Kim; Horning, Markus; Jonsen, Ian; Kooyman, Gerald L.; Lowe, Christopher G.; Madsen, Peter T.; Marsh, Helene; Phillips, Richard A.; Righton, David; Ropert-Coudert, Yan; Sato, Katsufumi; Shaffer, Scott A.; Simpfendorfer, Colin A.; Sims, David W.; Skomal, Gregory; Takahashi, Akinori; Trathan, Philip N.; Wikelski, Martin; Womble, Jamie N.; Thums, Michele

2016-01-01

It is a golden age for animal movement studies and so an opportune time to assess priorities for future work. We assembled 40 experts to identify key questions in this field, focussing on marine megafauna, which include a broad range of birds, mammals, reptiles, and fish. Research on these taxa has both underpinned many of the recent technical developments and led to fundamental discoveries in the field. We show that the questions have broad applicability to other taxa, including terrestrial animals, flying insects, and swimming invertebrates, and, as such, this exercise provides a useful roadmap for targeted deployments and data syntheses that should advance the field of movement ecology. Technical advances make this an exciting time for animal movement studies, with a range of small, reliable data-loggers and transmitters that can record horizontal and vertical movements as well as aspects of physiology and reproductive biology.Forty experts identified key questions in the field of movement ecology.Questions have broad applicability across species, habitats, and spatial scales, and apply to animals in both marine and terrestrial habitats as well as both vertebrates and invertebrates, including birds, mammals, reptiles, fish, insects, and plankton. © 2016 Elsevier Ltd.

Key Questions in Marine Megafauna Movement Ecology

KAUST Repository

Hays, Graeme C.

2016-03-12

It is a golden age for animal movement studies and so an opportune time to assess priorities for future work. We assembled 40 experts to identify key questions in this field, focussing on marine megafauna, which include a broad range of birds, mammals, reptiles, and fish. Research on these taxa has both underpinned many of the recent technical developments and led to fundamental discoveries in the field. We show that the questions have broad applicability to other taxa, including terrestrial animals, flying insects, and swimming invertebrates, and, as such, this exercise provides a useful roadmap for targeted deployments and data syntheses that should advance the field of movement ecology. Technical advances make this an exciting time for animal movement studies, with a range of small, reliable data-loggers and transmitters that can record horizontal and vertical movements as well as aspects of physiology and reproductive biology.Forty experts identified key questions in the field of movement ecology.Questions have broad applicability across species, habitats, and spatial scales, and apply to animals in both marine and terrestrial habitats as well as both vertebrates and invertebrates, including birds, mammals, reptiles, fish, insects, and plankton. © 2016 Elsevier Ltd.

Assessing the psychometric questioner for students rating teachers

Directory of Open Access Journals (Sweden)

Razaghi Reza Sharif

2016-07-01

Full Text Available Educational institutions use different ways to evaluate their teachers. Asking students to rate their teachers is common practice. The purpose of this research was to examine the reliability of the instruments used to evaluate the instructors in a college of medicine. This cross-sectional descriptive research used questioners that evaluated instructors. The questioner was targeting different dimensions of instructors. Item analysis in addition to exploratory factor analysis was performed on 1040questioners answered by the students of the College of Medicine of Kashan University of Medical Sciences. SPSS software was used to perform the analysis. The psychometric properties of questionnaires including Cronbach alpha was determined. The result of exploratory factor analysis and item analysis indicated that three of the subscales of the questioner showed sufficient reliability to evaluate the instructors and two subscales needed further examination. This type of evaluations is necessary to ensure quality of instructors working in an institution as well as providing reliable feedback to the instructors. The result showed that while some subscales of the questioner seems to target the concept of interest; a re-evaluation of the instrument would be valuable to increase its reliability for the administrators in the colleges.

Will a Black Hole Eventually Swallow Earth?” Fifth Graders' Interest in Questions from a Textbook, an Open Educational Resource and Other Students' Questions

Directory of Open Access Journals (Sweden)

Hani Swirski

2015-12-01

Full Text Available Can questions sent to Open-Educational-Resource (OER websites such as Ask-An-Expert serve as indicators for students’ interest in science? This issue was examined using an online questionnaire which included an equal number of questions about the topics “space” and “nutrition” randomly selected from three different sources: a 5th-grade science textbook, the “Ask-An-Expert” website, and questions collected from other students in the same age group. A sample of 113 5th-graders from two elementary schools were asked to rate their interest level in finding out the answer to these questions without knowledge of their source. Significant differences in students’ interest level were found between questions: textbook questions were ranked lowest for both subjects, and questions from the open-resource were ranked high. This finding suggests that questions sent to an open-resource could be used as an indicator of students’ interest in science. In addition, the high correlation of interests expressed by students from the two schools may point to a potential generalization of the findings. This study contributes by highlighting OER as a new and promising indicator of student interest, which may help bring “student voices” into mainstream science teaching to increase student interest in science.

Questions related to Bitcoin and other Informational Money

NARCIS (Netherlands)

Bergstra, J.A.; de Leeuw, K.

2013-01-01

A collection of questions about Bitcoin and its hypothetical relatives Bitguilder and Bitpenny is formulated. These questions concern technical issues about protocols, security issues, issues about the formalizations of informational monies in various contexts, and issues about forms of use and

Importance of questionnaire context for a physical activity question

DEFF Research Database (Denmark)

Jørgensen, M. E.; Sørensen, Mette Rosenlund; Ekholm, O.

2013-01-01

; however, this has never been shown for physical activity questions. The aim was to study the influence of different formulations and question order on self-report physical activity in a population-based health interview survey. Four samples of each 1000 adults were drawn at random from the National Person......Adequate information about physical activity habits is essential for surveillance, implementing, and evaluating public health initiatives in this area. Previous studies have shown that question order and differences in wording result in systematic differences in people's responses to questionnaires...... Register. A new question about physical activity was included with minor differences in formulations in samples 1–3. Furthermore, the question in sample 2 was included in sample 4 but was placed in the end of the questionnaire. The mean time spent on moderate physical activity varied between the four...

Questions for the nuclear installations inspectorate

International Nuclear Information System (INIS)

Conroy, C.; Flood, M.; MacRory, R.; Patterson, W.C.

1976-01-01

The responsibilities of the Nuclear Installations Inspectorate are considered, and the responsibilities of other bodies for (a) reprocessing and enrichment, and (b) security. Questions for the Nuclear Installations Inspectorate are then set out under the following heads: general (on such topics as vandalism, sabotage, threats, security, reactor incidents); magnox reactors; corrosion; advanced gas-cooled reactor; steam generating heavy water reactor; fast breeder reactor; reproces-sing and waste. Most of the questions are concerned with technical problems that have been reported or might possibly arise during construction or operation, affecting the safety of the reactor or process. (U.K.)

On the comprehensibility and perceived privacy protection of indirect questioning techniques.

Science.gov (United States)

Hoffmann, Adrian; Waubert de Puiseau, Berenike; Schmidt, Alexander F; Musch, Jochen

2017-08-01

On surveys that assess sensitive personal attributes, indirect questioning aims at increasing respondents' willingness to answer truthfully by protecting confidentiality. However, the assumption that subjects understand questioning procedures fully and trust them to protect their privacy is rarely tested. In a scenario-based design, we compared four indirect questioning procedures in terms of their comprehensibility and perceived privacy protection. All indirect questioning techniques were found to be less comprehensible by respondents than a conventional direct question used for comparison. Less-educated respondents experienced more difficulties when confronted with any indirect questioning technique. Regardless of education, the crosswise model was found to be the most comprehensible among the four indirect methods. Indirect questioning in general was perceived to increase privacy protection in comparison to a direct question. Unexpectedly, comprehension and perceived privacy protection did not correlate. We recommend assessing these factors separately in future evaluations of indirect questioning.

RESULTS OF THE QUALITATIVE QUESTIONS

International Development Research Centre (IDRC) Digital Library (Canada)

Adam Graham

In April of 2005, Governance, Equity and Health (GEH) held an all-partners' ... data collected – six respondents left a blank response for the question addressing level of ... Meeting participants were organized into five thematic working groups:.

A Flexible Question-and-Answer Task for Measuring Speech Understanding

Directory of Open Access Journals (Sweden)

Virginia Best

2016-11-01

Full Text Available This report introduces a new speech task based on simple questions and answers. The task differs from a traditional sentence recall task in that it involves an element of comprehension and can be implemented in an ongoing fashion. It also contains two target items (the question and the answer that may be associated with different voices and locations to create dynamic listening scenarios. A set of 227 questions was created, covering six broad categories (days of the week, months of the year, numbers, colors, opposites, and sizes. All questions and their one-word answers were spoken by 11 female and 11 male talkers. In this study, listeners were presented with question-answer pairs and asked to indicate whether the answer was true or false. Responses were given as simple button or key presses, which are quick to make and easy to score. Two preliminary experiments are presented that illustrate different ways of implementing the basic task. In the first experiment, question-answer pairs were presented in speech-shaped noise, and performance was compared across subjects, question categories, and time, to examine the different sources of variability. In the second experiment, sequences of question-answer pairs were presented amidst competing conversations in an ongoing, spatially dynamic listening scenario. Overall, the question-and-answer task appears to be feasible and could be implemented flexibly in a number of different ways.

IMPROVISATION OF SEEKER SATISFACTION IN YAHOO! COMMUNITY QUESTION ANSWERING PORTAL

Directory of Open Access Journals (Sweden)

K. Latha

2011-01-01

Full Text Available One popular Community question answering (CQA site, Yahoo! Answers, had attracted 120 million users worldwide, and had 400 million answers to questions available. A typical characteristic of such sites is that they allow anyone to post or answer any questions on any subject. Question Answering Community has emerged as popular, and often effective, means of information seeking on the web. By posting questions, for other participants to answer, information seekers can obtain specific answers to their questions. However, CQA is not always effective: in some cases, a user may obtain a perfect answer within minutes, and in others it may require hours and sometimes days until a satisfactory answer is contributed. We investigate the problem of predicting information seeker satisfaction in yahoo collaborative question answering communities, where we attempt to predict whether a question author will be satisfied with the answers submitted by the community participants. Our experimental results, obtained from a large scale evaluation over thousands of real questions and user ratings, demonstrate the feasibility of modeling and predicting asker satisfaction. We complement our results with a thorough investigation of the interactions and information seeking patterns in question answering communities that correlate with information seeker satisfaction. We also explore automatic ranking, creating abstract from retrieved answers, and history updation, which aims to provide users with what they want or need without explicitly ask them for user satisfaction. Our system could be useful for a variety of applications, such as answer selection, user feedback analysis, and ranking.

Wh-interrogative formats used for questioning and beyond

DEFF Research Database (Denmark)

Egbert, Maria; Vöge, Monika

2008-01-01

This paper contributes to a critical discussion of how ‘question' and ‘questioning' may be defined in terms of form and function by analyzing the interactional usage of two apparently synonymous ‘question' words, German warum (why) and wieso (why) and their common English translation why. Warum...... of German warum and wieso with English why (Schegloff 1984, Clayman and Heritage 2002a, Koshik 2003) shows that why allows for ambiguity, whereas warum and wieso are unambiguous. While there is a core usage of these lexical items, they are also employed differently with an orientation to institutionality...

