768 research outputs found
The Massive Remote Sensing Data Organization and Management Strategies
With the continuous development of earth observing technology of China, Remote sensing image data has characteristics of large volume, multisource, multi-type and multi-resolution, finding a way to store, manage, and publish the data is a big challenges. This paper proposes a massive Remote sensing tile data organization and management strategy based on spatial database, design a data distribution and node management strategy to solve the massive remote sensing data organization and management problem
Model Selection Principles in Misspecified Models
Model selection is of fundamental importance to high dimensional modeling
featured in many contemporary applications. Classical principles of model
selection include the Kullback-Leibler divergence principle and the Bayesian
principle, which lead to the Akaike information criterion and Bayesian
information criterion when models are correctly specified. Yet model
misspecification is unavoidable when we have no knowledge of the true model or
when we have the correct family of distributions but miss some true predictor.
In this paper, we propose a family of semi-Bayesian principles for model
selection in misspecified models, which combine the strengths of the two
well-known principles. We derive asymptotic expansions of the semi-Bayesian
principles in misspecified generalized linear models, which give the new
semi-Bayesian information criteria (SIC). A specific form of SIC admits a
natural decomposition into the negative maximum quasi-log-likelihood, a penalty
on model dimensionality, and a penalty on model misspecification directly.
Numerical studies demonstrate the advantage of the newly proposed SIC
methodology for model selection in both correctly specified and misspecified
models.Comment: 25 pages, 6 table
Effects of Supersymmetric Threshold Corrections on High-Scale Flavor Textures
Integration of superpartners out of the spectrum induces potentially large
contributions to Yukawa couplings. These corrections, the supersymmetric
threshold corrections, therefore influence the CKM matrix prediction in a
non-trivial way. We study effects of threshold corrections on high-scale flavor
structures specified at the gauge coupling unification scale in supersymmetry.
In our analysis, we first consider high-scale Yukawa textures which qualify
phenomenologically viable at tree level, and find that they get completely
disqualified after incorporating the threshold corrections. Next, we consider
Yukawa couplings, such as those with five texture zeroes, which are incapable
of explaining flavor-changing proceses. Incorporation of threshold corrections,
however, makes them phenomenologically viable textures. Therefore,
supersymmetric threshold corrections are found to leave observable impact on
Yukawa couplings of quarks, and any confrontation of high-scale textures with
experiments at the weak scale must take into account such corrections.Comment: 25 pages, submitted to JHE
Effects of Cyclosporin A Therapy Combined with Steroids and Angiotensin Converting Enzyme Inhibitors on Childhood IgA Nephropathy
To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14 children (mean age 8.9±2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8±48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9±1.9 months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1±35.1 mg/m2/hr to 7.4±2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3±0.6 g/dL to 4.3±0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients, remained the same in three (21%), and was aggravated in four (29%). Serum creatinine, creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN
Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer
INTRODUCTION
Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice.
METHODS
More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account.
RESULTS
The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working.
CONCLUSIONS
With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years
Mildronate treatment alters γ-butyrobetaine and l -carnitine concentrations in healthy volunteers
Objectives In this study, we aimed to investigate the effects of long-term administration of the cardioprotective drug mildronate on the concentrations of l-carnitine and γ-butyrobetaine in healthy volunteers. Methods Mildronate was administered perorally, at a dosage of 500 mg, twice daily. Plasma and urine samples were collected weekly. Daily meat consumption within an average, non-vegetarian diet was monitored. l-Carnitine, γ-butyrobetaine and mildronate concentrations were measured using the UPLC/MS/MS method. Key findings After 4 weeks, the average concentrations of l-carnitine in plasma significantly decreased by 18%. The plasma concentrations of γ-butyrobetaine increased about two-fold, and this effect was statistically significant in both the male and female groups. In urine samples, a significant increase in l-carnitine and γ-butyrobetaine levels was observed, which provides evidence for increased excretion of both substances during the mildronate treatment. At the end of the treatment period, the plasma concentration of mildronate was 20 μm on average. There were no significant differences between the effects observed in female and male volunteers. Meat consumption partially reduced the l-carnitine-lowering effects induced by mildronate. Conclusions Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.publishersversionPeer reviewe
Clinical implications of novel activating EGFR mutations in malignant peritoneal mesothelioma
<p>Abstract</p> <p>Background</p> <p>There is a paucity of information about the molecular perturbations involved in MPM tumor formation. We previously reported that EGFR-TK mutations in MPM were predictive of achieving optimal surgical cytoreduction, but the status of EGFR pathway activation potential of these mutations was not known. Here we present the mutant EGFR activating potential and the matured survival data of the EGFR mutant(mut+) relative to wild type EGFR(mut-) mesothelioma.</p> <p>Methods</p> <p>Twenty-nine patients were evaluated and their tumors were probed for mutations in the catalytic TK-domain. Twenty-five patients were treated with cytoreductive surgery and complete clinical data was available for comparison of the mut+ and mut- groups. A COS-7 cell expression model was used to determine mutation activating profiles and response to erlotinib.</p> <p>Results</p> <p>Functional mutations were found in 31%(9/29) of patients; 7 of these mutations were novel and another was the L858R mutation. All missense mutations were found to be activating mutations and responsive to erlotinib. Of the 25 patients managed surgically, there were 7 mut+ and 18 mut-. Two of 7 (29%) mut+ developed progressive disease and died with a median follow-up time of 22 months; while 13/18 (72%) mut- developed progressive disease and 10/18 (56%) died with median TTP of 12 months and median survival of 14 months.</p> <p>Conclusions</p> <p>The novel EGFR mutations identified are activating mutations responsive to erlotinib. The mut+ subset have a 'relative' improved outcome. Erlotinib may have a role in MPM and exploration for mutations in a larger patient cohort is warranted.</p
A Spoonful of Math Helps the Medicine Go Down: An Illustration of How Healthcare can Benefit from Mathematical Modeling and Analysis
<p>Abstract</p> <p>Objectives</p> <p>A recent joint report from the Institute of Medicine and the National Academy of Engineering, highlights the benefits of--indeed, the need for--mathematical analysis of healthcare delivery. Tools for such analysis have been developed over decades by researchers in Operations Research (OR). An OR perspective typically frames a complex problem in terms of its essential mathematical structure. This article illustrates the use and value of the tools of operations research in healthcare. It reviews one OR tool, queueing theory, and provides an illustration involving a hypothetical drug treatment facility.</p> <p>Method</p> <p>Queueing Theory (QT) is the study of waiting lines. The theory is useful in that it provides solutions to problems of waiting and its relationship to key characteristics of healthcare systems. More generally, it illustrates the strengths of modeling in healthcare and service delivery.</p> <p>Queueing theory offers insights that initially may be hidden. For example, a queueing model allows one to incorporate randomness, which is inherent in the actual system, into the mathematical analysis. As a result of this randomness, these systems often perform much worse than one might have guessed based on deterministic conditions. Poor performance is reflected in longer lines, longer waits, and lower levels of server utilization.</p> <p>As an illustration, we specify a queueing model of a representative drug treatment facility. The analysis of this model provides mathematical expressions for some of the key performance measures, such as average waiting time for admission.</p> <p>Results</p> <p>We calculate average occupancy in the facility and its relationship to system characteristics. For example, when the facility has 28 beds, the average wait for admission is 4 days. We also explore the relationship between arrival rate at the facility, the capacity of the facility, and waiting times.</p> <p>Conclusions</p> <p>One key aspect of the healthcare system is its complexity, and policy makers want to design and reform the system in a way that affects competing goals. OR methodologies, particularly queueing theory, can be very useful in gaining deeper understanding of this complexity and exploring the potential effects of proposed changes on the system without making any actual changes.</p
Future therapeutic targets in rheumatoid arthritis?
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches
Binary and Millisecond Pulsars at the New Millennium
We review the properties and applications of binary and millisecond pulsars.
Our knowledge of these exciting objects has greatly increased in recent years,
mainly due to successful surveys which have brought the known pulsar population
to over 1300. There are now 56 binary and millisecond pulsars in the Galactic
disk and a further 47 in globular clusters. This review is concerned primarily
with the results and spin-offs from these surveys which are of particular
interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living
Reviews in Relativity (http://www.livingreviews.org
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