Cancer Survivorship Care: An Emphasis On Rehabilitation Needs In Maine

The first section of this report addresses the evidence of causation concerning impairments developed as a result of a cancer diagnosis and cancer treatment. The second section investigates the evidence regarding rehabilitation and physical activity as an effective intervention in the prevention and treatment of impairments from cancer diagnosis and cancer treatment. The third section discusses the underlying behavioral change theory for incorporation of our Cancer Survivorship Rehabilitation Algorithm (Appendix 1), which details our proposed use of rehabilitation and wellness services in the continuum of cancer care and includes an outline for a survivorship care plan. This section also discusses the efficacy of delivery of our product to healthcare professionals. The fourth section outlines our proposed methods of evaluation for the utilization of our algorithm

A logarithmic epiperimetric inequality for the obstacle problem

For the general obstacle problem, we prove by direct methods an epiperimetric inequality at regular and singular points, thus answering a question of Weiss (Invent. Math., 138 (1999), 23--50). In particular at singular points we introduce a new tool, which we call logarithmic epiperimetric inequality, which yields an explicit logarithmic modulus of continuity on the $C^1$ regularity of the singular set, thus improving previous results of Caffarelli and Monneau

Inhibition of inner ear ornithine decarboxylase by neomycin in-vitro

We quantitated the activity of ornithine decarboxylase (ODC) in homogenates and subcellular fractions of inner ear tissues from the rat and guinea pig and demonstrate inhibition of cochlear ODC by the aminoglycoside neomycin. Subcellular fractionation showed the enzyme associated with the postmitochondrial supernatant fraction in each of the tissues: Specific activities of ODC, defined as [alpha]-difluoromethylornithine (DFMO)-sensitive decarboxylation of ornithine, in the supernatant fractions of combined inner ear tissues were: guinea pig=44 +/- 4 pmoles CO2 produced/hour/mg protein, and rat=133 +/- 30. In the guinea pig, supernatant fractions of the lateral wall tissues (stria vascularis and spiral ligament) had specific activities of 62 +/- 25, those of the organ of Corti (plus Vlllth nerve) 64 +/- 41. The ototoxic aminoglycoside neomycin produced a dose-dependent inhibition of ODC with half-maximal inhibition observed at 50 [mu]M drug and almost complete inhibition at 100 [mu]M. This is the first report of the presence of ODC in the inner ear and its inhibition by neomycin. Since both the ODC-inhibitors, DFMO and neomycin, can cause hearing loss in patients and experimental animals it is suggested that inhibition of ODC may be an important factor in the ototoxicity of these drugs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26494/1/0000030.pd

Arteriovenous fistulae complicating cardiac pacemaker lead extraction: Recognition, evaluation, and management

AbstractTransvenous pacemaker lead extraction has become a commonly performed procedure that is associated with a small but significant risk. We report two cases where lead extraction was complicated by arteriovenous fistulae between branches of the aortic arch and the left brachiocephalic vein. Presenting signs and symptoms included severe chest or back pain, persistent or copious bleeding from the venous puncture site, unexplained hypotension or anemia, superior vena cava syndrome, and signs of central venous hypertension or acute heart failure. One patient whose injury was not recognized immediately and who did not undergo repair died rapidly, whereas the other patient who was diagnosed quickly underwent successful repair. Immediate diagnosis with arteriography and rapid intervention with surgery or percutaneous techniques are indicated and may prevent mortality. (J Vasc Surg 2000;32:1225-8.

Federal Judicial Selection

“The First Two Centuries”: The first panel explored the provisions that the drafters made in the United States Constitution for federal judicial selection and traced the two-century history of the selection process following the constitution\u27s adoption. The panel consisted of Charles Cooper, Esq. of Cooper & Kirk PLLC; Gary L. McDowell, Haynes Professor of Leadership Studies and Political Science at the University of Richmond’s Jepson School of Leadership Studies; and Ms. Maeva Marcus, of the United States Supreme Court Historical Society. Rodney A. Smolla, the George E. Allen Chair in Law, served as program coordinator and moderator. “Modern Federal Judicial Selection”: The second panel explored modern federal judicial selection, tracing the selection process over the last two decades and analyzing how it has grown increasingly contentious. The panel consisted of Theresa M. Beiner, of the William H. Bowen School of Law at the University of Arkansas at Little Rock; Sheldon Goldman, Department of Political Science University of Massachusetts; Judge Edith Jones, U.S. Court of Appeals for the Fifth Circuit; and William P. Marshall, the Kenan Professor of Law University of North Carolina School of Law. Carl W. Tobias, Williams Professor of Law at the University of Richmond School of Law, served as moderator. “The Prospects of Reform”: The third panel explored numerous suggestions for remedying or ameliorating the difficulties that pervade modern federal judicial selection and the prospects for these measures\u27 success. The panel consisted of Terry Eastland, Publisher of The Weekly Standard; Michael Gerhardt, Hanson Professor of Law at the Marshall-Wythe School of Law, College of William and Mary; and Sanford V. Levinson, The W. St. John Garwood Centennial Chair in Law and Professor of Government at the University of Texas School of Law. Gary L. McDowell, the Haynes Professor of Leadership Studies and Political Science at the University of Richmond’s Jepson School of Leadership Studies, served as moderator

Far Ultraviolet Observations of Molecular Hydrogen in the Diffuse Interstellar Medium of Starburst Galaxies

(Abridged) We have used the Far Ultraviolet Spectroscopic Explorer (FUSE) to search for H_2 absorption in five starburst galaxies: NGC 1705, NGC 3310, NGC 4214, M83 (NGC 5236), and NGC 5253. We tentatively detect weak absorption by H_2 in M83 and NGC 5253, and set upper limits on the H_2 column density in the other galaxies. Conservative upper limits on the mass of molecular gas detected with FUSE are many orders of magnitude lower than the H_2 mass inferred from CO emission. This indicates that almost all of the H_2 is in the form of clouds with N(H_2)>10^20 cm^-2 that are opaque to far-UV light and therefore cannot be probed with far-UV absorption measurements. The far-UV continuum visible in the FUSE spectra passes between the dense clouds, which have a covering factor <1. The complex observational biases related to varying extinction across the extended UV emission in the FUSE apertures prevent an unambiguous characterization of the diffuse H_2 in these starbursts. However, the evidence is suggestive that there is less H_2 in the diffuse interstellar medium between the dense clouds compared to similarly reddened sight lines in the Milky Way. This holds with the expectation that the destructive UV radiation field is stronger in starbursts. However, previous UV observations of these starbursts have shown that there is reddening caused by the diffuse interstellar medium. This suggests that while diffuse H_2 may be destroyed in the starburst, dust still exists.Comment: 10 pages, 8 figures. Accepted by ApJ. For higher resolution versions of figures 1-6 please contact the primary autho

Adaptation of Microelectrode Array Technology for the Study of Anesthesia-Induced Neurotoxicity in the Intact Piglet Brain

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain. This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN

Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay.

Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA

Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay

Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. Overall, we present a framework for sensitive detection of allele-specific copy number changes in cfDNA