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The Brief Memory and Executive Test (BMET) for detecting vascular cognitive impairment in small vessel disease: a validation study.
Cognitive impairment is common in patients with cerebral small vessel disease, but is not well detected using common cognitive screening tests which have been primarily devised for cortical dementias. We developed the Brief Memory and Executive Test (BMET); a rapid screening measure sensitive to the impaired executive function and processing speed characteristic of small vessel disease (SVD). To assess the BMET's validity for general use, we evaluated it when administered by non-psychologists in a multicentre study and collected control data to derive normative scores.The BMET study was funded by The Stroke Association (TSA2010/08). Recruitment to BMET was supported by the NIHR Stroke Clinical Research Network. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Comprehensive BRC. Matthew Hollocks is supported by a Stroke Association/British Heart Foundation Grant (TSA BHF 2010/01). Robin Morris receives consultancy fees for P1Vital Limited. The authors disclose no competing interests financial or otherwise
Effects of Epistasis and Pleiotropy on Fitness Landscapes
The factors that influence genetic architecture shape the structure of the
fitness landscape, and therefore play a large role in the evolutionary
dynamics. Here the NK model is used to investigate how epistasis and pleiotropy
-- key components of genetic architecture -- affect the structure of the
fitness landscape, and how they affect the ability of evolving populations to
adapt despite the difficulty of crossing valleys present in rugged landscapes.
Populations are seen to make use of epistatic interactions and pleiotropy to
attain higher fitness, and are not inhibited by the fact that valleys have to
be crossed to reach peaks of higher fitness.Comment: 10 pages, 6 figures. To appear in "Origin of Life and Evolutionary
Mechanisms" (P. Pontarotti, ed.). Evolutionary Biology: 16th Meeting 2012,
Springer-Verla
Development of a residency program in radiation oncology physics: an inverse planning approach
Combining data-driven and domain knowledge components in an intelligent assistant to build personalized menus
In this paper, some new components that have been integrated in the Diet4You system for the generation of nutritional plans are introduced. Negative user preferences have been modelled and introduced in the system. Furthermore, the cultural eating styles originated from the location where the user lives have been taken into account dividing the original menu plan in sub-plans. Each sub-plan is in charge to optimize one of the meals of one day in the personal menu of the user. The main latent reasoning mechanism used is case-based reasoning, which reuses previous menu configurations according to the nutritional plan and the corresponding hard constraints and the user preferences to meet a personalized recommendation menu for a given user. It uses the cognitive analogical reasoning technique in addition to ontologies, nutritional databases and expert knowledge. The preliminary results with some examples of application to test the new contextual components have been very satisfactory according to the evaluation of the experts.This work has been partially supported by the project Diet4You (TIN2014-60557-R), the Spanish Thematic Network MAPAS [TIN2017-90567-REDT (MINECO/FEDER EU)], and the Consolidated Research Group Grant from AGAUR (Generalitat de Catalunya) IDEAI-UPC (AGAUR SGR2017-574).Peer ReviewedPostprint (author's final draft
What If Your Car Would Care? Exploring Use Cases For Affective Automotive User Interfaces
In this paper we present use cases for affective user interfaces (UIs) in
cars and how they are perceived by potential users in China and Germany.
