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

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

Five-year review of an international clinical research-training program

The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Early detection of left ventricular diastolic dysfunction in Chagas' disease

BACKGROUND: Chagas' disease may cause left ventricular diastolic dysfunction and its early detection in asymptomatic patients would allow to stratify the risk and to optimize medical treatment. The aim of this study is to investigate if transmitral Doppler flow can detect early abnormalities of the diastolic left ventricular function in patients during the indeterminate phase of Chagas' disease, in which the electrocardiogram (ECG), chest x-ray and 2-D echocardiogram (2D-echo) are normal. METHODS: a group of 54 patients with Chagas' disease was studied and compared to a control group of 27 subjects of similar age. All were assessed with an ECG, chest X-ray, 2-D echo, and transmitral Doppler flow. RESULTS: both groups had similar values in the 2D-echo. In patients with Chagas' disease, the transmitral Doppler showed a higher peak A velocity (control group: 0.44 m/sec, Chagas group: 0.55 m/sec, p = 0.001), a lower E/A ratio (control group: 1.45, Chagas group: 1.22, p < 0.05), and a lengthening of the deceleration time of early diastolic filling (control: 138.7 ± 26.8 msec, Chagas group: 167.9 ± 34.6 msec, p = 001), thus revealing an early disorder of the diastolic left ventricular function in patients with Chagas' disease. CONCLUSION: in patients with Chagas' disease who are in the indeterminate phase, transmitral Doppler flow allowed to identify early abnormalities of the left ventricular diastolic function, which provide useful clinical information for prognostic stratification and treatment

Summary of the BDS and MDI CLIC08 Working Group

This note summarizes the presentations held within the Beam Delivery System and Machine Detector Interface working group of the CLIC08 workshop. The written contributions have been provided by the presenters on a voluntary basis

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

<p>Abstract</p> <p>Background</p> <p>The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of <it>Helicobacter pylori </it>(<it>H. pylori)</it>. This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of <it>H. pylori </it>eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole.</p> <p>Methods</p> <p>Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and <it>H. pylori </it>infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval.</p> <p>Results</p> <p>The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high.</p> <p>Conclusion</p> <p>Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for <it>H. pylori </it>infection.</p

Giant intrinsic photoresponse in pristine graphene

When the Fermi level matches the Dirac point in graphene, the reduced charge screening can dramatically enhance electron-electron (e-e) scattering to produce a strongly interacting Dirac liquid. While the dominance of e-e scattering already leads to novel behaviors, such as electron hydrodynamic flow, further exotic phenomena have been predicted to arise specifically from the unique kinematics of e-e scattering in massless Dirac systems. Here, we use optoelectronic probes, which are highly sensitive to the kinematics of electron scattering, to uncover a giant intrinsic photocurrent response in pristine graphene. This photocurrent emerges exclusively at the charge neutrality point and vanishes abruptly at non-zero charge densities. Moreover, it is observed at places with broken reflection symmetry, and it is selectively enhanced at free graphene edges with sharp bends. Our findings reveal that the photocurrent relaxation is strongly suppressed by a drastic change of fast photocarrier kinematics in graphene when its Fermi level matches the Dirac point. The emergence of robust photocurrents in neutral Dirac materials promises new energy-harvesting functionalities and highlights intriguing electron dynamics in the optoelectronic response of Dirac fluids.Comment: Originally submitted versio

Monoculture of Leafcutter Ant Gardens

Background -- Leafcutter ants depend on the cultivation of symbiotic Attamyces fungi for food, which are thought to be grown by the ants in single-strain, clonal monoculture throughout the hundreds to thousands of gardens within a leafcutter nest. Monoculture eliminates cultivar-cultivar competition that would select for competitive fungal traits that are detrimental to the ants, whereas polyculture of several fungi could increase nutritional diversity and disease resistance of genetically variable gardens. Methodology/Principal Findings -- Using three experimental approaches, we assessed cultivar diversity within nests of Atta leafcutter ants, which are most likely among all fungus-growing ants to cultivate distinct cultivar genotypes per nest because of the nests' enormous sizes (up to 5000 gardens) and extended lifespans (10–20 years). In Atta texana and in A. cephalotes, we resampled nests over a 5-year period to test for persistence of resident cultivar genotypes within each nest, and we tested for genetic differences between fungi from different nest sectors accessed through excavation. In A. texana, we also determined the number of Attamyces cells carried as a starter inoculum by a dispersing queens (minimally several thousand Attamyces cells), and we tested for genetic differences between Attamyces carried by sister queens dispersing from the same nest. Except for mutational variation arising during clonal Attamyces propagation, DNA fingerprinting revealed no evidence for fungal polyculture and no genotype turnover during the 5-year surveys. Conclusions/Significance -- Atta leafcutter ants can achieve stable, fungal monoculture over many years. Mutational variation emerging within an Attamyces monoculture could provide genetic diversity for symbiont choice (gardening biases of the ants favoring specific mutational variants), an analog of artificial selection.The research was supported by National Science Foundation awards DEB-0920138, DEB-0639879, and DEB-0110073 to UGM; DEB-0949689 to T.R. Schultz, N. Mehdiabadi, and UGM; and a Fellowship (02/05) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico to AR. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o