Evolution of vocational rehabilitation competencies in Australia

Over the past decade, there has been growth in the delivery of vocational rehabilitation services globally, as countries seek to control disability-related expenditure, yet there has been minimal research outside the United States on competencies required to work in this area. This study reports on research conducted in Australia to determine current job function and knowledge areas in terms of their importance and frequency of use in the provision of vocational rehabilitation. A survey comprising items from the Rehabilitation Skills Inventory-Amended and International Survey of Disability Management was completed by 149 rehabilitation counselors and items submitted to factor analysis. T-tests and analyses of variance were used to determine differences between scores of importance and frequency and differences in scores based on work setting and professional training. Six factors were identified as important and frequently used: (i) vocational counseling, (ii) professional practice, (iii) personal counseling, (iv) rehabilitation case management, (v) workplace disability case management, and (vi) workplace intervention and program management. Vocational counseling, professional practice and personal counseling were significantly more important and performed more frequently by respondents in vocational rehabilitation settings than those in compensation settings. These same three factors were rated significantly higher in importance and frequency by those with rehabilitation counselor training when compared with those with other training. In conclusion, although ‘traditional’ knowledge and skill areas such as vocational counseling, professional practice, and personal counseling were identified as central to vocational rehabilitation practice in Australian rehabilitation agencies, mean ratings suggest a growing emphasis on knowledge and skills associated with disability management practice.

Wellness in older adults

Understanding perception of wellness in older adults is a question to be understood against the backdrop of concerns about whether global ageing and the ‘bulge’ of ageing baby boomers will increase health care cost beyond what modern economies can deal with. Older adults who age in a healthy way and who take responsibility for their own health offer a positive alternative and change the perception that older adults are a burden on their society’s health system. The concept of successful ageing introduced by Rowe and Kahn (1987; 1997) suggested that older adults age successfully if they avoid disease and disability, maintain high cognitive and physical functioning and remain actively engaged with life. This concept, however, did not reflect older adults’ own perceptions of what constitutes successful ageing or how perceptions of wellness or health-related quality of life influenced the older adult’s understanding of his or her own health and ageing. A research project was designed to examine older adults’ perceptions of wellness in order to gain an understanding of the factors that influence perception of their own wellness. Specifically, the research wanted to explore two aspects: whether belonging to a unique organisation, in this instance a Returned Services Club, influenced perceptions of wellness; and whether there are significant gender differences for the perception of wellness. A mixed method project with two consecutive studies was designed to answer these questions: a quantitative survey of members of a Returned Services Club and of the surrounding community in Queensland, Australia, and a qualitative study conducting focus groups to explore findings of the survey. The results of the survey were used to determine the composition of the focus groups. The participants for the first study, (N=257), community living adults 65 years and older, were chosen from the membership role of a Returned Services Club or recruited by personal approach from the community surrounding the Services Club. Participants completed a survey that consisted of a perception of wellness instrument, a health-related quality of life instrument, and questions on morbidities, modifiable life style factors and demographics. Data analysis found that a number of individual factors influenced perception of wellness and health-related quality of life. Positive influences were independent mobility, exercise and gambling at non-hazardous levels, and negative influences were hearing loss, memory problems, chronic disease and being single. Membership of the Services Club did not contribute to perception of wellness beyond being a member of a social group. While there may have been an expectation that members of an organisation that is traditionally associated with high alcohol use and problematic gambling may have lower perceptions of wellness, this study suggested that the negative influences may have been counteracted by the positive effects of social interaction, thus having neither negative nor positive influences on perception of wellness. There were significant differences in perception of wellness and in health-related quality of life for women and men. The most significant difference was for women aged 85-90 who had significantly lower scores for perception of wellness than men or than any other age group. This result was the impetus for conducting focus groups with adults aged 85-90 years of age. Focus groups were conducted with 24 women and four men aged 85-90 to explore the survey findings for this age group. Results from the focus groups indicated that for older adults perception of wellness was a multidimensional construct of more complexity than indicated by the survey instrument. Elite older women (women over 85 years of age) related their perception of wellness to their ability to do what they wanted to do, and what they wanted to do significantly more than anything else, was to stay connected to family, friends and the community to which they belonged. From the focus group results it appeared that elite older women identified with the three elements of successful ageing – low incidence of disability and disease, high physical and cognitive functioning, and active engagement with life – but not in a flat structure. It appears that for elite older women good physical and mental health function to enable social connectedness. It is the elements of health that impact on the ability to do what they wanted to do that were identified as key factors: independent mobility, hearing and memory - factors that impact on the ability to interact socially. These elements were only identified when they impacted on the person’s ability to do what they wanted to do, for example mobility problems that were managed were not considered a problem. The study also revealed that older women use selection, optimisation and compensation to meet their goal of staying socially connected. The shopping centre was a key factor in this goal and older women used shopping centres to stay connected to the community and for exercise as well as shopping. Personal and public safety and other environmental concerns were viewed in the same context of enabling or disabling social connectedness. This suggested that for elite older women the model of successful ageing was hierarchical rather than flat, with social connectedness at the top, supported by cognitive functioning and good physical and mental health. In conclusion, this research revealed that perception of wellness in older adults is a complex, multidimensional construct. For older adults good health is related to social connectedness and is not a goal in itself. Health professionals and the community at large have a responsibility to take into account the ability of the older adult to stay socially connected to their community and to enable this, if the goal is to keep older adults healthy for as long as possible. Maintaining or improving perception of wellness in older adults will require a broad biopsychosocial approach that utilises findings such as older adults’ use of shopping centres for non-shopping purposes, concerns about personal and environmental safety and supporting older adults to maintain or improve their social connectedness to their communities.

An investigation of foot and ankle problems experienced by nurses

Relatively little information has been reported about foot and ankle problems experienced by nurses, despite anecdotal evidence which suggests they are common ailments. The purpose of this study was to improve knowledge about the prevalence of foot and ankle musculoskeletal disorders (MSDs) and to explore relationships between these MSDs and proposed risk factors. A review of the literature relating to work-related MSDs, MSDs in nursing, foot and lower-limb MSDs, screening for work-related MSDs, foot discomfort, footwear and the prevalence of foot problems in the community was undertaken. Based on the review, theoretical risk factors were proposed that pertained to the individual characteristics of the nurses, their work activity or their work environment. Three studies were then undertaken. A cross-sectional survey of 304 nurses, working in a large tertiary paediatric hospital, established the prevalence of foot and ankle MSDs. The survey collected information about self-reported risk factors of interest. The second study involved the clinical examination of a subgroup of 40 nurses, to examine changes in body discomfort, foot discomfort and postural sway over the course of a single work shift. Objective measurements of additional risk factors, such as individual foot posture (arch index) and the hardness of shoe midsoles, were performed. A final study was used to confirm the test-retest reliability of important aspects of the survey and key clinical measurements. Foot and ankle problems were the most common MSDs experienced by nurses in the preceding seven days (42.7% of nurses). They were the second most common MSDs to cause disability in the last 12 months (17.4% of nurses), and the third most common MSDs experienced by nurses in the last 12 months (54% of nurses). Substantial foot discomfort (Visual Analogue Scale (VAS) score of 50mm or more) was experienced by 48.5% of nurses at sometime in the last 12 months. Individual risk factors, such as obesity and the number of self-reported foot conditions (e.g., callouses, curled toes, flat feet) were strongly associated with the likelihood of experiencing foot problems in the last seven days or during the last 12 months. These risk factors showed consistent associations with disabling foot conditions and substantial foot discomfort. Some of these associations were dependent upon work-related risk factors, such as the location within the hospital and the average hours worked per week. Working in the intensive care unit was associated with higher odds of experiencing foot problems within the last seven days, foot problems in the last 12 months and foot problems that impaired activity in the last 12 months. Changes in foot discomfort experienced within a day, showed large individual variability. Fifteen of the forty nurses experienced moderate/substantial foot discomfort at the end of their shift (VAS 25+mm). Analysis of the association between risk factors and moderate/substantial foot discomfort revealed that foot discomfort was less likely for nurses who were older, had greater BMI or had lower foot arches, as indicated by higher arch index scores. The nurses’ postural sway decreased over the course of the work shift, suggesting improved body balance by the end of the day. These findings were unexpected. Further clinical studies examining individual nurses on several work shifts are needed to confirm these results, particularly due to the small sample size and the single measurement occasion. There are more than 280,000 nurses registered to practice in Australia. The nursing workforce is ageing and the prevalence of foot problems will increase. If the prevalence estimates from this study are extrapolated to the profession generally, more than 70,000 hospital nurses have experienced substantial foot discomfort and 25-30,000 hospital nurses have been limited in their activity due to foot problems during the last 12 months. Nurses with underlying foot conditions were more likely to report having foot problems at work. Strategies to prevent or manage foot conditions exist and they should be disseminated to nurses. Obesity is a significant risk factor for foot and ankle MSDs and these nurses may need particular assistance to manage foot problems. The risk of foot problems for particular groups of nurses, e.g. obese nurses, may vary depending upon the location within the hospital. Further research is needed to confirm the findings of this study. Similar studies should be conducted in other occupational groups that require workers to stand for prolonged periods.

Automatic speaker recognition under adverse conditions

Speaker verification is the process of verifying the identity of a person by analysing their speech. There are several important applications for automatic speaker verification (ASV) technology including suspect identification, tracking terrorists and detecting a person’s presence at a remote location in the surveillance domain, as well as person authentication for phone banking and credit card transactions in the private sector. Telephones and telephony networks provide a natural medium for these applications. The aim of this work is to improve the usefulness of ASV technology for practical applications in the presence of adverse conditions. In a telephony environment, background noise, handset mismatch, channel distortions, room acoustics and restrictions on the available testing and training data are common sources of errors for ASV systems. Two research themes were pursued to overcome these adverse conditions: Modelling mismatch and modelling uncertainty. To directly address the performance degradation incurred through mismatched conditions it was proposed to directly model this mismatch. Feature mapping was evaluated for combating handset mismatch and was extended through the use of a blind clustering algorithm to remove the need for accurate handset labels for the training data. Mismatch modelling was then generalised by explicitly modelling the session conditions as a constrained offset of the speaker model means. This session variability modelling approach enabled the modelling of arbitrary sources of mismatch, including handset type, and halved the error rates in many cases. Methods to model the uncertainty in speaker model estimates and verification scores were developed to address the difficulties of limited training and testing data. The Bayes factor was introduced to account for the uncertainty of the speaker model estimates in testing by applying Bayesian theory to the verification criterion, with improved performance in matched conditions. Modelling the uncertainty in the verification score itself met with significant success. Estimating a confidence interval for the "true" verification score enabled an order of magnitude reduction in the average quantity of speech required to make a confident verification decision based on a threshold. The confidence measures developed in this work may also have significant applications for forensic speaker verification tasks.

The mechanism of maturation of insulin-like growth factor-1

This study, to elucidate the role of des(1-3)IGF-I in the maturation of IGF-I,used two strategies. The first was to detect the presence of enzymes in tissues, which would act on IGF-I to produce des(1-3)IGF-I, and the second was to detect the potential products of such enzymic activity, namely Gly-Pro-Glu(GPE), Gly-Pro(GP) and des(l- 3)IGF-I. No neutral tripeptidyl peptidase (TPP II), which would release the tripeptide GPE from IGF-I, was detected in brain, urine nor in red or white blood cells. The TPPlike activity which was detected, was attributed to a combined action of a dipeptidyl peptidase (DPP N) and an aminopeptidase (AP A). A true TPP II was, however, detected in platelets. Two purified TPP II enzymes were investigated but they did not release GPE from IGF-I under a variety of conditions. Consequently, TPP II seemed unlikely to participate in the formation of des(1-3)IGF-I. In contrast, an acidic tripeptidyl peptidase activity (TPP I) was detected in brain and colostrum, the former with a pH optimum of 4.5 and the latter 3.8. It seems likely that such an enzyme would participate in the formation of des( 1-3 )IGF-I in these tissues in vitro, ie. that des(1-3)IGF-I may have been produced as an artifact in the isolation of IGF-I from brain and colostrum in acidic conditions. This contrasts with suggestions of an in vivo role for des(1-3)IGF-I, as reported by others. The activity of a dipeptidyl peptidase N (DPP N) from urine, which should release the dipeptide GP from IGF-I, was assessed under a variety of conditions and with a variety of additives and potential enzyme stimulants, but there was no release of GP. The DPP N also exhibited a transferase activity with synthetic substrates in the presence of dipeptides, at lower concentrations than previously reported for other acceptors or other proteolytic enzymes. In addition, a low concentration of a product,possibly the tetrapeptide Gly-Pro-Gly-Leu, was detected with the action of the enzyme on IGF-I in the presence of the dipeptide Gly-Leu. As part of attempts to detect tissue production of des(1-3)IGF-I, a monoclonal antibody (MAb ), directed towards the GPE- end ofiGF-I was produced by immunisation with a 10-mer covalently attached to a carrier protein. By the use of indirect ELISA and inhibitor studies, the MAb was shown to selectively recognise peptides with anNterminal GPE- sequence, and applied to the indirect detection of des(1-3)IGF-I. The concentration of GPE in brain, measured by mass spectrometry ( MS), was low, and the concentration of total IGF-I (measured by ELISA with a commercial polyclonal antibody [P Ab]) was 40 times higher at 50 nmol/kg. This also, was not consistent with the action of a tripeptidyl peptidase in brain that converted all IGF-I to des(1-3)IGF-I plus GPE. Contrasting ELISA results, using the MAb prepared in this study, suggest an even higher concentration of intact IGF-I of 150 nmollkg. This would argue against the presence of any des( 1-3 )IGF-I in brain, but in turn, this indicates either the presence of other substances containing a GPE amino-terminus or other cross reacting epitope. Although the results of the specificity studies reported in Chapter 5 would make this latter possibility seem unlikely, it cannot be completely excluded. No GP was detected in brain by MS. No GPE was detected in colostrum by capillary electrophoresis (CE) but the interference from extraneous substances reduced the detectability of GPE by CE and this approach would require further, prior, purification and concentration steps. A molecule, with a migration time equal to that of the peptide GP, was detected in colostrum by CE, but the concentration (~ 10 11mo/L) was much higher than the IGF-I concentration measured by radio-immunoassay using a PAb (80 nmol/L) or using a Mab (300-400 nmolL). A DPP IV enzyme was detected in colostrum and this could account for the GP, derived from substrates other than IGF-1. Based on the differential results of the two antibody assays, there was no indication of the presence of des(1-3)IGF-I in brain or colostrum. In the absence of any enzyme activity directed towards the amino terminus of IGF-I and the absence any potential products, IGF-I, therefore, does not appear to "mature" via des(1-3)IGF-I in the brain, nor in the neutral colostrum. In spite of these results which indicate the absence of an enzymic attack on IGF-I and the absence of the expected products in tissues, the possibility that the conversion of IGF-I may occur in neutral conditions in limited amounts, cannot be ruled out. It remains possible that in the extracellular environment of the membrane, a complex interaction of IGF-I, binding protein, aminopeptidase(s) and receptor, produces des(1- 3)IGF-I as a transient product which is bound to the receptor and internalised.

The expression of ADAM-9 and -10 in prostate cancer and their regulation by dihydrotestosterone, insulin-like growth Factor-1 and epidermal growth factor

Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

Validation of the Algase Wandering Scale (Version 2) in a cross cultural sample

This study examined the psychometric properties of an expanded version of the Algase Wandering Scale (Version 2) (AWS-V2) in a cross-cultural sample. A cross-sectional survey design was used. Study subjects were 172 English-speaking persons with dementia (PWD) from long-term care facilities in the USA, Canada, and Australia. Two or more facility staff rated each subject on the AWS-V2. Demographic and cognitive data (MMSE) were also obtained. Staff provided information on their own knowledge of the subject and of dementia. Separate factor analyses on data from two samples of raters each explained greater than 66% of the variance in AWS-V2 scores and validated four (persistent walking, navigational deficit, eloping behavior, and shadowing) of five factors in the original scale. Items added to create the AWS-V2 strengthened the shadowing subscale, failed to improve the routinized walking subscale, and added a factor, attention shifting as compared to the original AWS. Evidence for validity was found in significant correlations and ANOVAs between the AWS-V2 and most subscales with a single item indicator of wandering and with the MMSE. Evidence of reliability was shown by internal consistency of the AWS-V2 (0.87, 0.88) and its subscales (range 0.88 to 0.66), with Kappa for individual items (17 of 27 greater than 0.4), and ANOVAs comparing ratings across rater groups (nurses, nurse aids, and other staff). Analyses support validity and reliability of the AWS-V2 overall and for persistent walking, spatial disorientation, and eloping behavior subscales. The AWS-V2 and its subscales are an appropriate way to measure wandering as conceptualized within the Need-driven Dementia-compromised Behavior Model in studies of English-speaking subjects. Suggestions for further strengthening the scale and for extending its use to clinical applications are described.

An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal [mu]-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. [mu]-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Governors highway safety associations and transportation planning: Exploratory factor analysis and structural equation modeling

The Intermodal Surface Transportation Efficiency Act (ISTEA) of 1991 mandated the consideration of safety in the regional transportation planning process. As part of National Cooperative Highway Research Program Project 8-44, "Incorporating Safety into the Transportation Planning Process," we conducted a telephone survey to assess safety-related activities and expertise at Governors Highway Safety Associations (GHSAs), and GHSA relationships with metropolitan planning organizations (MPOs) and state departments of transportation (DOTs). The survey results were combined with statewide crash data to enable exploratory modeling of the relationship between GHSA policies and programs and statewide safety. The modeling objective was to illuminate current hurdles to ISTEA implementation, so that appropriate institutional, analytical, and personnel improvements can be made. The study revealed that coordination of transportation safety across DOTs, MPOs, GHSAs, and departments of public safety is generally beneficial to the implementation of safety. In addition, better coordination is characterized by more positive and constructive attitudes toward incorporating safety into planning.