Emotion-aware interaction is enabled by the improvement of ubiquitous sensing
methods and provides potential benefits for both traffic safety and personal
well-being. To promote the adoption of affective interaction at an
international scale, we developed 20 mobile in-car use cases through an
inter-cultural design approach and evaluated them with 65 drivers in Germany
and China. Our data shows perceived benefits in specific areas of pragmatic
quality as well as cultural differences, especially for socially interactive
use cases. We also discuss general implications for future affective automotive
UI. Our results provide a perspective on cultural peculiarities and a concrete
starting point for practitioners and researchers working on emotion-aware
interfaces
Crystal sedimentation and stone formation
Mechanisms of crystal collision being the first step of aggregation (AGN) were analyzed for calcium oxalate monohydrate (COM) directly produced in urine. COM was produced by oxalate titration in urine of seven healthy men, in solutions of urinary macromolecules and in buffered distilled water (control). Crystal formation and sedimentation were followed by a spectrophotometer and analyzed by scanning electron microscopy. Viscosity of urine was measured at 37°C. From results, sedimentation rate (vS), particle diffusion (D) and incidences of collision of particles in suspension by sedimentation (IS) and by diffusion (ID) were calculated. Calculations were related to average volume and urinary transit time of renal collecting ducts (CD) and of renal pelvis. vS was in urine 0.026 ± 0.012, in UMS 0.022 ± 0.01 and in control 0.091 ± 0.02 cm min−1 (mean ± SD). For urine, a D of 9.53 ± 0.97 μm within 1 min can be calculated. At maximal crystal concentration, IS was only 0.12 and ID was 0.48 min−1 cm−3 which, even at an unrealistic permanent and maximal crystalluria, would only correspond to less than one crystal collision/week/CD, whereas to the same tubular wall being in horizontal position 1.3 crystals/min and to a renal stone 624 crystals/cm2 min could drop by sedimentation. Sedimentation to renal tubular or pelvic wall, where crystals can accumulate and meet with a tissue calcification or a stone, is probably essential for stone formation. Since vS mainly depends on particle size, reducing urinary supersaturation and crystal growth by dietary oxalate restriction seems to be an important measure to prevent aggregation
Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications
<p>Abstract</p> <p>Background</p> <p>Autoantibodies against glutamate decarboxylase-65 (GAD<sub>65</sub>Abs) are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD<sub>65</sub>Abs are a sensitive and specific marker for type 1 diabetes (T1D). These autoantibodies can also be found in 6-10% of patients classified with type 2 diabetes (T2D), as well as in 1-2% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD<sub>65</sub>Abs is only about 0.3%. It has, therefore, been suggested that the antibody binding to GAD<sub>65 </sub>in these three different GAD<sub>65</sub>Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD<sub>65 </sub>(ROS-GAD<sub>65</sub>) is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD<sub>65 </sub>(ROS-GAD<sub>65</sub>Abs) and quantitative assays in T1D associated complications.</p> <p>Results</p> <p>From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD<sub>65 </sub>as compared to native GAD<sub>65 </sub>(N-GAD<sub>65</sub>). Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD<sub>65</sub>. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC) indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10<sup>-6 </sup>M) followed by nephropathic (1.81 × 10<sup>-6 </sup>M) and uncomplicated (3.11 × 10<sup>-7 </sup>M) T1D patients for ROS-GAD<sub>65 </sub>compared to N-GAD<sub>65</sub>.</p> <p>Conclusion</p> <p>Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD<sub>65 </sub>that induce increased production of ROS-GAD<sub>65</sub>Abs. Hence regulation of ROS-GAD<sub>65</sub>Abs could offer novel tools for analysing and possibly treating T1D complications.</p
Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.
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Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment
THG113.31, a specific PGF2alpha receptor antagonist, induces human myometrial relaxation and BKCa channel activation
BACKGROUND: PGF2alpha exerts a significant contractile effect on myometrium and is central to human labour. THG113.31, a specific non-competitive PGF2alpha receptor (FP) antagonist, exerts an inhibitory effect on myometrial contractility. The BKCa channel is ubiquitously encountered in human uterine tissue and plays a significant role in modulating myometrial cell membrane potential and excitability. The objective of this study was to investigate potential BKCa channel involvement in the response of human myometrium to THG113.31. METHODS: Single and whole-cell electrophysiological BKCa channel recordings from freshly dispersed myocytes, were investigated in the presence and absence of THG113.31. Functional studies investigated the effects of THG113.31 on isolated spontaneous myometrial contractions, in the presence and absence of the BKCa channel blocker, iberiotoxin. RESULTS: Single channel recordings identified the BKCa channel as a target of THG113.31. THG113.31 significantly increased the open state probability of these channels [control 0.023+/-0.006; 10 microM THG113.31 0.087+/-0.012 (P = 0.009); and 50 microM THG113.31 0.1356+/-0.018 (P = 0.001)]. In addition, THG113.31 increased whole-cell BKCa currents over a range of membrane potentials, and this effect was reversed by 100 nanoM IbTX. Isometric tension studies demonstrated that THG113.31 exerted a significant concentration-dependent relaxant effect on human myometrial tissue and pre-incubation of strips with IbTX abolished this effect on spontaneously occurring contractions. CONCLUSION: These data suggests that activation of the BKCa channel may contribute, at least partially, to the uterorelaxant effect of THG113.31
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