Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by Multiscale Simulation

Nanoindentation processes in single crystal Ag thin film under different crystallographic orientations and various indenter widths are simulated by the quasicontinuum method. The nanoindentation deformation processes under influences of crystalline anisotropy and indenter size are investigated about hardness, load distribution, critical load for first dislocation emission and strain energy under the indenter. The simulation results are compared with previous experimental results and Rice-Thomson (R-T) dislocation model solution. It is shown that entirely different dislocation activities are presented under the effect of crystalline anisotropy during nanoindentation. The sharp load drops in the load–displacement curves are caused by the different dislocation activities. Both crystalline anisotropy and indenter size are found to have distinct effect on hardness, contact stress distribution, critical load for first dislocation emission and strain energy under the indenter. The above quantities are decreased at the indenter into Ag thin film along the crystal orientation with more favorable slip directions that easy trigger slip systems; whereas those will increase at the indenter into Ag thin film along the crystal orientation with less or without favorable slip directions that hard trigger slip systems. The results are shown to be in good agreement with experimental results and R-T dislocation model solution

Incomplete surgical excision of keratinocyte skin cancers: a systematic review and meta-analysis.

Background Keratinocyte or non‐melanoma skin cancer (NMSC) is the commonest malignancy worldwide. Usual treatment is surgical excision. Current guidelines underestimate incomplete excision rates. Objectives We aimed to determine the risk of incomplete excision of NMSCs through a systematic review and meta‐analysis of primary clinical studies. Methods A PRISMA‐compliant systematic review and meta‐analysis was performed using methodology proposed by Cochrane. A comprehensive search strategy was applied to MEDLINE, Embase, Scopus, CINAHL, EMCare, Cochrane Library and the grey literature (January 2000–27th November 2019). All studies were included except studies on Mohs micrographic surgery, frozen section or biopsies. Abstract screening and data extraction were performed in duplicate. The risk of bias was assessed using a tool for prevalence/incidence studies. The primary outcome was the proportion of incomplete surgical excisions. A random effects model for pooling of binominal data was used. Differences between proportions were assessed by sub‐group meta‐analysis and meta regression which were presented as risk ratios. PROSPERO CRD42019157936. Results Searching identified 3477 records, with 110 studies included, comprising 53 796 patients with 106 832 basal cell carcinomas (BCC) and 21 569 squamous cell carcinomas (SCC). The proportion of incomplete excisions for BCC was 11·0% (95% CI 9·7‐12·4%) and for SCC 9·4% (95% CI 7·6‐11·4%). Incomplete excisions by specialty were: dermatology 6·2% BCCs, 4·7% SCCs; plastic surgery 9·4% BCCs, 8·2% SCCs; general practitioners 20·4% BCCs, 19·9% SCCs. The risk of incomplete excision for general practitioners was four times that of dermatologists for both BCC (RR 3·9 [95% CI 2·0‐7·3]) and SCC (RR 4·8 [95% CI 1·0‐22·8]). Studies were heterogenous (I2=98%) and at high risk of bias. Conclusions The proportion of incomplete excisions is higher than previously reported. Excisions performed by specialists may lower the risk of incomplete excision

Association between Genetic Variants and Cisplatin-Induced Nephrotoxicity: A Genome-Wide Approach and Validation Study

This study aims to evaluate genetic risk factors for cisplatin-induced nephrotoxicity by investigating not previously studied genetic risk variants and further examining previously reported genetic associations. A genome-wide study (GWAS) was conducted in genetically estimated Europeans in a discovery cohort of cisplatin-treated adults from Toronto, Canada, followed by a candidate gene approach in a validation cohort from the Netherlands. In addition, previously reported genetic associations were further examined in both the discovery and validation cohorts. The outcome, nephrotoxicity, was assessed in two ways: (i) decreased estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) and (ii) increased serum creatinine according to the Common Terminology Criteria for Adverse Events v4.03 for acute kidney injury (AKI-CTCAE). Four different Illumina arrays were used for genotyping. Standard quality control was applied for pre- and post-genotype imputation data. In the discovery cohort (n = 608), five single-nucleotide polymorphisms (SNPs) reached genome-wide significance. The A allele in rs4388268 (minor allele frequency = 0.23), an intronic variant of the BACH2 gene, was consistently associated with increased risk of cisplatin-induced nephrotoxicity in both definitions, meeting genome-wide significance (β = −8.4, 95% CI −11.4–−5.4, p = 3.9 × 10−8) for decreased eGFR and reaching suggestive association (OR = 3.9, 95% CI 2.3–6.7, p = 7.4 × 10−7) by AKI-CTCAE. In the validation cohort of 149 patients, this variant was identified with the same direction of effect (eGFR: β = −1.5, 95% CI −5.3–2.4, AKI-CTCAE: OR = 1.7, 95% CI 0.8–3.5). Findings of our previously published candidate gene study could not be confirmed after correction for multiple testing. Genetic predisposition of BACH2 (rs4388268) might be important in the development of cisplatin-induced nephrotoxicity, indicating opportunities for mechanistic understanding, tailored therapy and preventive strategies

Association between Genetic Variants and Cisplatin-Induced Nephrotoxicity: A Genome-Wide Approach and Validation Study

This study aims to evaluate genetic risk factors for cisplatin-induced nephrotoxicity by investigating not previously studied genetic risk variants and further examining previously reported genetic associations. A genome-wide study (GWAS) was conducted in genetically estimated Europeans in a discovery cohort of cisplatin-treated adults from Toronto, Canada, followed by a candidate gene approach in a validation cohort from the Netherlands. In addition, previously reported genetic associations were further examined in both the discovery and validation cohorts. The outcome, nephrotoxicity, was assessed in two ways: (i) decreased estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) and (ii) increased serum creatinine according to the Common Terminology Criteria for Adverse Events v4.03 for acute kidney injury (AKI-CTCAE). Four different Illumina arrays were used for genotyping. Standard quality control was applied for pre- and post-genotype imputation data. In the discovery cohort (n = 608), five single-nucleotide polymorphisms (SNPs) reached genome-wide significance. The A allele in rs4388268 (minor allele frequency = 0.23), an intronic variant of the BACH2 gene, was consistently associated with increased risk of cisplatin-induced nephrotoxicity in both definitions, meeting genome-wide significance (β = −8.4, 95% CI −11.4–−5.4, p = 3.9 × 10−8) for decreased eGFR and reaching suggestive association (OR = 3.9, 95% CI 2.3–6.7, p = 7.4 × 10−7) by AKI-CTCAE. In the validation cohort of 149 patients, this variant was identified with the same direction of effect (eGFR: β = −1.5, 95% CI −5.3–2.4, AKI-CTCAE: OR = 1.7, 95% CI 0.8–3.5). Findings of our previously published candidate gene study could not be confirmed after correction for multiple testing. Genetic predisposition of BACH2 (rs4388268) might be important in the development of cisplatin-induced nephrotoxicity, indicating opportunities for mechanistic understanding, tailored therapy and preventive strategies.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche