After Sontag: Reclaiming Metaphor
Genre, Vol. 44, No. 3 Fall 2011a
Susan Sontag’s Illness as Metaphor and AIDS and Its Metaphors critiqued the use of metaphoric language, particularly... more Susan Sontag’s Illness as Metaphor and AIDS and Its Metaphors critiqued the use of metaphoric language, particularly military metaphors of invasion and battle, to describe illness experiences. Metaphors generate explanatory narratives, just as stories often use a resonant metaphor as shorthand for theme. Metaphors and narratives can suggest reductive or stereotypical ways of imagining illness, disability, and other experiences of embodiment. Rather than an end to metaphoric framing of illness, however, the agency to make metaphors needs to be conferred to a larger constituency that always includes the patient. The author’s first-person ovarian cancer narrative illustrates that not having the capacity to make metaphors for one’s embodied experiences can mean late diagnosis; the dearth of effective public metaphors for imagining some internal organs, such as the ovaries, contributes to the problem. Metaphors can be reductive, but they can also generate a wide range of relationships between illness and the person experiencing it, as illustrated by examples including Margaret Atwood’s short story “Hairball.” Simile in particular, which expresses similarity but not equivalence and thus does not erase difference, can generate a healthy way of imagining illness. Some recent literature has suggested that doctors use metaphor to communicate with patients; this gives doctors the power to determine which metaphors will frame the illness and direct its narrative. The lessons of narrative medicine, which advocate that patients and doctors use narrative collaboratively to generate a more effective understanding and treatment of illness, need to be extended to include metaphor.
PrognoScan: a new database for meta-analysis of the prognostic value of genes
Mizuno H, Kitada K, Nakai K, Sarai A. BMC Med Genomics. 2009, 2:18.
Background
In cancer research, the association between a gene and clinical outcome suggests the underlying... more
Background
In cancer research, the association between a gene and clinical outcome suggests the underlying etiology of the disease and consequently can motivate further studies. The recent availability of published cancer microarray datasets with clinical annotation provides the opportunity for linking gene expression to prognosis. However, the data are not easy to access and analyze without an effective analysis platform.
Description
To take advantage of public resources in full, a database named "PrognoScan" has been developed. This is 1) a large collection of publicly available cancer microarray datasets with clinical annotation, as well as 2) a tool for assessing the biological relationship between gene expression and prognosis. PrognoScan employs the minimum P-value approach for grouping patients for survival analysis that finds the optimal cutpoint in continuous gene expression measurement without prior biological knowledge or assumption and, as a result, enables systematic meta-analysis of multiple datasets.
Conclusion
PrognoScan provides a powerful platform for evaluating potential tumor markers and therapeutic targets and would accelerate cancer research. The database is publicly accessible at http://gibk21.bse.kyutech.ac.jp/PrognoScan/index.html webcite.
A Feminist “Nutt” Point of View by Shannon Nutt
Originally published on Feminism and Religion project
This is the first blog post I have written, so the concept of being a blogger is a little foreign to me. But I... more
This is the first blog post I have written, so the concept of being a blogger is a little foreign to me. But I will just jump in!
I grew up in a religious house that became far more religious after my mother passed away from brain cancer when I was thirteen. My single father became heavily involved in the Lutheran Church, thinking this was the best way to raise his two daughters. I was happy to go to church and get the structure that the church provided. I was also grateful that I went to a church that had a female pastor. Lacking a mother, it was nice to have a strong female role model who was breaking into the “boys’ club” that was the church. Having found a postitive, female role model, I was really upset when I heard very conservative members of other churches and my own family say that women have no business speaking or leading people in church.
A Network Perspective on Metabolic Inconsistency
Sonnenschein N, Golib Dzib JF, Lesne A, Eilebrecht S, Boulkroun S, Zennaro MC, Benecke A, Hütt MT.
BMC Syst Biol. 2012 May 14;6(1):41. [Epub ahead of print]
PMID: 22583819 [PubMed - as supplied by publisher]
Background
Integrating gene expression profiles and metabolic pathways under different experimental conditions is... more
Background
Integrating gene expression profiles and metabolic pathways under different experimental conditions is essential for understanding the coherence of these two layers of cellular organization. The network character of metabolic systems can be instrumental in developing concepts of agreement between expression data and pathways. A network-driven interpretation of gene expression data has the potential of suggesting novel classifiers for pathological cellular states and of contributing to a general theoretical understanding of gene regulation.
Results
Here, we analyze the coherence of gene expression patterns and a reconstruction of human metabolism, using consistency scores obtained from network and constraint-based analysis methods. We find a surprisingly strong correlation between the two measures, demonstrating that a substantial part of inconsistencies between metabolic processes and gene expression can be understood from a network perspective alone. Prompted by this finding, we investigate the topological context of the individual biochemical reactions responsible for the observed inconsistencies. On this basis, we are able to separate the differential contributions that bear physiological information about the system, from the unspecific contributions that unravel gaps in the metabolic reconstruction. We demonstrate the biological potential of our network-driven approach by analyzing transcriptome profiles of aldosterone producing adenomas that have been obtained from a cohort of Primary Aldosteronism patients. We unravel systematics in the data that could not have been resolved by conventional microarray data analysis. In particular, we discover two distinct metabolic states in the adenoma expression patterns.
Conclusions
The methodology presented here can help understand metabolic inconsistencies from a network perspective. It thus serves as a mediator between the topology of metabolic systems and their dynamical function. Finally, we demonstrate how physiologically relevant insights into the structure and dynamics of metabolic networks can be obtained using this novel approach.
Application of Genomic and Proteomic Technologies in Biomarker Discovery
by Elana Fertig
EJ Fertig, R Slebos, and CH Chung. Application of Genomic and Proteomic Technologies in Biomarker Discovery. In: Govindan R, ed. 2012 ASCO Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2012;377-382.
Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of... more Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of whole-exome sequencing, numerous cancer genomes have been sequenced, including head and neck squamous cell carcinoma (HNSCC) in 2011. Although DNA sequencing data reveals a complex genome with numerous mutations, the biologic interaction and clinical significance of the overall genetic aberrations are largely unknown. Comprehensive analyses of the tumors using genomics and proteomics beyond sequencing data can potentially accelerate the rate and number of biomarker discoveries to improve biology-driven classification of tumors for prognosis and patient selection for a specific therapy. In this review, we will summarize the current genomic and proteomic technologies, general biomarker-discovery paradigms using the technology and published data in HNSCC---including potential clinical applications and limitations.
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Seen by:Gene expression signatures modulated by epidermal growth factor receptor activation and their relationship to cetuximab resistance in head and neck squamous cell carcinoma
by Elana Fertig
Elana J Fertig, Qing Ren, Haixia Cheng, Hiromitsu Hatakeyama, Adam Dicker, Ulrich Rodeck, Michael Considine, Michael F Ochs and Christine H Chung (2012) BMC Genomics 13:160. Featured in http://www.biomedcentral.com/1741-7015/10/43/abstract.
Background: Aberrant activation of signaling pathways downstream of epidermal growth factor receptor (EGFR) has been... more
Background: Aberrant activation of signaling pathways downstream of epidermal growth factor receptor (EGFR) has been hypothesized to be one of the mechanisms of cetuximab (a monoclonal antibody against EGFR) resistance in head and neck squamous cell carcinoma (HNSCC). To infer relevant and specific pathway activation downstream of EGFR from gene expression in HNSCC, we generated gene expression signatures using immortalized keratinocytes (HaCaT) subjected to ligand stimulation and transfected with EGFR, RELA/p65, or HRASVal12D.
Results: The gene expression patterns that distinguished the HaCaT variants and conditions were inferred using the Markov chain Monte Carlo (MCMC) matrix factorization algorithm Coordinated Gene Activity in Pattern Sets (CoGAPS). This approach inferred gene expression signatures with greater relevance to cell signaling pathway activation than the expression signatures inferred with standard linear models. Furthermore, the pathway signature generated using HaCaT-HRASVal12D further associated with the cetuximab treatment response in isogenic cetuximab-sensitive (UMSCC1) and -resistant (1CC8) cell lines.
Conclusions: Our data suggest that the CoGAPS algorithm can generate gene expression signatures that are pertinent to downstream effects of receptor signaling pathway activation and potentially be useful in modeling resistance mechanisms to targeted therapies.
Queering the Temporality of Cancer Survivorship
by Mary Bryson
Jackie Stacey and Mary Bryson. (2012). Queering the Temporality of Cancer Survivorship. Aporia, 4(1).
http://www.oa.uottawa.ca/journals/aporia/
Survivorship suggests a temporal relation. It speaks to the endurance of past trauma and looks forward to a future... more Survivorship suggests a temporal relation. It speaks to the endurance of past trauma and looks forward to a future that it wills into being through the overcoming of adversity. This article traces the warped temporalities of cancer survivorship, exploring its queer dimensions by combining theoretical discussions with readings of two lesbian interventions that address normative visions and narrations of healthy/diseased bodies. Cancer survivorship in each case becomes a poetic narration of desire and disease through the queering of temporality. The authors argue that the extent to which cancer's time warp here belongs to queer temporality depends on whether the queerness refers only to the odd, the uncanny, the indeterminate and the undecidable. Or if, instead, cancer's time warp is queer in the sense that sexuality is already present in cancer's disturbance to temporality. In so far as queer carries with it the traces of sexualities deemed undesirable and perverse, then such connections move beyond an analogous and into an ontological register.
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Mitochondrial NADH-dehydrogenase polymorphisms as sporadic breast cancer risk factor.
Breast cancer is the most frequently diagnosed
female cancer all over the world. Although the molecular
female cancer all over the world. Although the molecular
genetics of this disease has been the focus of many projects
for over 20 years, the number of prognostic markers used in
clinics is still unsatisfactory. Mitochondrial DNA mutations
have been reported in many breast cancer studies. To
investigate the possible role of mitochondrial inherited
polymorphisms in breast cancer development we analyzed
the sequence of NADH-dehydrogenase genes in cancer
samples and their corresponding normal tissues. We detected
increased incidence of mtDNA polymorphisms, in particular
very rare polymorphisms such as A4727G, G9947A,
A10044G, A10283G, T11233C, and C11503T. Our report
supports the notion that mtDNA polymorphisms establish a
specific genetic background for breast cancer development
and that mtDNA analysis may help in selection of cohorts
that should undergo intensive screening and early detection
programs
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Seen by:Dynamic Mitochondrial Networks in Cancer
Published on the Scientific American Blog
Research projects evolve in a fortuitous manner, often guided by a convergence of novel observations, intuition,... more
Research projects evolve in a fortuitous manner, often guided by a convergence of novel observations, intuition, helpful colleagues and unique personal circumstances. It is precisely this constellation that prompted two cardiologists to study the mitochondrial networks in lung cancer cells.
In 2008, my colleague and friend Stephen Archer, a Professor of Medicine at the University of Chicago, asked me whether I would be interested in studying the role of mitochondrial networks in lung cancer cells. My first response was the question “Do mitochondria really form networks?”, because at that time the expression “mitochondria” evoked images of scattered oval-like organelles, a textbook image of electron microscopy.......
Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method.
Agostini M, Fransman W, Vocht FD, Joode BV, Kromhout H.
To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a... more
To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment Method (DREAM)].
METHODS:
Two skilled observers assessed dermal exposure to bitumen condensate among 85 asphalt workers from 12 crews from nine companies active within four European countries using the DREAM methodology, which produces an estimate of exposure expressed in dimensionless DREAM units. Both observers independently evaluated each crew member's job (N = 14 jobs) for road paving and mastic applications. Potential and actual dermal exposures were estimated for hands and for the rest of the body separately, taking into account the effect of protective clothing. To evaluate the reproducibility of the observational method intra-class correlation coefficients (ICCs) were estimated. The exposures in DREAM units were modelled using linear mixed models to estimate average relative scores for each job. Correlations between dermal exposure parameters were evaluated by estimating Pearson correlation coefficients.
RESULTS:
A total of 170 observations were completed by two observers independently (n = 118 and n = 52 for 59 road pavers and 26 mastic workers, respectively) in 11 days. The mean ICCs (for potential and actual exposure in DREAM units) varied between 0.74 and 0.80 with values for actual units being slightly higher. Geometric mean potential dermal exposure units of mastic workers were higher than for road pavers (factor 3 for hands and factor 4 for rest of the body). Differences for actual dermal exposure units were smaller for hands (factor 2) and larger for actual exposure units of rest of the body (factor 5). Differences in dermal exposure at the hands between jobs within a paving crew were much larger than between jobs within a mastic crew. Within paving crews, a consistent pattern for all exposure units emerged with 'screed man' and 'raker' as the two highest exposed jobs. Within mastic crews, 'driver dumper truck' and 'spreader of mastic' were scored as the two jobs with the highest exposure units. Potential and actual exposure units were highly correlated. Hands were more profoundly exposed than the rest of the body, with transfer from contaminated surface to the hands as the most important route.
CONCLUSIONS:
DREAM observations were reproducible and showed a consistent dermal exposure pattern among the observed crews. The study provided a clear picture of dermal exposure among road pavers and indoor mastic workers, with the mastic workers being considerably more highly exposed. The most important route of exposure appeared to be transferred from contaminated surfaces to the hands.
Exposure to rubber process dust and fume since 1970s in the United Kingdom; influence of origin of measurement data.
Agostini M, de Vocht F, van Tongeren M, Cherrie JW, Galea KS, Kromhout H.
The objective of this study was to compare measured concentrations of rubber process dust and rubber fume originating... more
The objective of this study was to compare measured concentrations of rubber process dust and rubber fume originating from different sources in the British rubber manufacturing industry. Almost 8000 exposure measurements were obtained from industry-based survey results collected by the British Rubber Manufacturers' Association (BRMA), and covering the years 1977 to 2002, and from a series of small surveys contained in the Health and Safety Executive's (HSE) National Exposure Database (HSE-NEDB) from 1980 to 2002. The analysis investigated temporal trends in the exposure concentrations and the underlying main factors responsible for these changes. Analyses were carried out using hierarchical linear mixed effects models. Average personal exposures to rubber process dust and rubber fumes were respectively a factor 2 and 4 higher for the HSE-NEDB data when compared to data originating from the industry (BRMA data). Personal exposure to rubber process dust decreased on average by 4.1% (95% CI 4.7-3.6) annually for the BRMA data and slightly less at 2.3% (95% CI 5.2-0.7%) per annum for the HSE-NEDB data. Personal exposure to rubber fume also showed a downward temporal trend of 2.9% (95% CI 3.6-2.3%) and 4.8% (95% CI 7.4-2.1%) annually for the BRMA and HSE-NEDB data, respectively. These trends differed considerably between departments. No major changes in the estimated temporal trends in exposure concentrations were observed after including the presence of local exhaust ventilation in the models for any department in the BRMA and HSE-NEDB datasets. Lack of information on the quality and status of the local exhaust ventilation is the most likely explanation for this. In conclusion, even though there were relatively similar downward time trends in both rubber process dust and fume concentrations in both datasets, the source of exposure data was an important determinant of average exposure concentrations present in the British rubber manufacturing industry. Lack of detailed auxiliary information on company size, reason for sampling, measurement strategy and other potentially important determinants of exposure prevented an explanation for the observed differences in exposure level.
