Pitfalls in Molecular Testing and the Added Value of the Cancer Research Biomedical Community

AbstractPost-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.

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Utilizing a collaborative working model to optimize molecular analysis of solid tumors in the Cancer Research UK's Stratified Medicine Programme.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.11094 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 11094-11094

Author(s):

Ian Walker ◽

Fiona MacDonald ◽

Helen Stuart ◽

Rachel Butler ◽

Rhianedd Ellwood-Thompson ◽

...

Keyword(s):

Cancer Research ◽

Molecular Analysis ◽

Large Scale ◽

Clinical Care ◽

Molecular Testing ◽

Failure Rates ◽

Stratified Medicine ◽

Detection Rates ◽

Collaborative Working ◽

The Uk

11094 Background: The Stratified Medicine Programme is demonstrating large scale molecular testing of solid tumours in the UK using a range of technologies. The collaborative model has allowed three laboratories to share and compare data on mutation frequencies including mutation exclusivity, test turnaround times and failure rates, to inform a future routine service for clinical care. Methods: Phase One is a two-year pilot study of molecular analysis of surplus diagnostic FFPE tumour tissue obtained from patients with cancer of the breast, colorectum, lung, ovary, prostate or malignant melanoma. Samples are tested for specified genes of clinical and research interest (for example KRAS, BRAF, NRAS, PIK3CA, TP53, PTEN, TMPRSS2-ERG, EGFR, EML4-ALK and KIT). The labs have developed and validated protocols with comparable sensitivity for the simultaneous molecular analysis of multiple genes. Results: By 31 December 2012, 4,734 sets of molecular results were completed with 60% of tumour-site specific reports issued within the target 15 days (from sample receipt). Failure rates vary with both sample quality and the type of analysis performed. The Table illustrates the link between turnaround times and failure rates, showing that repeat testing for specimens which initially fail may reduce overall failure rates but consequently increase average turnaround times. Conclusions: We will report comparative data across the three testing labs and identify multiple factors that affect mutation detection rates, failure rates, turnaround times and reporting procedures. The Stratified Medicine Programme acknowledges funding from Cancer Research UK, AstraZeneca, and Pfizer. [Table: see text]

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The Added Value of Graphical Input and Display for Electron Lens Design

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100179701 ◽

1990 ◽

Vol 48 (1) ◽

pp. 190-191

Author(s):

B. Lencova ◽

G. Wisselink

Keyword(s):

Flux Density ◽

Numerical Data ◽

Added Value ◽

Lens Design ◽

Step Size ◽

Magnetic Lens ◽

Flux Lines ◽

Fine Mesh ◽

Electron Lens ◽

User Friendly

Recent progress in computer technology enables the calculation of lens fields and focal properties on commonly available computers such as IBM ATs. If we add to this the use of graphics, we greatly increase the applicability of design programs for electron lenses. Most programs for field computation are based on the finite element method (FEM). They are written in Fortran 77, so that they are easily transferred from PCs to larger machines.The design process has recently been made significantly more user friendly by adding input programs written in Turbo Pascal, which allows a flexible implementation of computer graphics. The input programs have not only menu driven input and modification of numerical data, but also graphics editing of the data. The input programs create files which are subsequently read by the Fortran programs. From the main menu of our magnetic lens design program, further options are chosen by using function keys or numbers. Some options (lens initialization and setting, fine mesh, current densities, etc.) open other menus where computation parameters can be set or numerical data can be entered with the help of a simple line editor. The "draw lens" option enables graphical editing of the mesh - see fig. I. The geometry of the electron lens is specified in terms of coordinates and indices of a coarse quadrilateral mesh. In this mesh, the fine mesh with smoothly changing step size is calculated by an automeshing procedure. The options shown in fig. 1 allow modification of the number of coarse mesh lines, change of coordinates of mesh points or lines, and specification of lens parts. Interactive and graphical modification of the fine mesh can be called from the fine mesh menu. Finally, the lens computation can be called. Our FEM program allows up to 8000 mesh points on an AT computer. Another menu allows the display of computed results stored in output files and graphical display of axial flux density, flux density in magnetic parts, and the flux lines in magnetic lenses - see fig. 2. A series of several lens excitations with user specified or default magnetization curves can be calculated and displayed in one session.

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Preliminary Findings on the Use of Session Questionnaires to Improve Clinician-Client Alliance With Special Consideration to Clinical Education

Perspectives on Administration and Supervision ◽

10.1044/aas25.1.50 ◽

2015 ◽

Vol 25 (1) ◽

pp. 50-60

Author(s):

Anu Subramanian

Keyword(s):

Graduate Students ◽

Clinical Education ◽

Clinical Decision Making ◽

Rating Scale ◽

Treatment Effectiveness ◽

Clinical Decision ◽

Added Value ◽

Therapeutic Outcomes ◽

Specific Feedback ◽

Stakeholder Perspective

ASHA's focus on evidence-based practice (EBP) includes the family/stakeholder perspective as an important tenet in clinical decision making. The common factors model for treatment effectiveness postulates that clinician-client alliance positively impacts therapeutic outcomes and may be the most important factor for success. One strategy to improve alliance between a client and clinician is the use of outcome questionnaires. In the current study, eight parents of toddlers who attended therapy sessions at a university clinic responded to a session outcome questionnaire that included both rating scale and descriptive questions. Six graduate students completed a survey that included a question about the utility of the questionnaire. Results indicated that the descriptive questions added value and information compared to using only the rating scale. The students were varied in their responses regarding the effectiveness of the questionnaire to increase their comfort with parents. Information gathered from the questionnaire allowed for specific feedback to graduate students to change behaviors and created opportunities for general discussions regarding effective therapy techniques. In addition, the responses generated conversations between the client and clinician focused on clients' concerns. Involving the stakeholder in identifying both effective and ineffective aspects of therapy has advantages for clinical practice and education.

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