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This work introduces and evaluates ccheck, a lenient automatic grader and C style-checker, to guide students to improve their coding practices. Many computing classes rely heavily on autograders – software that automates grading and alleviates staff workload in classes with large enrollments. At best, autograders offer timely and consistent feedback to students. However, existing autograders primarily judge on functional correctness—they are generally strict and inflexible in marking beginner programming assignments. They tend not to provide feedback on programming style and structure, which instead requires delayed, tedious manual assessment. ccheck, the tool we introduce, aims to address this gap and provide more meaningful, real-time feedback with a pedagogical focus. We deploy ccheck in a class of 440 first-year computer science students. Teaching assistants employ the system for marking assistance, while students use the same system for self-evaluation prior to finalizing their submissions. Feedback was solicited through a survey of 76 students and a focus group of the teaching team. 82% of the students surveyed said that the system helped them learn good coding practices, while 75% emphasized that the feedback received from the system is meaningful and helpful. The teaching team focus group related to how they valued the automation of menial marking tasks, which enabled them to direct their time toward other meaningful feedback. Overall, we find that teaching, learning and student experiences are improved through the deployment of ccheck.

The development of the regulatory and incentives framework is a key opportunity to align Australian enterprises’ cybersecurity practice with latest research, particularly on consumer protections, and emerging cyber threats and security challenges. The Australian Government has an essential role in establishing incentives to encourage best practice and consequences to combat poor practice. It will be increasingly important for government at all levels to act as a role model, by following best practice in the conduct of its public business.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA). In 2009, the Australian TTP/TMA registry was established to collect data on patients presenting with TTP/TMA throughout Australia. Aim(s): To summarise information on the diagnosis and management of patients with TTP collected in the first 5years (2009-2014) of the Australian TTP registry. Method(s): Registry data from June 2009 to October 2014 were reviewed. Result(s): Fifty-seven patients were identified with TTP (defined as ADAMTS13 activity <10%), accounting for 72 clinical episodes. ADAMTS13 inhibitor testing was performed in nine out of 57 patients (16%), reflecting the limited availability of accredited testing facilities. Sixty-seven out of 72 episodes were treated with therapeutic plasma exchange (PEx) using cryodepleted plasma (40% of episodes), fresh frozen plasma (36%) or a mixture (22%). Median exposure to plasma products was 55.9L. PEx was commenced >=2days from stated diagnosis in 15% of episodes. Adverse reactions to PEx were common with documented allergic reactions (including life threatening) in 21% of episodes. Adjunctive immunosuppression was documented in 76% of episodes (corticosteroid 71% and rituximab 39%). Platelet transfusion was administered in 15% of episodes. Conclusion(s): Data from the Australian TTP/TMA registry suggest a heterogenous approach to the diagnosis and management of TTP in Australia over the assessed period. These observations highlight areas for improvement and standardisation of practice, including comprehensive diagnostic testing, more immediate access to PEx and a more uniform approach to adjunctive immunosuppression and supportive care.Copyright © 2016 Royal Australasian College of Physicians.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy. In 2009, the Australian TTP registry was established and began collecting data on patients presenting with TTP throughout Australia. Aim(s): To summarise findings of the first five years (2009-2014) of TTP diagnosis and management from the Australian TTP registry. Method(s): Registry data from June 2009 to October 2014 were reviewed. Result(s): 57 patients were identified with TTP (ADAMTS13 <10%) accounting for 72 clinical episodes. ADAMTS13 inhibitor testing was performed in 9/57 (16%) patients reflecting the limited availability of accredited testing facilities. 67/72 episodes were treated with therapeutic plasma exchange (PEX) with cryodepleted plasma (40% episodes), fresh frozen plasma (36%) or a mixture (22%). Exposure to plasma products was significant with a median exposure of 55.9L per episode. PEX was not commenced until 2 or more days after date of diagnosis in 15% of episodes. Adverse reactions to PEX were common with documented allergic reactions (including life-threatening) in 21% of episodes. Adjunctive immunosuppression was documented in 76% episodes (corticosteroid 71%, rituximab 39%). Platelets were transfused in 15% of episodes with no documented adverse reactions. Summary and Conclusion(s): Australian TTP registry data reveal a heterogenous approach to the diagnosis & management of TTP in Australia from 2009- 2014. Identified areas for potential practice improvement include a standardised approach to TTP diagnostic testing, improving access to timely PEX and a more uniform approach to adjunctive immunosuppression and supportive care.

Introduction: Donor-specific IgG anti-HLA antibodies (DSAbs) are associated with reduced allograft survival. Recent reports suggest that IgM antibodies can mask their detection. We aimed to establish if this phenomenon was relevant to our renal transplant recipients (RTRs) who had been treated for antibody mediated rejection (AMR) but were DSAb -ve. Method(s): Sera from patients who received specific therapy for acute or chronic AMR during the period 09/2005-09/2009 were retrospectively examined. DSAb testing by Luminex single antigen beads (LSAB) had been routinely performed at the time of AMR diagnosis in all patients. In DSAb -ve patients, sera were re-examined by LSAB after IgM depletion by Hypertonic Dialysis using Thermo Scientific Slide-A-Lyzer Dialysis units (Johns Hopkins University, School of Medicine protocol (Baltimore, USA)). Result(s): Forty Five (45) patients had been treated with protocols for acute (n=18) or chronic (n=27) AMR in the study period. These diagnoses were derived by allograft biopsies performed for renal dysfunction. Thirty five (78%) were DSAb +ve using non-depleted sera. In the 10 DSAb -ve patients (3 acute AMR and 7 chronic AMR patients), IgM-depletion unmasked DSAbs in 2 of 3 acute AMR and 6 of 7 chronic AMR (specificities and mean fluorescence indices (MFI) are shown below). Whilst many of the MFIs were relatively low, 4 patients had DSAbs with MFIs above 1000. Had these results been available at the time of AMR diagnosis, 6 of 10 patients would have received a more aggressive treatment regimen as our treatment protocols factor in the identification of a DSAb in decision making. Conclusion(s): Current highly sensitive antibody detection methods such as LSAB have refined our approach to the diagnosis and treatment of AMR. IgM depletion of sera may represent a further step towards improving sensitivity; however careful delineation of the clinical relevance of DSAbs found using IgM depleted sera requires further study. Our findings hi

Aim: The Thrombotic Thrombocytopenic Purpura (TTP) Registry was established to determine the incidence, clinical characteristics, and natural history, of patients with TTP. It has expanded to encompass atypical haemolytic syndrome (aHUS) and other thrombotic microangiopathies (TMA), though data on these are not yet available. Background and Methods: TTP and other TMAs are rare but cause significant morbidity and mortality. Their true incidence remains uncertain, and consensus is lacking regarding diagnosis and management, and needs to reflect the increased understanding of the molecular and pathophysiological basis of the TMAs. Result(s): 37 sites have agree to participate. Data received from 14 hospitals on 67 episodes in 60 patients. Age 16-83 years, 60% female. Presenting manifestations including: neurological (61%), gastrointestinal or genitourinary (50%), haemorrhagic (31%), fever (27%), thrombotic (19%), or other (31%). Clinical context/precipitants included infection (46%), autoimmune disease (27%), malignancy (11%), medication (11%), allogeneic stem cell transplant (4%) and postpartum (4%). ADAMTS13 levels requested in 38% of patients. The majority of patients initially received plasma exchange (PEx), at least daily. 42% had PEx tapered and 77% received additional therapy, either to augment PEx (48%), because of suboptimal response (20%) or other reasons (32%), including corticosteroids (84%), rituximab (28%). 15% are receiving ongoing therapy, 50% are in complete remission (CR) without impairment, 8% in CR with persisting impairment, and 27% died. Conclusion(s): TTP, aHUS and other TMA continue to cause significant morbidity and mortality. The increased understanding of pathophysiology and advent of new therapies makes the collection, and analysis of patient data critical to direct future treatment appropriately.

Background: Advances in the understanding of the pathogenesis of TMAs have led to recognition of distinct clinical entities: TTP (thrombotic thrombocytopenic purpura), STEC-HUS (Shiga-like toxin producing E.Coli hemolytic uremic syndrome) and atypical HUS. Where once precise classification of TMAs made little difference to the management plan, specific treatment strategies are now available for each disease, and consequently it is critical that a rapid and accurate diagnosis is made. This can be achieved, for example, when pre-plasma exchange ADAMTS13 activity levels are found to be<10%, diagnosing TTP. However, many patients with a TMA remain diagnostically challenging, including those with aHUS (primary complement dysregulation) and secondary TMAs (e.g. due to drugs, infections). Potential pitfalls to accurate diagnosis include the overlapping clinical symptomology of the syndromes and the lack of readily available diagnostic tests for aHUS; in particular, genetic analysis of complement mutations may not be rapidly available. Treatment as for aHUS (e.g. with eculizumab) in all TMA cases with ADAMTS13 activity >10% until another cause is identified has been suggested, but would incur substantial costs. Further study of the spectrum of TMAs presenting clinically is required to target areas where practice can be improved and develop viable strategies. Aim(s): To analyze data from a multicenter TMA registry to identify patients without low ADAMTS13 activity at presentation, and examine their clinical course through investigations, diagnosis, management and outcomes. Method(s): Monash University in Melbourne, Australia hosts a national multicenter TTP Registry that was expanded in 2012 to incorporate all TMAs. In 2013, senior clinicians with Hematology or nephrology backgrounds undertook validation of cases in the registry targeted at 13 sites that had entered patients with ADAMTS13 activity levels of >10%, excluding patients positive for STEC. Result(s): A total of 68

Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging non-inferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n = 77; discontinued in December 2011) or 200 mg (n = 73) b.i.d. plus standard tacrolimus (sTAC; 5-12 ng/mL), sotrastaurin 300 mg (n = 75) b.i.d. plus reduced tacrolimus (rTAC; 2-5 ng/mL) or enteric-coated mycophenolic acid (MPA) plus sTAC (n = 73); all patients received basiliximab and corticosteroids. Composite efficacy failure (treated biopsy-proven acute rejection ≥ grade IA, graft loss, death or loss to follow up) rates at Month 12 were 18.8%, 12.4%, 10.9% and 14.0% for the sotrastaurin 100, 200 and 300 mg, and MPA groups, respectively. The median estimated glomerular filtration rates were 55.7, 53.3, 64.9 and 59.2 mL/min, respectively. Mean heart rates were faster with higher sotrastaurin doses and discontinuations due to adverse events and gastrointestinal adverse events were more common. Fewer patients in the sotrastaurin groups experienced leukopenia than in the MPA group (1.3-5.5% vs. 16.5%). Sotrastaurin 200 and 300 mg had comparable efficacy to MPA in prevention of rejection with no significant difference in renal function between the groups.

Background: Thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA), such as atypical haemolytic uraemic syndrome are rare disorders in which plasma exchange (PEx) with fresh frozen plasma (FFP) or cryodepleted plasma (CDP) is current standard of care. The absence of clinical trials to guide management makes registry data valuable in assessing efficacy of current management. Aim(s): To analyse current management, complications of therapy and outcomes in Australian TTP Registry (TTPR) patients. Method(s): Accrual of cases to the TTPR started in 2009, and expanded in 2012 to include all TMA. All verified cases entered on the TTPR were analysed. Result(s): 79 cases were analysed in 72 patients from 17 sites. Median age was 47 years (15-83 years), 57% were female and 14% were relapses. 53% had one/more identified precipitant (infection 27%, autoimmune 19%, medication 13%, malignancy 11%, solid organ transplant 4%, allograft 2%, pregnant/postpartum 2%). ADAMTS13 levels were available in 57 cases and was <10% in 30/57. Plasma therapy data were available from 76 cases: 72/76 (95%) received PEx, with FFP in 31%, CDP in 28%, both in 40% and albumin/FFP in 1%. PEx was by centrifugation in 72%, membrane filtration in 14% and unknown in 14%. Plasma infusions were used in 9/ 77 cases (without PEx in 4). PEx was tapered in 53%: of these 18% were relapsed cases, and 39% received additional therapy. Additional therapy included: rituximab (30%), corticosteroids (73%), cyclophosphamide (4%), vincristine (3%), and azathioprine (1%). Of those who received rituximab 75% were de novo cases, 58% idiopathic and 29% within <7 days of presentation. Six cases received platelet transfusions. Platelet counts at presentation were not significantly different in those who did or did not receive platelet transfusion (median 23 vs 26 9 109/l; P = 0.4). Median haemoglobin at presentation (78 vs 101 g/l; P = 0.1) and LDH (912 vs 686; P = 0.4) were similar in cases who di

Background: The association between pre-transplant dialysis modality and transplant outcomes remains inconsistent. The aim of the present study is to address the association between alteration in dialysis modality and post-transplant outcomes and to examine whether the association remains constant in the era of modern immunosuppression and dialysis duration. Method(s): Using Australia and New Zealand Dialysis and Transplant Registry, primary live and deceased-donor renal transplant recipients between 1997 and 2009 were examined. Pre-emptive and multipleorgan transplants were excluded. The association between initial and pre-transplant dialysis modality and delayed graft function (DGF), acute rejection in the first 6 months, graft failure and recipient death were examined. Result(s): Of the 6701 renal transplant recipients, 18.6% were initiated and remained on peritoneal dialysis pre-transplant (PD-PD), 9.2% were initiated on PD but had changed to haemodialysis (HD) pre-transplant (PD-HD), 63.3% were HD-HD and 8.9% were HD-PD. PD-HD (odds ratio [OR] 1.44, 95%CI 1.21, 1.72) and HD-HD (OR 1.25, 95%CI 1.12, 1.41) were associated with a significantly greater risk of DGF compared to the overall mean of the groups, whereas a change in initial dialysis modality from HD to pre-transplant PD was associated with higher risk of overall graft failure (hazard ratio [HR] 1.19, 95%CI 1.04, 1.36) and recipient death (HR 1.34, 95%CI 1.13, 1.59), but not DCGF. Conclusion(s): Our registry analysis suggest that dialysis modality pretransplant may affect transplant outcomes and future studies evaluating patient selection, choice of modality and/or potential interventions in the pre and post-transplant period may have a beneficial effect on posttransplant outcomes.

Background: Historical approaches used to distinguish thrombotic thrombocytopenic purpura (TTP), haemolytic uremic syndrome (HUS) and other thrombotic microangiopathies (TMA) included underlying conditions/precipitants, predominant clinical presentation and laboratory parameters. Tests for ADAMTS13 are now incorporated into diagnosis and classification. Plasma exchange (PEx) with fresh frozen plasma (FFP) or cryodepleted plasma (CDP) remains the standard of care for TTP. Additional immunosuppression may be used in patients with low ADAMTS13 due to autoantibodies. Aim(s): To investigate differences between idiopathic and secondary TTP with regard to clinical presentation, management and outcomes. Method(s): The Australian TTP registry was established in 2009, and expanded in 2012 to include all TMA. Of 34 hospitals currently participate in the registry. Of 103 cases in 94 patients were registered from 18 sites; eight were excluded for incomplete data, leaving 95 episodes in 86 patients. Result(s): Median age was 46 years (15-83 years), 53% were female, 16% were relapses. Of 51% were idiopathic and 49% had >=1 identified precipitant, including infection 23%, autoimmune 18%, malignancy 12%, medication 14%, pregnant/postpartum 4%, solid organ transplant 3%, and allograft 3%. ADAMTS13 levels were available in 66 cases (37 idiopathic and 29 secondary). ADAMTS13 was <10% in 22/37 (59%) idiopathic and 9/29 (31%) secondary cases. Precipitants in cases with ADAMTS13 <10% included infection (n = 5), autoimmune (n = 5), medication (n = 1), and pregnancy (n = 1). Neurological, gastro-renal, bleeding and thrombotic presentations were similar in idiopathic and secondary cases. Data on plasma therapy were available in 88 cases (Table 1). Of 84/88 (95%) received PEx, by centrifugation in 28/84, membrane filtration in 25/84 (30%), and unknown method in 29/84 (35%). Plasma infusions were used in 11/88 cases (without PEx in 4). Data on additional therapy was available for 89 cases (Tab

The association between pretransplant dialysis modality and transplant outcomes remains inconsistent. The aim of this study is to address the association between alteration in dialysis modality and post-transplant outcomes. Using Australia and New Zealand Dialysis and Transplant Registry, primary live- and deceased-donor renal transplant recipients (RTR) between 1997 and 2009 were examined. Pre-emptive and multiple-organ transplants were excluded. The association between initial and pretransplant dialysis modality and transplant outcomes were examined. Of the 6701 RTR, 18.6% were initiated-maintained on peritoneal dialysis pretransplant (PD-PD), 9.2% were initiated on PD, but maintained on haemodialysis (HD) pretransplant (PD-HD), 63.3% were HD-HD and 8.9% were HD-PD. PD-HD [odds ratio(OR)1.44, 95% CI 1.21,1.72] and HD-HD (OR1.25, 95% CI 1.12,1.41) were associated with a significantly greater risk of slow graft function compared with the overall mean of the groups, whereas a change in initial dialysis modality from HD to pretransplant PD was associated with higher risk of overall graft failure [hazard ratio(HR)1.19, 95% CI 1.04,1.36) and recipient death (HR1.34, 95% CI 1.13,1.59). Our registry analysis suggest that dialysis modality pretransplant may affect transplant outcomes and future studies evaluating patient selection, choice of modality and/or potential interventions in the pre and post-transplant period may have a beneficial effect on post-transplant outcomes. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.

Thrombotic microangiopathy (TMA) is a pathological process involving thrombocytopenia, microangiopathic haemolytic anaemia and microvascular occlusion. TMA is common to haemolytic uraemic syndrome (HUS) associated with shiga toxin or invasive pneumococcal infection, atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP) and other disorders including malignant hypertension. HUS complicating infection with shiga toxin-producing Escherichia coli (STEC) is a significant cause of acute renal failure in children worldwide, occurring sporadically or in epidemics. Studies in aHUS have revealed genetic and acquired factors leading to dysregulation of the alternative complement pathway. TTP has been linked to reduced activity of the ADAMTS13 cleaving protease (typically with an autoantibody to ADAMTS13) with consequent disruption of von Willebrand factor multimer processing. However, the convergence of pathogenic pathways and clinical overlap create diagnostic uncertainty, especially at initial presentation. Furthermore, recent developments are challenging established management protocols. This review addresses the current understanding of molecular mechanisms underlying TMA, relating these to clinical presentation with an emphasis on renal manifestations. A diagnostic and therapeutic approach is presented, based on international guidelines, disease registries and published trials. Early treatment remains largely empirical, consisting of plasma replacement/exchange with the exception of childhood STEC-HUS or pneumococcal sepsis. Emerging therapies such as the complement C5 inhibitor eculizumab for aHUS and rituximab for TTP are discussed, as is renal transplantation for those patients who become dialysis-dependent as a result of aHUS.

Background and Methods: The Thrombotic Thrombocytopenic Purpura (TTP) Registry was established in 2009 to determine incidence and natural history of TTP, a rare disease with significant morbidity and mortality. The true incidence in Australasia is unknown and consensus is lacking regarding diagnosis and management. The register will analyse factors influencing outcomes, aiming to improve management and guide research. Inclusion of atypical haemolytic uraemic syndrome (aHUS) is planned. Result(s): To date 37 sites are participating; 19 have completed registration and ethics. Data have been received from 11 hospitals on 30 episodes in 26 patients (24 initial presentations, 6 relapses). Patients were aged 22-83 years and 14 (54%) were female. Patients presented with manifestations including: neurological (16), gastrointestinal or genitourinary (13), haemorrhagic (8), fever (7), thrombotic (5), or other (8). Clinical context and possible precipitants included infection (12), autoimmune disease (7), malignancy (3), medication (3), allogeneic stem cell transplant (1) and postpartum (1). ADAMTS13 levels were requested in 10 (38%) patients. Of 30 episodes, 28 received plasma exchange (PEx), initially at least daily. 12 (42%) had PEx tapered and 25 (77%) received additional therapy, either to augment PEx (12, 48%), because of suboptimal response (5, 20%) or other reasons (8, 32%), including corticosteroids (21, 84%), rituximab (7, 28%), and other (9, 36%). At time of entry on register, 4 (15%) patients were in ongoing therapy, 13 (50%) were in complete remission (CR) without impairment, 2 (8%) were in CR with persisting impairment, and 7 (27%) had died. Conclusion(s): Cases reported to date show significant morbidity and mortality, highlighting the need for additional research. More cases are now anticipated with recruitment of major participating institutions.

Aim: To assess an extended and broadened regimen of CMV prophylaxis in renal transplantation. Background(s): Cytomegalovirus (CMV) poses a mortality and morbidity risk in transplant recipients. Prophylaxis against CMV reduces mortality, but recent studies suggest that prophylaxis regimens delay rather than prevent disease. In 2004 we introduced a regimen in which CMV negative recipients (R-) receiving kidneys from CMV positive donors (D+) receive six months of valganciclovir, while D+/R+ and D-/R- receive three months. D-/R- were not routinely administered prophylaxis. Method(s): Data from all kidney transplantations at the Royal Melbourne Hospital between November 2004 and December 2009 were analysed, with a minimum of 180 days follow up post-prophylaxis. Result(s): 521 patient transplants were eligible for analysis; 64 D+/R-, 221 D+/ R+, 90 D-/R+, 75 D-/R- and 26 of unknown CMV status. CMV disease was reported in 7/476 patients, with 6/64 (9.4%) D+/R- and 1/221 (0.5%) D+/R+. In three cases CMV disease occurred greater than six months post-transplant. This compares with an incidence of 21.4% in D+/R- using our previous regimen of valacyclovir and CMVIg. At that time the incidence of CMV was 8.7% in D+/R- was 3% in D-/R+, who did not receive prophylaxis. Conclusion(s): Extending the duration of prophylaxis for D+/R- and broadening the regimen to include D+/R+, D-/R+ has had a significant effect in reducing the incidence of CMV disease. CMV prophylaxis for 90 days in D+/R+ and D-/ R+ is sufficient to prevent CMV disease and is well tolerated. In the higher risk D+/R- group CMV disease affected 9.4% of patients despite 180 days of prophylaxis. Although this prophylaxis regimen appears to delay CMV infection in some cases, it does not exclude it in high risk groups.