Effect of the time to intervention on the outcome of thrombosed dialysis access grafts managed percutaneously

PURPOSEWe aimed to investigate the effect of the time interval from the clinical presentation of a thrombosed dialysis access graft to intervention on procedure success. MATERIALS AND METHODSRecords from two academic institutions for patients who underwent percutaneous thrombectomy of occluded surgical hemodialysis graft access sites in interventional radiology from 2006 to 2011 were reviewed retrospectively. The following data were recorded: gender, age, time and date of the initial request for a thrombectomy and the procedure, age of the surgical access, angiographic outcome, and clinical outcome (successful or unsuccessful postinterventional dialysis). Univariate and multivariate logistic regression were used to evaluate whether the time to intervention significantly affected the study endpoint. RESULTSIn total, 268 percutaneous thrombectomies were performed in 139 patients. Of these 224 (83.5%) were categorized as successful and 44 (16.4%) as unsuccessful. The time to intervention was 19.9±30.1 vs. 22±35 hours for successful and unsuccessful procedures, respectively. The difference between the two was not significant, and there were also no significant differences in covariate distributions between successful and unsuccessful outcomes. CONCLUSIONDuring the first 72 hours following clinical presentation of a thrombosed dialysis access graft, time to intervention may be considered independent of procedure outcome

New records of biting midges of the genus \u3ci\u3eCulicoides\u3c/i\u3e Latreille from the southeastern United States (Diptera: Ceratopogonidae)

We provide new state and county records of biting midges in the genus Culicoides Latreille (Diptera: Ceratopogonidae) from the southeastern United States collected with CDC miniature light traps during 2007–2012 in Florida, Georgia, Alabama, Mississippi, Louisiana, Arkansas, and Texas. The primary goals of the surveys were to identify the presence of exotic Culicoides, and determine the ranges of known and possible vectors of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Included are the first records of: Culicoides (Amossovia) beckae Wirth and Blanton from Louisiana and Mississippi, C. (A.) oklahomensis Khalaf from Alabama and Arkansas, C. (Avaritia) alachua Jamnback and Wirth from Alabama, C. (Culicoides) neopulicaris Wirth from Alabama, C. (Drymodesmyia) butleri Wirth and Hubert from Texas, C. (Hoffmania) insignis Lutz from Mississippi, C. (Oecacta) barbosai Wirth and Blanton from Georgia, C. (Silvaticulicoides) loisae Jamnback from Alabama, and C. kirbyi Glick and Mullen from Mississippi. We also provide new Florida county records for C. alachua, C. barbosai, C. (Beltranmyia) hollensis (Melander and Brues), C. insignis, and C. (Monoculicoides) sonorensis Wirth and Jones; a new Georgia county record for C. alachua; and new Alabama county records for C. insignis, and C. sonorensis

Yangian in the Twistor String

We study symmetries of the quantized open twistor string. In addition to global PSL(4|4) symmetry, we find non-local conserved currents. The associated non-local charges lead to Ward identities which show that these charges annihilate the string gluon tree amplitudes, and have the same form as symmetries of amplitudes in N=4 super conformal Yang Mills theory. We describe how states of the open twistor string form a realization of the PSL(4|4) Yangian superalgebra.Comment: 37 pages, 4 figure

Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series

PURPOSE: Develop and deploy a robust discovery platform that encompasses heterogeneity, clinical annotation, and molecular characterization and overcomes the limited availability of prostate cancer models. This initiative builds on the rich MD Anderson (MDA) prostate cancer (PCa) patient-derived xenograft (PDX) resource to complement existing publicly available databases by addressing gaps in clinically annotated models reflecting the heterogeneity of potentially lethal and lethal prostate cancer. EXPERIMENTAL DESIGN: We performed whole-genome, targeted, and RNA sequencing in representative samples of the same tumor from 44 PDXs derived from 38 patients linked to donor tumor metadata and corresponding organoids. The cohort includes models derived from different morphologic groups, disease states, and involved organ sites (including circulating tumor cells), as well as paired samples representing heterogeneity or stages before and after therapy. RESULTS: The cohort recapitulates clinically reported alterations in prostate cancer genes, providing a data resource for clinical and molecular interrogation of suitable experimental models. Paired samples displayed conserved molecular alteration profiles, suggesting the relevance of other regulatory mechanisms (e.g., epigenomic) influenced by the microenvironment and/or treatment. Transcriptomically, models were grouped on the basis of morphologic classification. DNA damage response-associated mechanisms emerged as differentially regulated between adenocarcinoma and neuroendocrine prostate cancer in a cross-interrogation of PDX/patient datasets. CONCLUSIONS: We addressed the gap in clinically relevant prostate cancer models through comprehensive molecular characterization of MDA PCa PDXs, providing a discovery platform that integrates with patient data and benchmarked to therapeutically relevant consensus clinical groupings. This unique resource supports robust hypothesis generation and testing from basic, translational, and clinical perspectives

Mastering the Hard Stuff: The History of College Concrete-Canoe Races and the Growth of Engineering Competition Culture

This article details the history of college engineering competitions, originating with student concrete-canoe racing in the 1970s, through today’s multi-million-dollar international multiplicity of challenges. Despite initial differences between engineering educators and industry supporters over the ultimate purpose of undergraduate competitions, these events thrived because they evolved to suit many needs of students, professors, schools, corporations, professional associations, and the engineering profession itself. The twenty-first-century proliferation of university-level competitions in turn encouraged a trickling-down of technical contests to elementary-age children and high schools, fostering the institutionalization of what might be called a competition culture in engineering

A De Novo Protein Binding Pair By Computational Design and Directed Evolution

The de novo design of protein-protein interfaces is a stringent test of our understanding of the principles underlying protein-protein interactions and would enable unique approaches to biological and medical challenges. Here we describe a motif-based method to computationally design protein-protein complexes with native-like interface composition and interaction density. Using this method we designed a pair of proteins, Prb and Pdar, that heterodimerize with a Kd of 130 nM, 1000-fold tighter than any previously designed de novo protein-protein complex. Directed evolution identified two point mutations that improve affinity to 180 pM. Crystal structures of an affinity- matured complex reveal binding is entirely through the designed interface residues. Surprisingly, in the in vitro evolved complex one of the partners is rotated 180 relative to the original design model, yet still maintains the central computationally designed hotspot interaction and preserves the character of many peripheral interactions. This work demon- strates that high-affinity protein interfaces can be created by designing complementary interaction surfaces on two noninteracting partners and under- scores remaining challenges.Chemistry and Chemical Biolog

A Novel Multi-Antigen Virally Vectored Vaccine against Mycobacterium avium Subspecies paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis causes systemic infection and chronic intestinal inflammation in many species including primates. Humans are exposed through milk and from sources of environmental contamination. Hitherto, the only vaccines available against Mycobacterium avium subspecies paratuberculosis have been limited to veterinary use and comprised attenuated or killed organisms. METHODS: We developed a vaccine comprising a fusion construct designated HAV, containing components of two secreted and two cell surface Mycobacterium avium subspecies paratuberculosis proteins. HAV was transformed into DNA, human Adenovirus 5 (Ad5) and Modified Vaccinia Ankara (MVA) delivery vectors. Full length expression of the predicted 95 kDa fusion protein was confirmed. PRINCIPAL FINDINGS: Vaccination of naïve and Mycobacterium avium subspecies paratuberculosis infected C57BL/6 mice using DNA-prime/MVA-boost or Ad5-prime/MVA-boost protocols was highly immunogenic resulting in significant IFN-gamma ELISPOT responses by splenocytes against recombinant vaccine antigens and a range of HAV specific peptides. This included strong recognition of a T-cell epitope GFAEINPIA located near the C-terminus of the fusion protein. Antibody responses to recombinant vaccine antigens and HAV specific peptides but not GFAEINPIA, also occurred. No immune recognition of vaccine antigens occurred in any sham vaccinated Mycobacterium avium subspecies paratuberculosis infected mice. Vaccination using either protocol significantly attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection measured by qPCR in spleen and liver and the Ad5-prime/MVA-boost protocol also conferred some protection against subsequent challenge. No adverse effects of vaccination occurred in any of the mice. CONCLUSIONS/SIGNIFICANCE: A range of modern veterinary and clinical vaccines for the treatment and prevention of disease caused by Mycobacterium avium subspecies paratuberculosis are needed. The present vaccine proved to be highly immunogenic without adverse effect in mice and both attenuated pre-existing Mycobacterium avium subspecies paratuberculosis infection and conferred protection against subsequent challenge. Further studies of the present vaccine in naturally infected animals and humans are indicated

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation