PEER Testbed Study on a Laboratory Building: Exercising Seismic Performance Assessment

From 2002 to 2004 (years five and six of a ten-year funding cycle), the PEER Center organized the majority of its research around six testbeds. Two buildings and two bridges, a campus, and a transportation network were selected as case studies to “exercise” the PEER performance-based earthquake engineering methodology. All projects involved interdisciplinary teams of researchers, each producing data to be used by other colleagues in their research. The testbeds demonstrated that it is possible to create the data necessary to populate the PEER performancebased framing equation, linking the hazard analysis, the structural analysis, the development of damage measures, loss analysis, and decision variables. This report describes one of the building testbeds—the UC Science Building. The project was chosen to focus attention on the consequences of losses of laboratory contents, particularly downtime. The UC Science testbed evaluated the earthquake hazard and the structural performance of a well-designed recently built reinforced concrete laboratory building using the OpenSees platform. Researchers conducted shake table tests on samples of critical laboratory contents in order to develop fragility curves used to analyze the probability of losses based on equipment failure. The UC Science testbed undertook an extreme case in performance assessment—linking performance of contents to operational failure. The research shows the interdependence of building structure, systems, and contents in performance assessment, and highlights where further research is needed. The Executive Summary provides a short description of the overall testbed research program, while the main body of the report includes summary chapters from individual researchers. More extensive research reports are cited in the reference section of each chapter

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^>0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus

Purpose Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus. Materials and Methods Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models. Results A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). Conclusions We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials

Appropriate disclosure of a diagnosis of dementia : identifying the key behaviours of 'best practice'

Background: Despite growing evidence that many people with dementia want to know their diagnosis, there is wide variation in attitudes of professionals towards disclosure. The disclosure of the diagnosis of dementia is increasingly recognised as being a process rather than a one-off behaviour. However, the different behaviours that contribute to this process have not been comprehensively defined. No intervention studies to improve diagnostic disclosure in dementia have been reported to date. As part of a larger study to develop an intervention to promote appropriate disclosure, we sought to identify important disclosure behaviours and explore whether supplementing a literature review with other methods would result in the identification of new behaviours. Methods: To identify a comprehensive list of behaviours in disclosure we conducted a literature review, interviewed people with dementia and informal carers, and used a consensus process involving health and social care professionals. Content analysis of the full list of behaviours was carried out. Results: Interviews were conducted with four people with dementia and six informal carers. Eight health and social care professionals took part in the consensus panel. From the interviews, consensus panel and literature review 220 behaviours were elicited, with 109 behaviours over-lapping. The interviews and consensus panel elicited 27 behaviours supplementary to the review. Those from the interviews appeared to be self-evident but highlighted deficiencies in current practice and from the panel focused largely on balancing the needs of people with dementia and family members. Behaviours were grouped into eight categories: preparing for disclosure; integrating family members; exploring the patient's perspective; disclosing the diagnosis; responding to patient reactions; focusing on quality of life and well-being; planning for the future; and communicating effectively. Conclusion: This exercise has highlighted the complexity of the process of disclosing a diagnosis of dementia in an appropriate manner. It confirms that many of the behaviours identified in the literature (often based on professional opinion rather than empirical evidence) also resonate with people with dementia and informal carers. The presence of contradictory behaviours emphasises the need to tailor the process of disclosure to individual patients and carers. Our combined methods may be relevant to other efforts to identify and define complex clinical practices for further study.This project is funded by UK Medical Research Council, Grant reference number G0300999

Superinfection exclusion creates spatially distinct influenza virus populations

Interactions between viruses during coinfections can influence viral fitness and population diversity, as seen in the generation of reassortant pandemic influenza A virus (IAV) strains. However, opportunities for interactions between closely related viruses are limited by a process known as superinfection exclusion (SIE), which blocks coinfection shortly after primary infection. Using IAVs, we asked whether SIE, an effect which occurs at the level of individual cells, could limit interactions between populations of viruses as they spread across multiple cells within a host. To address this, we first measured the kinetics of SIE in individual cells by infecting them sequentially with 2 isogenic IAVs, each encoding a different fluorophore. By varying the interval between addition of the 2 IAVs, we showed that early in infection SIE does not prevent coinfection, but that after this initial lag phase the potential for coinfection decreases exponentially. We then asked how the kinetics of SIE onset controlled coinfections as IAVs spread asynchronously across monolayers of cells. We observed that viruses at individual coinfected foci continued to coinfect cells as they spread, because all new infections were of cells that had not yet established SIE. In contrast, viruses spreading towards each other from separately infected foci could only establish minimal regions of coinfection before reaching cells where coinfection was blocked. This created a pattern of separate foci of infection, which was recapitulated in the lungs of infected mice, and which is likely to be applicable to many other viruses that induce SIE. We conclude that the kinetics of SIE onset segregate spreading viral infections into discrete regions, within which interactions between virus populations can occur freely, and between which they are blocked