Indagine modellistica sulla tenuta idraulica delle difese arginali deputate alla protezione idraulica del territorio

La prima parte di questo lavoro di tesi tratta dell’interazione tra un bacino di laminazione e il sottostante acquifero: è in fase di progetto, infatti, la costruzione di una cassa di espansione sul torrente Baganza, a monte della città di Parma. L’obiettivo di tale intervento è di ridurre il rischio di esondazione immagazzinando temporaneamente, in un serbatoio artificiale, la parte più pericolosa del volume di piena che verrebbe rilasciata successivamente con portate che possono essere agevolmente contenute nel tratto cittadino del torrente. L’acquifero è stato preliminarmente indagato e monitorato permettendone la caratterizzazione litostratigrafica. La stratigrafia si può riassumere in una sequenza di strati ghiaioso-sabbiosi con successione di lenti d’argilla più o meno spesse e continue, distinguendo due acquiferi differenti (uno freatico ed uno confinato). Nel presente studio si fa riferimento al solo acquifero superficiale che è stato modellato numericamente, alle differenze finite, per mezzo del software MODFLOW_2005. L'obiettivo del presente lavoro è di rappresentare il sistema acquifero nelle condizioni attuali (in assenza di alcuna opera) e di progetto. La calibrazione è stata condotta in condizioni stazionarie utilizzando i livelli piezometrici raccolti nei punti d’osservazione durante la primavera del 2013. I valori di conducibilità idraulica sono stati stimati per mezzo di un approccio geostatistico Bayesiano. Il codice utilizzato per la stima è il bgaPEST, un software gratuito per la soluzione di problemi inversi fortemente parametrizzati, sviluppato sulla base dei protocolli del software PEST. La metodologia inversa stima il campo di conducibilità idraulica combinando osservazioni sullo stato del sistema (livelli piezometrici nel caso in esame) e informazioni a-priori sulla struttura dei parametri incogniti. La procedura inversa richiede il calcolo della sensitività di ciascuna osservazione a ciascuno dei parametri stimati; questa è stata valutata in maniera efficiente facendo ricorso ad una formulazione agli stati aggiunti del codice in avanti MODFLOW_2005_Adjoint. I risultati della metodologia sono coerenti con la natura alluvionale dell'acquifero indagato e con le informazioni raccolte nei punti di osservazione. Il modello calibrato può quindi essere utilizzato come supporto alla progettazione e gestione dell’opera di laminazione. La seconda parte di questa tesi tratta l'analisi delle sollecitazioni indotte dai percorsi di flusso preferenziali causati da fenomeni di piping all’interno dei rilevati arginali. Tali percorsi preferenziali possono essere dovuti alla presenza di gallerie scavate da animali selvatici. Questo studio è stato ispirato dal crollo del rilevato arginale del Fiume Secchia (Modena), che si è verificato in gennaio 2014 a seguito di un evento alluvionale, durante il quale il livello dell'acqua non ha mai raggiunto la sommità arginale. La commissione scientifica, la cui relazione finale fornisce i dati utilizzati per questo studio, ha attribuito, con molta probabilità, il crollo del rilevato alla presenza di tane di animali. Con lo scopo di analizzare il comportamento del rilevato in condizioni integre e in condizioni modificate dall'esistenza di un tunnel che attraversa il manufatto arginale, è stato realizzato un modello numerico 3D dell’argine mediante i noti software Femwater e Feflow. I modelli descrivono le infiltrazioni all'interno del rilevato considerando il terreno in entrambe le porzioni sature ed insature, adottando la tecnica agli elementi finiti. La tana è stata rappresentata da elementi con elevata permeabilità e porosità, i cui valori sono stati modificati al fine di valutare le diverse influenze sui flussi e sui contenuti idrici. Per valutare se le situazioni analizzate presentino o meno il verificarsi del fenomeno di erosione, sono stati calcolati i valori del fattore di sicurezza. Questo è stato valutato in differenti modi, tra cui quello recentemente proposto da Richards e Reddy (2014), che si riferisce al criterio di energia cinetica critica. In ultima analisi è stato utilizzato il modello di Bonelli (2007) per calcolare il tempo di erosione ed il tempo rimanente al collasso del rilevato.

Sustained delivery by leucine-modified chitosan spray-dried respirable powders

The controlled co-delivery of multiple agents to the lung offers potential benefits to patients. This study investigated the preparation and characterisation of highly respirable spray-dried powders displaying the sustained release of two chemically distinct therapeutic agents. Spray-dried powders were produced from 30% (v/v) aqueous ethanol formulations that contained hydrophilic (terbutaline sulphate) and hydrophobic (beclometasone dipropionate) model drugs, chitosan (as a drug release modifier) and leucine (aerosolisation enhancer). The influence of chitosan molecular weight on spray-drying thermal efficiency, aerosol performance and drug release profile was investigated. Resultant powders were physically characterised: with in vitro aerosolisation performance and drug release profile investigated by the Multi-Stage Liquid Impinger and modified USP II dissolution apparatus, respectively. It was found that increased chitosan molecular weight gave increased spray-drying thermal efficiency. The powders generated were of a suitable size for inhalation—with emitted doses over 90% and fine particle fractions up to 72% of the loaded dose. Sustained drug release profiles were observed in dissolution tests for both agents: increased chitosan molecular weight associated with increased duration of drug release. The controlled co-delivery of hydrophilic and hydrophobic entities underlines the capability of spray drying to produce respirable particles with sustained release for delivery to the lung. (c) 2009 Elsevier B.V. All rights reserved.

Modified release of beclometasone dipropionate from chitosan-basedd spray-dried respirable powders

Dry powders for inhalation were prepared by spray drying a 30% v/v aqueous ethanol formulation containing beclometasone dipropionate (BDP), lactose, leucine and chitosan (low, medium or high molecular weight (MW), or combinations thereof). Following physical characterisation of the powders, the aerosolisation and dissolution properties of the powders were investigated using Multi-Stage Liquid Impinger and USP II dissolution apparatus, respectively. The powders were highly dispersible, with emitted doses in excess of 90% of loaded powder aerosolised from a Spinhaler dry powder inhaler. The fine particle fraction (FPF) was observed to decrease, whereas the time for 100% drug release increased, with increasing chitosan MW. For example, the low MW formulation exhibited an FPF of 64% and a 100% dissolution time of 2 h, whereas the high MW formulation demonstrated an FPF of 54% and a dissolution time of 12 h. These powders would be anticipated to deposit predominately in the lower regions of the lung following inhalation, and then undergo delayed rather than instantaneous drug release, offering the potential to reduce dosing frequency and improve patient compliance. (c) 2008 Elsevier B.V. All rights reserved.

Chitosan-based spray-dried respirable powders for sustained delivery of terbutaline sulfate

In this study, we describe the preparation of highly dispersible dry powders for pulmonary drug delivery that display sustained drug release characteristics. Powders were prepared by spray-drying 30% v/v aqueous ethanol formulations containing terbutaline sulfate as a model drug, chitosan as a drug release modifier and leucine as an aerosolisation enhancer. The influence of chitosan molecular weight on the drug release profile was investigated by using low, medium and high molecular weight chitosan or combinations thereof. Following spray-drying, resultant powders were characterised using scanning electron microscopy, laser diffraction, tapped density analysis, differential scanning calorimetry and thermogravitational analysis. The in vitro aerosolisation performance and drug release profile were investigated using Multi-Stage Liquid Impinger analysis and modified USP II dissolution apparatus, respectively. The powders generated were of a suitable aerodynamic size for inhalation, had low moisture content and were amorphous in nature. The powders were highly dispersible, with emitted doses of over 90% and fine particle fractions of up to 82% of the total loaded dose, and mass median aerodynamic diameters of less than 2.5microm. A sustained drug release profile was observed during dissolution testing; increasing the molecular weight of the chitosan in the formulation increased the duration of drug release. (c)2007 Elsevier B.V. All rights reserved.

Spatial aspects of MRSA epidemiology:A case study using stochastic simulation, kernel estimation and SaTScan

The identification of disease clusters in space or space-time is of vital importance for public health policy and action. In the case of methicillin-resistant Staphylococcus aureus (MRSA), it is particularly important to distinguish between community and health care-associated infections, and to identify reservoirs of infection. 832 cases of MRSA in the West Midlands (UK) were tested for clustering and evidence of community transmission, after being geo-located to the centroids of UK unit postcodes (postal areas roughly equivalent to Zip+4 zip code areas). An age-stratified analysis was also carried out at the coarser spatial resolution of UK Census Output Areas. Stochastic simulation and kernel density estimation were combined to identify significant local clusters of MRSA (p<0.025), which were supported by SaTScan spatial and spatio-temporal scan. In order to investigate local sampling effort, a spatial 'random labelling' approach was used, with MRSA as cases and MSSA (methicillin-sensitive S. aureus) as controls. Heavy sampling in general was a response to MRSA outbreaks, which in turn appeared to be associated with medical care environments. The significance of clusters identified by kernel estimation was independently supported by information on the locations and client groups of nursing homes, and by preliminary molecular typing of isolates. In the absence of occupational/ lifestyle data on patients, the assumption was made that an individual's location and consequent risk is adequately represented by their residential postcode. The problems of this assumption are discussed, with recommendations for future data collection.

The development and applications of the combined use of NMR and ultrasound

The objective of the research carried out in this report was to observe the first ever in-situ sonochemical reaction in the NMR Spectrometer in the megahertz region of ultrasound. Several reactions were investigated as potential systems for a sonochemical reaction followed by NMR spectroscopy. The primary problem to resolve when applying ultrasound to a chemical reaction is that of heating. Ultrasound causes the liquid to move and produces 'hot spots' resulting in an increase in sample temperature. The problem was confronted by producing a device that would counteract this effect and so remove the need to account for heating. However, the design of the device limited the length of time during which it would function. Longer reaction times were required to enable observations to be carried out in the NMR spectrometer. The fIrst and most obvious reactions attempted were those of the well-known ultrasonic dosimeter. Such a reaction would, theoretically, enable the author to simultaneously observe a reaction and determine the exact power entering the system for direct comparison of results. Unfortunately, in order to monitor the reactions in the NMR spectrometer the reactant concentrations had to be signifIcantly increased, which resulted in a notable increase in reaction time, making the experiment too lengthy to follow in the time allocated. The Diels-Alder Reaction is probably one of the most highly investigated reaction systems in the field of chemistry and it was this to which the author turned her attention. Previous authors have carried out ultrasonic investigations, with considerable success, for the reaction of anthracene with maleic anhydride. It was this reaction in particular that was next attempted. The first ever sonochemically enhanced reaction using a frequency of ultrasound in the megahertz (MHz) region was successfully carried out as bench experiments. Due to the complexity of the component reactants the product would precipitate from the solution and because the reaction could only be monitored by its formation, it was not possible to observe the reaction in the NMR spectrometer. The solvolysis of 2-chloro-2-methylpropane was examined in various solvent systems; the most suitable of which was determined to be aqueous 2-methylpropan-2-ol. The experiment was successfully enhanced by the application of ultrasound and monitored in-situ in the NMR spectrometer. The increase in product formation of an ultrasonic reaction over that of a traditional thermal reaction occurred. A range of 1.4 to 2.9 fold improvement was noted, dependent upon the reaction conditions investigated. An investigation into the effect of sonication upon a large biological molecule, in this case aqueous lysozyme, was carried out. An easily observed effect upon the sample was noted but no explanation for the observed effects could be established.

Epidemiology of community-acquired meticillin-resistant Staphylococcus aureus obtained from the UK West Midlands region

Between January 2005 and December 2005, 199 meticillin-resistant Staphylococcus aureus (MRSA) isolates were obtained from nonhospitalised patients presenting skin and soft tissue infections to local general practitioners. The study area incorporated 57 surgeries from three Primary Care Trusts in the Lichfield, Tamworth, Burntwood, North and East Birmingham regions of Central England, UK. Following antibiotic susceptibility testing, pulsed-field gel electrophoresis, Panton-Valentine leukocidin gene detection and SCCmec element assignment, 95% of the isolates were shown to be related to hospital epidemic strains EMRSA-15 and EMRSA-16. In total 87% of the isolate population harboured SCCmec IV, 9% had SCCmec II and 4% were identified as carrying novel SCCmec IIIa-mecI. When mapped to patient home postcode, a diverse distribution of isolates harbouring SCCmec II and SCCmec IV was observed; however, the majority of isolates harbouring SCCmec IIIa-mecI were from patients residing in the north-west of the study region, highlighting a possible localised clonal group. Transmission of MRSA from the hospital setting into the surrounding community population, as demonstrated by this study, warrants the need for targeted patient screening and decolonisation in both the clinical and community environments.

Where are UK manufacturers along the journey to Lean?

Lean manufacturing is now widely accepted amongst UK based manufacturers as a valuable aid to achieving competitiveness. The associated principles, tools and techniques have been well documented since the 1980s and there are many competent practitioners, consultants and academics promoting Lean manufacturing. Therefore, it is useful to ask how well UK manufacturers are progressing along the Lean journey? This paper therefore provides an insight into this question by presenting the results, based on indepth case studies of five representative companies, that reflect progress being made within the UK manufacturing sector.