Cas1 and Fen1 Display Equivalent Functions During Archaeal DNA Repair

CRISPR-Cas constitutes an adaptive prokaryotic defence system against invasive nucleic acids like viruses and plasmids. Beyond their role in immunity, CRISPR-Cas systems have been shown to closely interact with components of cellular DNA repair pathways, either by regulating their expression or via direct protein-protein contact and enzymatic activity. The integrase Cas1 is usually involved in the adaptation phase of CRISPR-Cas immunity but an additional role in cellular DNA repair pathways has been proposed previously. Here, we analysed the capacity of an archaeal Cas1 from Haloferax volcanii to act upon DNA damage induced by oxidative stress and found that a deletion of the cas1 gene led to reduced survival rates following stress induction. In addition, our results indicate that Cas1 is directly involved in DNA repair as the enzymatically active site of the protein is crucial for growth under oxidative conditions. Based on biochemical assays, we propose a mechanism by which Cas1 plays a similar function to DNA repair protein Fen1 by cleaving branched intermediate structures. The present study broadens our understanding of the functional link between CRISPR-Cas immunity and DNA repair by demonstrating that Cas1 and Fen1 display equivalent roles during archaeal DNA damage repair

Perceptions of surgical specialists in general surgery, orthopaedic surgery, urology and gynaecology on teaching endoscopic surgery in The Netherlands

BACKGROUND: Specific training in endoscopic skills and procedures has become a necessity for profession with embedded endoscopic techniques in their surgical palette. Previous research indicates endoscopic skills training to be inadequate, both from subjective (resident interviews) and objective (skills measurement) viewpoint. Surprisingly, possible shortcomings in endoscopic resident education have never been measured from the perspective of those individuals responsible for resident training, e.g. the program directors. Therefore, a nation-wide survey was conducted to inventory current endoscopic training initiatives and its possible shortcomings among all program directors of the surgical specialties in the Netherlands. METHODS: Program directors for general surgery, orthopaedic surgery, gynaecology and urology were surveyed using a validated 25-item questionnaire. RESULTS: A total of 113 program directors responded (79%). The respective response percentages were 73.6% for general surgeons, 75% for orthopaedic surgeon, 90.9% for urologists and 68.2% for gynaecologists. According to the findings, 35% of general surgeons were concerned about whether residents are properly skilled endoscopically upon completion of training. Among the respondents, 34.6% were unaware of endoscopic training initiatives. The general and orthopaedic surgeons who were aware of these initiatives estimated the number of training hours to be satisfactory, whereas the urologists and gynaecologists estimated training time to be unsatisfactory. Type and duration of endoscopic skill training appears to be heterogeneous, both within and between the specialties. Program directors all perceive virtual reality simulation to be a highly effective training method, and a multimodality training approach to be key. Respondents agree that endoscopic skills education should ideally be coordinated according to national consensus and guidelines. CONCLUSIONS: A delicate balance exists between training hours and clinical working hours during residency. Primarily, a re-allocation of available training hours, aimed at core-endoscopic basic and advanced procedures, tailored to the needs of the resident and his or her phase of training is in place. The professions need to define which basic and advanced endoscopic procedures are to be trained, by whom, and by what outcome standards. According to the majority of program directors, virtual reality (VR) training needs to be integrated in procedural endoscopic training course

Inter-relationship between performance of Bursa Malaysia and foreign stock markets / T. Chantrathevi P. Thuraisingam, Tew You Hoo and Dalila Daud

This paper explores the general perception that the Malaysian stock market is influenced by leading overseas stock markets. Employing correlation analysis comparison was made between the performance ofBiirsa Malaysia's Composite Index and six stock market indices namely Straits Times Index, Hang Seng Index, Nikkei 225 Stock Average, Australia All Ordinaries Index, Dow Jones Industrial Average Index and Financial Times 100 Index. This study also seeks to determine ifthere is any significant stability ofcorrelations over time. These indices were studied over a period offifteen years from I January 1990 to 31 December 2004, beginning with the cessation oftrading ofMalaysian shares on the Singapore stock exchange, which is synonymous with the pre-Asian financial crisis period, the crisis period and a post crisis period of almost five years. The study found that the, daily returns of the Composite Index over the period is positively co-related with the foreign indices indicating that the markets were moving in the same direction, in other words there is interdependency between the stock markets. However, the low to moderate correlation refutes the belief that the Malaysian stock market is influenced by the performance ofthe major stock markets. The study also found that generally the correlations are unstable over lime

Collaborative Approaches to Moderation of Assessment in Transnational Education

Transnational education (TNE) teaching and professional teams conduct assessment work across organisational, national and cultural boundaries. Achieving a shared set of principles and understandings, and through that, fair assessment processes within and across programs, is a complex task that requires ongoing dialogue and collaboration between all members of the teaching team. Collaborative approaches facilitate development of a community of practice in transnational programs with input of all staff involved in the teaching team. Our research, from a two-year study into moderation of assessment in TNE, has revealed a number of challenges to collaboration amongst transnational teaching teams undertaking moderation of assessment including issues of trust and control, communication and cultural differences. Our research has also identified many examples of good practice in developing a community of practice and aspirations in working towards developing and maintaining collegial relationships and sharing power

An Activity Theory Approach to Moderation for Fair Assessment in Transnational Education

This paper presents research from an Australian Learning and Teaching Council (ALTC) priority project which focuses on the assessment moderation practices between Australian and transnational partner universities. This paper addresses the challenges faced by transnational academic staff in ensuring comparable assessment standards. The data illuminates many issues of culture, language, relationships, trust, power and control. Using activity theory and its principles of contradictions, these issues are analyzed in terms of Engestrom's expanded mediated triangle. The components of subject, mediating tools, objects, rules, community and division of labor are interconnected and in constant dynamic interaction emphasizing the social and contextualized nature of moderation practices and policies. Systemic tensions are bound to emerge between and among these components. This paper sets out to identify these systemic tensions or contradictions for their heuristic value andpotential as the driving force for change, indicating points of intervention to improve assessment moderation practices and policies. Among the three indicated contradiction triads, some fundamental secondary contradictions exist between subject-community-object, subject-mediating tools-object and subject-division of labor-object. These help identify the weaknesses in the existing collaborative pattern, lack of efficacy of the mediating tools for ignoring the 'culture of use' of the tools anda clear understanding of roles and responsibilities on the ground

Developing prediction models for total knee replacement surgery in patients with osteoarthritis: Statistical analysis plan

Background Approximately 12–20% of those with osteoarthritis (OA) in Australia who undergo total knee replacement (TKR) surgery do not report any clinical improvement. There is a need to develop prediction tools for use in general practice that allow early identification of patients likely to undergo TKR and those unlikely to benefit from the surgery. First-line treatment strategies can then be implemented and optimised to delay or prevent the need for TKR. The identification of potential non-responders to TKR may provide the opportunity for new treatment strategies to be developed and help ensure surgery is reserved for those most likely to benefit. This statistical analysis plan (SAP) details the statistical methodology used to develop such prediction tools. Objective To describe in detail the statistical methods used to develop and validate prediction models for TKR surgery in Australian patients with OA for use in general practice. Methods This SAP contains a brief justification for the need for prediction models for TKR surgery in general practice. A description of the data sources that will be linked and used to develop the models, and estimated sample sizes is provided. The planned methodologies for candidate predictor selection, model development, measuring model performance and internal model validation are described in detail. Intended table layouts for presentation of model results are provided. Conclusion Consistent with best practice guidelines, the statistical methodologies outlined in this SAP have been pre-specified prior to data pre-processing and model development