Object Database Scalability for Scientific Workloads

We describe the PetaByte-scale computing challenges posed by the next generation of particle physics experiments, due to start operation in 2005. The computing models adopted by the experiments call for systems capable of handling sustained data acquisition rates of at least 100 MBytes/second into an Object Database, which will have to handle several PetaBytes of accumulated data per year. The systems will be used to schedule CPU intensive reconstruction and analysis tasks on the highly complex physics Object data which need then be served to clients located at universities and laboratories worldwide. We report on measurements with a prototype system that makes use of a 256 CPU HP Exemplar X Class machine running the Objectivity/DB database. Our results show excellent scalability for up to 240 simultaneous database clients, and aggregate I/O rates exceeding 150 Mbytes/second, indicating the viability of the computing models

What is important to the GP in recognizing acute appendicitis in children:a delphi study

Background: For diagnostic research on appendicitis in registration data, insight is needed in the way GPs generate medical records. We aimed to reach a consensus on the features that GPs consider important in the consultation and medical records when evaluating a child with suspected appendicitis. Methods: We performed a three-round Delphi study among Dutch GPs selected by purposive sampling. An initial feature list was created based on a literature search and features in the relevant Dutch guideline. Finally, using a vignette describing a child who needed later reassessment, we asked participants to complete an online questionnaire about which consultation features should be addressed and recorded. Results: A literature review and Dutch guideline yielded 95 consultation features. All three rounds were completed by 22 GPs, with the final consensus list containing 26 symptoms, 29 physical assessments and signs, 2 additional tests, and 8 further actions (including safety-netting, i.e., informing the patient about when to contact the GP again). Of these, participants reached consensus that 37 should be actively addressed and that 20 need to be recorded if findings are negative. Conclusions: GPs agreed that negative findings do not need to be recorded for most features and that records should include the prognostic and safety-netting advice given. The results have implications in three main domains: for research, that negative findings are likely to be missing; for medicolegal purposes, that documentation cannot be expected to be complete; and for clinical practice, that safety-netting advice should be given and documented.</p

Murine versus human apolipoprotein E4: Differential facilitation of and co-localization in cerebral amyloid angiopathy and amyloid plaques in APP transgenic mouse models

INTRODUCTION: Amyloid β (Aβ) accumulates in the extracellular space as diffuse and neuritic plaques in Alzheimer’s disease (AD). Aβ also deposits on the walls of arterioles as cerebral amyloid angiopathy (CAA) in most cases of AD and sometimes independently of AD. Apolipoprotein E (apoE) ɛ4 is associated with increases in both Aβ plaques and CAA in humans. Studies in mouse models that develop Aβ deposition have shown that murine apoE and human apoE4 have different abilities to facilitate plaque or CAA formation when studied independently. To better understand and compare the effects of murine apoE and human apoE4, we bred 5XFAD (line 7031) transgenic mice so that they expressed one copy of murine apoE and one copy of human apoE4 under the control of the normal murine apoE regulatory elements (5XFAD/apoE(m/4)). RESULTS: The 5XFAD/apoE(m/4) mice contained levels of parenchymal CAA that were intermediate between 5XFAD/apoE(m/m) and 5XFAD/apoE(4/4) mice. In 5XFAD/apoE(m/4) mice, we found that Aβ parenchymal plaques co-localized with much more apoE than did parenchymal CAA, suggesting differential co-aggregation of apoE with Aβ in plaques versus CAA. More importantly, within the brain parenchyma of the 5XFAD/apoE(m/4) mice, plaques contained more murine apoE, which on its own results in more pronounced and earlier plaque formation, while CAA contained more human apoE4 which on its own results in more pronounced CAA formation. We further confirmed the co-aggregation of mouse apoE with Aβ in plaques by showing a strong correlation between insoluble mouse apoE and insoluble Aβ in PS1APP-21/apoE(m/4) mice which develop plaques without CAA. CONCLUSIONS: These studies suggest that both murine apoE and human apoE4 facilitate differential opposing effects in influencing Aβ plaques versus CAA via different co-aggregation with these two amyloid lesions and set the stage for understanding these effects at a molecular level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0250-y) contains supplementary material, which is available to authorized users

Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein.

EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG). These T cells drive the EAE pathogenesis to irreversible neurologic deficit. The aim of this study was to determine why LCV infection is important for this pathogenic role of B cells. Transcriptome comparison of LCV-infected B cells and CD20(+) spleen cells from rhesus monkeys shows increased expression of genes encoding elements of the Ag cross-presentation machinery (i.e., of proteasome maturation protein and immunoproteasome subunits) and enhanced expression of MHC-E and of costimulatory molecules (CD70 and CD80, but not CD86). It was also shown that altered expression of endolysosomal proteases (cathepsins) mitigates the fast endolysosomal degradation of the MOG40-48 core epitope. Finally, LCV infection also induced expression of LC3-II(+) cytosolic structures resembling autophagosomes, which seem to form an intracellular compartment where the MOG40-48 epitope is protected against proteolytic degradation by the endolysosomal serine protease cathepsin G. In conclusion, LCV infection induces a variety of changes in B cells that underlies the conversion of destructive processing of the immunodominant MOG40-48 epitope into productive processing and cross-presentation to strongly autoaggressive CTLs

Diagnostic accuracy of follow-up tests for detecting colorectal cancer recurrences in primary care:A systematic review and meta-analysis

Introduction Traditionally, follow-up of colorectal cancer (CRC) is performed in secondary care. In new models of care, the screening part care could be replaced to primary care. We aimed to synthesise evidence on the diagnostic accuracy of commonly used screeners in CRC follow-up applicable in primary care: carcinoembryonic antigen (CEA), ultrasound and physical examination. Methods Medline, EMBASE, Cochrane Trial Register and Web of Science databases were systematically searched. Studies were included if they provided sufficient data for a 2 × 2 contingency tables. QUADAS-2 was used to assess methodological quality. We performed bivariate random effects meta-analysis, generated a hypothetical cohort, and reported sensitivity and specificity. Results We included 12 studies (n = 3223, median recurrence rate 19.6%). Pooled estimates showed a sensitivity for CEA (≤ 5 μg/l) of 59% [47%–70%] and a specificity of 89% [80%–95%]. Only few studies reported sensitivities and specificities for ultrasound (36–70% and 97–100%, respectively) and clinical examination (23% and 27%, respectively). Conclusion In practice, GPs could perform CEA screening. Radiological examination in a hospital setting should remain part of the surveillance strategy. Personalised algorithms accounting for recurrence risk and changes of CEA-values over time might add to the diagnostic value of CEA in primary care

Superheavy Dark Matter and Thermal Inflation

The thermal inflation is the most plausible mechanism that solves the cosmological moduli problem naturally. We discuss relic abundance of superheavy particle $X$ in the presence of the thermal inflation assuming that its lifetime is longer than the age of the universe, and show that the long-lived particle $X$ of mass $10^{12}$--$10^{14}$ GeV may form a part of the dark matter in the present universe in a wide region of parameter space of the thermal inflation model. The superheavy dark matter of mass $\sim 10^{13}$ GeV may be interesting in particular, since its decay may account for the observed ultra high-energy cosmic rays if the lifetime of the $X$ particle is sufficiently long.Comment: 13 pages (RevTex file) including 8 figures, revised version to be published in Physical Review

Big Bang Nucleosynthesis and Lepton Number Asymmetry in the Universe

Recently it is reported that there is the discrepancy between big bang nucleosynthesis theory and observations (BBN crisis). We show that BBN predictions agree with the primordial abundances of light elements, He4, D, He3 and Li7 inferred from the observational data if an electron neutrino has a net chemical potential xi_{nu_e} due to lepton asymmetry. We estimate that xi_{nu_e} = 0.043^{+0.040}_{-0.040} (95% C.L.) and Omega_bh^2 = 0.015^{+0.006}_{-0.003} (95% C.L.).Comment: 10 pages, using AAS LATEX and three postscript figure