423 research outputs found

    Existence of immersed spheres minimizing curvature functionals in compact 3-manifolds

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    We study curvature functionals for immersed 2-spheres in a compact, three-dimensional Riemannian manifold M. Under the assumption that the sectional curvature of M is strictly positive, we prove the existence of a smoothly immersed sphere minimizing the L^{2} integral of the second fundamental form. Assuming instead that the sectional curvature is less than or equal to 2, and that there exists a point in M with scalar curvature bigger than 6, we obtain a smooth 2-sphere minimizing the integral of 1/4|H|^{2} +1, where H is the mean curvature vector

    Simulating complex social behaviour with the genetic action tree kernel

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    The concept of genetic action trees combines action trees with genetic algorithms. In this paper, we create a multi-agent simulation on the base of this concept and provide the interested reader with a software package to apply genetic action trees in a multi-agent simulation to simulate complex social behaviour. An example model is introduced to conduct a feasibility study with the described method. We find that our library can be used to simulate the behaviour of agents in a complex setting and observe a convergence to a global optimum in spite of the absence of stable states

    Classification of ductal carcinoma in situ by gene expression profiling

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    INTRODUCTION: Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. METHODS: Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. RESULTS: DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. CONCLUSION: Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples

    Psychometric properties of two physical activity questionnaires, the AQuAA and the PASE, in cancer patients

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    Background: This study aimed to evaluate the reliability and validity of two self-report physical activity (PA) questionnaires - the AQuAA (Activity Questionnaire for Adults and Adolescents) and PASE (Physical Activity Scale for the Elderly) - in cancer patients. Methods: Test-retest reliability was determined by administering the questionnaires twice within 5 days. Intraclass correlation coefficient (ICC), standard error of measurement (SEM) and smallest detectable difference (SDD) were calculated. Construct validity was determined by comparing the questionnaire results with ActiGraph accelerometer scores using Spearman correlation coefficients (r(s)) and ICCs. Content validity was examined using the Three-Step Test-Interview (TSTI). Results: Reliability for the AQuAA scores were fair to excellent (ICC = 0.57 to 0.78). Reliability for the PASE scores ranged from good to excellent (ICC = 0.67 to 0.90). Correlations between the ActiGraph and the AQuAA and the PASE were low (r(s) = 0.05 and 0.16 respectively, and ICC = -0.001 to 0.44). The TSTI showed that participants experienced difficulties with the examples provided with the questions, the perceptions of intensity level of PA, and with recalling the time spent on PA. Conclusions: Both questionnaires showed good to excellent test-retest reliability for most scores. Construct validity of both questionnaires was low, as indicated by the low correlations with the ActiGraph. Except for a few difficulties that participants perceived when filling out the questionnaires, the content validity of both questionnaires was goo

    The Circadian Deadenylase Nocturnin Is Necessary for Stabilization of the iNOS mRNA in Mice

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    Nocturnin is a member of the CCR4 deadenylase family, and its expression is under circadian control with peak levels at night. Because it can remove poly(A) tails from mRNAs, it is presumed to play a role in post-transcriptional control of circadian gene expression, but its target mRNAs are not known. Here we demonstrate that Nocturnin expression is acutely induced by the endotoxin lipopolysaccharide (LPS). Mouse embryo fibroblasts (MEFs) lacking Nocturnin exhibit normal patterns of acute induction of TNFα and iNOS mRNAs during the first three hours following LPS treatment, but by 24 hours, while TNFα mRNA levels are indistinguishable from WT cells, iNOS message is significantly reduced 20-fold. Accordingly, analysis of the stability of the mRNAs showed that loss of Nocturnin causes a significant decrease in the half-life of the iNOS mRNA (t1/2 = 3.3 hours in Nocturnin knockout MEFs vs. 12.4 hours in wild type MEFs), while having no effect on the TNFα message. Furthermore, mice lacking Nocturnin lose the normal nighttime peak of hepatic iNOS mRNA, and have improved survival following LPS injection. These data suggest that Nocturnin has a novel stabilizing activity that plays an important role in the circadian response to inflammatory signals

