Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK

We describe a family-based sample of individuals with reading disability collected as part of a quantitative trait loci (QTL) mapping study. Eighty-nine nuclear families (135 independent sib-pairs) were identified through a single proband using a traditional discrepancy score of predicted/actual reading ability and a known family history. Eight correlated psychometric measures were administered to each sibling, including single word reading, spelling, similarities, matrices, spoonerisms, nonword and irregular word reading, and a pseudohomophone test. Summary statistics for each measure showed a reduced mean for the probands compared to the co-sibs, which in turn was lower than that of the population. This partial co-sib regression back to the mean indicates that the measures are influenced by familial factors and therefore, may be suitable for a mapping study. The variance of each of the measures remained largely unaffected, which is reassuring for the application of a QTL approach. Multivariate genetic analysis carried out to explore the relationship between the measures identified a common factor between the reading measures that accounted for 54% of the variance. Finally the familiality estimates (range 0.32–0.73) obtained for the reading measures including the common factor (0.68) supported their heritability. These findings demonstrate the viability of this sample for QTL mapping, and will assist in the interpretation of any subsequent linkage findings in an ongoing genome scan

Rewriting Semantics of Meta-Objects and Composable Distributed Services1 1Supported by DARPA through Rome Laboratories Contract F30602-97-C-0312, by DARPA and NASA through Contract NAS2-98073, by Office of Naval Research Contract N00014-99-C-0198, and by National Science Foundation Grants CCR-9505960 and CCR-9633363, and CCR-9900334.

AbstractCommunication between distributed objects may have to be protected against random failures and malicious attacks; also, communication timeliness may be essential or highly desired. Therefore, a distributed application often has to be extended with communication services providing some kind of fault-tolerance, secrecy, or quality-of-service guarantees. Ideally, such services should be defined in a highly modular and dynamically composable way, so that the combined assurance of several services can be achieved by composition in certain cases, and so that services can be added or removed from applications at runtime in response to changes in the environment. To reason about the formal properties of such composable communication services one first needs to give them a precise semantics. This paper proposes a rewriting logic semantics for the so-called “onion skin” model of distributed object reflection, in which different meta-objects, providing different communication services, can be stacked on top of a basic application object. Since the correct behavior of a service depends on the type of hostile environment, against which the service must protect the application, rewriting logic should also be used to specify such hostile environments. The service guarantees are then guarantees about the behavior specified by the union of the rewrite theories specifying the basic application, the services, and the hostile environment

Breif Announcement: A Calculus of Policy-Based Routing Systems

The BGP (Border Gateway Protocol) is the single inter-domain routing protocol that enables network operators within each autonomous system (AS) to influence routing decisions by independently setting local policies on route filtering and selection. This independence leads to fragile networking and makes analysis of policy configurations very complex. To aid the systematic and efficient study of the policy configuration space, this paper presents a reduction calculus on policy-based routing systems. In the calculus, we provide two types of reduction rules that transform policy configurations by merging duplicate and complementary router configurations to simplify analysis. We show that the reductions are sound, dual of each other and are locally complete. The reductions are also computationally attractive, requiring only local configuration information and modification. These properties establish our reduction calculus as a sound, efficient, and complete theory for scaling up existing analysis techniques

Measurement of gut permeability using fluorescent tracer agent technology

Abstract The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use

Management of febrile neutropenia in the United Kingdom: time for a national trial?

Recent advances in febrile neutropenia (FN) have highlighted the value of risk stratification and the evolving role of oral antibiotics with early hospital discharge in low-risk patients. The aim of this study was to survey whether these advances have been translated into routine clinical practice in the UK. Questionnaires were sent to cancer clinicians across the UK to determine clinicians' routine management of FN, including use of risk stratification, antibiotic regimen and criteria for hospital discharge. In all, 128 clinicians responded, representing 50 cancer departments (83%). Only 38% of respondents stratify patients according to risk and with substantial variation in the criteria defining ‘low-risk'. Furthermore, only 22% of clinicians use oral antibiotics as first-line treatment in any patients with FN, but this was significantly greater among clinicians who do compared to those who do not stratify patients by risk, 51 vs 4% (P<0.0001). These findings suggest a slow and/or cautious introduction of newer strategies for the management of low-risk FN in the UK. However, 84% of respondents confirmed their willingness to participate in a trial of oral antibiotics combined with early discharge in low-risk FN