On IT Control Weaknesses in Auditors’ Reports on Internal Control

By analysing auditors’ SOX 404 reports from 2004 to 2009 we find after 2006 that reporting of information technology control weaknesses (ITWs) decreased significantly, primarily by Big 4 firms. This change appears to reflect Big 4 reporting practices in response to a change in auditing standards rather than the nature of Big 4 clients’ internal control systems, suggesting that SOX 404 auditors’ reports have become less informative. We find associations between ITW reporting and both non-ITW and financial misstatement reporting are moderated by auditor type and time period (2004-2006 vs. 2007-2009). Based on frequency of reporting, the relative ordering of individual ITWs, while differing over time, is similar over auditor type, company size and industry. We identify a small number of non-ITWs in SOX 404 reporting that may hold practical implications for an auditor’s consideration of IT control testing and an educator’s teaching of IT and non-IT controls

Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis

Objectives To investigate the distribution of month of birth in people with multiple sclerosis in Australia. To use the large regional and seasonal variation in ambient ultraviolet radiation in Australia to explore the association between exposure to ultraviolet radiation during pregnancy and subsequent risk of multiple sclerosis in offspring

Point of care testing of Influenza A/B and RSV in an adult respiratory assessment unit is associated with improvement in isolation practices and reduction in hospital length of stay

Introduction. Every winter seasonal influenza and other viral respiratory infections increase pressure on the health services and are associated with nosocomial infection and morbidity.Aim. To compare provision of point-of-care (POC) testing with laboratory-based testing for influenza and RSV detection on an adult respiratory assessment unit to assess the impact on isolation practices and length of stay (LOS).Methodology. Prospective interrupted ‘on-off’ study in adults admitted to the respiratory unit between December 2018 and April 2019 with a suspected respiratory tract infection. Nasopharyngeal samples were tested using either the GeneXpert rapid POC test for influenza and RSV (on-period), or were sent to the laboratory for multiplex PCR testing against a panel of 12 respiratory viruses (off-period). Outcome measures were time to patient isolation for infection control, LOS and turnaround time from admission to test results.Results. Of 1145 patients evaluated, 755 were tested with POC and 390 with laboratory multiplex; a respiratory virus was identified in 164 (21.7 %) and 138 (35.4 %) patients respectively. A positive POC test was associated with a shorter time to isolation (mean difference 16.9 h, P [less than] 0.001), shorter LOS (mean difference 15.5 h, P=0.05,) and shorter turnaround time (mean difference 28.3 h, P[less than] 0.001), compared to laboratory testing.Conclusion. Use of GeneXpert POC testing for Flu/RSV is associated with rapid reporting of results with significant improvements in isolation practices and reductions in LOS

Novel Therapies in Oestrogen Receptor Positive Breast Cancer.

PhD ThesesAbstract Background: There is increasing preclinical and clinical evidence that inhibition of the PI3K/mTOR pathway can improve the efficacy of endocrine treatment and overcome resistance, but patient stratification remains challenging due to the complex nature of the pathway which is characterised by multiple regulatory nodes and extensive crosstalk with other signalling pathways. Preoperative window studies are a validated clinical trial strategy to evaluate the impact of targeted therapies alongside endocrine agents in patients with early ER-positive breast cancer using the nuclear proliferation marker Ki67 as a surrogate endpoint of treatment benefit. The OPPORTUNE trial was designed to assess whether addition of the PI3K inhibitor Pictilisib can increase the anti-tumour effects of two-week preoperative anastrozole treatment in ER-positive breast cancer. Aims: The 3 aims of this project were to 1. evaluate changes in tumour cell proliferation (by Ki67 expression pre and post-treatment) and apoptosis (by Caspase 3 expression) between patients treated with endocrine therapy alone and those treated with PI3K inhibitor Pictilisib plus Anastrozole. 2. characterise the subgroup of patients that derives the maximum benefit of addition of pictilisib with a focusing on the activation status of the PI3K pathway, using targeted next generation sequencing and gene expression analysis, and 3. to evaluate treatment-induced changes in molecular profiles between both treatment groups. Results: We demonstrated that adding pictilisib to anastrozole significantly increased the anti-proliferative response compared anastrozole alone as measured by suppression of Ki67 expression. The rate of apoptosis however was low and there was no clear evidence of a treatment-associated increase in apoptosis. When characterising the subgroup of patients that derives the maximum benefit of the addition of pictilisib, NGS identified patients with and without activating PIK3CA mutations but found no correlation between overall PIK3CA mutation status and added benefit of pictilisib. Our results suggested possible differences between helical and kinase domain PIK3CA mutations as patients with helical domain but not kinase domain mutations demonstrated a substantial benefit from pictilisib. Further assessment of PI3K pathway activation demonstrated an inverse association of a previously established PI3K inhibition gene signature with treatment response to anastrozole, suggesting this signature might be useful for selecting patients with partial endocrine resistance who might benefit from the addition of pictilisib. PAM50 analysis demonstrated that patients with Luminal B tumours but not patients with Luminal A tumours derive a benefit from PI3K inhibition. The third aim of this project was to investigate treatment-associated changes in gene expression and protein expression and phosphorylation in the tumour and stroma. Using RNA and protein analysis, we were able to identify down-regulation of ERmediated transcription and cell cycle progression, but found no differences in the expression of ER target genes between both study arms, suggesting that the preclinically observed induction of ER target genes by PI3K inhibition is not relevant in the context of combined endocrine and PI3K inhibitor therapy. Surprisingly, there was no discernible differences between both groups in the expression and phosphorylation of PI3K downstream targets Phospho-AKT, pS6 and p4E-BP1. Gene expression analysis furthermore demonstrated that short-term treatment with pictilisib and/or anastrozole has a modest impact on the tumour immune microenvironment but the potential clinical implications remain to be determined. Conclusions: In summary, we were able to demonstrate that addition of the PI3K inhibitor pictilisib significantly increases the anti-proliferative response to anastrozole in ER-positive early breast cancers. By characterising PI3K activation and gene expression subtypes, we provided important information on the subgroup of patients who might benefit most from combined therapy which should guide optimal patient selection for future trials

Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence

The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA) , eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77 ; p = 0.026) and decreasing regional annual ambient UVR (r = -0.80 ; p = 0.018) ; a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72 ; p = 0.046) , although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia, and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are require

Learning gains of students in differing delivery modes of physiology laboratory classes

Inquiry-based laboratory classes provide opportunities for students to reinforce knowledge and develop skills in scientific methodologies (Colthorpe et al., 2017). However, with many courses now delivered in dual modes, it is unclear whether gains are equivalent when classes are delivered face-to-face or online. This study evaluated students’ perceptions of gains from inquiry-based laboratory classes in alternate delivery modes. Biomedical science students undertaking ‘Systems Physiology’ enrolled in internal (n=341) or external (n=117) modes. The course has a blended design, incorporating inquiry-based laboratory classes delivered either face-to-face or via Zoom. Students worked in groups to design and present an experiment proposal. Internal students undertook their experiment and analysed the data, whereas external students analysed data generated by prior students. All students completed an individual laboratory report. Through open-ended questions, students identified learning gains they achieved. Responses were thematically analysed against an existing framework (Brinson, 2015). Internal students reported gaining skills in data acquisition and presentations more than external students. Whereas, external students more frequently reported gaining skills in formulating aims and hypotheses. Students’ grades were identical in each mode. Although students appear to cope well with differing delivery modes, external students may need targeted support to assist development of specific skills. REFERENCES Brinson, JR. (2015). Learning outcome achievement in non-traditional (virtual and remote) versus traditional (hands-on) laboratories: A review of the empirical research. Computers & Education, 87, 218-237. Colthorpe, K., H. M. Abraha, K. Zimbardi, L. Ainscough, J. G. Spiers, H.-J. C. Chen, & N. A. Lavidis. (2017). Assessing students’ ability to critically evaluate evidence in an inquiry-based undergraduate laboratory course. Advances in Physiology Education, 41(1), 154-162

An environmental scan of wellness initiatives and programs at Canadian academic emergency medicine programs: How far have we come?

Objectives We sought to conduct a major objective of the Canadian Association of Emergency Physicians (CAEP) Wellness Committee, an environmental scan of the academic emergency medicine programs across the 17 Canadian medical schools. Methods An 89-question questionnaire was distributed to academic heads or wellness leads. The responses were verified by the lead author to ensure that the questions were answered completely and consistently. Results While formal wellness programs may exist in varying degrees across the 17 universities, most were found to exist only at local, divisional, or departmental levels. A broad variability of established leadership positions exists. Shift practices varied greatly. In day to day practice, availability for food and debriefing were high and childcare, sleep rooms, and follow-up following critical incidents were low. Sabbaticals existed in the majority of centers. Roughly 50% of departments have gender equity program and annual retreats. Centers report programs for the initiation of leaves (82%), onboarding (64%), and reorientation (94%). Support of health benefits (76%) and pensions (76%) depended on type of appointment and relationship to the university. Fiscal transparency was reported in 53% of programs. Conclusion Wellness and burnout are critical issues for emergency medicine in Canada. This comprehensive review of wellness programs identifies areas of strength, but also allows identification of areas of improvement for future work. Individual centers can identify common options when developing or expanding their wellness programs