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Nogueira L.M.,TX | Koch L.,University of Illinois at Springfield | Copeland G.,Mi | Lynch C.F.,University of Iowa | And 4 more authors.
American Journal of Transplantation

US transplant centers are required to report cancers in transplant recipients to the transplant network. The accuracy and completeness of these data, collected in the Scientific Registry of Transplant Recipients (SRTR), are unknown. We compared diagnoses in the SRTR and 15 linked cancer registries for colorectal, liver, lung, breast, prostate and kidney cancers; melanoma; and non-Hodgkin lymphoma (NHL). Among 187 384 transplants, 9323 cancers were documented in the SRTR or cancer registries. Only 36.8% of cancers were in both, with 47.5% and 15.7% of cases additionally documented solely in cancer registries or the SRTR, respectively. Agreement between the SRTR and cancer registries varied (kappa = 0.28 for liver cancer and kappa = 0.52-0.66 for lung, prostate, kidney, colorectum, and breast cancers). Upon evaluation, some NHLs documented only in cancer registries were identified in the SRTR as another type of posttransplant lymphoproliferative disorder. Some SRTR-only cases were explained by miscoding (colorectal cancer instead of anal cancer, metastases as lung or liver cancers) or missed matches with cancer registries, partly due to recipients' outmigration from catchment areas. Estimated sensitivity for identifying cancer was 52.5% for the SRTR and 84.3% for cancer registries. In conclusion, SRTR cancer data are substantially incomplete, limiting their usefulness for surveillance and research. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons. Source

Newell T.L.,Mi
Journal for healthcare quality : official publication of the National Association for Healthcare Quality

The inpatient medication delivery system used at a large regional acute care hospital in the Midwest had become antiquated and inefficient. The existing 24-hr medication cart-fill exchange process with delivery to the patients' bedside did not always provide ordered medications to the nursing units when they were needed. In 2007 the principles of the Toyota Production System (TPS) were applied to the system. Project objectives were to improve medication safety and reduce the time needed for nurses to retrieve patient medications. A multidisciplinary team was formed that included representatives from nursing, pharmacy, informatics, quality, and various operational support departments. Team members were educated and trained in the tools and techniques of TPS, and then designed and implemented a new pull system benchmarking the TPS Ideal State model. The newly installed process, providing just-in-time medication availability, has measurably improved delivery processes as well as patient safety and satisfaction. Other positive outcomes have included improved nursing satisfaction, reduced nursing wait time for delivered medications, and improved efficiency in the pharmacy. After a successful pilot on two nursing units, the system is being extended to the rest of the hospital. © 2010 National Association for Healthcare Quality. Source

The human body is a microbe's playground: interspersed among the 37 trillion cells of the human body [1] are at least ten times as many bacteria, fungi, viruses, and archaea. That amounts to 100 times as many microbial genes as human genes. ©2014IEEE. Source

Nelson J.,Harvard University | Price E.,Mi | Wootters M.,University of Michigan
Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms

In this paper, we present novel constructions of matrices with the restricted isometry property (RIP) that support fast matrix-vector multiplication. Our guarantees are the best known, and can also be used to obtain the best known guarantees for fast Johnson Lindenstrauss transforms. In compressed sensing, the restricted isometry property is a sufficient condition for the efficient reconstruction of a nearly k-sparse vector x ∈ C d from m linear measurements Φx. It is desirable for to to be small, and further it is desirable for Φ to support fast matrix- vector multiplication. Among other applications, fast multiplication improves the runtime of iterative recovery algorithms which repeatedly multiply by Φ or Φ*. The main contribution of this work is a novel randomized construction of RIP matrices Φ ∈ Cm×d, preserving the ℓ2 norms of all k-sparse vectors with distortion 1 + ε, where the matrix-vector multiply Φx can be computed in nearly linear time. The number of rows m is on the order of ε-2klog d log2(k log d), an improvement on previous analyses by a logarithmic factor. Our construction, together with a connection between RIP matrices and the Johnson-Lindenstrauss lemma in [Krahmer-Ward, SIAM. J. Math. Anal. 2011], also implies fast Johnson-Lindenstrauss embeddings with asymptotically fewer rows than previously known. Our construction is actually a recipe for improving any existing family of RIP matrices. Briefly, we apply an appropriate sparse hash matrix with sign flips to any suitable family of RIP matrices. We show that the embedding properties of the original family are maintained, while at the same time improving the number of rows. The main tool in our analysis is a recent bound for the supremum of certain types of Rademacher chaos processes in [Krahmer-Mendelson- Rauhut, Comm. Pure Appl. Math, to appear]. Copyright © 2014 by the Society for Industrial and Applied Mathematics. Source

Ladd B.,Mi | Ladd B.,Harvard University | Ackroyd J.J.,Mi | Hicks J.K.,Mi | And 4 more authors.
DNA Repair

The nucleoside analog ganciclovir (GCV) elicits cytotoxicity in tumor cells via a novel mechanism in which drug incorporation into DNA produces minimal disruption of replication, but numerous DNA double strand breaks occur during the second S-phase after drug exposure. We propose that homologous recombination (HR), a major repair pathway for DNA double strand breaks, can prevent GCV-induced DNA damage, and that inhibition of HR will enhance cytotoxicity with GCV. Survival after GCV treatment in cells expressing a herpes simplex virus thymidine kinase was strongly dependent on HR (>14-fold decrease in IC50 in HR-deficient vs. HR-proficient CHO cells). In a homologous recombination reporter assay, the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA; vorinostat), decreased HR repair events up to 85%. SAHA plus GCV produced synergistic cytotoxicity in U251tk human glioblastoma cells. Elucidation of the synergistic mechanism demonstrated that SAHA produced a concentration-dependent decrease in the HR proteins Rad51 and CtIP. GCV alone produced numerous Rad51 foci, demonstrating activation of HR. However, the addition of SAHA blocked GCV-induced Rad51 foci formation completely and increased γH2AX, a marker of DNA double strand breaks. SAHA plus GCV also produced synergistic cytotoxicity in HR-proficient CHO cells, but the combination was antagonistic or additive in HR-deficient CHO cells. Collectively, these data demonstrate that HR promotes survival with GCV and compromise of HR by SAHA results in synergistic cytotoxicity, revealing a new mechanism for enhancing anticancer activity with GCV. © 2013 Elsevier B.V. Source

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