Operationalizing the resource based view for nascent and young firms : developing scales for resource advantages and disadvantages

Principal Topic: It is well known that most new ventures suffer from a significant lack of resources, which increases the risk of failure (Shepherd, Douglas and Shanley, 2000) and makes it difficult to attract stakeholders and financing for the venture (Bhide & Stevenson, 1999). The Resource-Based View (RBV) (Barney, 1991; Wernerfelt, 1984) is a dominant theoretical base increasingly drawn on within Strategic Management. While theoretical contributions applying RBV in the domain of entrepreneurship can arguably be traced back to Penrose (1959), there has been renewed attention recently (e.g. Alvarez & Busenitz, 2001; Alvarez & Barney, 2004). This said, empirical work is in its infancy. In part, this may be due to a lack of well developed measuring instruments for testing ideas derived from RBV. The purpose of this study is to develop a measurement scales that can serve to assist such empirical investigations. In so doing we will try to overcome three deficiencies in current empirical measures used for the application of RBV to the entrepreneurship arena. First, measures for resource characteristics and configurations associated with typical competitive advantages found in entrepreneurial firms need to be developed. These include such things as alertness and industry knowledge (Kirzner, 1973), flexibility (Ebben & Johnson, 2005), strong networks (Lee et al., 2001) and within knowledge intensive contexts, unique technical expertise (Wiklund and Shepard, 2003). Second, the RBV has the important limitations of being relatively static and modelled on large, established firms. In that context, traditional RBV focuses on competitive advantages. However, newly established firms often face disadvantages, especially those associated with the liabilities of newness (Aldrich & Auster, 1986). It is therefore important in entrepreneurial contexts to expand to an investigation of responses to competitive disadvantage through an RBV lens. Conversely, recent research has suggested that resource constraints actually have a positive effect on firm growth and performance under some circumstances (e.g., George, 2005; Katila & Shane, 2005; Mishina et al., 2004; Mosakowski, 2002; cf. also Baker & Nelson, 2005). Third, current empirical applications of RBV measured levels or amounts of particular resources available to a firm. They infer that these resources deliver firms competitive advantage by establishing a relationship between these resource levels and performance (e.g. via regression on profitability). However, there is the opportunity to directly measure the characteristics of resource configurations that deliver competitive advantage, such as Barney´s well known VRIO (Valuable, Rare, Inimitable and Organized) framework (Barney, 1997). Key Propositions and Methods: The aim of our study is to develop and test scales for measuring resource advantages (and disadvantages) and inimitability for entrepreneurial firms. The study proceeds in three stages. The first stage developed our initial scales based on earlier literature. Where possible, we adapt scales based on previous work. The first block of the scales related to the level of resource advantages and disadvantages. Respondents were asked the degree to which each resource category represented an advantage or disadvantage relative to other businesses in their industry on a 5 point response scale: Major Disadvantage, Slight Disadvantage, No Advantage or Disadvantage, Slight Advantage and Major Advantage. Items were developed as follows. Network capabilities (3 items) were adapted from (Madsen, Alsos, Borch, Ljunggren & Brastad, 2006). Knowledge resources marketing expertise / customer service (3 items) and technical expertise (3 items) were adapted from Wiklund and Shepard (2003). flexibility (2 items), costs (4 items) were adapted from JIBS B97. New scales were developed for industry knowledge / alertness (3 items) and product / service advantages. The second block asked the respondent to nominate the most important resource advantage (and disadvantage) of the firm. For the advantage, they were then asked four questions to determine how easy it would be for other firms to imitate and/or substitute this resource on a 5 point likert scale. For the disadvantage, they were asked corresponding questions related to overcoming this disadvantage. The second stage involved two pre-tests of the instrument to refine the scales. The first was an on-line convenience sample of 38 respondents. The second pre-test was a telephone interview with a random sample of 31 Nascent firms and 47 Young firms (< 3 years in operation) generated using a PSED method of randomly calling households (Gartner et al. 2004). Several items were dropped or reworded based on the pre-tests. The third stage (currently in progress) is part of Wave 1 of CAUSEE (Nascent Firms) and FEDP (Young Firms), a PSED type study being conducted in Australia. The scales will be tested and analysed with a random sample of approximately 700 Nascent and Young firms respectively. In addition, a judgement sample of approximately 100 high potential businesses in each category will be included. Findings and Implications: The paper will report the results of the main study (stage 3 – currently data collection is in progress) will allow comparison of the level of resource advantage / disadvantage across various sub-groups of the population. Of particular interest will be a comparison of the high potential firms with the random sample. Based on the smaller pre-tests (N=38 and N=78) the factor structure of the items confirmed the distinctiveness of the constructs. The reliabilities are within an acceptable range: Cronbach alpha ranged from 0.701 to 0.927. The study will provide an opportunity for researchers to better operationalize RBV theory in studies within the domain of entrepreneurship. This is a fundamental requirement for the ability to test hypotheses derived from RBV in systematic, large scale research studies.

Rural and remote road safety study : final report

• Introduction: Concern and action for rural road safety is relatively new in Australia in comparison to the field of traffic safety as a whole. In 2003, a program of research was begun by the Centre for Accident Research and Road Safety - Queensland (CARRS-Q) and the Rural Health Research Unit (RHRU) at James Cook University to investigate factors contributing to serious rural road crashes in the North Queensland region. This project was funded by the Premier’s Department, Main Roads Department, Queensland Transport, QFleet, Queensland Rail, Queensland Ambulance Service, Department of Natural Resources and Queensland Police Service. Additional funding was provided by NRMA Insurance for a PhD scholarship. In-kind support was provided through the four hospitals used for data collection, namely Cairns Base Hospital, The Townsville Hospital, Mount Isa Hospital and Atherton Hospital.----- The primary aim of the project was to: Identify human factors related to the occurrence of serious traffic incidents in rural and remote areas of Australia, and to the trauma suffered by persons as a result of these incidents, using a sample drawn from a rural and remote area in North Queensland.----- The data and analyses presented in this report are the core findings from two broad studies: a general examination of fatalities and casualties from rural and remote crashes for the period 1 March 2004 until 30 June 2007, and a further linked case-comparison study of hospitalised patients compared with a sample of non-crash-involved drivers.----- • Method: The study was undertaken in rural North Queensland, as defined by the Australian Bureau of Statistics (ABS) statistical divisions of North Queensland, Far North Queensland and North-West Queensland. Urban areas surrounding Townsville, Thuringowa and Cairns were not included. The study methodology was centred on serious crashes, as defined by a resulting hospitalisation for 24 hours or more and/or a fatality. Crashes meeting this criteria within the North Queensland region between 1 March 2004 and 30 June 2007 were identified through hospital records and interviewed where possible. Additional data was sourced from coroner’s reports, the Queensland Transport road crash database, the Queensland Ambulance Service and the study hospitals in the region.----- This report is divided into chapters corresponding to analyses conducted on the collected crash and casualty data.----- Chapter 3 presents an overview of all crashes and casualties identified during the study period. Details are presented in regard to the demographics and road user types of casualties; the locations, times, types, and circumstances of crashes; along with the contributing circumstances of crashes.----- Chapter 4 presents the results of summary statistics for all casualties for which an interview was able to be conducted. Statistics are presented separately for drivers and riders, passengers, pedestrians and cyclists. Details are also presented separately for drivers and riders crashing in off-road and on-road settings. Results from questionnaire data are presented in relation to demographics; the experience of the crash in narrative form; vehicle characteristics and maintenance; trip characteristics (e.g. purpose and length of journey; periods of fatigue and monotony; distractions from driving task); driving history; alcohol and drug use; medical history; driving attitudes, intentions and behaviour; attitudes to enforcement; and experience of road safety advertising.----- Chapter 5 compares the above-listed questionnaire results between on-road crash-involved casualties and interviews conducted in the region with non-crash-involved persons. Direct comparisons as well as age and sex adjusted comparisons are presented.----- Chapter 6 presents information on those casualties who were admitted to one of the study hospitals during the study period. Brief information is given regarding the demographic characteristics of these casualties. Emergency services’ data is used to highlight the characteristics of patient retrieval and transport to and between hospitals. The major injuries resulting from the crashes are presented for each region of the body and analysed by vehicle type, occupant type, seatbelt status, helmet status, alcohol involvement and nature of crash. Estimates are provided of the costs associated with in-hospital treatment and retrieval.----- Chapter 7 describes the characteristics of the fatal casualties and the nature and circumstances of the crashes. Demographics, road user types, licence status, crash type and contributing factors for crashes are presented. Coronial data is provided in regard to contributing circumstances (including alcohol, drugs and medical conditions), cause of death, resulting injuries, and restraint and helmet use.----- Chapter 8 presents the results of a comparison between casualties’ crash descriptions and police-attributed crash circumstances. The relative frequency of contributing circumstances are compared both broadly within the categories of behavioural, environmental, vehicle related, medical and other groupings and specifically for circumstances within these groups.----- Chapter 9 reports on the associated research projects which have been undertaken on specific topics related to rural road safety.----- Finally, Chapter 10 reports on the conclusions and recommendations made from the program of research.---- • Major Recommendations : From the findings of these analyses, a number of major recommendations were made: + Male drivers and riders - Male drivers and riders should continue to be the focus of interventions, given their very high representation among rural and remote road crash fatalities and serious injuries.----- - The group of males aged between 30 and 50 years comprised the largest number of casualties and must also be targeted for change if there is to be a meaningful improvement in rural and remote road safety.----- + Motorcyclists - Single vehicle motorcycle crashes constitute over 80% of serious, on-road rural motorcycle crashes and need particular attention in development of policy and infrastructure.----- - The motorcycle safety consultation process currently being undertaken by Queensland Transport (via the "Motorbike Safety in Queensland - Consultation Paper") is strongly endorsed. As part of this process, particular attention needs to be given to initiatives designed to reduce rural and single vehicle motorcycle crashes.----- - The safety of off-road riders is a serious problem that falls outside the direct responsibility of either Transport or Health departments. Responsibility for this issue needs to be attributed to develop appropriate policy, regulations and countermeasures.----- + Road safety for Indigenous people - Continued resourcing and expansion of The Queensland Aboriginal Peoples and Torres Strait Islander Peoples Driver Licensing Program to meet the needs of remote and Indigenous communities with significantly lower licence ownership levels.----- - Increased attention needs to focus on the contribution of geographic disadvantage (remoteness) factors to remote and Indigenous road trauma.----- + Road environment - Speed is the ‘final common pathway’ in determining the severity of rural and remote crashes and rural speed limits should be reduced to 90km/hr for sealed off-highway roads and 80km/hr for all unsealed roads as recommended in the Austroads review and in line with the current Tasmanian government trial.----- - The Department of Main Roads should monitor rural crash clusters and where appropriate work with local authorities to conduct relevant audits and take mitigating action. - The international experts at the workshop reviewed the data and identified the need to focus particular attention on road design management for dangerous curves. They also indicated the need to maximise the use of audio-tactile linemarking (audible lines) and rumble strips to alert drivers to dangerous conditions and behaviours.----- + Trauma costs - In accordance with Queensland Health priorities, recognition should be given to the substantial financial costs associated with acute management of trauma resulting from serious rural and remote crashes.----- - Efforts should be made to develop a comprehensive, regionally specific costing formula for road trauma that incorporates the pre-hospital, hospital and post-hospital phases of care. This would inform health resource allocation and facilitate the evaluation of interventions.----- - The commitment of funds to the development of preventive strategies to reduce rural and remote crashes should take into account the potential cost savings associated with trauma.----- - A dedicated study of the rehabilitation needs and associated personal and healthcare costs arising from rural and remote road crashes should be undertaken.----- + Emergency services - While the study has demonstrated considerable efficiency in the response and retrieval systems of rural and remote North Queensland, relevant Intelligent Transport Systems technologies (such as vehicle alarm systems) to improve crash notification should be both developed and evaluated.----- + Enforcement - Alcohol and speed enforcement programs should target the period between 2 and 6pm because of the high numbers of crashes in the afternoon period throughout the rural region.----- + Drink driving - Courtesy buses should be advocated and schemes such as the Skipper project promoted as local drink driving countermeasures in line with the very high levels of community support for these measures identified in the hospital study.------ - Programs should be developed to target the high levels of alcohol consumption identified in rural and remote areas and related involvement in crashes.----- - Referrals to drink driving rehabilitation programs should be mandated for recidivist offenders.----- + Data requirements - Rural and remote road crashes should receive the same quality of attention as urban crashes. As such, it is strongly recommended that increased resources be committed to enable dedicated Forensic Crash Units to investigate rural and remote fatal and serious injury crashes.----- - Transport department records of rural and remote crashes should record the crash location using the national ARIA area classifications used by health departments as a means to better identifying rural crashes.----- - Rural and remote crashes tend to be unnoticed except in relatively infrequent rural reviews. They should receive the same level of attention and this could be achieved if fatalities and fatal crashes were coded by the ARIA classification system and included in regular crash reporting.----- - Health, Transport and Police agencies should collect a common, minimal set of data relating to road crashes and injuries, including presentations to small rural and remote health facilities.----- + Media and community education programmes - Interventions seeking to highlight the human contribution to crashes should be prioritised. Driver distraction, alcohol and inappropriate speed for the road conditions are key examples of such behaviours.----- - Promotion of basic safety behaviours such as the use of seatbelts and helmets should be given a renewed focus.----- - Knowledge, attitude and behavioural factors that have been identified for the hospital Brief Intervention Trial should be considered in developing safety campaigns for rural and remote people. For example challenging the myth of the dangerous ‘other’ or ‘non-local’ driver.----- - Special educational initiatives on the issues involved in rural and remote driving should be undertaken. For example the material used by Main Roads, the Australian Defence Force and local initiatives.

Nurse-determined assessment of cardiac output. Comparing a non-invasive cardiac output device and pulmonary artery catheter: a prospective observational study.

Background The accurate measurement of Cardiac output (CO) is vital in guiding the treatment of critically ill patients. Invasive or minimally invasive measurement of CO is not without inherent risks to the patient. Skilled Intensive Care Unit (ICU) nursing staff are in an ideal position to assess changes in CO following therapeutic measures. The USCOM (Ultrasonic Cardiac Output Monitor) device is a non-invasive CO monitor whose clinical utility and ease of use requires testing. Objectives To compare cardiac output measurement using a non-invasive ultrasonic device (USCOM) operated by a non-echocardiograhically trained ICU Registered Nurse (RN), with the conventional pulmonary artery catheter (PAC) using both thermodilution and Fick methods. Design Prospective observational study. Setting and participants Between April 2006 and March 2007, we evaluated 30 spontaneously breathing patients requiring PAC for assessment of heart failure and/or pulmonary hypertension at a tertiary level cardiothoracic hospital. Methods SCOM CO was compared with thermodilution measurements via PAC and CO estimated using a modified Fick equation. This catheter was inserted by a medical officer, and all USCOM measurements by a senior ICU nurse. Mean values, bias and precision, and mean percentage difference between measures were determined to compare methods. The Intra-Class Correlation statistic was also used to assess agreement. The USCOM time to measure was recorded to assess the learning curve for USCOM use performed by an ICU RN and a line of best fit demonstrated to describe the operator learning curve. Results In 24 of 30 (80%) patients studied, CO measures were obtained. In 6 of 30 (20%) patients, an adequate USCOM signal was not achieved. The mean difference (±standard deviation) between USCOM and PAC, USCOM and Fick, and Fick and PAC CO were small, −0.34 ± 0.52 L/min, −0.33 ± 0.90 L/min and −0.25 ± 0.63 L/min respectively across a range of outputs from 2.6 L/min to 7.2 L/min. The percent limits of agreement (LOA) for all measures were −34.6% to 17.8% for USCOM and PAC, −49.8% to 34.1% for USCOM and Fick and −36.4% to 23.7% for PAC and Fick. Signal acquisition time reduced on average by 0.6 min per measure to less than 10 min at the end of the study. Conclusions In 80% of our cohort, USCOM, PAC and Fick measures of CO all showed clinically acceptable agreement and the learning curve for operation of the non-invasive USCOM device by an ICU RN was found to be satisfactorily short. Further work is required in patients receiving positive pressure ventilation.

Older patients request more information : a survey of use of written patient education materials in general practice

Objectives: To determine GPs' reported use of written education materials with older patients and older patients' reported receipt of these materials. To determine GPs' and older patients' perceptions of written materials.---------- Method: Using self-report questionnaires, two populations were surveyed; a randomised sample of 50 GPs (29 males and 21 females) practising in Brisbane's southern suburbs and a convenience sample of 188 older community-dwelling people (aged over 64 years).----------- Results: All GPs reported using written materials with patients, although 28% had not given any to the Last 10 patients. This increased to 46% when patients were older. Twenty percent of patients wanted more written information from their GP, while some GPs believed that older patients preferred verbal information and gave out written information only when they perceived patient interest. All GPs reported giving written materials at the time of consultation and over two thirds discussed the content with patients. Just over 50% of patients reported receiving written information from GPs in the Last six months and only hall of these again discussed it directly with their GP. Overall, patients were more positive than GPs about the value of written education materials.---------- Conclusions: Older patients' desire for written information may be better met if they are more assertive in requesting this of GPs and GPs may better serve their patients' needs if they make written information more readily available to them. Better access to materials and more financial incentives to give them out might also increase GPs' use of written materials.

Lateral bone density variations in the scoliotic spine

Adolescent Idiopathic Scoliosis (AIS) is the most common deformity of the spine, affecting 2-4% of the population. Previous studies have shown that the vertebrae in scoliotic spines undergo abnormal shape changes, however there has been little exploration of how scoliosis affects bone density distribution within the vertebrae. In this study, existing CT scans of 53 female idiopathic scoliosis patients with right-sided main thoracic curves were used to measure the lateral (right to left) bone density profile at mid-height through each vertebral body. Five key bone density profile measures were identified from each normalised bone density distribution, and multiple regression analysis was performed to explore the relationship between bone density distribution and patient demographics (age, height, weight, body mass index (BMI), skeletal maturity, time since Menarche, vertebral level, and scoliosis curve severity). Results showed a marked convex/concave asymmetry in bone density for vertebral levels at or near the apex of the scoliotic curve. At the apical vertebra, mean bone density at the left side (concave) cortical shell was 23.5% higher than for the right (convex) cortical shell, and cancellous bone density along the central 60% of the lateral path from convex to concave increased by 13.8%. The centre of mass of the bone density profile at the thoracic curve apex was located 53.8% of the distance along the lateral path, indicating a shift of nearly 4% toward the concavity of the deformity. These lateral bone density gradients tapered off when moving away from the apical vertebra. Multi-linear regressions showed that the right cortical shell peak bone density is significantly correlated with skeletal maturity, with each Risser increment corresponding to an increase in mineral equivalent bone density of 4-5%. There were also statistically significant relationships between patient height, weight and BMI, and the gradient of cancellous bone density along the central 60% of the lateral path. Bone density gradient is positively correlated with weight, and negatively correlated with height and BMI, such that at the apical vertebra, a unit decrease in BMI corresponds to an almost 100% increase in bone density gradient.

The relationship between deformity correction and clinical outcomes after thoracoscopic scoliosis surgery

Surgical treatment of scoliosis is quantitatively assessed in the clinic using radiographic measures of deformity correction, as well as the rib hump, but it is important to understand the extent to which these quantitative measures correlate with self-reported improvements in patients’ quality of life following surgery. The purpose of this prospective study was to evaluate the relationship between clinical outcomes of thoracoscopic anterior scoliosis surgery and deformity correction using the Scoliosis Research Society questionnaire (SRS-24). Patients undergoing thoracoscopic anterior scoliosis correction report good SRS scores which are comparable to those reported in previous studies for both open and thoracoscopic scoliosis correction procedures. Major Cobb correction is a significant predictor of patient satisfaction when comparing subgroups of patients with the highest and lowest major curve corrections.

LCADesign

LCADesign software package is a real-time environmental impact calculator for commercial property that works directly from the building designer's model. It enables developers, building designers, architects, engineers, builders, manufacturers and government bodies to optimise the eco-impact of a building as the design model evolves instead of waiting months for expert analysis. By integrating with the Building Information Models (BIMs) generated by 3D computer-aided drafting, LCADesign builds eco-efficiency into the design stage and measures the environmental values and risks of materials in commercial buildings

User-Generated Content als Qualitätsmedium? Alternative Anreize für Qualitätscontent

Angetrieben und unterstützt durch Web-2.0-Technologien, gibt es heute einen Trend zur Verbindung der Nutzung und Produktion von Inhalten als Produtzung (engl. produsage ). Um dabei die Qualität der erstellten Inhalte und eine nachhaltige Teilnahme der Nutzer sicherzustellen, müsen vier grundlegende Prinzipien eingehalten werden: * Größtmögliche Offenheit. * Ankurbeln der Gemeinschaft durch Inhalte und Hilfsmittel. * Unterstützung der Gruppendynamik und Abtretung von Verantwortung. * Keine Ausbeutung der Gemeinschaft und ihrer Arbeit.

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.

Cellular senescence and longevity of osteophyte-derived mesenchymal stem cells compared to patient-matched bone marrow stromal cells

This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence. J. Cell. Biochem. 108: 839-850, 2009. (c) 2009 Wiley-Liss, Inc.

The Queensland study of melanoma : Environmental and genetic associations (Q-MEGA); Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002-2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Development of self-efficacy and expectancy measures for benzodiazepines

This study aimed to develop and assess the reliability and validity of a pair of self-report questionnaires to measure self-efficacy and expectancy associated with benzodiazepine use, the Benzodiazepine Refusal Self- Efficacy Questionnaire (BRSEQ) and the Benzodiazepine Expectancy Questionnaire (BEQ). Internal structure of the questionnaireswas established by principal component analysis (PCA) in a sample of 155 respondents, and verified by confirmatory factor analyses (CFA) in a second independent sample (n=139) using structural equation modeling. The PCA of the BRSEQ resulted in a 16-item, 4-factor scale, and the BEQ formed an 18-item, 2-factor scale. Both scales were internally reliable. CFA confirmed these internal structures and reduced the questionnaires to a 14-item self-efficacy scale and a 12-item expectancy scale. Lower self-efficacy and higher expectancy were moderately associated with higher scores on the SDS-B. The scales provide reliable measures for assessing benzodiazepine self-efficacy and expectancies. Future research will examine the utility of the scales in prospective prediction of benzodiazepine cessation.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

Measuring the effect of patient comfort rounds on practice environment and patient satisfaction : A pilot study

Hourly rounding in the acute hospital setting has been proposed as an intervention to increase patient satisfaction and safety, and improve the nursing practice environment, but the innovation has not been adequately tested. A quasiexperimental pretest post-test non-randomized parallel group trial design was used to test the effect of hourly patient comfort rounds on patient satisfaction and nursing perceptions of the practice environment, and to evaluate research processes and instruments for a proposed larger study. A Patient Satisfaction Survey instrument was developed and used in conjunction with the Practice Environment Scale of the Nursing Work Index. Results on patient satisfaction showed no significant changes. Significant changes were found for three of the five practice environment subscales. Consistent with the aim of a pilot study, this research has provided important information related to design, instruments and process that will inform a larger sufficiently powered study.