Device model for FETSIM circuit simulation program

A description of the MOS transistor used in the FETSIM analysis program is presented. CMOS/SOS device parameters are included. Typical device mobilities are given as well as the empirically determined constants necessary to model second-order effect conductance variations due to gate voltage and saturated drain voltage

Expansion of CMOS array design techniques

The important features of the multiport (double entry) automatic placement and routing programs for standard cells are described. Measured performance and predicted performance were compared for seven CMOS/SOS array types and hybrids designed with the high speed CMOS/SOS cell family. The CMOS/SOS standard cell data sheets are listed and described

CMOS array design automation techniques

A low cost, quick turnaround technique for generating custom metal oxide semiconductor arrays using the standard cell approach was developed, implemented, tested and validated. Basic cell design topology and guidelines are defined based on an extensive analysis that includes circuit, layout, process, array topology and required performance considerations particularly high circuit speed

Silicon-gate CMOS/SOS processing

Major silicon-gate CMOS/SOS processes are described. Sapphire substrate preparation is also discussed, as well as the following process variations: (1) the double epi process; and (2) ion implantation

Knowledge About the Human Papillomavirus Vaccine Among Employees at a Tertiary Cancer Center: Room for Improvement

Introduction: The human papillomavirus (HPV) vaccine is recommended by the U.S. Centers for Disease Control and Prevention for routine vaccination of boys and girls to protect against HPV-related cancers and genital warts. To meet the Healthy People 2020 target for HPV vaccination, health care providers must understand the importance of strongly recommending the HPV vaccine to all eligible adolescents. We sought to determine HPV vaccination patterns among employees at a tertiary cancer center and their children and attitudes regarding HPV vaccination among the employees. Methods: All employees at a tertiary cancer center were invited to participate in a cross-sectional survey administered online during July and August 2015. The survey included questions about HPV vaccination of participants and their children, including reasons why vaccine-eligible employees and children had not been vaccinated. Results: Of those eligible, 13% of male and 33% of female employees and 44% of daughters and 24% of sons of employees had completed the vaccine series. The main reasons for not completing the series or not having one’s son completing the series were not knowing that the vaccine was needed and vaccine not recommended by a health care provider. The main reasons for not having one’s daughter complete the series were the two aforementioned reasons and daughter not yet sexually active. Conclusion: Opportunities exist to educate health care workers about the benefits of the HPV vaccine and to increase the number of providers who recommend HPV vaccination to their patients

Immune checkpoint inhibitor associated vitiligo and its impact on survival in patients with metastatic melanoma: an Italian Melanoma Intergroup study

Background: Checkpoint inhibitors in melanoma can lead to self-immune side-effects such as vitiligo-like depigmentation (VLD). Beyond the reported association with favorable prognosis, there are limited data regarding VLD patient features and their echo on the therapeutic outcomes. Methods: To assess the association between VLD and a series of clinical and biological features as well as therapeutic outcomes, we built an observational cohort study by recruiting patients who developed VLD during checkpoint inhibitors. Results: A total of 148 patients from 15 centers (101 men, median age 66 years, BRAF mutated 23%, M1c 42%, Eastern Cooperative Oncology Group (ECOG) status 0/1 99%, normal lactate dehydrogenase 74%) were enrolled. VLD was induced by ipilimumab, programmed cell death-1 (PD-1) inhibitors, and their combination in 32%, 56%, and 12%, respectively. The median onset was 26 weeks and it was associated with other skin and nonskin toxicities in 27% and 28%, respectively. After 3 years of VLD onset, 52% (95% confidence interval 39% to 63%) were progression free and 82% (95% confidence interval 70% to 89%) were still alive. The overall response rate was 73% with 26% complete response. Univariable analysis indicated that BRAF V600 mutation was associated with a better overall survival (P = 0.028), while in multivariable analysis a longer progression-free survival was associated with BRAF V600 (P = 0.093), female sex (P = 0.008), and M stage other than 1a (P = 0.024). When VLD occurred, there was a significant decrease of white blood cell (WBC) count (P = 0.05) and derived WBC-to-lymphocytes ratio (dWLR; P = 0.003). A lower monocyte count (P = 0.02) and dWLR (P = 0.01) were also reported in responder patients. Conclusions: Among VLD population, some features might help to identify patients with an effective response to immunotherapy, allowing clinicians to make more appropriate choices in terms of therapeutic options and duration

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment