APMAT, A Multi-Centre observational study of patients with microangiopathic thrombocytopenia

Microangiopathic Thrombocytopenia (MAT) is a rare but often fatal collection of disorders. The disorder can be categorised by distinct disease states including thrombotic thrombocytopenia purpura (TTP) and atypical haemolytic uremic syndrome. Clinical presentations of MAT, however, often represent di_erent but related aetiologies from overlapping syndromes. TTP has an incidence rate of 2-15 cases per million people-years. When left untreated, it has a mortality rate of ~90%; with treatment the mortality rate remains relatively high (~20%). Moreover, TTP patients often su_er a high rate of recurrent relapses. Aetiologically, TTP is a result of insu_cient cleavage of high molecular weight von Willebrand Factor multimers due to abrogated ADAMTS13 activity. Current diagnosis lacks disease _delity and temporal resolution, making clinical management di_cult. There exists, therefore, a need for a faster and standardised clinical management for TTP. The APMAT project is a retrospective study instigated to _ll this information gap. The study aims to collect a total of 150 patient samples from various study centres in the Asia-Paci_c (AP) region, with WACTH Murdoch University acting as a repository, co-ordinating and R&D centre. Five key outcomes of APMAT will be: 1. Develop the APMAT research network protocol, 2. Formation of an AP medical advisory panel of APMAT experts for individual clinical advice, 3. Establish a clinical adjudication committee for independent classi_cation of MAT patients, 4. Standardise laboratory testing for ADAMTS13 and any other novel assays in the AP region, 5. Facilitate basic science and translational clinical research into MAT

A Systematic Tradeoff Methodology for Acquiring and Validating Imprecise Requirements

Requirement analysis is one of the most important phases in a software development process. Existing requirement methodologies are limited in specifying requirements that are usually vague and imprecise, and in supporting tradeoff analysis between the conflicting requirements. In this paper, the elasticity of imprecise requirements is captured using fuzzy logic to facilitate tradeoffs between conflicting requirements. Based on the marginal rate of substitution in decision science, we have developed a systematic approach to elicit the structures and the parameters of imprecise requirements, to validate the scheme for aggregating requirements, and to assess relative priorities of conflicting requirements

Quantum Hydrodynamic Model by Moment Closure of Wigner Equation

In this paper, we derive the quantum hydrodynamics models based on the moment closure of the Wigner equation. The moment expansion adopted is of the Grad type firstly proposed in \cite{Grad}. The Grad's moment method was originally developed for the Boltzmann equation. In \cite{Fan_new}, a regularization method for the Grad's moment system of the Boltzmann equation was proposed to achieve the globally hyperbolicity so that the local well-posedness of the moment system is attained. With the moment expansion of the Wigner function, the drift term in the Wigner equation has exactly the same moment representation as in the Boltzmann equation, thus the regularization in \cite{Fan_new} applies. The moment expansion of the nonlocal Wigner potential term in the Wigner equation is turned to be a linear source term, which can only induce very mild growth of the solution. As the result, the local well-posedness of the regularized moment system for the Wigner equation remains as for the Boltzmann equation

Statistical diagnostic and correction of a chemistry-transport model for the prediction of total column ozone

International audienceIn this paper, we introduce a statistical method for examining and adjusting chemical-transport models. We illustrate the findings with total column ozone predictions, based on the University of Illinois at Urbana-Champaign 2-D (UIUC 2-D) chemical-transport model of the global atmosphere. We propose a general diagnostic procedure for the model outputs in total ozone over the latitudes ranging from 60° South to 60° North to see if the model captures some typical patterns in the data. The method proceeds in two steps to avoid possible collinearity issues. First, we regress the measurements given by a cohesive data set from the SBUV(/2) satellite system on the model outputs with an autoregressive noise component. Second, we regress the residuals of this first regression on the solar flux, the annual cycle, the Antarctic or Arctic Oscillation, and the Quasi Biennial Oscillation. If the coefficients from this second regression are statistically significant, then they mean that the model did not simulate properly the pattern associated with these factors. Systematic anomalies of the model are identified using data from 1979 to 1995, and statistically corrected afterwards. The 1996?2003 validation sample confirms that the combined approach yields better predictions than the direct UIUC 2-D outputs

Human motion data refinement unitizing structural sparsity and spatial-temporal information

Human motion capture techniques (MOCAP) are widely applied in many areas such as computer vision, computer animation, digital effect and virtual reality. Even with professional MOCAP system, the acquired motion data still always contains noise and outliers, which highlights the need for the essential motion refinement methods. In recent years, many approaches for motion refinement have been developed, including signal processing based methods, sparse coding based methods and low-rank matrix completion based methods. However, motion refinement is still a challenging task due to the complexity and diversity of human motion. In this paper, we propose a data-driven-based human motion refinement approach by exploiting the structural sparsity and spatio-temporal information embedded in motion data. First of all, a human partial model is applied to replace the entire pose model for a better feature representation to exploit the abundant local body posture. Then, a dictionary learning which is for special task of motion refinement is designed and applied in parallel. Meanwhile, the objective function is derived by taking the statistical and locality property of motion data into account. Compared with several state-of-art motion refine methods, the experimental result demonstrates that our approach outperforms the competitors

Characterization of Pulmonary Metastases in Children With Hepatoblastoma Treated on Children\u27s Oncology Group Protocol AHEP0731 (The Treatment of Children With All Stages of Hepatoblastoma): A Report From the Children\u27s Oncology Group.

Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates with outcome. Methods Thirty-two patients with metastatic HB were enrolled on Children\u27s Oncology Group Protocol AHEP0731 and treated with vincristine and irinotecan (VI). Responders to VI received two additional cycles of VI intermixed with six cycles of cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), and nonresponders received six cycles of C5VD alone. Patients were imaged after every two cycles and at the conclusion of therapy. All computed tomography scans and pathology reports were centrally reviewed, and information was collected regarding lung nodule number, size, laterality, timing of resolution, and pulmonary surgery. Results Among the 29 evaluable patients, only 31% met Response Evaluation Criteria in Solid Tumors (RECIST) for measurable metastatic disease. The presence of measurable disease by RECIST, the sum of nodule diameters greater than or equal to the cumulative cohort median size, bilateral disease, and ≥ 10 nodules were each associated with an increased risk for an event-free survival event ( P = .48, P = .08, P = .065, P = .03, respectively), with nodule number meeting statistical significance. Ten patients underwent pulmonary resection/metastasectomy at various time points, the benefit of which could not be determined because of small patient numbers. Conclusion Children with metastatic HB have a poor prognosis. Overall tumor burden may be an important prognostic factor for these patients. Lesions that fail to meet RECIST size criteria (ie, those \u3c 10 mm) at diagnosis may contain viable tumor, whereas residual lesions at the end of therapy may constitute eradicated tumor/scar tissue. Patients may benefit from risk stratification on the basis of the burden of lung metastatic disease at diagnosis

KCTD Hetero-oligomers confer unique kinetic properties on Hippocampal GABA B Receptor-Induced K + Currents

GABAB receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, GABA. GABAB receptors were shown to associate with homo-oligomers of auxiliary KCTD8, KCTD12, KCTD12b, and KCTD16 subunits (named after their T1 K+-channel tetramerization domain) that regulate G-protein signaling of the receptor. Here we provide evidence that GABAB receptors also associate with hetero-oligomers of KCTD subunits. Coimmunoprecipitation experiments indicate that two-thirds of the KCTD16 proteins in the hippocampus of adult mice associate with KCTD12. We show that the KCTD proteins hetero-oligomerize through self-interacting T1 and H1 homology domains. Bioluminescence resonance energy transfer measurements in live cells reveal that KCTD12/KCTD16 hetero-oligomers associate with both the receptor and the G-protein. Electrophysiological experiments demonstrate that KCTD12/KCTD16 hetero-oligomers impart unique kinetic properties on G-protein-activated Kir3 currents. During prolonged receptor activation (one min) KCTD12/KCTD16 hetero-oligomers produce moderately desensitizing fast deactivating K+ currents, whereas KCTD12 and KCTD16 homo-oligomers produce strongly desensitizing fast deactivating currents and nondesensitizing slowly deactivating currents, respectively. During short activation (2 s) KCTD12/KCTD16 hetero-oligomers produce nondesensitizing slowly deactivating currents. Electrophysiological recordings from hippocampal neurons of KCTD knock-out mice are consistent with these findings and indicate that KCTD12/KCTD16 hetero-oligomers increase the duration of slow IPSCs. In summary, our data demonstrate that simultaneous assembly of distinct KCTDs at the receptor increases the molecular and functional repertoire of native GABAB receptors and modulates physiologically induced K+ current responses in the hippocampus

Limiting distributions for explosive PAR(1) time series with strongly mixing innovation

This work deals with the limiting distribution of the least squares estimators of the coefficients a r of an explosive periodic autoregressive of order 1 (PAR(1)) time series X r = a r X r--1 +u r when the innovation {u k } is strongly mixing. More precisely {a r } is a periodic sequence of real numbers with period P \textgreater{} 0 and such that P r=1 |a r | \textgreater{} 1. The time series {u r } is periodically distributed with the same period P and satisfies the strong mixing property, so the random variables u r can be correlated

The mutational constraint spectrum quantified from variation in 141,456 humans

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes(1). Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.Peer reviewe

Trends in the Vertical Distribution of Ozone: A Comparison of Two Analyses of Ozonesonde Data

We present the results of two independent analyses of ozonesonde measurements of the vertical profile of ozone. For most of the ozonesonde stations we use data that were recently reprocessed and reevaluated to improve their quality and internal consistency. The two analyses give similar results for trends in ozone. We attribute differences in results primarily to differences in data selection criteria and in utilization of data correction factors, rather than in statistical trend models. We find significant decreases in stratospheric ozone at all stations in middle and high latitudes of the northern hemisphere from 1970 to 1996, with the largest decreases located between 12 and 21 km, and trends of -3 to -10 %/decade near 17 km. The decreases are largest at the Canadian and the most northerly Japanese station, and are smallest at the European stations, and at Wallops Island, U.S.A. The mean mid-latitude trend is largest, -7 %/decade, from 12 to 17.5 km for 1970-96. For 1980-96, the decrease is more negative by 1-2 %/decade, with a maximum trend of -9 %/decade in the lowermost stratosphere. The trends vary seasonally from about 12 to 17.5 km, with largest ozone decreases in winter and spring. Trends in tropospheric ozone are highly variable and depend on region. There are decreases or zero trends at the Canadian stations for 1970-96, and decreases of -2 to -8 %/decade for the mid-troposphere for 1980-96; the three European stations show increases for 1970-96, but trends are close to zero for two stations for 1980-96 and positive for one; there are increases in ozone for the three Japanese stations for 1970-96, but trends are either positive or zero for 1980-96; the U.S. stations show zero or slightly negative trends in tropospheric ozone after 1980. It is not possible to define reliably a mean tropospheric ozone trend for northern mid-latitudes, given the small number of stations and the large variability in trends. The integrated column trends derived from the sonde data are consistent with trends derived from both surface based and satellite measurements of the ozone column