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Keith Anderson

Publications and source records attributed to Keith Anderson.

14 recordsLinked to original sources
PubMed2006

Accuracy of the combination of mammography and sonography in predicting tumor response in breast cancer patients after neoadjuvant chemotherapy.

BACKGROUND: Residual tumor size after neoadjuvant chemotherapy is an important consideration in surgical planning. We examined the accuracy of the combination of mammography and sonography in predicting pathologic residual tumor size. METHODS: Tumor size was evaluated by physical examination, mammography, and sonography at diagnosis and before surgery in 162 breast cancer patients who received neoadjuvant chemotherapy. Agreement between the predicted and the pathologic responses and the predicted and the pathologic tumor sizes was calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone receptor positivity, and the presence of an extensive intraductal component on the accuracy of mammography and sonography in predicting pathologic residual tumor size was analyzed. RESULTS: Forty-two patients (25.9%) had a pathologic complete response (pCR). Overall agreement between predicted and pathologic responses was 53% for physical examination, 67% for mammography plus sonography, and 63% for physical examination plus mammography and sonography. The sensitivity of mammography and sonography in predicting pCR was 78.6%, and the specificity was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography and sonography correlated with pathologic residual tumor size (r = .662); pathologic tumor size was within .5 cm of predicted in 69.1% of patients. Multivariate analysis showed that pathologic residual tumor size was underestimated for lobular carcinoma and overestimated for poorly differentiated tumors. CONCLUSIONS: The combination of mammography and sonography has a high accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual tumor size in mammography and sonography with pathologic residual tumor size was moderate.

Adult↗
PubMed2006

Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.

PURPOSE: We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. PATIENTS AND METHODS: One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. RESULTS: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. CONCLUSION: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Adult↗
PubMed2006

Cutting edge: apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide.

IFN regulatory factor (IRF) 3 participates in the transcriptional induction of IFN-alpha, IFN-beta, and a subset of IFN-stimulated genes (ISGs) as a result of viral infection. In addition, bacterial cell wall components such as LPS activate IRF3 in a p38-dependent manner. In this study we show that IRF3-mediated ISG induction by LPS requires the production of reactive oxygen species (ROS) by the NADPH-dependent oxidase NOX4. Furthermore, we present evidence that LPS-mediated ROS production leads to activation of apoptosis-regulating-signal kinase (ASK) 1, a MAPK kinase kinase family member capable of activating the MAP kinase 6/p38 axis. ASK1 kinase activity proved essential for IRF3-mediated ISG induction by LPS. Thus, our results presented here suggest a novel role for ROS and ASK1 in the innate immune response as signaling intermediates in the IRF3 activation pathway.

Animals↗
PubMed2006

Reproducibility of gene expression signature-based predictions in replicate experiments.

PURPOSE: The goals of this analysis were to (a) determine concordance of gene expression results from replicate experiments, (b) examine prediction agreement of multigene predictors on replicate data, and (c) assess the robustness of prediction results in the face of noise. PATIENTS AND METHODS: Affymetrix U133A gene chips were used for gene expression profiling of 97 fine-needle aspiration biopsies from breast cancer. Thirty-five cases were profiled in replicates: 17 within the same laboratory, 11 in two different laboratories, and 15 to assess manual and robotic labeling. We used data from 62 cases to develop 111 distinct pharmacogenomic predictors of response to therapy. These were tested on cases profiled in duplicates to determine prediction agreement and accuracy. To evaluate the robustness of the pharmacogenomic predictors, we also introduced random noise into the informative genes in one half of the replicates. RESULTS: The average concordance correlation coefficient was 0.978 (range, 0.96-0.99) for intralaboratory replicates, 0.962 (range, 0.94-0.98) for between-laboratory replicates, and 0.971 (range, 0.93-0.99) for manual versus robotic labeling. The mean % prediction agreement on replicate data was 97% (95% CI, 0.96-0.98; SD, 0.006), 92% (95% CI, 0.90-0.93; SD, 0.009), and 94% (95% CI, 0.92-0.95; SD, 0.008) for support vector machines, diagonal linear discriminant analysis, and k-nearest neighbor prediction methods, respectively. Mean accuracy in the test set was 77% (95% CI, 0.74-0.79; SD, 0.014), 66% (95% CI, 0.63-0.73; SD, 0.015), and 64% (95% CI, 0.60-0.67; SD, 0.016), respectively. CONCLUSION: Gene expression results obtained with Affymetrix U133A chips are highly reproducible within and across two high-volume laboratories. Pharmacogenomic predictions yielded >90% agreement in replicate data.

Biopsy, Needle↗
PubMed2006

A real-time automated system for the recognition of human facial expressions.

A fully automated, multistage system for real-time recognition of facial expression is presented. The system uses facial motion to characterize monochrome frontal views of facial expressions and is able to operate effectively in cluttered and dynamic scenes, recognizing the six emotions universally associated with unique facial expressions, namely happiness, sadness, disgust, surprise, fear, and anger. Faces are located using a spatial ratio template tracker algorithm. Optical flow of the face is subsequently determined using a real-time implementation of a robust gradient model. The expression recognition system then averages facial velocity information over identified regions of the face and cancels out rigid head motion by taking ratios of this averaged motion. The motion signatures produced are then classified using Support Vector Machines as either nonexpressive or as one of the six basic emotions. The completed system is demonstrated in two simple affective computing applications that respond in real-time to the facial expressions of the user, thereby providing the potential for improvements in the interaction between a computer user and technology.

Algorithms↗
PubMed2006

Molecular classification of breast cancer: limitations and potential.

Reverse transcription polymerase chain reaction and DNA microarrays are increasingly used in the clinic and in clinical research as prognostic or predictive tests. Results from these tests led to novel risk stratification methods and to new molecular classification of breast cancer. Some of these tools already complement existing diagnostic tests and can aid medical decision making in some situations. Better understanding of the molecular classes of breast cancer, independent of their prognostic and predictive values, may also lead to new biological insights and eventually to better therapies that are directed toward particular molecular subsets. However, there is substantially less experience with these emerging technologies than with the more established methods, the accuracy of which is often overestimated. This review discusses some of the limitations and strengths of current gene expression-based molecular classification of breast cancer. To provide context for this discussion, we also briefly examine the performance of estrogen receptor immunohistochemistry, which represents an essential part of the routine diagnostic workup for all breast cancer patients.

Biomarkers, Tumor↗
PubMed2005

The use of an anaesthetic simulator to assess single-use laryngoscopy equipment.

OBJECTIVE: To compare the view at simulated direct laryngoscopy obtained with a standard laryngoscope, with and without a disposable cover and a disposable laryngoscope blade. DESIGN: Randomized non-blinded comparison. SETTING: The high-fidelity human patient simulator at the Scottish Clinical Simulation Centre. PARTICIPANTS: Thirty-two anaesthetists with between 11 months and 25 years of experience. INTERVENTIONS: A randomized comparison of ease of laryngoscopy with each laryngoscope option for simulated easy and difficult laryngoscopy. MAIN OUTCOME MEASURES: The best grade achievable at laryngoscopy (Cormack and Lehane grade) for each laryngoscope, for both easy and difficult laryngoscopy. RESULTS: For the easy setting, 34% (P = 0.001) of anaesthetists graded laryngoscopy more difficult with the covered laryngoscope, and 22% (P = 0.008) with the disposable laryngoscope considered laryngoscopy more difficult than with the standard laryngoscope. For the difficult simulator setting, 69% (P < 0.001) found laryngoscopy more difficult with the covered laryngoscope and 69% (P < 0.001) with the disposable laryngoscope, when compared with the standard laryngoscope. There was no difference between the laryngoscopy grades for the covered and disposable laryngoscope for either easy (P = 0.21) or difficult (P = 0.87) simulation. CONCLUSIONS: Single-use equipment, as presently recommended for tonsillectomy surgery by the UK Department of Health, makes laryngoscopy more difficult for anaesthetists.

Anesthesiology↗
PubMed2005

Breast cancer molecular subtypes respond differently to preoperative chemotherapy.

PURPOSE: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. EXPERIMENTAL DESIGN: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported "breast intrinsic" gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. RESULTS: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor-negative subtypes. CONCLUSIONS: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.

Adult↗
PubMed2005

Implementing information technology to improve workplace health: a web-based information needs assessment of managers in Fraser Health, British Columbia.

A web-based questionnaire-survey was administered primarily to determine what information is useful to managers in Fraser Health, of British Columbia to support decision-making for workplace health and safety. The results indicated that managers prefer electronic quarterly reports, with targets, goals, and historical trends rated as "very important." Over 85.7% "agree" that if information was readily available in the "most beneficial" format, they would be able to improve workplace health. Recommendations include that managers be presented with clear and concise workplace health reports that facilitate analysis for decision-making.

Administrative Personnel↗
PubMed2005

Desmoplastic nested spindle cell tumor of liver: report of four cases of a proposed new entity.

We describe a distinctive tumor of the liver in four children composed of nested spindled and epithelioid cells with extensive desmoplasia that we have termed "desmoplastic nested spindle cell tumor of the liver." All four patients were previously healthy. One patient had a presumptive diagnosis of hepatic hemangioma 11 years prior to presentation. Grossly, the tumors were well circumscribed, lobular white masses, ranging from 2.8 to 15 cm in diameter. These tumors were characterized by the presence of cohesive nests of plump, bland spindle cells arranged in short fascicles with an accompanying desmoplastic stroma. Epithelioid areas ranging from palisading epithelioid cells at the periphery of some nests to pseudoglandular and polygonal cells with intercellular bridges were invariably present. Mitotic activity was low. Calcification and ossification were present. Non-neoplastic bile ducts and hepatic elements were seen both within and surrounding the tumor cell nests. Each tumor displayed cytoplasmic reactivity for vimentin, pan-cytokeratin, CD57, and nuclear staining for WT1. Neuroendocrine markers were negative. Ultrastructurally, the tumor cells showed focally well-developed cell junctions, basal lamina, and few cytoplasmic organelles. All tumors were confined to the liver and were resected without complication. Two patients received postoperative adjuvant therapy for presumed hepatoblastoma. The patients are doing well without recurrence at 7.5 years, 7 years, 5 years, and 8 months post-surgery. The morphologic appearance and immunohistochemical profile of these lesions are unique in our experience and represent a new category of pediatric liver tumor.

Adolescent↗
PubMed2004

Cutting edge: anthrax lethal toxin inhibits activation of IFN-regulatory factor 3 by lipopolysaccharide.

IFN-regulatory factor 3 (IRF3) is known to participate in the transcriptional induction of chemokines and cytokines, including IFNs, as a result of viral or bacterial infection. In this study, we demonstrate that the LPS-mediated activation of IRF3 and subsequent induction of chemokine genes or IRF3-responsive reporter constructs are inhibited after exposure of human or murine macrophages to the Bacillus anthracis toxin lethal factor. The inhibitory effect is caused by interference with the activation of the stress-activated protein kinase, p38, due to a proteolytic cleavage of mitogen-activated protein kinase kinase 6, and can be overcome by the ectopic expression of a cleavage-resistant mutant of mitogen-activated protein kinase kinase 6 or a constitutively active IRF3. The lethal factor-mediated inhibition of IRF3 activation and subsequent cytokine production through bacterial membrane components offers Bacillus anthracis an efficient mechanism to evade the innate immune response.

Animals↗
PubMed2003

The effectiveness of palliative care education delivered by videoconferencing compared with face-to-face delivery.

As part of a four-year study into the use of videoconferencing in palliative care, the delivery of workshops on palliative care to community nurses was evaluated by the Open University. Twenty nurses were randomly allocated to alternating videoconferencing and face-to-face modes of presentation. The quantitative study measured the amount of learning that occurred in each workshop with pre-tests and post-tests, and the mode of presentation. Forty-nine workshop attendances were analysed. The qualitative study used observation and analysis of videorecordings to assess the activity and attention spans in interactive communication during workshops, while a combination of interviews and questionnaires was used to assess the participants' level of satisfaction with presentation. The results showed that the nurses' level of satisfaction with the instructional presentation was high in both modes of presentation. Despite difficulties at the start of the project in the videoconferencing presentation, there was little difference between the modes of presentation in achievement scores or the gain in achievement scores. Although the learners preferred face-to-face workshops, they learnt as much from a videoconferenced workshop. Videoconferencing was less suitable for psychological or emotional discussions, but this may have been due to the time constraints on the workshops. Some features of videoconferencing suggest it could be used effectively in helping learners discuss sensitive issues. The Current Learning in Palliative Care (CLiP) worksheets were found to be an effective means of delivering learning.

Attitude of Health Personnel↗
PubMed2002

Functional profiling of the Saccharomyces cerevisiae genome.

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.

Cell Size↗