Virtual design process : design validation tool schematic approach in car carrier

An important aspect of designing any product is validation. Virtual design process (VDP) is an alternative to hardware prototyping in which analysis of designs can be done without manufacturing physical samples. In recent years, VDP have been generated either for animation or filming applications. This paper proposes a virtual reality design process model on one of the applications when used as a validation tool. This technique is used to generate a complete design guideline and validation tool of product design. To support the design process of a product, a virtual environment and VDP method were developed that supports validation and an initial design cycle performed by a designer. The product model car carrier is used as illustration for which virtual design was generated. The loading and unloading sequence of the model for the prototype was generated using automated reasoning techniques and was completed by interactively animating the product in the virtual environment before complete design was built. By using the VDP process critical issues like loading, unloading, Australian Design rules (ADR) and clearance analysis were done. The process would save time, money in physical sampling and to large extent in complete math generation. Since only schematic models are required, it saves time in math modelling and handling of bigger size assemblies due to complexity of the models. This extension of VDP process for design evaluation is unique and was developed, implemented successfully. In this paper a Toll logistics and J Smith and Sons car carrier which is developed under author’s responsibility has been used to illustrate our approach of generating design validation via VDP.

Development of a colorimetric assay for heparanase activity suitable for kinetic analysis and inhibitor screening

The role that heparanase plays during metastasis and angiogenesis in tumors makes it an attractive target for cancer therapeutics. Despite this enzyme’s significance, most of the assays developed to measure its activity are complex. Moreover, they usually rely on labeling variable preparations of the natural substrate heparan sulfate, making comparisons across studies precarious. To overcome these problems, we have developed a convenient assay based on the cleavage of the synthetic heparin oligosaccharide fondaparinux. The assay measures the appearance of the disaccharide product of heparanase-catalyzed fondaparinux cleavage colorimetrically using the tetrazolium salt WST-1. Because this assay has a homogeneous substrate with a single point of cleavage, the kinetics of the enzyme can be reliably characterized, giving a Km of 46 μM and a kcat of 3.5 s−1 with fondaparinux as substrate. The inhibition of heparanase by the published inhibitor, PI-88, was also studied, and a Ki of 7.9 nM was determined. The simplicity and robustness of this method, should, not only greatly assist routine assay of heparanase activity but also could be adapted for high-throughput screening of compound libraries, with the data generated being directly comparable across studies.

The Children's Depression Scale : assessment of factor structure with data from a normal population

A study investigated the reliability and construct validity of the Children's Depression Scale. The revised subscales were shown to have strong construct and face validity and high reliability.

Vision, functional and cognitive determinants of motor vehicle incidents in older drivers

Background: The proportion of older individuals in the driving population is predicted to increase in the next 50 years. This has important implications for driving safety as abilities which are important for safe driving, such as vision (which accounts for the majority of the sensory input required for driving), processing ability and cognition have been shown to decline with age. The current methods employed for screening older drivers upon re-licensure are also vision based. This study, which investigated social, behavioural and professional aspects involved with older drivers, aimed to determine: (i) if the current visual standards in place for testing upon re-licensure are effective in reducing the older driver fatality rate in Australia; (ii) if the recommended visual standards are actually implemented as part of the testing procedures by Australian optometrists; and (iii) if there are other non-standardised tests which may be better at predicting the on-road incident-risk (including near misses and minor incidents) in older drivers than those tests recommended in the standards. Methods: For the first phase of the study, state-based age- and gender-stratified numbers of older driver fatalities for 2000-2003 were obtained from the Australian Transportation Safety Bureau database. Poisson regression analyses of fatality rates were considered by renewal frequency and jurisdiction (as separate models), adjusting for possible confounding variables of age, gender and year. For the second phase, all practising optometrists in Australia were surveyed on the vision tests they conduct in consultations relating to driving and their knowledge of vision requirements for older drivers. Finally, for the third phase of the study to investigate determinants of on-road incident risk, a stratified random sample of 600 Brisbane residents aged 60 years and were selected and invited to participate using an introductory letter explaining the project requirements. In order to capture the number and type of road incidents which occurred for each participant over 12 months (including near misses and minor incidents), an important component of the prospective research study was the development and validation of a driving diary. The diary was a tool in which incidents that occurred could be logged at that time (or very close in time to which they occurred) and thus, in comparison with relying on participant memory over time, recall bias of incident occurrence was minimised. Association between all visual tests, cognition and scores obtained for non-standard functional tests with retrospective and prospective incident occurrence was investigated. Results: In the first phase,rivers aged 60-69 years had a 33% lower fatality risk (Rate Ratio [RR] = 0.75, 95% CI 0.32-1.77) in states with vision testing upon re-licensure compared with states with no vision testing upon re-licensure, however, because the CIs are wide, crossing 1.00, this result should be regarded with caution. However, overall fatality rates and fatality rates for those aged 70 years and older (RR=1.17, CI 0.64-2.13) did not differ between states with and without license renewal procedures, indicating no apparent benefit in vision testing legislation. For the second phase of the study, nearly all optometrists measured visual acuity (VA) as part of a vision assessment for re-licensing, however, 20% of optometrists did not perform any visual field (VF) testing and only 20% routinely performed automated VF on older drivers, despite the standards for licensing advocating automated VF as part of the vision standard. This demonstrates the need for more effective communication between the policy makers and those responsible for carrying out the standards. It may also indicate that the overall higher driver fatality rate in jurisdictions with vision testing requirements is resultant as the tests recommended by the standards are only partially being conducted by optometrists. Hence a standardised protocol for the screening of older drivers for re-licensure across the nation must be established. The opinions of Australian optometrists with regard to the responsibility of reporting older drivers who fail to meet the licensing standards highlighted the conflict between maintaining patient confidentiality or upholding public safety. Mandatory reporting requirements of those drivers who fail to reach the standards necessary for driving would minimise potential conflict between the patient and their practitioner, and help maintain patient trust and goodwill. The final phase of the PhD program investigated the efficacy of vision, functional and cognitive tests to discriminate between at-risk and safe older drivers. Nearly 80% of the participants experienced an incident of some form over the prospective 12 months, with the total incident rate being 4.65/10 000 km. Sixty-three percent reported having a near miss and 28% had a minor incident. The results from the prospective diary study indicate that the current vision screening tests (VA and VF) used for re-licensure do not accurately predict older drivers who are at increased odds of having an on-road incident. However, the variation in visual measurements of the cohort was narrow, also affecting the results seen with the visual functon questionnaires. Hence a larger cohort with greater variability should be considered for a future study. A slightly lower cognitive level (as measured with the Mini-Mental State Examination [MMSE]) did show an association with incident involvement as did slower reaction time (RT), however the Useful-Field-of-View (UFOV) provided the most compelling results of the study. Cut-off values of UFOV processing (>23.3ms), divided attention (>113ms), selective attention (>258ms) and overall score (moderate/ high/ very high risk) were effective in determining older drivers at increased odds of having any on-road incident and the occurrence of minor incidents. Discussion: The results have shown that for the 60-69 year age-group, there is a potential benefit in testing vision upon licence renewal. However, overall fatality rates and fatality rates for those aged 70 years and older indicated no benefit in vision testing legislation and suggests a need for inclusion of screening tests which better predict on-road incidents. Although VA is routinely performed by Australian optometrists on older drivers renewing their licence, VF is not. Therefore there is a need for a protocol to be developed and administered which would result in standardised methods conducted throughout the nation for the screening of older drivers upon re-licensure. Communication between the community, policy makers and those conducting the protocol should be maximised. By implementing a standardised screening protocol which incorporates a level of mandatory reporting by the practitioner, the ethical dilemma of breaching patient confidentiality would also be resolved. The tests which should be included in this screening protocol, however, cannot solely be ones which have been implemented in the past. In this investigation, RT, MMSE and UFOV were shown to be better determinants of on-road incidents in older drivers than VA and VF, however, as previously mentioned, there was a lack of variability in visual status within the cohort. Nevertheless, it is the recommendation from this investigation, that subject to appropriate sensitivity and specificity being demonstrated in the future using a cohort with wider variation in vision, functional performance and cognition, these tests of cognition and information processing should be added to the current protocol for the screening of older drivers which may be conducted at licensing centres across the nation.

Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort

Abstract Background Recent studies show that advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism, bipolar disorder and schizophrenia. A body of evidence also suggests that individuals who develop schizophrenia show subtle deviations in a range of behavioural domains during their childhood. The aim of the study was to examine the relationship between paternal and maternal ages and selected behavioural measures in children using a large birth cohort. Method Participants were singleton children (n = 21,753) drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 7 years. The main analyses examined the relationship between parental age and behavioural measures when adjusted for a range of potentially confounding variables, including age of the other parent, maternal race, socio-economic measures, sex, gestation length, maternal marital status, parental mental illness, and child's age-at-testing. Results Advanced paternal age was associated with a significantly increased risk of adverse ‘externalizing’ behaviours at age seven years. For every five year increase in paternal age, the odds of higher ‘externalizing’ behaviours was increased by 12% (OR = 1.12; 95% CI = 1.03, 1.21, p < 0.0001). The relationship persisted after adjusting for potential confounding factors. ‘Internalizing’ behavioural outcome was not associated with advanced paternal age. In contrast, advanced maternal age was significantly protective against adverse ‘externalizing’ behavioural outcomes, but associated with an increased risk of adverse ‘internalizing’ behavioural outcomes. Discussion The offspring of older fathers show a distinctly different pattern of behaviours compared to the offspring of older mothers. The diverse socio-cultural and biologically-mediated factors that underpin these findings remain to be clarified. In light of secular trends related to delayed parenthood, the mechanisms underlying these findings warrant closer scrutiny.

Development and validation of 3-Minute Nutrition Screening (3-MinNS) tool for acute hospital patients in Singapore

It is important to detect and treat malnutrition in hospital patients so as to improve clinical outcome and reduce hospital stay. The aim of this study was to develop and validate a nutrition screening tool with a simple and quick scoring system for acute hospital patients in Singapore. In this study, 818 newly admitted patients aged above 18 years old were screened using five parameters that contribute to the risk of malnutrition. A dietitian blinded to the nutrition screening score assessed the same patients using the reference standard, Subjective Global Assessment (SGA) within 48 hours. The sensitivity and specificity were established using the Receiver Operator Characteristics (ROC) curve and the best cutoff scores determined. The nutrition parameter with the largest Area Under the ROC Curve (AUC) was chosen as the final screening tool, which was named 3-Minute Nutrition Screening (3-MinNS). The combination of the parameters weight loss, intake and muscle wastage (3-MinNS), gave the largest AUC when compared with SGA. Using 3-MinNS, the best cutoff point to identify malnourished patients is three (sensitivity 86%, specificity 83%). The cutoff score to identify subjects at risk of severe malnutrition is five (sensitivity 93%, specificity 86%). 3-Minute Nutrition Screening is a valid, simple and rapid tool to identify patients at risk of malnutrition in Singapore acute hospital patients. It is able to differentiate patients at risk of moderate malnutrition and severe malnutrition for prioritization and management purposes.

Validation of the Edinburgh Postnatal Depression Scale for men, and comparison of item endorsement with their partners

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) has been validated and used extensively in screening for depression in new mothers, both in English speaking and non-English speaking communities. While some studies have reported the use of the EPDS with fathers, none have validated it for this group, and thus the appropriate cut-off score for screening for depression or anxiety caseness for this population is not known. METHODS: Couples were recruited antenatally and interviewed at six weeks postpartum. EPDS scores and distress caseness (depression or anxiety disorders) for 208 fathers and 230 mothers were determined using the Diagnostic Interview Schedule. RESULTS: Analyses of the EPDS for fathers using distress caseness (depression or anxiety disorders) as the criterion shows that a cut-off of 5/6 has optimum receiver operating characteristics. Furthermore acceptable reliability (split-half and internal consistency) and validity (concurrent) coefficients were obtained. For mothers the optimum cut-off screening value to detect distress caseness was 7/8. Item analysis revealed that fathers endorsed seven of the ten items at lower rates to mothers, with the most significant being that referring to crying. CONCLUSIONS: The EPDS is a reliable and valid measure of mood in fathers. Screening for depression or anxiety disorders in fathers requires a two point lower cut-off than screening for depression or anxiety in mothers, and we recommend this cut-off to be 5/6

A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer

First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in prostate-specific antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.

Population Monte Carlo Algorithm in High Dimensions

The population Monte Carlo algorithm is an iterative importance sampling scheme for solving static problems. We examine the population Monte Carlo algorithm in a simplified setting, a single step of the general algorithm, and study a fundamental problem that occurs in applying importance sampling to high-dimensional problem. The precision of the computed estimate from the simplified setting is measured by the asymptotic variance of estimate under conditions on the importance function. We demonstrate the exponential growth of the asymptotic variance with the dimension and show that the optimal covariance matrix for the importance function can be estimated in special cases.

Developing a quick and practical screen to improve the identification of poor hydration in geriatric and rehabilitative care

Dehydration has been associated with increased morbidity and mortality. Dehydration risk increases with advancing age, and will progressively become an issue as the aging population increases. Worldwide, those aged 60 years and over are the fastest growing segment of the population. The study aimed to develop a clinically practical means to identify dehydration amongst older people in the clinical care setting. Older people aged 60 years or over admitted to the Geriatric and Rehabilitation Unit (GARU) of two tertiary teaching hospitals were eligible for participation in the study. Ninety potential screening questions and 38 clinical parameters were initially tested on a single sample (n=33) with the most promising 11 parameters selected to undergo further testing in an independent group (n=86). Of the almost 130 variables explored, tongue dryness was most strongly associated with poor hydration status, demonstrating 64% sensitivity and 62% specificity within the study participants. The result was not confounded by age, gender or body mass index. With minimal training, inter-rater repeatability was over 90%. This study identified tongue dryness as a potentially practical tool to identify dehydration risk amongst older people in the clinical care setting. Further studies to validate the potential screen in larger and varied populations of older people are required

A population survey of the penetrance of contact lens wear in Australia : rationale, methodology and results

Purpose: A population based, cross-sectional telephone survey was conducted to estimate the total penetrance of contact lens wear in Australia. Methods: A total of 42,749 households around Australia were randomly selected from the national electronic telephone directory based on postcode distribution. Before contact was attempted, letters of introduction were sent. The number of individuals and contact lens wearers in each household was ascertained and lens wearers were interviewed to determine details of lens type and mode of wear using a structured questionnaire. Results: Of households contacted, 59.2% (19,171/32,405) agreed to participate. Response rates were only marginally higher amongst households that first received a letter of introduction. In these households, 35,914 individuals were identified, of which, 1,798 were contact lens wearers. The penetrance of contact lens wear during the study period was 5.01% (95% CI: 4.78-5.24). Soft hydrogel lenses had the largest penetrance in the community, (66.7% of all wearers), however, their market share decreased significantly over the study period with increased uptake of newly introduced lens types. Conclusions: The penetrance of contact lens wear concurs with market estimates and equates to approximately 680,000 contact lens wearers aged between 15 and 64 years in Australia. The low response rate obtained in this study highlights the difficulty in contemporary use of telephone survey methodology

Clinical whole-body skin examination reduces the incidence of thick melanomas

Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence-based assessments do not recommend population screening. We aimed to assess whether clinical whole-body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). A population-based case-control study of all Queensland residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%) Whole-body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75mm) (OR= 0.86, 95% CI=0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76-1.49mm was reduced by 7% (OR=0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50-2.99mm (OR=0.83, 95% CI=0.65, 1.05) and by 40% for melanomas ≥3mm (OR=0.60, 95% CI=0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (≤0.75mm) (OR=1.38, 95% CI=1.22, 1.56). This is the strongest evidence to date that whole-body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.

Substance misuse in patients with schizophrenia : Epidemiology and management

Substance misuse in individuals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.

Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.

The malnutrition screening tool is a useful tool for identifying malnutrition risk in residential aged care

Background: The Malnutrition Screening Tool (MST) is a valid nutrition screening tool in the acute hospital setting but has not been assessed in residential aged care facilities. The aim of this secondary analysis was to determine whether the MST could be a useful nutrition screening tool when compared with a full nutrition assessment by Subjective Global Assessment (SGA) in the residential aged care setting. ----- Methods: Two hundred and eighty-five residents (29% male; mean age: 84 ± 9 years) from eight residential aged care facilities in Australia participated. A secondary analysis of data collected during a nutrition intervention study was conducted. The MST consists of two questions related to recent weight loss and appetite. While the MST was not specifically applied, weight loss and appetite information was available and an estimated MST score (0-5) calculated. Nutritional status was assessed by a research assistant trained in using SGA. ----- Results: Malnutrition prevalence was 42.8% (122 malnourished out of 285 residents). Compared to the SGA, the MST was an effective predictor of nutritional risk (sensitivity = 83.6%, specificity = 65.6%, positive predictive value = 0.65, negative predictive value =0.84). ----- Conclusions: The components of the MST have acceptable sensitivity and specificity suggesting it can play a valuable role in quickly identifying malnutrition risk in the residential aged care setting. Further prospective research using the MST tool against a broader array of objective and subjective nutritional parameters is required to confirm its validity as a screening tool in aged care settings.