A process-oriented approach to supporting Off-site Manufacture in construction projects

It is well-known that the use of off-site manufacture (OSM) techniques can assist in timely completion of a construction project though the utilisation of such techniques may have other disadvantages. Currently, OSM uptake within the Australian construction industry is limited. To successfully incorporate OSM practices within a construction project, it is crucial to understand the impact of OSM adoption on the processes used during a construction project. This paper presents how a systematic process-oriented approach may be able to support OSM utilisation within a construction project. Process modelling, analysis and automation techniques which are well-known within the Business Process Management (BPM) discipline have been applied to develop a collection of construction process models that represent the end-to-end generic construction value chain. The construction value chain enables researchers to identify key activities, resources, data, and stakeholders involved in construction processes in each defined construction phase. The collection of construction process models is then used as a basis for identification of potential OSM intervention points in collaboration with domain experts from the Australian construction industry. This ensures that the resulting changes reflect the needs of various stakeholders within the construction industry and have relevance in practice. Based on the input from the domain experts, these process models are further refined and operational requirements are taken into account to develop a prototype process automation (workflow) system that can support and coordinate OSM-related process activities. The resulting workflow system also has the potential to integrate with other IT solutions used within the construction industry (e.g., BIM, Acconex). As such, the paper illustrates the role that process-oriented thinking can play in assisting OSM adoption within the industry.

A qualitative investigation of drug use among Pakistani road users

Background Statistics on drug use by Pakistani drivers are not available, yet considerable numbers of drivers are believed to be drug addicted. The National Drug Abuse Assessment 2006/07, conducted by the United Nation Office on Drugs and Crime and the Ministry of Narcotics Control Pakistan reported that opiate users numbered 628,000, of which 77%were chronic heroin abusers. Injecting drug users have reportedly doubled in the decade to 2006 and drug use has been linked with many major crashes involving professional drivers. Aims This study explored a broad range of risk taking behaviours of road users, including drug use. It also investigated associations between risky road use and fatalism and other cultural beliefs. Methods This paper reports findings relating to drug driving in the cities of Lahore, Rawalpindi and Islamabad. Thirty semi-structured interviews were conducted with bus, truck, and taxi drivers, policy makers and field police officers. Results Interviews suggested widespread use of illicit drugs, particularly among bus, truck and taxi drivers. Reasons for drug use included recreational purposes, stimulants during long driving episodes, and substance addiction. Furthermore, the use of drugs and any association with road crashes was generally viewed as linked to fatalism rather than to any fault of an individual. In other words, people did not believe there was an association between drug use and road crashes, even if they had personally experienced such. Police knowledge of drug use among drivers was evident, although there is no formal drug driving testing regime in Pakistan. Discussion and conclusions The substantial increase in drug use among the population in recent years highlights a significant public health challenge in Pakistan. This qualitative research, although recognized as not representative of the broader population, suggests that there is significant cause for concern about drug driving, especially among professional drivers, and a need for further investigation and intervention.

Results of the Queensland 2007-2012 roadside drug testing program : the prevalence of three illicit drugs

The purpose of this investigation is to present an overview of roadside drug driving enforcement and detections in Queensland, Australia since the introduction of oral fluid screening. Drug driving is a problematic issue for road safety and investigations of the prevalence and impact of drug driving suggest that, in particular, the use of illicit drugs may increase a driver’s involvement in a road crash when compared to a driver who is drug free. In response to the potential increased crash involvement of drug impaired drivers, Australian police agencies have adopted the use of oral fluid analysis to detect the presence of illicit drugs in drivers. This paper describes the results of roadside drug testing for over 80,000 drivers in Queensland, Australia, from December 2007 to June 2012. It provides unique data on the prevalence of methamphetamine, cannabis and ecstasy in the screened population for the period. When prevalence rates are examined over time, drug driving detection rates have almost doubled from around 2.0% at the introduction of roadside testing operations to just under 4.0% in the latter years. The most common drug type detected was methamphetamine (40.8%) followed by cannabis (29.8%) and methamphetamine/cannabis combination (22.5%). By comparison, the rate of ecstasy detection was very low (1.7%). The data revealed a number of regional, age and gender patterns and variations of drug driving across the state. Younger drivers were more likely to test positive for cannabis whilst older drivers were more likely to test positive for methamphetamine. The overall characteristics of drivers who tested positive to the presence of at least one of the target illicit drugs are they are likely to be male, aged 30-39 years, be driving a car on Friday, Saturday or Sunday between 6:00PM and 6:00AM and to test positive for methamphetamine.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Modeling predictors of risky drug use behavior among male street laborers in urban Vietnam

