Prophylactic ranitidine treatment in critically ill children - a population pharmacokinetic study

Aims - To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. Methods - Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. Results - A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (−12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h−1 for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h−1 and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. Conclusions - Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary.

Average error exponent in Gallager low-density parity-check codes

We present a theoretical method for a direct evaluation of the average error exponent in Gallager error-correcting codes using methods of statistical physics. Results for the binary symmetric channel(BSC)are presented for codes of both finite and infinite connectivity.

Average and reliability error exponents in low-density parity-check codes

We present a theoretical method for a direct evaluation of the average and reliability error exponents in low-density parity-check error-correcting codes using methods of statistical physics. Results for the binary symmetric channel are presented for codes of both finite and infinite connectivity.

Relating two simultaneous events in discourse: the role of on-goingness devices in L1 Tunisian Arabic, L1 French and L2 French by Tunisian learners

Our PhD study focuses on the role of aspectual marking in expressing simultaneity of events in Tunisian Arabic as a first language, French as a first language, as well as in French as a second language by Tunisian learners at different acquisitional stages. We examine how the explicit markers of on-goingness qa:’id and «en train de» in Tunisian Arabic and in French respectively are used to express this temporal relation, in competition with the simple forms, the prefixed verb form in Tunisian Arabic and the présent de l’indicatif in French. We use a complex verbal task of retelling simultaneous events sharing an interval on the time axis based on eight videos presenting two situations happening in parallel. Two types of simultaneity are exploited: perfect simultaneity (when the two situations are parallel to each other) and inclusion (one situation is framed by the second one). Our informants in French and in Tunisian Arabic have two profiles, highly educated and low educated speakers. We show that the participants’ response to the retelling task varies according to their profiles, and so does their use of the on-goingness devices in the expression of simultaneity. The differences observed between the two profile groups are explained by the degree to which the speakers have developed a habit of responding to tasks. This is a skill typically acquired during schooling. We notice overall that the use of qa:’id as well as of «en train de» is less frequent in the data than the use of the simple forms. However, qa:’id as well as «en train de» are employed to play discursive roles that go beyond the proposition level. We postulate that despite the shared features between Tunisian Arabic and French regarding marking the concept of on-goingness, namely the presence of explicit lexical, not fully grammaticalised markers competing with other non-marked forms, the way they are used in the discourse of simultaneous events shows clear differences. We explain that «en train de» plays a more contrastive role than qa:’id and its use in discourse obeys a stricter rule. In cases of the inclusion type of simultaneity, it is used to construe the ‘framing’ event that encloses the second event. In construing perfectly simultaneneous events, and when both «en train de» and présent de l’indicatif are used, the proposition with «en train de» generally precedes the proposition with présent de l’indicatif, and not the other way around. qa:id obeys, but to a less strict rule as it can be used interchangeably with the simple form regardless of the order of propositions. The contrastive analysis of French L1 and L2 reveals learners’ deviations from natives’ use of on-goingness devices. They generalise the use of «en train de» and apply different rules to the interaction of the different marked and unmarked forms in discourse. Learners do not master its role in discourse even at advanced stages of acquisition despite its possible emergence around the basic and intermediate varieties. We conclude that the native speakers’ use of «en train de» involves mastering its role at the macro-structure level. This feature, not explicitly available to learners in the input, might persistently present a challenge to L2 acquisition of the periphrasis.

An investigation into formal and functional characteristics of qualifications in legislative writing and its application to English for academic legal purposes.

The present investigation is based on a linguistic analysis of the 'Housing Act 1980' and attempts to examine the role of qualifications in the structuring of the legislative statement. The introductory chapter isolates legislative writing as a "sub-variety “of legal language and provides an overview of the controversies surrounding the way it is written and the problems it poses to its readers. Chapter two emphasizes the limitations of the available work on the description of language-varieties for the analysis of legislative writing and outlines the approach adopted for the present analysis. This chapter also gives some idea of the information-structuring of legislative provisions and establishes qualification as a key element in their textualisation. The next three chapters offer a detailed account of the ten major qualification-types identified in the corpus, concentrating on the surface form they take, the features of legislative statements they textualize and the syntactic positions to which they are generally assigned in the statement of legislative provisions. The emerging hypotheses in these chapters have often been verified through a specialist reaction from a Parliamentary Counsel, largely responsible for the writing of the ‘Housing Act 1980’• The findings suggest useful correlations between a number of qualificational initiators and the various aspects of the legislative statement. They also reveal that many of these qualifications typically occur in those clause-medial syntactic positions which are sparingly used in other specialist discourse, thus creating syntactic discontinuity in the legislative sentence. Such syntactic discontinuities, on the evidence from psycholinguistic experiments reported in chapter six, create special problems in the processing and comprehension of legislative statements. The final chapter converts the main linguistic findings into a series of pedagogical generalizations, offers indications of how this may be applied in EALP situations and concludes with other considerations of possible applications.

Intelligent execution monitoring and error analysis in planning involving processes

An intelligent agent, operating in an external world which cannot be fully described in its internal world model, must be able to monitor the success of a previously generated plan and to respond to any errors which may have occurred. The process of error analysis requires the ability to reason in an expert fashion about time and about processes occurring in the world. Reasoning about time is needed to deal with causality. Reasoning about processes is needed since the direct effects of a plan action can be completely specified when the plan is generated, but the indirect effects cannot. For example, the action `open tap' leads with certainty to `tap open', whereas whether there will be a fluid flow and how long it might last is more difficult to predict. The majority of existing planning systems cannot handle these kinds of reasoning, thus limiting their usefulness. This thesis argues that both kinds of reasoning require a complex internal representation of the world. The use of Qualitative Process Theory and an interval-based representation of time are proposed as a representation scheme for such a world model. The planning system which was constructed has been tested on a set of realistic planning scenarios. It is shown that even simple planning problems, such as making a cup of coffee, require extensive reasoning if they are to be carried out successfully. The final Chapter concludes that the planning system described does allow the correct solution of planning problems involving complex side effects, which planners up to now have been unable to solve.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. © 2009 Elsevier B.V. and ECNP.

