The development and validation of Australian Indices of Child Development — Part I: conceptualisation and development

The Longitudinal Study of Australian Children (LSAC) is a major national study examining the lives of Australian children, using a cross-sequential cohort design and data from parents, children, and teachers for 5,107 infants (3–19 months) and 4,983 children (4–5 years). Its data are publicly accessible and are used by researchers from many disciplinary backgrounds. It contains multiple measures of children’s developmental outcomes as well as a broad range of information on the contexts of their lives. This paper reports on the development of summary outcome indices of child development using the LSAC data. The indices were developed to fill the need for indicators suitable for use by diverse data users in order to guide government policy and interventions which support young children’s optimal development. The concepts underpinning the indices and the methods of their development are presented. Two outcome indices (infant and child) were developed, each consisting of three domains—health and physical development, social and emotional functioning, and learning competency. A total of 16 measures are used to make up these three domains in the Outcome Index for the Child Cohort and six measures for the Infant Cohort. These measures are described and evidence supporting the structure of the domains and their underlying latent constructs is provided for both cohorts. The factorial structure of the Outcome Index is adequate for both cohorts, but was stronger for the child than infant cohort. It is concluded that the LSAC Outcome Index is a parsimonious measure representing the major components of development which is suitable for non-specialist data users. A companion paper (Sanson et al. 2010) presents evidence of the validity of the Index.

Legislative and security requirements of audit material for evidentiary purpose

This research used the Queensland Police Service, Australia, as a major case study. Information on principles, techniques and processes used, and the reason for the recording, storing and release of audit information for evidentiary purposes is reported. It is shown that Law Enforcement Agencies have a two-fold interest in, and legal obligation pertaining to, audit trails. The first interest relates to the situation where audit trails are actually used by criminals in the commission of crime and the second to where audit trails are generated by the information systems used by the police themselves in support of the recording and investigation of crime. Eleven court cases involving Queensland Police Service audit trails used in evidence in Queensland courts were selected for further analysis. It is shown that, of the cases studied, none of the evidence presented was rejected or seriously challenged from a technical perspective. These results were further analysed and related to normal requirements for trusted maintenance of audit trail information in sensitive environments with discussion on the ability and/or willingness of courts to fully challenge, assess or value audit evidence presented. Managerial and technical frameworks for firstly what is considered as an environment where a computer system may be considered to be operating “properly” and, secondly, what aspects of education, training, qualifications, expertise and the like may be considered as appropriate for persons responsible within that environment, are both proposed. Analysis was undertaken to determine if audit and control of information in a high security environment, such as law enforcement, could be judged as having improved, or not, in the transition from manual to electronic processes. Information collection, control of processing and audit in manual processes used by the Queensland Police Service, Australia, in the period 1940 to 1980 was assessed against current electronic systems essentially introduced to policing in the decades of the 1980s and 1990s. Results show that electronic systems do provide for faster communications with centrally controlled and updated information readily available for use by large numbers of users who are connected across significant geographical locations. However, it is clearly evident that the price paid for this is a lack of ability and/or reluctance to provide improved audit and control processes. To compare the information systems audit and control arrangements of the Queensland Police Service with other government departments or agencies, an Australia wide survey was conducted. Results of the survey were contrasted with the particular results of a survey, conducted by the Australian Commonwealth Privacy Commission four years previous, to this survey which showed that security in relation to the recording of activity against access to information held on Australian government computer systems has been poor and a cause for concern. However, within this four year period there is evidence to suggest that government organisations are increasingly more inclined to generate audit trails. An attack on the overall security of audit trails in computer operating systems was initiated to further investigate findings reported in relation to the government systems survey. The survey showed that information systems audit trails in Microsoft Corporation's “Windows” operating system environments are relied on quite heavily. An audit of the security for audit trails generated, stored and managed in the Microsoft “Windows 2000” operating system environment was undertaken and compared and contrasted with similar such audit trail schemes in the “UNIX” and “Linux” operating systems. Strength of passwords and exploitation of any security problems in access control were targeted using software tools that are freely available in the public domain. Results showed that such security for the “Windows 2000” system is seriously flawed and the integrity of audit trails stored within these environments cannot be relied upon. An attempt to produce a framework and set of guidelines for use by expert witnesses in the information technology (IT) profession is proposed. This is achieved by examining the current rules and guidelines related to the provision of expert evidence in a court environment, by analysing the rationale for the separation of distinct disciplines and corresponding bodies of knowledge used by the Medical Profession and Forensic Science and then by analysing the bodies of knowledge within the discipline of IT itself. It is demonstrated that the accepted processes and procedures relevant to expert witnessing in a court environment are transferable to the IT sector. However, unlike some discipline areas, this analysis has clearly identified two distinct aspects of the matter which appear particularly relevant to IT. These two areas are; expertise gained through the application of IT to information needs in a particular public or private enterprise; and expertise gained through accepted and verifiable education, training and experience in fundamental IT products and system.

Non-invasive assessment of tear film surface quality

The tear film plays an important role preserving the health of the ocular surface and maintaining the optimal refractive power of the cornea. Moreover dry eye syndrome is one of the most commonly reported eye health problems. This syndrome is caused by abnormalities in the properties of the tear film. Current clinical tools to assess the tear film properties have shown certain limitations. The traditional invasive methods for the assessment of tear film quality, which are used by most clinicians, have been criticized for the lack of reliability and/or repeatability. A range of non-invasive methods of tear assessment have been investigated, but also present limitations. Hence no “gold standard” test is currently available to assess the tear film integrity. Therefore, improving techniques for the assessment of the tear film quality is of clinical significance and the main motivation for the work described in this thesis. In this study the tear film surface quality (TFSQ) changes were investigated by means of high-speed videokeratoscopy (HSV). In this technique, a set of concentric rings formed in an illuminated cone or a bowl is projected on the anterior cornea and their reflection from the ocular surface imaged on a charge-coupled device (CCD). The reflection of the light is produced in the outer most layer of the cornea, the tear film. Hence, when the tear film is smooth the reflected image presents a well structure pattern. In contrast, when the tear film surface presents irregularities, the pattern also becomes irregular due to the light scatter and deviation of the reflected light. The videokeratoscope provides an estimate of the corneal topography associated with each Placido disk image. Topographical estimates, which have been used in the past to quantify tear film changes, may not always be suitable for the evaluation of all the dynamic phases of the tear film. However the Placido disk image itself, which contains the reflected pattern, may be more appropriate to assess the tear film dynamics. A set of novel routines have been purposely developed to quantify the changes of the reflected pattern and to extract a time series estimate of the TFSQ from the video recording. The routine extracts from each frame of the video recording a maximized area of analysis. In this area a metric of the TFSQ is calculated. Initially two metrics based on the Gabor filter and Gaussian gradient-based techniques, were used to quantify the consistency of the pattern’s local orientation as a metric of TFSQ. These metrics have helped to demonstrate the applicability of HSV to assess the tear film, and the influence of contact lens wear on TFSQ. The results suggest that the dynamic-area analysis method of HSV was able to distinguish and quantify the subtle, but systematic degradation of tear film surface quality in the inter-blink interval in contact lens wear. It was also able to clearly show a difference between bare eye and contact lens wearing conditions. Thus, the HSV method appears to be a useful technique for quantitatively investigating the effects of contact lens wear on the TFSQ. Subsequently a larger clinical study was conducted to perform a comparison between HSV and two other non-invasive techniques, lateral shearing interferometry (LSI) and dynamic wavefront sensing (DWS). Of these non-invasive techniques, the HSV appeared to be the most precise method for measuring TFSQ, by virtue of its lower coefficient of variation. While the LSI appears to be the most sensitive method for analyzing the tear build-up time (TBUT). The capability of each of the non-invasive methods to discriminate dry eye from normal subjects was also investigated. The receiver operating characteristic (ROC) curves were calculated to assess the ability of each method to predict dry eye syndrome. The LSI technique gave the best results under both natural blinking conditions and in suppressed blinking conditions, which was closely followed by HSV. The DWS did not perform as well as LSI or HSV. The main limitation of the HSV technique, which was identified during the former clinical study, was the lack of the sensitivity to quantify the build-up/formation phase of the tear film cycle. For that reason an extra metric based on image transformation and block processing was proposed. In this metric, the area of analysis was transformed from Cartesian to Polar coordinates, converting the concentric circles pattern into a quasi-straight lines image in which a block statistics value was extracted. This metric has shown better sensitivity under low pattern disturbance as well as has improved the performance of the ROC curves. Additionally a theoretical study, based on ray-tracing techniques and topographical models of the tear film, was proposed to fully comprehend the HSV measurement and the instrument’s potential limitations. Of special interested was the assessment of the instrument’s sensitivity under subtle topographic changes. The theoretical simulations have helped to provide some understanding on the tear film dynamics, for instance the model extracted for the build-up phase has helped to provide some insight into the dynamics during this initial phase. Finally some aspects of the mathematical modeling of TFSQ time series have been reported in this thesis. Over the years, different functions have been used to model the time series as well as to extract the key clinical parameters (i.e., timing). Unfortunately those techniques to model the tear film time series do not simultaneously consider the underlying physiological mechanism and the parameter extraction methods. A set of guidelines are proposed to meet both criteria. Special attention was given to a commonly used fit, the polynomial function, and considerations to select the appropriate model order to ensure the true derivative of the signal is accurately represented. The work described in this thesis has shown the potential of using high-speed videokeratoscopy to assess tear film surface quality. A set of novel image and signal processing techniques have been proposed to quantify different aspects of the tear film assessment, analysis and modeling. The dynamic-area HSV has shown good performance in a broad range of conditions (i.e., contact lens, normal and dry eye subjects). As a result, this technique could be a useful clinical tool to assess tear film surface quality in the future.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area highspeed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring’s regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion,this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

Recognition of expertise : an important concept in the acquisition of nephrology nursing expertise

The present article, which is abstracted from a larger study into the acquisition and exercise of nephrology nursing expertise, aims to explore the concept of recognition of expertise. The study used grounded theory methodology and involved 17 registered nurses who were practising in a metropolitan renal unit in New South Wales, Australia. Concurrent data collection and analysis was undertaken, incorporating participant observations and interviews. According to nurses in this study, patients, doctors and other nurses recognized that some nurses were experts while others were not. In addition, being trusted, being a role model and teaching others were important components of being recognized as an expert nephrology nurse. Of importance for nursing, the results of the present study indicate that knowledge and experience are not sufficient to ensure expert practice; recognition of expertise by others is an important function of expertise acquisition.

Artful inquiry : an arts-based facilitation approach for individual and organisational learning and development

The research undertaken in these two major doctoral studies investigates the field of artsbased learning, a pedagogical approach to individual and organisational learning and development, my professional creative facilitation practice and development as a researcher. While the studies are stand-alone projects they are intended to build on each other in order to tell the evolving story of my research and professional practice. The first study combines The Role of Arts-based Learning in a Creative Economy; The Need for Artistry in Professional Education the art of knowing what to do when you don’t know what to do and Lines of Inquiry: Making Sense of Research and Professional Practice. The Role of Arts-based Learning in a Creative Economy provides an overview of the field of arts-based learning in business. The study focuses on the relevant literature and interviews with people working in the field. The paper argues that arts-based learning is a valuable addition to organisations for building a culture of creativity and innovation. The Need for Artistry in Professional Education continues that investigation. It explores the way artists approach their work and considers what skills and capabilities from artistic practice can be applied to other professions’ practices. From this research the Sphere of Professional Artistry model is developed and depicts the process of moving toward professional artistry. Lines of Inquiry: making sense of research and professional practice through artful inquiry is a self-reflective study. It explores my method of inquiry as a researcher and as a creative facilitation practitioner using arts-based learning processes to facilitate groups of people for learning, development and change. It discusses how my research and professional practice influence and inspire the other and draws on cased studies. The second major research study Artful Inquiry: Arts-based Learning for Inquiry, Reflection and Action in Professional Practice is a one year practice-led inquiry. It continues the research into arts-based and aesthetic learning experiences and my arts-based facilitation practice. The research is conducted with members of a Women’s Network in a large government service agency. It develops the concept of ‘Artful Inquiry’’ a creative, holistic, and embodied approach for facilitation, inquiry, learning, reflection, and action. Storytelling as Inquiry is used as a methodology for understanding participants’ experiences of being involved in arts-based learning experiences. The study reveals the complex and emergent nature of practice and research. It demonstrates what it can mean to do practice-led research with others, within an organisational context, and to what effect.

Evaluating multivariate volatility forecasts : how effective are statistical and economic loss functions?

Multivariate volatility forecasts are an important input in many financial applications, in particular portfolio optimisation problems. Given the number of models available and the range of loss functions to discriminate between them, it is obvious that selecting the optimal forecasting model is challenging. The aim of this thesis is to thoroughly investigate how effective many commonly used statistical (MSE and QLIKE) and economic (portfolio variance and portfolio utility) loss functions are at discriminating between competing multivariate volatility forecasts. An analytical investigation of the loss functions is performed to determine whether they identify the correct forecast as the best forecast. This is followed by an extensive simulation study examines the ability of the loss functions to consistently rank forecasts, and their statistical power within tests of predictive ability. For the tests of predictive ability, the model confidence set (MCS) approach of Hansen, Lunde and Nason (2003, 2011) is employed. As well, an empirical study investigates whether simulation findings hold in a realistic setting. In light of these earlier studies, a major empirical study seeks to identify the set of superior multivariate volatility forecasting models from 43 models that use either daily squared returns or realised volatility to generate forecasts. This study also assesses how the choice of volatility proxy affects the ability of the statistical loss functions to discriminate between forecasts. Analysis of the loss functions shows that QLIKE, MSE and portfolio variance can discriminate between multivariate volatility forecasts, while portfolio utility cannot. An examination of the effective loss functions shows that they all can identify the correct forecast at a point in time, however, their ability to discriminate between competing forecasts does vary. That is, QLIKE is identified as the most effective loss function, followed by portfolio variance which is then followed by MSE. The major empirical analysis reports that the optimal set of multivariate volatility forecasting models includes forecasts generated from daily squared returns and realised volatility. Furthermore, it finds that the volatility proxy affects the statistical loss functions’ ability to discriminate between forecasts in tests of predictive ability. These findings deepen our understanding of how to choose between competing multivariate volatility forecasts.

Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts

Chlamydiae are intracellular bacteria that commonly cause infections of the respiratory and genital tracts, which are major clinical problems. Infections are also linked to the aetiology of diseases such as asthma, emphysema and heart disease. The clinical management of infection is problematic and antibiotic resistance is emerging. Increased understanding of immune processes that are involved in both clearance and immunopathology of chlamydial infection is critical for the development of improved treatment strategies. Here, we show that IL-13 was produced in the lungs of mice rapidly after Chlamydia muridarum (Cmu) infection and promoted susceptibility to infection. Wild-type (WT) mice had increased disease severity, bacterial load and associated inflammation compared to IL-13 deficient (−/−) mice as early as 3 days post infection (p.i.). Intratracheal instillation of IL-13 enhanced bacterial load in IL-13−/− mice. There were no differences in early IFN-g and IL-10 expression between WT and IL-13−/− mice and depletion of CD4+ T cells did not affect infection in IL-13−/− mice. Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. We also showed that IL-13 deficiency increased macrophage uptake of Cmu in vitro and in vivo. Moreover, the depletion of IL-13 during infection of lung epithelial cells in vitro decreased the percentage of infected cells and reduced bacterial growth. Our results suggest that enhanced IL-13 responses in the airways, such as that found in asthmatics, may promote susceptibility to chlamydial lung infection. Importantly the role of IL-13 in regulating infection was not limited to the lung as we showed that IL-13 also promoted susceptibility to Cmu genital tract infection. Collectively our findings demonstrate that innate IL-13 release promotes infection that results in enhanced inflammation and have broad implications for the treatment of chlamydial infections and IL-13-associated diseases.

How much do residential aged care staff members know about the nutritional needs of residents?

Background Undernutrition, weight loss and dehydration are major clinical issues for people with dementia in residential care, with excessive weight loss contributing to increased risk of frailty, immobility, illness and premature morbidity. This paper discusses a nutritional knowledge and attitudes survey conducted as part of a larger project focused on improving nutritional intake of people with dementia within a residential care facility in Brisbane, Australia. Aims The specific aims of the survey were to identify (i) knowledge of the nutritional needs of aged care facility residents; (ii) mealtime practices; and (iii) attitudes towards mealtime practices and organisation. Methods A survey based on those used in other healthcare settings was completed by 76 staff members. The survey included questions about nutritional knowledge, opinions of the food service, frequency of feeding assistance provided and feeding assessment practices. Results Nutritional knowledge scores ranged from 1 to 9 of a possible 10, with a mean score of 4.67. While 76% of respondents correctly identified risk factors associated with malnutrition in nursing home residents, only 38% of participants correctly identified the need for increased protein and energy in residents with pressure ulcers, and just 15% exhibited correct knowledge of fluid requirements. Further, while nutritional assessment was considered an important part of practice by 83% of respondents, just 53% indicated that they actually carried out such assessments. Identified barriers to promoting optimal nutrition included insufficient time to observe residents (56%); being unaware of residents' feeding issues (46%); poor knowledge of nutritional assessments (44%); and unappetising appearance of food served (57%). Conclusion An important step towards improving health and quality of life for residents of aged care facilities would be to enhance staff nutritional awareness and assessment skills. This should be carried out through increased attention to both preservice curricula and on-the-job training. Implications for practice The residential facility staff surveyed demonstrated low levels of nutrition knowledge, which reflects findings from the international literature. This has implications for the provision of responsive care to residents of these facilities and should be explored further.

Communicating personal amnesty : a dismodernist approach to arts intersections between disability, personal stories and well-being

This thesis investigates the role of narrative devices in the process of improving an individual’s psychological and physiological experience of health and well-being using two methods of inquiry: a theoretical research project and a comparative analysis of two case studies. Through these two approaches the research examines how the health status of people experiencing disability can be re-positioned and re-designed to develop creative, narrative-based approaches to strengthen communication between the mainstream community and those marginalised by pathological, social and biological illness-centric policy. The theoretical section of the thesis examines two different, but complementary bodies of research: health and well-being, and narrative reconstruction. By invoking Antonovksy’s (1985a) theory of salutogenesis and Davis’s (2002) theory of dismodernism, the study examines the role of language and narrative in the defining of health in social, pathological and ableist spheres. The research positions health and well-being as disparate from historical and contemporary readings of illness and disability and presents literature to support the potential to improve health well-being through a creative re-narration of the experience of disability. The research examines the theoretical concepts of resilience, autonomy and social inclusion through a detailed examination of narratology and the amnesty narrative. The study links these theoretical approaches to a practical Arts-Health intersection program developed for the research project called Communicating Personal Amnesty. Through a comparative analysis of a Pilot Study and Major Case study, the research presents findings derived from theory-building participatory action research showing the efficacy of the program. The research provides a detailed analysis of key narrative structures through a variety of experimental methodological approaches to encourage an important dialogue between the creative components of the thesis and the more traditional health-based academic critique. The research is an example of emergent translational health methodologies, in disability studies.

Lung recruitment and endotracheal suction in ventilated preterm infants measured with electrical impedance tomography

Aims Although suctioning is a standard airway maintenance procedure, there are significant associated risks, such as loss of lung volume due to high negative suction pressures. This study aims to assess the extent and duration of change in end-expiratory level (EEL) resulting from endotracheal tube (ETT) suction and to examine the relationship between EEL and regional lung ventilation in ventilated preterm infants with respiratory distress syndrome. Methods A prospective observational clinical study of the effect of ETT suction on 20 non-muscle-relaxed preterm infants with respiratory distress syndrome (RDS) on conventional mechanical ventilation was conducted in a neonatal intensive care unit. Ventilation distribution was measured with regional impedance amplitudes and EEL using electrical impedance tomography. Results ETT suction resulted in a significant increase in EEL post-suction (P < 0.01). Regionally, anterior EEL decreased and posterior EEL increased post-suction, suggesting heterogeneity. Tidal volume was significantly lower in volume-guarantee ventilation compared with pressure-controlled ventilation (P = 0.04). Conclusions ETT suction in non-muscle-relaxed and ventilated preterm infants with RDS results in significant lung volume increase that is maintained for at least 90 min. Regional differences in distribution of ventilation with ETT suction suggest that the behaviour of the lung is heterogeneous in nature.

miRNAs in head and neck cancer revisited

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer. Tobacco smoking, alcohol consumption and human papilloma virus (HPV) infections have been associated with the occurrence of HNSCC. Despite advances that have been made in HNSCC treatment, smoking-associated HNSCC patients still exhibit a poor 5 year survival rate (30-50 %) and a concomitant poor quality of life. The major clinical challenge to date lies in the early detection of dysplastic lesions,which can progress to malignancy. In addition, there are currently no tools available to monitor HNSCC patients for early stages of local recurrences or distant metastases. In the recent past, micro-RNAs (miRNA) have been assessed for their role in cancer initiation and progression, including HNSCC. It is now well-established that deregulation of these single stranded, small non-coding, 19-25 nt RNAs can e.g. enhance the expression of oncogenes or subdue the expression of tumor suppressor genes. The aims of this review are three-fold: first to retrieve from the literature miRNAs that have specifically been associated with HNSCC, second to group these miRNAs into those regulating tumor initiation, progression and metastasis, and third to discern miRNAs related to smoking-associated HNSCC versus HPV-associated HNSCC development. This review gives an overview on the miRNAs regulating the development of head and neck cancers. The ultimate establishment of miRNA expression profiles that are HNSCC specific, and miRNAs that orchestrate altered gene and protein expression levels in HNSCC, could pave the way for a better understanding of the mechanism underlying its pathogenesis and the development of novel, targeted therapies.

Visual rehabilitation in low-moderate keratoconus : intracorneal ring segment implantation followed by same-day topography-guided photorefractive keratectomy and collagen cross linking

AIM: To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen crosslinking (CXL) after previous intrastromal corneal ring segment (ISCR) implantation for keratoconus. METHODS: An experimental clinical study on twenty-one eyes of 19 patients aged, 27.1±6.6 years (range: 19 – 43 years), with low to moderate keratoconus who were selected to undergo customized TG-PRK immediately followed by same-day CXL, 9 months after ISCR implantation in a university ophthalmology clinic. Refraction, uncorrected (UDVA) and corrected distance visual acuities (CDVA), keratometry (K) values, central corneal thickness (CCT) and coma were assessed 3 months after TG/PRK and CXL. RESULTS: After TG-PRK/CXL: the mean UDVA (logMAR) improved significantly from 0.66±0.41 to 0.20±0.25 (P<0.05); K flat value decreased from: 48.44±3.66 D to 43.71±1.95 D; K steep value decreased from 45.61±2.40 D to 41.56±2.05D; K average also decreased from 42.42±2.07 D to 47.00±2.66 D (P<0.05 for all). The mean sphere and cylinder decreased significantly post-surgery from, -3.10±2.99 D to -0.11±0.93 D and from, -3.68±1.53 to -1.11±0.75D respectively, while the CDVA, CCT and coma showed no significant changes. Compared to post-ISCR, significant reductions (P ˂ 0.05 or all) in all K-values, sphere and cylinder were observed after TG-PRK/CXL. CONCLUSION: Same-day combined topography-guided PRK and corneal crosslinking following placement of ICRS is a safe and potentially effective option in treating low-moderate keratoconus. It significantly improved all visual acuity, reduced keratometry, sphere and astigmatism, but caused no change in central corneal thickness and coma.

The lipophilic opioids: Fentanyl, alfentanil, sufentanil and remifentanil

discusses fentanyl, alfentanil, sufentanil, and remifentanil which are synthetic opioid analgesics with high affinity for the mu opioid receptor. They have been widely adopted in anaesthetic practice for various surgical procedures (e.g. in cardiac surgery) and for long-term analgesia and sedation. Important pharmacokinetic differences between these analgesics have been described, and this chapter addresses how the pharmacokinetic profile of each analgesic is affected by many factors, including patient age, plasma protein content, acid–base balance status, cardiopulmonary bypass, changes in hepatic blood flow, and the co-administration of other drugs which compete for plasma protein carriers and metabolic pathways, although their profile is not significantly affected by renal insufficiency or compensated hepatic dysfunction, which has major clinical implications.

The potential for production of freeze-dried oral vaccines using alginate hydrogel microspheres as protein carriers

Oral administration of dry vaccine formulations is acknowledged to offer major clinical and logistical benefits by eliminating the cold chain required for liquid preparations. A model antigen, bovine serum albumin (BSA) was encapsulated in alginate microspheres using aerosolisation. Hydrated microspheres 25 to 65 μm in size with protein loading of 3.3 % w/w were obtained. Environmental scanning electron microscopy indicated a stabilizing effect of encapsulated protein on alginate hydrogels revealed by an increase in dehydration resistance. Freeze drying of alginate microspheres without use of a cryoprotectant resulted in fragmentation and subsequent rapid loss of the majority of the protein load in simulated intestinal fluid in 2 h, whereas intact microspheres were observed following freeze-drying of BSA-loaded microspheres in the presence of maltodextrin. BSA release from freeze-dried preparations was limited to less than 7 % in simulated gastric fluid over 2 h, while 90 % of the protein load was gradually released in simulated intestinal fluid over 10 h. SDS-PAGE analysis indicated that released BSA largely preserved its molecular weight. These findings demonstrate the potential for manufacturing freeze-dried oral vaccines using alginate microspheres.