Background The application of theoretical frameworks for modeling predictors of drug risk among male street laborers remains limited. The objective of this study was to test a modified version of the IMB (Information-Motivation-Behavioral Skills Model), which includes psychosocial stress, and compare this modified version with the original IMB model in terms of goodness-of-fit to predict risky drug use behavior among this population. Methods In a cross-sectional study, social mapping technique was conducted to recruit 450 male street laborers from 135 street venues across 13 districts of Hanoi city, Vietnam, for face-to-face interviews. Structural equation modeling (SEM) was used to analyze data from interviews. Results Overall measures of fit via SEM indicated that the original IMB model provided a better fit to the data than the modified version. Although the former model was able to predict a lesser variance than the latter (55% vs. 62%), it was of better fit. The findings suggest that men who are better informed and motivated for HIV prevention are more likely to report higher behavioral skills, which, in turn, are less likely to be engaged in risky drug use behavior. Conclusions This was the first application of the modified IMB model for drug use in men who were unskilled, unregistered laborers in urban settings. An AIDS prevention program for these men should not only distribute information and enhance motivations for HIV prevention, but consider interventions that could improve self-efficacy for preventing HIV infection. Future public health research and action may also consider broader factors such as structural social capital and social policy to alter the conditions that drive risky drug use among these men.

Governing young people’s drug use: Crime, harm and contemporary drug use practices

Since the nineteenth century, drug use has been variously understood as a problem of epidemiology, psychiatry, physiology, and criminality. Consequently drug research tends to be underpinned by assumptions of inevitable harm, and is often directed towards preventing drug use or solving problems. These constructions of the drug problem have generated a range of law enforcement responses, drug treatment technologies and rehabilitative programs that are intended to prevent drug related harm and resituate drug users in the realm of neo-liberal functional citizenship. This paper is based on empirical research of young people’s illicit drug use in Brisbane. The research rejects the idea of a pre-given drug problem, and seeks to understand how drugs have come to be defined as a problem. Using Michel Foucault’s conceptual framework of governmentality, the paper explores how the governance of illicit drugs, through law, public health and medicine, intersects with self-governance to shape young people’s drug use practices. It is argued that constructions of the drug problem shape what drug users believe about themselves and the ways in which they use drugs. From this perspective, drug use practices are ‘practices of the self’, formed through an interaction of the government of illicit drugs and the drug users own subjectivity.

Dry powder inhaler formulations-effect of polymer carrier size on the drug dispersion

Background The size of the carrier influences the aerosolization of drug from a dry powder inhaler (DPI) formulation. Currently, lactose monohydrate particles in a variety of sizes are preferably used in carrier based DPI formulations of various drugs; however, contradictory reports exist regarding the effect of the size of the carrier on the dispersion of drug. In this study we examined the influence of the intrinsic particle size of the polymeric carrier on the aerosolization of a model drug salbutamol sulphate (SS). Methods Four different sizes (20–150 lm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS particles from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were by laser diffraction and SEM, respectively. Results The FPF from these carriers was found to be increasing from 5.6% to 21.3% with increasing the carrier size. The FPF was found to be greater (21%) with the highest particle size of the carrier (150 lm). Conclusions The aerosolization of drug was dependent on the size of polymer carriers. The smaller size of the carrier resulted in lower FPF which was increased with increasing the carrier size. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation

Purpose: This study investigated the effect of chemical conjugation of the amino acid L-leucine to the polysaccharide chitosan on the dispersibility and drug release pattern of a polymeric nanoparticle (NP)-based controlled release dry powder inhaler (DPI) formulation. Methods: A chemical conjugate of L-leucine with chitosan was synthesized and characterized by Infrared (IR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and X-ray Photoelectron Spectroscopy (XPS). Nanoparticles of both chitosan and its conjugate were prepared by a water-in-oil emulsification – glutaraldehyde cross-linking method using the antihypertensive agent, diltiazem (Dz) hydrochloride as the model drug. The surface morphology and particle size distribution of the nanoparticles were determined by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The dispersibility of the nanoparticle formulation was analysed by a Twin Stage Impinger (TSI) with a Rotahaler as the DPI device. Deposition of the particles in the different stages was determined by gravimetry and the amount of drug released was analysed by UV spectrophotometry. The release profile of the drug was studied in phosphate buffered saline at 37 ⁰C and analyzed by UV spectrophotometry. Results: The TSI study revealed that the fine particle fractions (FPF), as determined gravimetrically, for empty and drug-loaded conjugate nanoparticles were significantly higher than for the corresponding chitosan nanoparticles (24±1.2% and 21±0.7% vs 19±1.2% and 15±1.5% respectively; n=3, p<0.05). The FPF of drug-loaded chitosan and conjugate nanoparticles, in terms of the amount of drug determined spectrophotometrically, had similar values (21±0.7% vs 16±1.6%). After an initial burst, both chitosan and conjugate nanoparticles showed controlled release that lasted about 8 to 10 days, but conjugate nanoparticles showed twice as much total drug release compared to chitosan nanoparticles (~50% vs ~25%). Conjugate nanoparticles also showed significantly higher dug loading and entrapment efficiency than chitosan nanoparticles (conjugate: 20±1% & 46±1%, chitosan: 16±1% & 38±1%, n=3, p<0.05). Conclusion: Although L-leucine conjugation to chitosan increased dispersibility of formulated nanoparticles, the FPF values are still far from optimum. The particles showed a high level of initial burst release (chitosan, 16% and conjugate, 31%) that also will need further optimization.

Failure to administer a drug and causation

Case note on King v Western Sydney Local Health Network In King v Western Sydney Local Health Network [2013] NSWCA 162 the appellant sought damages for the severe physical and intellectual disability she suffered as a result of foetal varicella syndrome (FVS) caused by her mother contracting varicella (chickenpox) in the second trimester of her pregnancy. The mother had been exposed to the virus and sought advice from a doctor at Blacktown Hospital as she had not had the virus herself and therefore did not possess immunity. In such circumstances at the time, the standard medical practice was to offer the mother varicellazoster immunoglobulin (VZIG) to boost her defence to the virus. The appellant’s mother however was not offered this treatment and contracted chickenpox resulting the appellant’s condition...

Phenytoin metabolism by human cytochrome P450 : involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation

The anticonvulsant phenytoin (5,5-diphenylhydantoin) provokes a skin rash in 5 to 10% of patients, which heralds the start of an idiosyncratic reaction that may result from covalent modification of normal self proteins by reactive drug metabolites. Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins. The aim of this study was to determine which P450s catalyze HPPH metabolism to the catechol, proposed to be the final enzymatic step in phenytoin bioactivation. Recombinant human P450s were coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. Novel bicistronic expression vectors were constructed for P450 2C19 and the three major variants of P450 2C9, i.e., 2C9*1, 2C9*2, and 2C9*3. HPPH metabolism and covalent adduct formation were assessed in parallel. P450 2C19 was the most effective catalyst of HPPH oxidation to the catechol metabolite and was also associated with the highest levels of covalent adduct formation. P450 3A4, 3A5, 3A7, 2C9*1, and 2C9*2 also catalyzed bioactivation of HPPH, but to a lesser extent. Fluorographic analysis showed that the major targets of adduct formation in bacterial membranes were the catalytic P450 forms, as suggested from experiments with human liver microsomes. These results suggest that P450 2C19 and other forms from the 2C and 3A subfamilies may be targets as well as catalysts of drug-protein adduct formation from phenytoin.

Development of Contact Lenses from a Biomaterial Point of View – Materials, Manufacture, and Clinical Application

Rigid lenses, which were originally made from glass (between 1888 and 1940) and later from polymethyl methacrylate or silicone acrylate materials, are uncomfortable to wear and are now seldom fitted to new patients. Contact lenses became a popular mode of ophthalmic refractive error correction following the discovery of the first hydrogel material – hydroxyethyl methacrylate – by Czech chemist Otto Wichterle in 1960. To satisfy the requirements for ocular biocompatibility, contact lenses must be transparent and optically stable (for clear vision), have a low elastic modulus (for good comfort), have a hydrophilic surface (for good wettability), and be permeable to certain metabolites, especially oxygen, to allow for normal corneal metabolism and respiration during lens wear. A major breakthrough in respect of the last of these requirements was the development of silicone hydrogel soft lenses in 1999 and techniques for making the surface hydrophilic. The vast majority of contact lenses distributed worldwide are mass-produced using cast molding, although spin casting is also used. These advanced mass-production techniques have facilitated the frequent disposal of contact lenses, leading to improvements in ocular health and fewer complications. More than one-third of all soft contact lenses sold today are designed to be discarded daily (i.e., ‘daily disposable’ lenses).

Proton-transfer and non-transfer compounds of the multi-purpose drug dapsone [4-(4-Aminophenylsulfonyl)aniline] with 3,5-dinitrosalicylic acid and 5-nitroisophthalic acid

The structures of the compounds from the reaction of the drug dapsone [4-(4-aminophenylsulfonyl)aniline] with 3,5-dinitrosalicylic acid, the salt hydrate [4-(4-aminohenylsulfonyl)anilinium 2-carboxy-4,6-dinitrophenolate monohydrate] (1) and the 1:1 adduct with 5-nitroisophthalic acid [4-(4-aminophenylsulfonyl)aniline 5-nitrobenzene-1,3-dicarboxylic acid] (2) have been determined. Crystals of 1 are triclinic, space group P-1, with unit cell dimensions a = 8.2043(3), b = 11.4000(6), c = 11.8261(6)Å, α = 110.891(5), β = 91.927(3), γ = 98.590(4)deg. and Z = 4. Compound 2 is orthorhombic, space group Pbcn, with unit cell dimensions a = 20.2662(6), b = 12.7161(4), c = 15.9423(5)Å and Z = 8. In 1, intermolecular analinium N-H…O and water O-H…O and O-H…N hydrogen-bonding interactions with sulfone, carboxyl, phenolate and nitro O-atom and aniline N-atom acceptors give a two-dimensional layered structure. With 2, the intermolecular interactions involve both aniline N-H…O and carboxylic acid O-H…O and O-H…N hydrogen bonds to sulfone, carboxyl, nitro and aniline acceptors, giving a three-dimensional network structure. In both structures π--π aromatic ring associations are present.