Delayed Matching to Sample: Reinforcement has Opposite Effects on Resistance to Change in Two Related Procedures

The effects of reinforcement on delayed matching to sample (DMTS) have been studied in two within-subjects procedures. In one, reinforcer magnitudes or probabilities vary from trial to trial and are signaled within trials (designated signaled DMTS trials). In the other, reinforcer probabilities are consistent for a series of trials produced by responding on variable-interval (VI) schedules within multiple-schedule components (designated multiple VI DMTS). In both procedures, forgetting functions in rich trials or components are higher than and roughly parallel to those in lean trials or components. However, during disruption, accuracy has been found to decrease more in rich than in lean signaled DMTS trials and, conversely, to decrease more in lean than in rich multiple VI DMTS components. In the present study, we compared these procedures in two groups of pigeons. In baseline, forgetting functions in rich trials or components were higher than and roughly parallel to those in lean trials or components, and were similar between the procedures. During disruption by prefeeding or extinction, accuracy decreased more in rich signaled DMTS trials, whereas accuracy decreased more in lean multiple VI DMTS components. These results replicate earlier studies and are predicted by a model of DMTS from Nevin, Davison, Odum, and Shahan (2007)

Detecting thermal discrepancies in vessel walls

An infrared, heat-sensing catheter particularly useful for identifying potentially fatal arterial plaques in patients with disease of the coronary or other arteries and its use are detailed. In one embodiment, an infrared fiberoptic system (with or without ultrasound) is employed at the tip of the catheter to locate inflamed, heat-producing, atherosclerotic plaque, which is at greater risk for rupture, fissure, or ulceration, and consequent thrombosis and occlusion of the artery. In another embodiment, a catheter with an infrared detector (with or without ultrasound) employed at its tip will likewise locate inflamed heat-producing atherosclerotic plaque. The devices and methods of the invention may be used to detect abscesses, infection, and cancerous regions by the heat such regions differentially display over the ambient temperature of immediately adjacent tissues. The methods and devices of the invention may also be used to detect regions of cooler than ambient tissue in a vessel or organ which indicate cell death, thrombosis, cell death, hemorrhage, calcium or cholesterol accumulations, or foreign materials

Tailoring Capture-Recapture Methods to Estimate Registry-Based Case Counts Based on Error-Prone Diagnostic Signals

Surveillance research is of great importance for effective and efficient epidemiological monitoring of case counts and disease prevalence. Taking specific motivation from ongoing efforts to identify recurrent cases based on the Georgia Cancer Registry, we extend recently proposed "anchor stream" sampling design and estimation methodology. Our approach offers a more efficient and defensible alternative to traditional capture-recapture (CRC) methods by leveraging a relatively small random sample of participants whose recurrence status is obtained through a principled application of medical records abstraction. This sample is combined with one or more existing signaling data streams, which may yield data based on arbitrarily non-representative subsets of the full registry population. The key extension developed here accounts for the common problem of false positive or negative diagnostic signals from the existing data stream(s). In particular, we show that the design only requires documentation of positive signals in these non-anchor surveillance streams, and permits valid estimation of the true case count based on an estimable positive predictive value (PPV) parameter. We borrow ideas from the multiple imputation paradigm to provide accompanying standard errors, and develop an adapted Bayesian credible interval approach that yields favorable frequentist coverage properties. We demonstrate the benefits of the proposed methods through simulation studies, and provide a data example targeting estimation of the breast cancer recurrence case count among Metro Atlanta area patients from the Georgia Cancer Registry-based Cancer Recurrence Information and Surveillance Program (CRISP) database

Bilateral pyosalpinx in a peripubescent female with Hirschsprung's disease: a case report

This is a case report of bilateral pyosalpinx in a peripubescent female with a history of Hirschsprung's disease. Bilateral pyosalpinx is a rare condition in non-sexually active females. The presence of this disease in a patient with a history of Hirschsprung's disease is concerning for an association of the two processes

