The costs arising from pressure ulcers attributable to malnutrition

Aim To estimate the economic consequences of pressure ulcers attributable to malnutrition. Method Statistical models were developed to predict the number of cases of pressure ulcer, associated bed days lost and the dollar value of these losses in public hospitals in 2002/2003 in Queensland, Australia. The following input parameters were specified and appropriate probability distributions fitted • Number of at risk discharges per annum • Incidence rate for pressure ulcer • Attributable fraction of malnutrition in the development of pressure ulcer • Independent effect of pressure ulcer on length of hospital stay • Opportunity cost of hospital bed day One thousand random re-samples were made and the results expressed as (output) probabilistic distributions. Results The model predicts a mean 16060 (SD 5 671) bed days lost and corresponding mean economic cost of AU$12 968 668 (SD AU$4 924 148) (EUROS 6 925 268 SD 2 629 495; US$ 7 288 391 SD 2 767 371) of pressure ulcer attributable to malnutrition in 2002/2003 in public hospitals in Queensland, Australia. Conclusion The cost of pressure ulcer attributable to malnutrition in bed days and dollar terms are substantial. The model only considers costs of increased length of stay associated with pressure ulcer and not other factors associated with care.

Recombinant protein production using a Tobacco yellow dwarf virus-based episomal expression vector : control of Rep activity

Over the past decade, plants have been used as expression hosts for the production of pharmaceutically important and commercially valuable proteins. Plants offer many advantages over other expression systems such as lower production costs, rapid scale up of production, similar post-translational modification as animals and the low likelihood of contamination with animal pathogens, microbial toxins or oncogenic sequences. However, improving recombinant protein yield remains one of the greatest challenges to molecular farming. In-Plant Activation (InPAct) is a newly developed technology that offers activatable and high-level expression of heterologous proteins in plants. InPAct vectors contain the geminivirus cis elements essential for rolling circle replication (RCR) and are arranged such that the gene of interest is only expressed in the presence of the cognate viral replication-associated protein (Rep). The expression of Rep in planta may be controlled by a tissue-specific, developmentally regulated or chemically inducible promoter such that heterologous protein accumulation can be spatially and temporally controlled. One of the challenges for the successful exploitation of InPAct technology is the control of Rep expression as even very low levels of this protein can reduce transformation efficiency, cause abnormal phenotypes and premature activation of the InPAct vector in regenerated plants. Tight regulation over transgene expression is also essential if expressing cytotoxic products. Unfortunately, many tissue-specific and inducible promoters are unsuitable for controlling expression of Rep due to low basal activity in the absence of inducer or in tissues other than the target tissue. This PhD aimed to control Rep activity through the production of single chain variable fragments (scFvs) specific to the motif III of Tobacco yellow dwarf virus (TbYDV) Rep. Due to the important role played by the conserved motif III in the RCR, it was postulated that such scFvs can be used to neutralise the activity of the low amount of Rep expressed from a “leaky” inducible promoter, thus preventing activation of the TbYDV-based InPAct vector until intentional induction. Such scFvs could also offer the potential to confer partial or complete resistance to TbYDV, and possibly heterologous viruses as motif III is conserved between geminiviruses. Studies were first undertaken to determine the levels of TbYDV Rep and TbYDV replication-associated protein A (RepA) required for optimal transgene expression from a TbYDV-based InPAct vector. Transient assays in a non-regenerable Nicotiana tabacum (NT-1) cell line were undertaken using a TbYDV-based InPAct vector containing the uidA reporter gene (encoding GUS) in combination with TbYDV Rep and RepA under the control of promoters with high (CaMV 35S) or low (Banana bunchy top virus DNA-R, BT1) activity. The replication enhancer protein of Tomato leaf curl begomovirus (ToLCV), REn, was also used in some co-bombardment experiments to examine whether RepA could be substituted by a replication enhancer from another geminivirus genus. GUS expression was observed both quantitatively and qualitatively by fluorometric and histochemical assays, respectively. GUS expression from the TbYDV-based InPAct vector was found to be greater when Rep was expected to be expressed at low levels (BT1 promoter) rather than high levels (35S promoter). GUS expression was further enhanced when Rep and RepA were co-bombarded with a low ratio of Rep to RepA. Substituting TbYDV RepA with ToLCV REn also enhanced GUS expression but more importantly highest GUS expression was observed when cells were co-transformed with expression vectors directing low levels of Rep and high levels of RepA irrespective of the level of REn. In this case, GUS expression was approximately 74-fold higher than that from a non-replicating vector. The use of different terminators, namely CaMV 35S and Nos terminators, in InPAct vectors was found to influence GUS expression. In the presence of Rep, GUS expression was greater using pInPActGUS-Nos rather than pInPActGUS-35S. The only instance of GUS expression being greater from vectors containing the 35S terminator was when comparing expression from cells transformed with Rep, RepA and REnexpressing vectors and either non-replicating vectors, p35SGS-Nos or p35SGS-35S. This difference was most likely caused by an interaction of viral replication proteins with each other and the terminators. These results indicated that (i) the level of replication associated proteins is critical to high transgene expression, (ii) the choice of terminator within the InPAct vector may affect expression levels and (iii) very low levels of Rep can activate InPAct vectors hence controlling its activity is critical. Prior to generating recombinant scFvs, a recombinant TbYDV Rep was produced in E. coli to act as a control to enable the screening for Rep-specific antibodies. A bacterial expression vector was constructed to express recombinant TbYDV Rep with an Nterminal His-tag (N-His-Rep). Despite investigating several purification techniques including Ni-NTA, anion exchange, hydrophobic interaction and size exclusion chromatography, N-His-Rep could only be partially purified using a Ni-NTA column under native conditions. Although it was not certain that this recombinant N-His-Rep had the same conformation as the native TbYDV Rep and was functional, results from an electromobility shift assay (EMSA) showed that N-His-Rep was able to interact with the TbYDV LIR and was, therefore, possibly functional. Two hybridoma cell lines from mice, immunised with a synthetic peptide containing the TbYDV Rep motif III amino acid sequence, were generated by GenScript (USA). Monoclonal antibodies secreted by the two hybridoma cell lines were first screened against denatured N-His-Rep in Western analysis. After demonstrating their ability to bind N-His-Rep, two scFvs (scFv1 and scFv2) were generated using a PCR-based approach. Whereas the variable heavy chain (VH) from both cell lines could be amplified, only the variable light chain (VL) from cell line 2 was amplified. As a result, scFv1 contained VH and VL from cell line 1, whereas scFv2 contained VH from cell line 2 and VL from cell line 1. Both scFvs were first expressed in E. coli in order to evaluate their affinity to the recombinant TbYDV N-His-Rep. The preliminary results demonstrated that both scFvs were able to bind to the denatured N-His-Rep. However, EMSAs revealed that only scFv2 was able to bind to native N-His-Rep and prevent it from interacting with the TbYDV LIR. Each scFv was cloned into plant expression vectors and co-bombarded into NT-1 cells with the TbYDV-based InPAct GUS expression vector and pBT1-Rep to examine whether the scFvs could prevent Rep from mediating RCR. Although it was expected that the addition of the scFvs would result in decreased GUS expression, GUS expression was found to slightly increase. This increase was even more pronounced when the scFvs were targeted to the cell nucleus by the inclusion of the Simian virus 40 large T antigen (SV40) nuclear localisation signal (NLS). It was postulated that the scFvs were binding to a proportion of Rep, leaving a small amount available to mediate RCR. The outcomes of this project provide evidence that very high levels of recombinant protein can theoretically be expressed using InPAct vectors with judicious selection and control of viral replication proteins. However, the question of whether the scFvs generated in this project have sufficient affinity for TbYDV Rep to prevent its activity in a stably transformed plant remains unknown. It may be that other scFvs with different combinations of VH and VL may have greater affinity for TbYDV Rep. Such scFvs, when expressed at high levels in planta, might also confer resistance to TbYDV and possibly heterologous geminiviruses.

The neuro-muscular and musculo-skeletal characterization of children with joint hypermobility

In children, joint hypermobility (typified by structural instability of joints) manifests clinically as neuro-muscular and musculo-skeletal conditions and conditions associated with development and organization of control of posture and gait (Finkelstein, 1916; Jahss, 1919; Sobel, 1926; Larsson, Mudholkar, Baum and Srivastava, 1995; Murray and Woo, 2001; Hakim and Grahame, 2003; Adib, Davies, Grahame, Woo and Murray, 2005:). The process of control of the relative proportions of joint mobility and stability, whilst maintaining equilibrium in standing posture and gait, is dependent upon the complex interrelationship between skeletal, muscular and neurological function (Massion, 1998; Gurfinkel, Ivanenko, Levik and Babakova, 1995; Shumway-Cook and Woollacott, 1995). The efficiency of this relies upon the integrity of neuro-muscular and musculo-skeletal components (ligaments, muscles, nerves), and the Central Nervous System’s capacity to interpret, process and integrate sensory information from visual, vestibular and proprioceptive sources (Crotts, Thompson, Nahom, Ryan and Newton, 1996; Riemann, Guskiewicz and Shields, 1999; Schmitz and Arnold, 1998) and development and incorporation of this into a representational scheme (postural reference frame) of body orientation with respect to internal and external environments (Gurfinkel et al., 1995; Roll and Roll, 1988). Sensory information from the base of support (feet) makes significant contribution to the development of reference frameworks (Kavounoudias, Roll and Roll, 1998). Problems with the structure and/ or function of any one, or combination of these components or systems, may result in partial loss of equilibrium and, therefore ineffectiveness or significant reduction in the capacity to interact with the environment, which may result in disability and/ or injury (Crotts et al., 1996; Rozzi, Lephart, Sterner and Kuligowski, 1999b). Whilst literature focusing upon clinical associations between joint hypermobility and conditions requiring therapeutic intervention has been abundant (Crego and Ford, 1952; Powell and Cantab, 1983; Dockery, in Jay, 1999; Grahame, 1971; Childs, 1986; Barton, Bird, Lindsay, Newton and Wright, 1995a; Rozzi, et al., 1999b; Kerr, Macmillan, Uttley and Luqmani, 2000; Grahame, 2001), there has been a deficit in controlled studies in which the neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility have been quantified and considered within the context of organization of postural control in standing balance and gait. This was the aim of this project, undertaken as three studies. The major study (Study One) compared the fundamental neuro-muscular and musculo-skeletal characteristics of 15 children with joint hypermobility, and 15 age (8 and 9 years), gender, height and weight matched non-hypermobile controls. Significant differences were identified between previously undiagnosed hypermobile (n=15) and non-hypermobile children (n=15) in passive joint ranges of motion of the lower limbs and lumbar spine, muscle tone of the lower leg and foot, barefoot CoP displacement and in parameters of barefoot gait. Clinically relevant differences were also noted in barefoot single leg balance time. There were no differences between groups in isometric muscle strength in ankle dorsiflexion, knee flexion or extension. The second comparative study investigated foot morphology in non-weight bearing and weight bearing load conditions of the same children with and without joint hypermobility using three dimensional images (plaster casts) of their feet. The preliminary phase of this study evaluated the casting technique against direct measures of foot length, forefoot width, RCSP and forefoot to rearfoot angle. Results indicated accurate representation of elementary foot morphology within the plaster images. The comparative study examined the between and within group differences in measures of foot length and width, and in measures above the support surface (heel inclination angle, forefoot to rearfoot angle, normalized arch height, height of the widest point of the heel) in the two load conditions. Results of measures from plaster images identified that hypermobile children have different barefoot weight bearing foot morphology above the support surface than non-hypermobile children, despite no differences in measures of foot length or width. Based upon the differences in components of control of posture and gait in the hypermobile group, identified in Study One and Study Two, the final study (Study Three), using the same subjects, tested the immediate effect of specifically designed custom-made foot orthoses upon balance and gait of hypermobile children. The design of the orthoses was evaluated against the direct measures and the measures from plaster images of the feet. This ascertained the differences in morphology of the modified casts used to mould the orthoses and the original image of the foot. The orthoses were fitted into standardized running shoes. The effect of the shoe alone was tested upon the non-hypermobile children as the non-therapeutic equivalent condition. Immediate improvement in balance was noted in single leg stance and CoP displacement in the hypermobile group together with significant immediate improvement in the percentage of gait phases and in the percentage of the gait cycle at which maximum plantar flexion of the ankle occurred in gait. The neuro-muscular and musculo-skeletal characteristics of children with joint hypermobility are different from those of non-hypermobile children. The Beighton, Solomon and Soskolne (1973) screening criteria successfully classified joint hypermobility in children. As a result of this study joint hypermobility has been identified as a variable which must be controlled in studies of foot morphology and function in children. The outcomes of this study provide a basis upon which to further explore the association between joint hypermobility and neuro-muscular and musculo-skeletal conditions, and, have relevance for the physical education of children with joint hypermobility, for footwear and orthotic design processes, and, in particular, for clinical identification and treatment of children with joint hypermobility.

Structural health monitoring of bridges using acoustic emission technology

Bridges are an important part of society's infrastructure and reliable methods are necessary to monitor them and ensure their safety and efficiency. Bridges deteriorate with age and early detection of damage helps in prolonging the lives and prevent catastrophic failures. Most bridges still in used today were built decades ago and are now subjected to changes in load patterns, which can cause localized distress and if not corrected can result in bridge failure. In the past, monitoring of structures was usually done by means of visual inspection and tapping of the structures using a small hammer. Recent advancements of sensors and information technologies have resulted in new ways of monitoring the performance of structures. This paper briefly describes the current technologies used in bridge structures condition monitoring with its prime focus in the application of acoustic emission (AE) technology in the monitoring of bridge structures and its challenges.

Resilience in chronic disease : the relationships among risk factors, protective factors, adaptive outcomes, and the level of resilience in adults with diabetes

Background: There are innumerable diabetes studies that have investigated associations between risk factors, protective factors, and health outcomes; however, these individual predictors are part of a complex network of interacting forces. Moreover, there is little awareness about resilience or its importance in chronic disease in adulthood, especially diabetes. Thus, this is the first study to: (1) extensively investigate the relationships among a host of predictors and multiple adaptive outcomes; and (2) conceptualise a resilience model among people with diabetes. Methods: This cross-sectional study was divided into two research studies. Study One was to translate two diabetes-specific instruments (Problem Areas In Diabetes, PAID; Diabetes Coping Measure, DCM) into a Chinese version and to examine their psychometric properties for use in Study Two in a convenience sample of 205 outpatients with type 2 diabetes. In Study Two, an integrated theoretical model is developed and evaluated using the structural equation modelling (SEM) technique. A self-administered questionnaire was completed by 345 people with type 2 diabetes from the endocrine outpatient departments of three hospitals in Taiwan. Results: Confirmatory factor analyses confirmed a one-factor structure of the PAID-C which was similar to the original version of the PAID. Strong content validity of the PAID-C was demonstrated. The PAID-C was associated with HbA1c and diabetes self-care behaviours, confirming satisfactory criterion validity. There was a moderate relationship between the PAID-C and the Perceived Stress Scale, supporting satisfactory convergent validity. The PAID-C also demonstrated satisfactory stability and high internal consistency. A four-factor structure and strong content validity of the DCM-C was confirmed. Criterion validity demonstrated that the DCM-C was significantly associated with HbA1c and diabetes self-care behaviours. There was a statistical correlation between the DCM-C and the Revised Ways of Coping Checklist, suggesting satisfactory convergent validity. Test-retest reliability demonstrated satisfactory stability of the DCM-C. The total scale of the DCM-C showed adequate internal consistency. Age, duration of diabetes, diabetes symptoms, diabetes distress, physical activity, coping strategies, and social support were the most consistent factors associated with adaptive outcomes in adults with diabetes. Resilience was positively associated with coping strategies, social support, health-related quality of life, and diabetes self-care behaviours. Results of the structural equation modelling revealed protective factors had a significant direct effect on adaptive outcomes; however, the construct of risk factors was not significantly related to adaptive outcomes. Moreover, resilience can moderate the relationships among protective factors and adaptive outcomes, but there were no interaction effects of risk factors and resilience on adaptive outcomes. Conclusion: This study contributes to an understanding of how risk factors and protective factors work together to influence adaptive outcomes in blood sugar control, health-related quality of life, and diabetes self-care behaviours. Additionally, resilience is a positive personality characteristic and may be importantly involved in the adjustment process among people living with type 2 diabetes.

Concentrations of polybrominated diphenyl ethers (PBDEs) in matched samples of human milk, dust and indoor air

Polybrominated diphenyl ethers (PBDEs) are lipophilic, persistent pollutants found worldwide in environmental and human samples. Exposure pathways for PBDEs remain unclear but may include food, air and dust. The aim of this study was to conduct an integrated assessment of PBDE exposure and human body burden using 10 matched samples of human milk, indoor air and dust collected in 2007–2008 in Brisbane, Australia. In addition, temporal analysis was investigated comparing the results of the current study with PBDE concentrations in human milk collected in 2002–2003 from the same region. PBDEs were detected in all matrices and the median concentrations of BDEs -47 and -209 in human milk, air and dust were: 4.2 and 0.3 ng/g lipid; 25 and 7.8 pg/m3; and 56 and 291 ng/g dust, respectively. Significant correlations were observed between the concentrations of BDE-99 in air and human milk (r = 0.661, p = 0.038) and BDE-153 in dust and BDE-183 in human milk (r = 0.697, p = 0.025). These correlations do not suggest causal relationships — there is no hypothesis that can be offered to explain why BDE-153 in dust and BDE-183 in milk are correlated. The fact that so few correlations were found in the data could be a function of the small sample size, or because additional factors, such as sources of exposure not considered or measured in the study, might be important in explaining exposure to PBDEs. There was a slight decrease in PBDE concentrations from 2002–2003 to 2007–2008 but this may be due to sampling and analytical differences. Overall, average PBDE concentrations from these individual samples were similar to results from pooled human milk collected in Brisbane in 2002–2003 indicating that pooling may be an efficient, cost-effective strategy of assessing PBDE concentrations on a population basis. The results of this study were used to estimate an infant's daily PBDE intake via inhalation, dust ingestion and human milk consumption. Differences in PBDE intake of individual congeners from the different matrices were observed. Specifically, as the level of bromination increased, the contribution of PBDE intake decreased via human milk and increased via dust. As the impacts of the ban of the lower brominated (penta- and octa-BDE) products become evident, an increased use of the higher brominated deca-BDE product may result in dust making a greater contribution to infant exposure than it does currently. To better understand human body burden, further research is required into the sources and exposure pathways of PBDEs and metabolic differences influencing an individual's response to exposure. In addition, temporal trend analysis is necessary with continued monitoring of PBDEs in the human population as well as in the suggested exposure matrices of food, dust and air.

Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks—Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control.

A multiple-control fuzzy vault

We introduce multiple-control fuzzy vaults allowing generalised threshold, compartmented and multilevel access structure. The presented schemes enable many useful applications employing multiple users and/or multiple locking sets. Introducing the original single control fuzzy vault of Juels and Sudan we identify several similarities and differences between their vault and secret sharing schemes which influence how best to obtain working generalisations. We design multiple-control fuzzy vaults suggesting applications using biometric credentials as locking and unlocking values. Furthermore we assess the security of our obtained generalisations for insider/ outsider attacks and examine the access-complexity for legitimate vault owners.