Shedding Light on the Off-Hours Coverage Gap in Radiology: Improving Turnaround Times and Critical Results Reporting

Objective: Devise a plan to optimize off-hours faculty and trainee staffing within the Department of Radiology Measure the magnitude of patient safety gains in terms of report turnaround times (TAT) and critical results communication times (CRC)https://jdc.jefferson.edu/patientsafetyposters/1044/thumbnail.jp

Increasing Ultrasound-Guided Thyroid Biopsy Yield

Objectives: Conduct Plan-Do-Study-Act (PDSA) performance improvement project to improve thyroid biopsy yield Short Term\u3ereduce unsuccessful biopsies by 50% Long-Term\u3eeliminate unsuccessful biopsieshttps://jdc.jefferson.edu/patientsafetyposters/1064/thumbnail.jp

A new modelling approach of evaluating preventive and reactive strategies for mitigating supply chain risks

Supply chains are becoming more complex and vulnerable due to globalization and interdependency between different risks. Existing studies have focused on identifying different preventive and reactive strategies for mitigating supply chain risks and advocating the need for adopting specific strategy under a particular situation. However, current research has not addressed the issue of evaluating an optimal mix of preventive and reactive strategies taking into account their relative costs and benefits within the supply network setting of interconnected firms and organizations. We propose a new modelling approach of evaluating different combinations of such strategies using Bayesian belief networks. This technique helps in determining an optimal solution on the basis of maximum improvement in the network expected loss. We have demonstrated our approach through a simulation study and discussed practical and managerial implications

Adaptive Lévy processes and area-restricted search in human foraging

A considerable amount of research has claimed that animals’ foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods–comparing alternative distributions using maximum likelihood methods–showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments–where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources–as both patched and dispersed conditions led to similar Lévy-like movement distributions

Gravitational collapse and thermalization in the hard wall model

We study a simple example of holographic thermalization in a confining field theory: the homogeneous injection of energy in the hard wall model. Working in an amplitude expansion, we find black brane formation for sufficiently fast energy injection and a scattering wave solution for sufficiently slow injection. We comment on our expectations for more sophisticated holographic QCD models.Comment: 33 pages, 5 figure

Predicting Phenotypic Diversity and the Underlying Quantitative Molecular Transitions

During development, signaling networks control the formation of multicellular patterns. To what extent quantitative fluctuations in these complex networks may affect multicellular phenotype remains unclear. Here, we describe a computational approach to predict and analyze the phenotypic diversity that is accessible to a developmental signaling network. Applying this framework to vulval development in C. elegans, we demonstrate that quantitative changes in the regulatory network can render ~500 multicellular phenotypes. This phenotypic capacity is an order-of-magnitude below the theoretical upper limit for this system but yet is large enough to demonstrate that the system is not restricted to a select few outcomes. Using metrics to gauge the robustness of these phenotypes to parameter perturbations, we identify a select subset of novel phenotypes that are the most promising for experimental validation. In addition, our model calculations provide a layout of these phenotypes in network parameter space. Analyzing this landscape of multicellular phenotypes yielded two significant insights. First, we show that experimentally well-established mutant phenotypes may be rendered using non-canonical network perturbations. Second, we show that the predicted multicellular patterns include not only those observed in C. elegans, but also those occurring exclusively in other species of the Caenorhabditis genus. This result demonstrates that quantitative diversification of a common regulatory network is indeed demonstrably sufficient to generate the phenotypic differences observed across three major species within the Caenorhabditis genus. Using our computational framework, we systematically identify the quantitative changes that may have occurred in the regulatory network during the evolution of these species. Our model predictions show that significant phenotypic diversity may be sampled through quantitative variations in the regulatory network without overhauling the core network architecture. Furthermore, by comparing the predicted landscape of phenotypes to multicellular patterns that have been experimentally observed across multiple species, we systematically trace the quantitative regulatory changes that may have occurred during the evolution of the Caenorhabditis genus

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure

Is TIMP-1 immunoreactivity alone or in combination with other markers a predictor of benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial?

INTRODUCTION: Predictive cancer biomarkers to guide the right treatment to the right patient at the right time are strongly needed. The purpose of the present study was to validate prior results that tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or in combination with either HER2 or TOP2A copy number can be used to predict benefit from epirubicin (E) containing chemotherapy compared with cyclophosphamide, methotrexate and fluorouracil (CMF) treatment. METHODS: For the purpose of this study, formalin fixed paraffin embedded tumor tissue from women recruited into the BR9601 clinical trial, which randomized patients to E-CMF versus CMF, were analyzed for TIMP-1 immunoreactivity. Using previously collected data for HER2 amplification and TOP2A gene aberrations, we defined patients as "anthracycline non-responsive", that is, 2T (TIMP-1 immunoreactive and TOP2A normal) and HT (TIMP-1 immunoreactive and HER2 negative) and anthracycline responsive (all other cases). RESULTS: In total, 288 tumors were available for TIMP-1 analysis with (183/274) 66.8%, and (181/274) 66.0% being classed as 2T and HT responsive, respectively. TIMP-1 was neither associated with patient prognosis (relapse free survival or overall survival) nor with a differential effect of E-CMF and CMF. Also, TIMP-1 did not add to the predictive value of HER2, TOP2A gene aberrations, or to Ki67 immunoreactivity. CONCLUSION: This study could not confirm the predictive value of TIMP-1 immunoreactivity in patients randomized to receive E-CMF versus CMF as adjuvant treatment for primary breast cancer

A Rare Case of a Systemic Non-Langerhans Histiocytosis Presenting with Diabetes Insipidus and a Tentorial Mass

Introduction The histiocytoses are a group of clinically diverse diseases distinguished from one another based on the specific immunophenotype of the lesional cells, implying derivation from the same precursor cell. Langerhans cell histiocytoses (LCH) diseases stem from abnormal dendritic cell lineages, while the non-Langerhans cell histiocytoses (non-LCH) are usually derived from an abnormal monocyte/macrophage cell line.1 Non-LCH with central nervous system (CNS) involvement is predictive of poor outcome. Histopathology is used to make a diagnosis of non-LCH. Immunohistochemistry and the clinical setting are used to differentiate between the various subtypes of non-LCH.1 The non-LCH can be divided into cutaneous non-LCH, cutaneous with a major systemic component, and systemic non-LCH.1 Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are systemic non-LCH diseases. First described in 1930, ECD is characterized by xanthogranulomatous accumulations. The extent of infiltration is heterogeneous and can include skin, bones, lungs, kidneys, and the CNS. Approximately 500 cases have been reported so far.2 The majority of ECD patients harbor an activating mutation of the proto-oncogene BRAF, namely BRAF-V600E.3 Recent studies indicate CNS involvement as a predictor of highest mortality among ECD patients.4 First described in 1969, RDD is characterized by accumulation of histiocytes exhibiting emperipolesis in lymph nodes, in the head and neck or in extranodal sites. Extranodal sites include the CNS, skin, soft tissue and gastrointestinal tract. The clinical presentation is typically painless cervical lymphadenopathy with leukocytosis and a fever.5 The etiology of RDD is unknown.6 RDD with CNS involvement is rare and approximately 210 cases have been reported. CNS involvement typically lacks extracranial lymphadenopathy and resembles meningioma radiologically and clinically. 1 Select cases have demonstrated a combined presentation of ECD and RDD.2 In this report we describe a rare case presenting with headache and with clinically and pathologically overlapping features of RDD and ECD. We describe treatment and complications and review the existing literature regarding diagnosis and treatment for these rare conditions

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al