    Determining the interviewer effect on CQ Index outcomes: a multilevel approach

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    <p>Abstract</p> <p>Background</p> <p>The CQ Index for the elderly, a quality-of-care questionnaire administered by conducting interviews, is used to assess clients' experiences in Dutch nursing homes and homes for the elderly. This article describes whether inter-interviewer differences influence the perceived quality of healthcare services reported by residents, the size of this interviewer effect and the influence of the interviewer characteristics on CQ Index dimensions for public reporting.</p> <p>Methods</p> <p>Data from 4345 questionnaires was used. Correlations were calculated, reliability analyses were performed, and a multilevel analysis was used to calculate the degree of correlation between two interviewers within one health care institution. Five models were constructed and the Intra Class Correlation (ICC) was calculated. Healthcare institutions were given 1-5 stars on every quality dimensions (1 = worst and 5 = best), adjusted for resident and interviewer characteristics. The effect of these characteristics on the assignment of the stars was investigated.</p> <p>Results</p> <p>In a multilevel approach, the ICC showed a significant amount of variance on five quality dimensions. Of the interviewer characteristics, only previous interviewing experience, the reason of interviewing and general knowledge of health care had a significant effect on the quality dimensions. Adjusting for interviewer characteristics did not affect the overall star assignment to the institutions regarding 7 of 12 quality dimensions. For the other five dimensions (Shared decision-making, Meals, Professional competency, Autonomy, and Availability of personnel) a minor effect was found.</p> <p>Conclusions</p> <p>We have shown that training, the use of experienced interviewers, written instructions, supervision and educational meetings do not automatically prevent interviewer effects. While the results of this study can be used to improve the quality of services provided by these institutions, several CQ index dimensions should be interpreted with caution for external purposes (accountability and transparency).</p

    Adaptive Significance of the Formation of Multi-Species Fish Spawning Aggregations near Submerged Capes

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    BACKGROUND: Many fishes are known to spawn at distinct geomorphological features such as submerged capes or "promontories," and the widespread use of these sites for spawning must imply some evolutionary advantage. Spawning at these capes is thought to result in rapid offshore transport of eggs, thereby reducing predation levels and facilitating dispersal to areas of suitable habitat. METHODOLOGY/PRINCIPAL FINDINGS: To test this "off-reef transport" hypothesis, we use a hydrodynamic model and explore the effects of topography on currents at submerged capes where spawning occurs and at similar capes where spawning does not occur, along the Mesoamerican Barrier Reef. All capes modeled in this study produced eddy-shedding regimes, but specific eddy attributes differed between spawning and non-spawning sites. Eddies at spawning sites were significantly stronger than those at non-spawning sites, and upwelling and fronts were the products of the eddy formation process. Frontal zones, present particularly at the edges of eddies near the shelf, may serve to retain larvae and nutrients. Spawning site eddies were also more predictable in terms of diameter and longevity. Passive particles released at spawning and control sites were dispersed from the release site at similar rates, but particles from spawning sites were more highly aggregated in their distributions than those from control sites, and remained closer to shore at all times. CONCLUSIONS/SIGNIFICANCE: Our findings contradict previous hypotheses that cape spawning leads to high egg dispersion due to offshore transport, and that they are attractive for spawning due to high, variable currents. Rather, we show that current regimes at spawning sites are more predictable, concentrate the eggs, and keep larvae closer to shore. These attributes would confer evolutionary advantages by maintaining relatively similar recruitment patterns year after year

    Decreased 3D observer variation with matched CT-MRI, for target delineation in Nasopharynx cancer

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    Contains fulltext : 88137.pdf (publisher's version ) (Open Access)PURPOSE: To determine the variation in target delineation of nasopharyngeal carcinoma and the impact of measures to minimize this variation. MATERIALS AND METHODS: For ten nasopharyngeal cancer patients, ten observers each delineated the Clinical Target Volume (CTV) and the CTV elective. After 3D analysis of the delineated volumes, a second delineation was performed. This implied improved delineation instructions, a combined delineation on CT and co-registered MRI, forced use of sagittal reconstructions, and an on-line anatomical atlas. RESULTS: Both for the CTV and the CTV elective delineations, the 3D SD decreased from Phase 1 to Phase 2, from 4.4 to 3.3 mm for the CTV and from 5.9 to 4.9 mm for the elective. There was an increase agreement, where the observers intended to delineate the same structure, from 36 to 64 surface % (p = 0.003) for the CTV and from 17 to 59% (p = 0.004) for the elective. The largest variations were at the caudal border of the delineations but these were smaller when an observer utilized the sagittal window. Hence, the use of sagittal side windows was enforced in the second phase and resulted in a decreased standard deviation for this area from 7.7 to 3.3 mm (p = 0.001) for the CTV and 7.9 to 5.6 mm (p = 0.03) for the CTV elective. DISCUSSION: Attempts to decrease the variation need to be tailored to the specific causes of the variation. Use of delineation instructions multimodality imaging, the use of sagittal windows and an on-line atlas result in a higher agreement on the intended target

    P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

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    Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage
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