Estimating the efficiency of healthcare facilities providing HIV/AIDS treatment in Zambia:a data envelopment approach

Zambia and many other countries in Sub-Saharan Africa face a key challenge of sustaining high levels of coverage of AIDS treatment under prospects of dwindling global resources for HIV/AIDS treatment. Policy debate in HIV/AIDS is increasingly paying more focus to efficiency in the use of available resources. In this chapter, we apply Data Envelopment Analysis (DEA) to estimate short term technical efficiency of 34 HIV/AIDS treatment facilities in Zambia. The data consists of input variables such as human resources, medical equipment, building space, drugs, medical supplies, and other materials used in providing HIV/AIDS treatment. Two main outputs namely, numbers of ART-years (Anti-Retroviral Therapy-years) and pre-ART-years are included in the model. Results show the mean technical efficiency score to be 83%, with great variability in efficiency scores across the facilities. Scale inefficiency is also shown to be significant. About half of the facilities were on the efficiency frontier. We also construct bootstrap confidence intervals around the efficiency scores.

Potassium canrenoate treatment in paediatric patients:a population pharmacokinetic study using novel dried blood spot sampling

Objective: To characterize the population pharmacokinetics of canrenone following administration of potassium canrenoate (K-canrenoate) in paediatric patients. Methods: Data were collected prospectively from 37 paediatric patients (median weight 2.9 kg, age range 2 days–0.85 years) who received intravenous K-canrenoate for management of retained fluids, for example in heart failure and chronic lung disease. Dried blood spot (DBS) samples (n = 213) from these were analysed for canrenone content and the data subjected to pharmacokinetic analysis using nonlinear mixed-effects modelling. Another group of patients (n = 16) who had 71 matching plasma and DBS samples was analysed separately to compare canrenone pharmacokinetic parameters obtained using the two different matrices. Results: A one-compartment model best described the DBS data. Significant covariates were weight, postmenstrual age (PMA) and gestational age. The final population models for canrenone clearance (CL/F) and volume of distribution (V/F) in DBS were CL/F (l/h) = 12.86 ×  (WT/70.0)0.75 × e [0.066 ×  (PMA - 40]) and V/F (l) = 603.30 ×  (WT/70) × (GA/40)1.89 where weight is in kilograms. The corresponding values of CL/F and V/F in a patient with a median weight of 2.9 kg are 1.11 l/h and 20.48 l, respectively. Estimated half-life of canrenone based on DBS concentrations was similar to that based on matched plasma concentrations (19.99 and 19.37 h, respectively, in 70 kg patient). Conclusion: The range of estimated CL/F in DBS for the study population was 0.12–9.62 l/h; hence, bodyweight-based dosage adjustment of K-canrenoate appears necessary. However, a dosing scheme that takes into consideration both weight and age (PMA/gestational age) of paediatric patients seems more appropriate.

Non-Gaussian error probability in optical soliton transmission

We find the probability distribution of the fluctuating parameters of a soliton propagating through a medium with additive noise. Our method is a modification of the instanton formalism (method of optimal fluctuation) based on a saddle-point approximation in the path integral. We first solve consistently a fundamental problem of soliton propagation within the framework of noisy nonlinear Schrödinger equation. We then consider model modifications due to in-line (filtering, amplitude and phase modulation) control. It is examined how control elements change the error probability in optical soliton transmission. Even though a weak noise is considered, we are interested here in probabilities of error-causing large fluctuations which are beyond perturbation theory. We describe in detail a new phenomenon of soliton collapse that occurs under the combined action of noise, filtering and amplitude modulation. © 2004 Elsevier B.V. All rights reserved.

Adherence to treatment in children and adolescents with cystic fibrosis:a cross-sectional, multi-method study investigating the influence of beliefs about treatment and parental depressive symptoms

Background: Adherence to treatment is often reported to be low in children with cystic fibrosis. Adherence in cystic fibrosis is an important research area and more research is needed to better understand family barriers to adherence in order for clinicians to provide appropriate intervention. The aim of this study was to evaluate adherence to enzyme supplements, vitamins and chest physiotherapy in children with cystic fibrosis and to determine if any modifiable risk factors are associated with adherence. Methods: A sample of 100 children (≤18 years) with cystic fibrosis (44 male; median [range] 10.1 [0.2-18.6] years) and their parents were recruited to the study from the Northern Ireland Paediatric Cystic Fibrosis Centre. Adherence to enzyme supplements, vitamins and chest physiotherapy was assessed using a multi-method approach including; Medication Adherence Report Scale, pharmacy prescription refill data and general practitioner prescription issue data. Beliefs about treatments were assessed using refined versions of the Beliefs about Medicines Questionnaire-specific. Parental depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Results: Using the multi-method approach 72% of children were classified as low-adherers to enzyme supplements, 59% low-adherers to vitamins and 49% low-adherers to chest physiotherapy. Variations in adherence were observed between measurement methods, treatments and respondents. Parental necessity beliefs and child age were significant independent predictors of child adherence to enzyme supplements and chest physiotherapy, but parental depressive symptoms were not found to be predictive of adherence. Conclusions: Child age and parental beliefs about treatments should be taken into account by clinicians when addressing adherence at routine clinic appointments. Low adherence is more likely to occur in older children, whereas, better adherence to cystic fibrosis therapies is more likely in children whose parents strongly believe the treatments are necessary. The necessity of treatments should be reinforced regularly to both parents and children.