Trick questions: cosmopolitan hospitality

Directory of Open Access Journals (Sweden)

Eleanor Byrne

2013-08-01

Full Text Available Byrne’s paper consists of two parallel texts. The first explores the limits of cosmopolitanism in practice, taking as its subject the Life in the UK Citizenship Test, inaugurated under the Labour Government in 2005. It argues that the test exemplifies the predicament of all attempts at cosmopolitan hospitality as unconditional welcoming, through a discussion of the relation between questioning and welcoming the stranger. Establishing the relationship between cosmopolitanism and hospitality as envisaged in Derrida’s reading of Kant it asks what kind of cosmopolitan hospitality is either possible or desirable by exploring what Derrida calls the ‘perversions’ inherent in the structures of hospitality. It focuses on the concept of the ‘trick questions’ that the state asks the foreigner observed by Derrida in his reading of The Apology of Socrates; questions that seem to invite answers but foreclose the possibilities of a free response. The second text asks how this logic that Derrida identifies can be pushed or coaxed into new ways of addressing the perceived threats of ‘unconditional’ hospitality through a reading of ‘unconditional hospitality’ as queer in the work of Tove Jansson.

Continuing the Conversation: Questions about the Framework

Directory of Open Access Journals (Sweden)

Megan E. Dempsey

2015-12-01

Full Text Available Given the prevalence of the Information Literacy Competency Standards in the library profession for the past 15 years, and the heated debate that took place regarding whether or not the Framework for Information Literacy and the Standards could harmoniously co-exist, the article raises questions about the future of information literacy in higher education. We do not necessarily have answers to these questions, but offer our own perspectives, some insight into how the Standards have served New Jersey academic librarians in the past, and how we envision using the Framework and the Standards together to further information literacy instruction at our institutions. Discussions of these questions have led us to the conclusion that the Framework and the Standards serve different purposes and have different intended audiences and are thus both valuable to the library profession.

The use of questions as problem-solving strategies during early childhood.

Science.gov (United States)

Legare, Cristine H; Mills, Candice M; Souza, André L; Plummer, Leigh E; Yasskin, Rebecca

2013-01-01

This study examined the strategic use of questions to solve problems across early childhood. Participants (N=54, 4-, 5-, and 6-year-olds) engaged in two tasks: a novel problem-solving question task that required asking questions to an informant to determine which card in an array was located in a box and a cognitive flexibility task that required classifying stimuli by multiple dimensions. The results from the question task indicated that there were age differences in the types of questions asked, with 6-year-olds asking more constraint-seeking questions than 4- and 5-year-olds. The number of constraint-seeking questions asked was the only significant predictor of accuracy. Performance on the cognitive flexibility task correlated with both constraint-seeking strategy use and accuracy in the question task. In sum, our results provide evidence that the capacity to use questions to generate relevant information develops before the capacity to apply this information successfully and consistently to solve complex problems. We propose that the process of using questions as strategic tools is an ideal context for examining how children come to gain active and intentional control over problem solving. Copyright © 2012 Elsevier Inc. All rights reserved.

Automatic Generation System of Multiple-Choice Cloze Questions and its Evaluation

Directory of Open Access Journals (Sweden)

Takuya Goto

2010-09-01

Full Text Available Since English expressions vary according to the genres, it is important for students to study questions that are generated from sentences of the target genre. Although various questions are prepared, it is still not enough to satisfy various genres which students want to learn. On the other hand, when producing English questions, sufficient grammatical knowledge and vocabulary are needed, so it is difficult for non-expert to prepare English questions by themselves. In this paper, we propose an automatic generation system of multiple-choice cloze questions from English texts. Empirical knowledge is necessary to produce appropriate questions, so machine learning is introduced to acquire knowledge from existing questions. To generate the questions from texts automatically, the system (1 extracts appropriate sentences for questions from texts based on Preference Learning, (2 estimates a blank part based on Conditional Random Field, and (3 generates distracters based on statistical patterns of existing questions. Experimental results show our method is workable for selecting appropriate sentences and blank part. Moreover, our method is appropriate to generate the available distracters, especially for the sentence that does not contain the proper noun.

Can Questions Facilitate Learning from Illustrated Science Texts?

Science.gov (United States)

Iding, Marie K.

1997-01-01

Examines the effectiveness of using questions to facilitate processing of diagrams in science texts. Investigates three different elements in experiments on college students. Finds that questions about illustrations do not facilitate learning. Discusses findings with reference to cognitive load theory, the dual coding perspective, and the…

Open Questions Limiting the Practice of Interorganizational Development.

Science.gov (United States)

Schermerhorn, John R., Jr.

1981-01-01

Summarizes the open questions that must be answered by researchers if practioners of interorganizational development are to have adequate planning-and-action guidelines. Suggests the questions should help practitioners become more sensitive to potential action considerations that may require special thought and attention until a firmer knowledge…

Multiple choice questions in electronics and electrical engineering

CERN Document Server

DAVIES, T J

2013-01-01

A unique compendium of over 2000 multiple choice questions for students of electronics and electrical engineering. This book is designed for the following City and Guilds courses: 2010, 2240, 2320, 2360. It can also be used as a resource for practice questions for any vocational course.

Do older adults change their eyewitness reports when re-questioned?

Science.gov (United States)

Henkel, Linda A

2014-05-01

This study examined how older adults responded to different types of pressure to change their responses when questioned a second time about their memory for a crime. After watching a video of a crime and answering questions about remembered details, younger (18-22 years) and older adults (64-91 years) were either given negative feedback about their memory performance, were told that most people their age did poorly on the memory test (stereotype threat), or were simply asked to answer the questions again. This was done regardless of their actual accuracy, and the questions were then repeated. Results showed that both younger and older adults changed significantly more responses following negative feedback and changed more responses on misleading than on nonleading questions. Among older adults, as age increased, accuracy decreased and rate of response change increased. People were moderately confident overall about both their correct and incorrect responses. These results highlight the dangers of repeatedly questioning older witnesses with misleading questions and suggest that the responses that are changed may come to be remembered confidently-regardless of whether they are correct or incorrect.

On the intonation of German intonation questions

DEFF Research Database (Denmark)

Petrone, Caterina; Niebuhr, Oliver

2014-01-01

German questions and statements are distinguished not only by lexical and syntactic but also by intonational means. This study revisits, for Northern Standard German, how questions are signalled intonationally in utterances that have neither lexical nor syntactic cues. Starting from natural......, but represents a separate attitudinal meaning dimension. Moreover, the findings support that both prenuclear and nuclear fundamental frequency (F0) patterns must be taken into account in the analysis of tune meaning....

Some open questions in 'wave chaos'

International Nuclear Information System (INIS)

Nonnenmacher, Stéphane

2008-01-01

The subject area referred to as 'wave chaos', 'quantum chaos' or 'quantum chaology' has been investigated mostly by the theoretical physics community in the last 30 years. The questions it raises have more recently also attracted the attention of mathematicians and mathematical physicists, due to connections with number theory, graph theory, Riemannian, hyperbolic or complex geometry, classical dynamical systems, probability, etc. After giving a rough account on 'what is quantum chaos?', I intend to list some pending questions, some of them having been raised a long time ago, some others more recent. The choice of problems (and of references) is of course partial and personal. (open problem)

An Examination of Music Teacher Job Interview Questions

Science.gov (United States)

Juchniewicz, Jay

2016-01-01

The purpose of this study was to examine which interview questions principals consider most important when interviewing prospective music teachers. Additionally, data were examined to determine any differences between school grade level, school setting, or years of experience as a principal in preferences for specific interview questions.…

Questions answers renewable energies (02/08/99); Questions reponses energies renouvelables (02/08/99)

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

This document collected some questions about the use of renewable energies sources in the domain of the financial and technical assistance of the customer by EDF (photovoltaic cells or wind turbines for residential houses) and for electrification of independent sites which are not connected to EDF power grid. (A.L.B.)