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Hamish Scott and colleagues report that germline mutations in GATA2 segregate with myelodysplastic syndrome and acute myeloid leukemia in four pedigrees. The resulting alterations occur in a conserved zinc finger DNA-binding domain of GATA2. We report the discovery of GATA2 as a new myelodysplastic syndrome (MDS)-acute myeloid leukemia (AML) predisposition gene. We found the same, previously unidentified heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2 transcription factor gene segregating with the multigenerational transmission of MDS-AML in three families and a GATA2 c.1063_1065delACA (p.Thr355del) mutation at an adjacent codon in a fourth MDS family. The resulting alterations reside within the second zinc finger of GATA2, which mediates DNA-binding and protein-protein interactions. We show differential effects of the mutations on the transactivation of target genes, cellular differentiation, apoptosis and global gene expression. Identification of such predisposing genes to familial forms of MDS and AML is critical for more effective diagnosis and prognosis, counseling, selection of related bone marrow transplant donors and development of therapies.

Background Previous randomized studies have compared high- versus low-fidelity laparoscopic simulators; however, no proficiency criteria were defined and results have been mixed. The purpose of this research was to determine whether there were any differences in the learning outcomes of participants who had trained to proficiency on low- or high-fidelity laparoscopic surgical simulators. Methods We conducted a randomized, prospective crossover trial with participants recruited from New South Wales, Western Australia, and South Australia. Participants were randomized to high-fidelity (LapSim, Surgical Science) or low-fidelity (FLS, SAGES) laparoscopic simulators and trained to proficiency in a defined number of tasks. They then crossed over to the other fidelity simulator and were tested. The outcomes of interest were the crossover mean scores, the proportion of tasks passed, and percentage passes for the crossover simulator tasks. Results Of the 228 participants recruited, 100 were randomized to LapSim and 128 to FLS. Mean crossover score increased from baseline for both simulators, but there was no significant difference between them (11.0 % vs. 11.9 %). FLS-trained participants passed a significantly higher proportion of crossover tasks compared with LapSim-trained participants (0.26 vs. 0.20, p  = 0.016). A significantly higher percentage of FLS-trained participants passed intracorporeal knot tying than LapSim-trained participants (35 % vs. 8 %, p  < 0.001). Conclusion Similar increases in participant score from baseline illustrate that training on either simulator type is beneficial. However, FLS-trained participants demonstrated a greater ability to translate their skills to successfully complete LapSim tasks. The ability of FLS-trained participants to transfer their skills to new settings suggests the benefit of this simulator type compared with the LapSim.

Background Laparoscopic skills development via simulation-based medical education programs has gained support in recent years. However, the impact of training site type on skills acquisition has not been examined. The objective of this research was to determine whether laparoscopic skills training outcomes differ as a result of training in a Mobile Simulation Unit (MSU) compared with fixed simulation laboratories. Methods An MSU was developed to provide delivery of training. Fixed-site and MSU laparoscopic skills training outcomes data were compared. Fixed-site participants from three Australian states were pooled to create a cohort of 144 participants, which was compared with a cohort derived from pooled MSU participants in one Australian state. Data were sourced from training periods held from October 2009 to December 2010. LapSim and Fundamentals of laparoscopic surgery (FLS) simulators were used at the MSU and fixed sites. Participants self-reported on demographic and experience variables. They trained to a level of competence on one simulator and were assessed on the other simulator, thus producing crossover scores. No participants trained at both site types. Results When FLS-trained participants were assessed on LapSim, those who received MSU training achieved a significantly higher crossover score than their fixed-site counterparts ( p  < 0.001). Compared with baseline data, MSU LapSim-trained participants assessed on FLS displayed a performance increase of 23.1 %, whereas MSU FLS-trained participants assessed on LapSim demonstrated a 12.4 % increase in performance skills. Participants at fixed sites displayed performance increases of 5.2 and 10.9 %, respectively. Conclusions Mobile Simulation Unit-delivered laparoscopic simulation training is not inferior to fixed-site training.