Mahamdallie, Shazia S
Hanks, Sandra
Karlin, Kristen L
Zachariou, Anna
Perdeaux, Elizabeth R
Ruark, Elise
Shaw, Chad A
Renwick, Alexander
Ramsay, Emma
Yost, Shawn
Elliott, Anna
Birch, Jillian
Capra, Michael
Gray, Juliet
Hale, Juliet
Kingston, Judith
Levitt, Gill
McLean, Thomas
Sheridan, Eamonn
Renwick, Anthony
Seal, Sheila
Stiller, Charles
Sebire, Neil
Westbrook, Thomas F
Rahman, Nazneen
Wilms tumor is the most common childhood renal cancer. To identify mutations that predispose to Wilms tumor, we are conducting exome sequencing studies. Here we describe 11 different inactivating mutations in the REST gene (encoding RE1-silencing transcription factor) in four familial Wilms tumor pedigrees and nine non-familial cases. Notably, no similar mutations were identified in the ICR1000 control series (13/558 versus 0/993; P < 0.0001) or in the ExAC series (13/558 versus 0/61,312; P < 0.0001). We identified a second mutational event in two tumors, suggesting that REST may act as a tumor-suppressor gene in Wilms tumor pathogenesis. REST is a zinc-finger transcription factor that functions in cellular differentiation and embryonic development. Notably, ten of 11 mutations clustered within the portion of REST encoding the DNA-binding domain, and functional analyses showed that these mutations compromise REST transcriptional repression. These data establish REST as a Wilms tumor predisposition gene accounting for 2% of Wilms tumor. =20
Biographies of Edmund Kean occasionally mention his disastrous one-night performance in Jane Porter's play Switzerland in February 1819. While several commentators have blamed the work's failure on its inferior quality, Porter's unpublished letters tell a more complicated story. Using Porter's correspondence with Mary Kean, the Drury Lane committee, and various friends, this essay sheds light on her experiences in the London theatrical world and suggests interesting parallels between the careers of Porter and John Keats. Porter read Endymion with interest and hoped to meet the author, but she probably did not know that they shared a dangerous fascination with Edmund Kean.
An increased supply of physicians in high income countries both from domestic production and from immigration from low and middle income countries has made medical employment increasingly competitive. This has been heightened by the introduction of reputational incentives, such as public reporting of physicians' outcomes, and the use of other health care professionals, such as nurses. An unanticipated consequence might be a reversal of the 'brain drain', with physicians migrating to low and middle income countries.
Telemedicine improves access to medical care. However, telemedicine will also increase market volatility because of its ability to stimulate price competition and the insidious way it shifts liability for providing medical services. To cope with increased volatility, other economic sectors have evolved commodities markets by making greater use of standardized forward/future contracts. In the past, the need for medical services to be produced and consumed locally and a lack of an objective definition for medical quality, prohibited the use of forward contracts for health-care services. However, telemedicine, and the increasing use of statistical definitions of medical quality now make standardized forward contracts for health-care services conceivable. Commoditization of teleradiology would offer several advantages including increasing market transparency, a mechanism for ensuring medical quality, and a means for bringing capital into the health-care sector. To reap the benefits of a commodities market in teleradiology, the key will be for market stakeholders to overcome their fear of the unknown in order to organize a central exchange.
Mahamdallie, Shazia S.
Hanks, Sandra
Karlin, Kristen L.
Zachariou, Anna
Perdeaux, Elizabeth R.
Ruark, Elise
Shaw, Chad A.
Renwick, Alexander
Ramsay, Emma
Yost, Shawn
Elliott, Anna
Birch, Jillian
Capra, Michael
Gray, Juliet
Hale, Juliet
Kingston, Judith
Levitt, Gill
McLean, Thomas
Sheridan, Eamonn
Renwick, Anthony
Seal, Sheila
Stiller, Charles
Sebire, Neil
Westbrook, Thomas F.
Rahman, Nazneen
An apparatus (100) in one example comprises a buffer layer (110, 112) located on a face (106) that serves as a primary support for an optical fiber winding (208) along a first general direction (172). The face is coupled with a body (104) that serves as a primary support for the optical fiber winding along a second general direction (170). The optical fiber winding comprises an optical fiber (111) wound about the body. The buffer layer serves to promote a decrease of one or more strain gradients among a plurality of portions (146, 148, 150) of the optical fiber winding.
Single and multi-level structures provide neatly organized, secure and easily repairable optical fiber connections between a pump source laser diode (54) and optical fiber coils represented by x-axis coil (22), y-axis coil (24) and z-axis coil (26). The structures employ specially organized trays (60, 62) for supporting such components as a 1x3 fiber optic coupler (46), an optical isolator (ISO) (48), a wavelength division multiplexer (WDM) (50), a doped fiber coil (52) and a tap coupler (56), and for holding and routing the optical fibers coupled to and between the components. Routing and secure holding of the fibers are facilitated by a built-in optical fiber holder (120), integral with tray (60), and individual optical fiber holders (140), which are stackable upon the built-in holder or upon each other. Each tray includes internal guides, such as a guide post (118), and segmented internal and external walls which provide optical fiber routing paths (96, 100, 160) and wall separations and/or openings (102, 104, 106, 132, 162) to permit ingress and/or egress of fibers or attachment points, similar to wall separations (145) in the stackable holders. Special resilient clam-shell holders (168, 172) safely hold the fragile components, and are incorporated within the trays to facilitate inter-structural and exterior coupling.
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