Wireless Application Middleware

The use of middleware has been acknowledged as the principal means of simplifying distributed applications building in the enterprise. Wireless messaging middleware, in particular, allows loosely coupled distributed components and has emerged as being well suited to the wireless environment. In this paper we present a lightweight wireless messaging middleware solution which addresses the reliability and bandwidth issues associated with wireless links

Hypertensive Encephalopathy and Renal Failure in a Young Man

No abstract available

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Determining Possible Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma

PURPOSE: To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). // METHODS: We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. // RESULTS: We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup-disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 × 10-3) and a significant association between PRS for myopia and disc area (P = 1.59 × 10-9). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10-3), supporting the findings of the PRS approach. // CONCLUSIONS: Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

High-resolution genetic mapping with pooled sequencing

Background: Modern genetics has been transformed by high-throughput sequencing. New experimental designs in model organisms involve analyzing many individuals, pooled and sequenced in groups for increased efficiency. However, the uncertainty from pooling and the challenge of noisy sequencing data demand advanced computational methods. Results: We present MULTIPOOL, a computational method for genetic mapping in model organism crosses that are analyzed by pooled genotyping. Unlike other methods for the analysis of pooled sequence data, we simultaneously consider information from all linked chromosomal markers when estimating the location of a causal variant. Our use of informative sequencing reads is formulated as a discrete dynamic Bayesian network, which we extend with a continuous approximation that allows for rapid inference without a dependence on the pool size. MULTIPOOL generalizes to include biological replicates and case-only or case-control designs for binary and quantitative traits. Conclusions: Our increased information sharing and principled inclusion of relevant error sources improve resolution and accuracy when compared to existing methods, localizing associations to single genes in several cases. MULTIPOOL is freely available at http://cgs.csail.mit.edu/multipool/ webcite.National Science Foundation (U.S.) (Graduate Research Fellowship Grant 0645960

International practice patterns and factors associated with non-conventional hemodialysis utilization

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to determine characteristics that influence the utilization of non-conventional hemodialysis (NCHD) therapies and its subtypes (nocturnal (NHD), short daily (SDHD), long conventional (LCHD) and conventional hemodialysis (CHD) as well as provider attitudes regarding the evidence for NCHD use.</p> <p>Methods</p> <p>An international cohort of subscribers of a nephrology education website <url>http://www.nephrologynow.com</url> was invited to participate in an online survey. Non-conventional hemodialysis was defined as any forms of hemodialysis delivered > 3 treatments per week and/or > 4 hours per session. NHD and SDHD included both home and in-centre. Respondents were categorized as CHD if their centre only offered conventional thrice weekly hemodialysis. Variables associated with NCHD and its subtypes were determined using multivariate logistic regression analysis. The survey assessed multiple domains regarding NCHD including reasons for initiating and discontinuing, for not offering and attitudes regarding evidence.</p> <p>Results</p> <p>544 surveys were completed leading to a 15.6% response rate. The final cohort was limited to 311 physicians. Dialysis modalities utilized among the respondents were as follows: NCHD194 (62.4%), NHD 83 (26.7%), SDHD 107 (34.4%), LCHD 81 (26%) and CHD 117 (37.6%). The geographic regions of participants were as follows: 11.9% Canada, 26.7% USA, 21.5% Europe, 6.1% Australia/New Zealand, 10% Africa/Middle East, 10.9% Asia and 12.9% South America. Variables associated with NCHD utilization included NCHD training (OR 2.47 CI 1.25-4.16), government physician reimbursement (OR 2.66, CI 1.11-6.40), practicing at an academic centre (OR 2.28 CI 1.25-4.16), higher national health care expenditure and number of ESRD patients per centre. Hemodialysis providers with patients on NCHD were significantly more likely to agree with the statements that NCHD improves quality of life, improves nutritional status, reduces EPO requirements and is cost effective. The most common reasons to initiate NCHD were driven by patient preference and the desire to improve volume control and global health outcomes.</p> <p>Conclusion</p> <p>Physician attitudes toward the evidence for NCHD differ significantly between NCHD providers and conventional HD providers. Interventions and health policy targeting these areas along with increased physician education and training in NCHD modalities may be effective in increasing its utilization.</p

Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis

BACKGROUND: The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS) on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP). METHODS: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. RESULTS: The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model. CONCLUSION: Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation

Non-thermal emission processes in massive binaries

In this paper, I present a general discussion of several astrophysical processes likely to play a role in the production of non-thermal emission in massive stars, with emphasis on massive binaries. Even though the discussion will start in the radio domain where the non-thermal emission was first detected, the census of physical processes involved in the non-thermal emission from massive stars shows that many spectral domains are concerned, from the radio to the very high energies. First, the theoretical aspects of the non-thermal emission from early-type stars will be addressed. The main topics that will be discussed are respectively the physics of individual stellar winds and their interaction in binary systems, the acceleration of relativistic electrons, the magnetic field of massive stars, and finally the non-thermal emission processes relevant to the case of massive stars. Second, this general qualitative discussion will be followed by a more quantitative one, devoted to the most probable scenario where non-thermal radio emitters are massive binaries. I will show how several stellar, wind and orbital parameters can be combined in order to make some semi-quantitative predictions on the high-energy counterpart to the non-thermal emission detected in the radio domain. These theoretical considerations will be followed by a census of results obtained so far, and related to this topic... (see paper for full abstract)Comment: 47 pages, 5 postscript figures, accepted for publication in Astronomy and Astrophysics Review. Astronomy and Astrophysics Review, in pres

The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma

Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell–inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (β = –0.13 μm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; β = –0.20 μm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 μm vs. 71.9 μm; P = 0.011) and pRNFL (77.6 μm vs. 79.2 μm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma