Early detection of delirium in older medical inpatients: prodrome, predictors and motor subtyping

Background Delirium is highly prevalent, especially in older patients. It independently leads to adverse outcomes, but remains under-detected, particularly hypoactive forms. Although early identification and intervention is important, delirium prevention is key to improving outcomes. The delirium prodrome concept has been mooted for decades, but remains poorly characterised. Greater understanding of this prodrome would promote prompt identification of delirium-prone patients, and facilitate improved strategies for delirium prevention and management. Methods Medical inpatients of ≥70 years were screened for prevalent delirium using the Revised Delirium Rating Scale (DRS--‐R98). Those without prevalent delirium were assessed daily for delirium development, prodromal features and motor subtype. Survival analysis models identified which prodromal features predicted the emergence of incident delirium in the cohort in the first week of admission. The Delirium Motor Subtype Scale-4 was used to ascertain motor subtype. Results Of 555 patients approached, 191 patients were included in the prospective study. The median age was 80 (IQR 10) and 101 (52.9%) were male. Sixty-one patients developed incident delirium within a week of admission. Several prodromal features predicted delirium emergence in the cohort. Firstly, using a novel Prodromal Checklist based on the existing literature, and controlling for confounders, seven predictive behavioural features were identified in the prodromal period (for example, increasing confusion; and being easily distractible). Additionally, using serial cognitive tests and the DRS-R98 daily, multiple cognitive and other core delirium features were detected in the prodrome (for example inattention; and sleep-wake cycle disturbance). Examining longitudinal motor subtypes in delirium cases, subtypes were found to be predominantly stable over time, the most prevalent being hypoactive subtype (62.3%). Discussion This thesis explored multiple aspects of delirium in older medical inpatients, with particular focus on the characterisation of the delirium prodrome. These findings should help to inform future delirium educational programmes, and detection and prevention strategies.

Luna Language Report

Luna is an object-oriented language. It does not, as do many other object-oriented languages, have a conventional procedural language as a base. It is strongly typed and modular. The elegance of Luna is that it is entirely reference based, there are no static objects. Luna is similar to Oberon in that inheritance and subtyping is based on type extension.

Comparison of PCR, nested PCR, and random amplified polymorphic DNA PCR for detection and typing of Ureaplasma urealyticum in specimens from pregnant women

A PCR assay, using three primer pairs, was developed for the detection of Ureaplasma urealyticum, parvo biovar, mba types 1, 3, and 6, in cultured clinical specimens. The primer pairs were designed by using the polymorphic base positions within a 310- to 311-bp fragment of the 5* end and upstream control region of the mba gene. The specificity of the assay was confirmed with reference serovars 1, 3, 6, and 14 and by the amplified-fragment sizes (81 bp for mba 1, 262 bp for mba 3, and 193 bp for mba 6). A more sensitive nested PCR was also developed. This involved a first-step PCR, using the primers UMS-125 and UMA226, followed by the nested mba-type PCR described above. This nested PCR enabled the detection and typing of small numbers of U. urealyticum cells, including mixtures, directly in original clinical specimens. By using random amplified polymorphic DNA (RAPD) PCR with seven arbitrary primers, we were also able to differentiate the two biovars of U. urealyticum and to identify 13 RAPD-PCR subtypes. By applying these subtyping techniques to clinical samples collected from pregnant women, we established that (i) U. urealyticum is often a persistent colonizer of the lower genital tract from early midtrimester until the third trimester of pregnancy, (ii) mba type 6 was isolated significantly more often (P 5 0.048) from women who delivered preterm than from women who delivered at term, (iii) no particular ureaplasma subtype(s) was associated with placental infections and/or adverse pregnancy outcomes, and (iv) the ureaplasma subtypes most frequently isolated from women were the same subtypes most often isolated from infected placentas.

The phylogeny of Ureaplasma urealyticum based on the mba gene fragment

Sequencing of mba gene fragments of reference strains of Ureaplasma urealyticum serovars 1, 3, 6, 14, in addition to 33 clinical U. urealyticum isolates is reported. A phylogenetic tree deduced from an alignment of these sequences clearly demonstrates two major clusters (confidence limit 100%), which equate to the parvo and T960 biovars, and five types which we have designated mba 1, 3, 6, 8 and X. These relationships are supported by bootstrap analysis. Polymorphisms within the mba fragment of types mba 1, 3, and 6 were used to define nine subtypes (mba 1a, 1b, 3a, 3b, 3c, 3d, 3e, 6a, and 6b) thus facilitating high resolution typing of U. urealyticum. Inclusion of the reference strains for serovars 1, 3, 6, and 8 in the mba typing scheme showed that the results of this analysis are broadly consistent with currently accepted serotyping. In addition a ure gene fragment from nine of the clinical isolates was amplified and sequenced. Comparisons of the sequences clearly distinguished the two biovars of U. urealyticum; however this fragment was invariant within the parvo biovar. This study has shown that the sequence of the mba can reveal the fine details of the relationships between U. urealyticum isolates and also supports the significant evolutionary gap between the two biovars.

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom

Objective - To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods - HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. Results - The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10-99). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10-5), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HkA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. Conclusion - HLA-B27 and -B60 are associated with susceptibility to AS, but differences in BLA-B27 subtype do not affect susceptibility to AS in this white population.

采用了剪枝优化的子类型关系判定算法

静态类型化XML处理语言为处理XML数据提供了新的途径,但现有的此类语言大多数效率较低.研究此类语言的一个重要问题——子类型关系的判定,并使用剪枝优化策略对XDuce的子类型关系判定算法进行优化.实验数据显示,优化后算法的执行效率平均提高20%.该策略具有普遍性,对所有使用类似算法的静态类型化XML处理语言都有效.

Typability is Undecidable for F+Eta

System F is the well-known polymorphically-typed λ-calculus with universal quantifiers ("∀"). F+η is System F extended with the eta rule, which says that if term M can be given type τ and M η-reduces to N, then N can also be given the type τ. Adding the eta rule to System F is equivalent to adding the subsumption rule using the subtyping ("containment") relation that Mitchell defined and axiomatized [Mit88]. The subsumption rule says that if M can be given type τ and τ is a subtype of type σ, then M can be given type σ. Mitchell's subtyping relation involves no extensions to the syntax of types, i.e., no bounded polymorphism and no supertype of all types, and is thus unrelated to the system F≤("F-sub"). Typability for F+η is the problem of determining for any term M whether there is any type τ that can be given to it using the type inference rules of F+η. Typability has been proven undecidable for System F [Wel94] (without the eta rule), but the decidability of typability has been an open problem for F+η. Mitchell's subtyping relation has recently been proven undecidable [TU95, Wel95b], implying the undecidability of "type checking" for F+η. This paper reduces the problem of subtyping to the problem of typability for F+η, thus proving the undecidability of typability. The proof methods are similar in outline to those used to prove the undecidability of typability for System F, but the fine details differ greatly.

System F with Constraint Types

System F is a type system that can be seen as both a proof system for second-order propositional logic and as a polymorphic programming language. In this work we explore several extensions of System F by types which express subtyping constraints. These systems include terms which represent proofs of subtyping relationships between types. Given a proof that one type is a subtype of another, one may use a coercion term constructor to coerce terms from the first type to the second. The ability to manipulate type constraints as first-class entities gives these systems a lot of expressive power, including the ability to encode generalized algebraic data types and intensional type analysis. The main contributions of this work are in the formulation of constraint types and a proof of strong normalization for an extension of System F with constraint types.

Type Inference for Variant Object Types

Existing type systems for object calculi are based on invariant subtyping. Subtyping invariance is required for soundness of static typing in the presence of method overrides, but it is often in the way of the expressive power of the type system. Flexibility of static typing can be recovered in different ways: in first-order systems, by the adoption of object types with variance annotations, in second-order systems by resorting to Self types. Type inference is known to be P-complete for first-order systems of finite and recursive object types, and NP-complete for a restricted version of Self types. The complexity of type inference for systems with variance annotations is yet unknown. This paper presents a new object type system based on the notion of Split types, a form of object types where every method is assigned two types, namely, an update type and a select type. The subtyping relation that arises for Split types is variant and, as a result, subtyping can be performed both in width and in depth. The new type system generalizes all the existing first-order type systems for objects, including systems based on variance annotations. Interestingly, the additional expressive power does not affect the complexity of the type inference problem, as we show by presenting an O(n^3) inference algorithm.

Safe Compositional Specification of Network Systems With Polymorphic, Constrained Types

In the framework of iBench research project, our previous work created a domain specific language TRAFFIC [6] that facilitates specification, programming, and maintenance of distributed applications over a network. It allows safety property to be formalized in terms of types and subtyping relations. Extending upon our previous work, we add Hindley-Milner style polymorphism [8] with constraints [9] to the type system of TRAFFIC. This allows a programmer to use for-all quantifier to describe types of network components, escalating power and expressiveness of types to a new level that was not possible before with propositional subtyping relations. Furthermore, we design our type system with a pluggable constraint system, so it can adapt to different application needs while maintaining soundness. In this paper, we show the soundness of the type system, which is not syntax-directed but is easier to do typing derivation. We show that there is an equivalent syntax-directed type system, which is what a type checker program would implement to verify the safety of a network flow. This is followed by discussion on several constraint systems: polymorphism with subtyping constraints, Linear Programming, and Constraint Handling Rules (CHR) [3]. Finally, we provide some examples to illustrate workings of these constraint systems.

Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome

The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification model was investigated to distinguish the distinct subclasses of pediatric and adult leukemia, as well as MDS. Overall, the accuracy of the diagnostic classification model for subtyping leukemia was approximately 93%, but this was not reflected for the MDS samples giving only approximately 50% accuracy. Discordant samples of MDS were classified either into acute myeloid leukemia (AML) or