Tyrosine Phosphorylation of Tau by the Src Family Kinases Lck and Fyn

<p>Abstract</p> <p>Background</p> <p>Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.</p> <p>Results</p> <p>In this study we show that Lck is a tau kinase. <it>In vitro</it>, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.</p> <p>Conclusions</p> <p>Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.</p

Electron Beam-Treated Enzymatically Mineralized Gelatin Hydrogels for Bone Tissue Engineering

Biological hydrogels are highly promising materials for bone tissue engineering (BTE) due to their high biocompatibility and biomimetic characteristics. However, for advanced and customized BTE, precise tools for material stabilization and tuning material properties are desired while optimal mineralisation must be ensured. Therefore, reagent-free crosslinking techniques such as high energy electron beam treatment promise effective material modifications without formation of cytotoxic by-products. In the case of the hydrogel gelatin, electron beam crosslinking further induces thermal stability enabling biomedical application at physiological temperatures. In the case of enzymatic mineralisation, induced by Alkaline Phosphatase (ALP) and mediated by Calcium Glycerophosphate (CaGP), it is necessary to investigate if electron beam treatment before mineralisation has an influence on the enzymatic activity and thus affects the mineralisation process. The presented study investigates electron beam-treated gelatin hydrogels with previously incorporated ALP and successive mineralisation via incubation in a medium containing CaGP. It could be shown that electron beam treatment optimally maintains enzymatic activity of ALP which allows mineralisation. Furthermore, the precise tuning of material properties such as increasing compressive modulus is possible. This study characterizes the mineralised hydrogels in terms of mineral formation and demonstrates the formation of CaP in dependence of ALP concentration and electron dose. Furthermore, investigations of uniaxial compression stability indicate increased compression moduli for mineralised electron beam-treated gelatin hydrogels. In summary, electron beam-treated mineralized gelatin hydrogels reveal good cytocompatibility for MG-63 osteoblast like cells indicating a high potential for BTE applications

The Grizzly, April 2, 1982

PA Special Olympics This Weekend • Room Selection Continues • Student Publications Staffs Chosen • Parents Day Plans Offer Variety of Talents • USGA Notes • Letters to the Editor • Dean of College Accepting Nominations for Lindback Award • Class Elections Next Week • News Briefs: Hooters Concert Tickets Now Available; Friends of Library Book Sale; Senior Women Invited to Parents Day Reception; Photography in Space Topic of Final Forum; Scholarship Offered for Students of Hellenic Descent • Food Day: A Chance to Share the Wealth • New Library Survey Conducted • Alumna Presents DuPont Grant • Students Direct Comedy Series • Duet Takes First in Talent Show • F&M Tops Track Team • W\u27s Tennis Drops Warm-up • Division 1 West Chester a Little Too Strong • MAC Champs Back • Harvard Slips by Lady Bears • Batsmen Split Twin Bill • Softball Team Takes Two Out of Threehttps://digitalcommons.ursinus.edu/grizzlynews/1077/thumbnail.jp

A phase 1 study evaluating rovalpituzumab tesirine in frontline treatment of patients with extensive-stage SCLC

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC. METHODS: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk × 2) overlapping with CE q21 × 4 (cohort 3; n = 14); and Rova-T maintenance (0.3 mg/kg, q6 wk × 2) after CE q21 × 4 (cohort 4; n = 3). RESULTS: A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with cohorts 1, 2, and 4 combined, cohort 3 had lower frequency of some Rova-T-related adverse events of special interest, such as pleural effusion (0 versus 33%), pericardial effusion (0 versus 17%), ascites (0 versus 8%), peripheral edema (36% versus 42%), generalized edema (0 versus 8%), pneumonia (7% versus 25%), and hypoalbuminemia (0 versus 17%). CONCLUSIONS: Lower Rova-T doses may be associated with lower incidence of some Rova-T-related adverse events of special interest. Rova-T 0.2 mg/kg plus CE (cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE

Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment

Background: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. Conclusions: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis