Citations

BACKGROUND AND OBJECTIVE: Pediatrics has embraced technology-enhanced simulation (TES) as an educational modality, but its effectiveness for pediatric education remains unclear. The objective of this study was to describe the characteristics and evaluate the effectiveness of TES for pediatric education. METHODS: This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. A systematic search of Medline, Embase, CINAHL, ERIC, Web of Science, Scopus, key journals, and previous review bibliographies through May 2011 and an updated Medline search through October 2013 were conducted. Original research articles in any language evaluating the use of TES for educating health care providers at any stage, where the content solely focuses on patients 18 years or younger, were selected. Reviewers working in duplicate abstracted information on learners, clinical topic, instructional design, study quality, and outcomes. We coded skills (simulated setting) separately for time and nontime measures and similarly classified patient care behaviors and patient effects. RESULTS: We identified 57 studies (3666 learners) using TES to teach pediatrics. Effect sizes (ESs) were pooled by using a random-effects model. Among studies comparing TES with no intervention, pooled ESs were large for outcomes of knowledge, nontime skills (eg, performance in simulated setting), behaviors with patients, and time to task completion (ES = 0.80–1.91). Studies comparing the use of high versus low physical realism simulators showed small to moderate effects favoring high physical realism (ES = 0.31–0.70). CONCLUSIONS: TES for pediatric education is associated with large ESs in comparison with no intervention. Future research should include comparative studies that identify optimal instructional methods and incorporate pediatric-specific issues into educational interventions.

BACKGROUNDThe 1996 National Cancer Institute Working Group (NCI‐WG 96) guidelines classified disease in individuals who had a B‐cell clone with chronic lymphocytic leukemia (CLL) immunophenotype as CLL if their absolute lymphocyte count was ≥5 × 109/L. The 2008 International Workshop on CLL guidelines (IWCLL 2008) classified disease as CLL if the absolute B‐cell count was ≥5 × 109/L or as monoclonal B‐cell lymphocytosis (MBL) if the absolute B‐cell count was <5 × 109/L. The objective of the current study of Olmsted County, Minnesota, was to assess the effects of these changes on incidence rates and presentation from 2000 to 2010.METHODSUsing diagnostic indices available through the Rochester Epidemiology Project and the Mayo CLL database, the authors identified all patients with newly diagnosed CLL and high‐count MBL from 2000 to 2010. Age‐specific and sex‐specific incidence rates were determined.RESULTSAccording to NCI‐WG 96 criteria, there were 115 patients with CLL and 8 patients with MBL during the period studied. Using the IWCLL 2008 classification, there were 79 patients with CLL and 40 patients with MBL. Rai stage distribution (low risk, intermediate risk, and high risk) using NCI‐WG 96 criteria was 60.9%, 33.9%, and 5.2%, respectively, compared with 43%, 49.4%, and 7.6%, respectively, using IWCLL 2008 criteria. The age‐adjusted and sex‐adjusted incidence rates (per 100,000) for CLL and MBL were 10.0 and 0.66, respectively, using NCI‐WG 96 criteria versus 6.8 and 3.5, respectively, using IWCLL 2008 criteria. The median time to treatment according to NCI‐WG 96 criteria was 9.2 years versus 6.5 years with IWCLL 2008 criteria.CONCLUSIONSUse of the IWCLL 2008 guidelines reduced the incidence of CLL, altered the distribution of initial Rai stage at diagnosis, and shortened the median time to treatment. Cancer 2014;120:2000–2005. © 2014 American Cancer Society.

SUMMARYUnderstanding the flow alteration in side branches during flow diversion treatment of cerebral aneurysms is important to prevent ischemic complications and improve device designs. Flow diverters were placed in the aorta of four rabbits crossing the origin of side arteries. Subject‐specific computational models were constructed from 3D angiographies and Doppler ultrasounds (DUSs). Flow simulations were run before and after virtually deploying the flow diverters, assuming distal resistances remained unchanged after treatment. All jailed arteries remained patent angiographically 8 weeks after treatment. The computational models estimated decreases compared to pretreatment in the mean flow rates between 2% and 20% and in peak flow rates between 5% and 36%. The major changes were observed during systole. Flow patterns did not exhibit recirculation zones before treatment. Implantation of the flow diverters altered the flow structure only locally near the device wires. No major recirculation regions were created or destroyed. Flow diverters seem safe with respect to perforator or side branch occlusion. Relatively small changes in flow rates through jailed arteries are expected, even for moderate to large degrees of coverage of their origins. These results seem consistent with previous clinical experiences where no or very few complications related to perforator occlusion have been reported.Copyright © 2014 John Wiley & Sons, Ltd.

Abstract Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm−/− cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm−/− cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm−/− cells Sμ DSBs accumulate as they lack a recombination partner.

AbstractPurpose: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3′ untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression. We evaluated the LCS6 genotype and its association with KRAS mutation status, clinicopathologic features, and disease-free survival (DFS) in patients with stage III colon cancer who enrolled in a phase III clinical trial (NCCTG N0147).Experimental Design: The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood (n = 2,834) and compared with paired tumor tissue (n = 977). χ2 and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status. Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS, respectively.Results: We identified 432 (15.2%) blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%) tumor samples homozygous for the LCS6 T-allele. Genotype results were highly concordant (99.8%) in cases with paired blood and tumor tissue (n = 977). G-allele carriers were significantly more frequent in Caucasians versus other races (χ2 test, P &lt; 0.0001). The LCS6 genotype was not associated with KRAS mutation status, clinicopathologic features (all P &gt; 0.2), or DFS (log-rank P = 0.49; HR, 0.929; 95% confidence interval, 0.76–1.14), even after combining LCS6 genotype with KRAS mutation status.Conclusions: In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors. Clin Cancer Res; 20(12); 3319–27. ©2014 AACR.