Application of Monte Carlo simulations to identify an appropriate dosage strategy for patients receiving a continuous intravenous infusion of enoxaparin

Aim: To identify an appropriate dosage strategy for patients receiving enoxaparin by continuous intravenous infusion (CII). Methods: Monte Carlo simulations were performed in NONMEM, (200 replicates of 1000 patients) to predict steady state anti-Xa concentrations (Css) for patients receiving a CII of enoxaparin. The covariate distribution model was simulated based on covariate demographics in the CII study population. The impact of patient weight, renal function (creatinine clearance (CrCL)) and patient location (intensive care unit (ICU)) were evaluated. A population pharmacokinetic model was used as the input-output model (1-compartment first order output model with mixed residual error structure). Success of a dosing regimen was based on the percent of Css that is between the therapeutic range of 0.5 IU/ml to 1.2 IU/ml. Results: The best dose for patients in the ICU was 4.2IU/kg/h (success mean 64.8% and 90% prediction interval (PI): 60.1–69.8%) if CrCL60ml/min, the best dose was 8.3IU/kg/h (success mean 65.4%, 90% PI: 58.5–73.2%). Simulations suggest that there was a 50% improvement in the success of the CII if the dose rate for ICU patients with CrCL

The dark side of romantic relationships: The role of person and situational variable in the experience and expression of jealousy

The aim of this study was to further our understanding of the factors that influence the experience of jealousy in romantic relationships. More specifically, the person variables of neuroticism, gender, and attachment style were examined, together with situational determinants such as past infidelity. The research also assessed the interaction between person and situadonal determinants of jealousy, and the relative importance of the various predictors. Questionnaires were completed by 102 undergraduate psychology students and an addidonal five participants from the researcher's social network. Consistent with past research, there was a positive association between neurodcism and chronic, emodonal, and behavioural jealousy. Furthermore, there was a posidve associadon between anxious attachment and jealousy, even when neurodcism was controlled. Past experience of infidelity and attachment dimensions had interacdve effects on jealousy. Interesdngly, the reladve importance of the predictors varied across the dimensions of jealousy. The results extend research in the area of person and situadonal determinants of jealousy, and are discussed in terms of attachment theory.

Drug combination: pharmaceutical technologies applied to the manufacturing of combined dosage forms for oral administration

Lo scopo di questa ricerca di dottorato è stato lo studio di una forma di dosaggio flessibile e personalizzabile, indirizzata alle necessità individuali di ogni paziente, per il trattamento dell’iperplasia prostatica benigna. La terapia proposta prevede l’utilizzo di due farmaci, un alfa bloccante (farmaco A) e un inibitore delle 5- fosfodiesterasi (farmaco B) e, somministrati in una singola forma di dosaggio contenenti differenti dosi e combinazioni dei due farmaci. Lo sviluppo di un sistema di rilascio per la somministrazione orale di farmaco A e farmaco B è stato realizzato grazie alla tecnologia Dome Matrix. La tecnologia si basa sull’assemblaggio di moduli utilizzati come elementi di controllo del rilascio. L’assemblaggio dei moduli può essere ottenuto attraverso diverse configurazioni. Sono stati quindi realizzati sistemi assemblati in grado di galleggiare sul contenuto gastrico; la prolungata permanenza della forma farmaceutica nello stomaco favorisce la solubilizzazione dei due principi attivi che quindi potrebbero raggiungere il sito di assorbimento nel primo tratto intestinale già in dispersione molecolare, condizione ideale per essere assorbiti. La prima parte della ricerca è stata focalizzata sulla realizzazione di un sistema assemblato a rilascio modificato di farmaco A. Moduli contenenti diversi dosaggi di farmaco sono stati assemblati in varie configurazioni e dosi differenti per ottenere una forma di dosaggio flessibile, adattabile alle esigenze terapeutiche del paziente. La seconda parte del lavoro di tesi ha riguardato la realizzazione di un sistema assemblato, contenente entrambi i farmaci in associazione. L’ultima parte della ricerca è stata svolta presso la “University of Texas at Austin” sotto la supervisione del Professor Nicholas Peppas. Il lavoro svolto è stato focalizzato sullo studio delle caratteristiche di rigonfiamento dei singoli moduli di farmaco e dei loro sistemi assemblati; il comportamento di tali sistemi è stato investigato anche grazie all’utilizzo della tecnica di tomografia computerizzata a raggi X.

Time trials on second-order and variable-learning-rate algorithms

The performance of seven minimization algorithms are compared on five neural network problems. These include a variable-step-size algorithm, conjugate gradient, and several methods with explicit analytic or numerical approximations to the Hessian.

A representation of representation applied to a discussion of variable binding

States or state sequences in neural network models are made to represent concepts from applications. This paper motivates, introduces and discusses a formalism for denoting such representations; a representation for representations. The formalism is illustrated by using it to discuss the representation of variable binding and inference abstractly, and then to present four specific representations. One of these is an apparently novel hybrid of phasic and tensor-product representations which retains the desirable properties of each.