Marshall University Music Department Presents a Faculty Recital, The Romantic Flute, Wendell Dobbs

https://mds.marshall.edu/music_perf/1196/thumbnail.jp

Marshall University School of Music and Theatre presents Faculty Recital Wendell Dobbs, flute and guest artist John Ingram, piano and Ezgi Karakus, violoncello

https://mds.marshall.edu/music_perf/1187/thumbnail.jp

Marshall University Music Department Presents a Faculty Recital, Wendell Dobbs, flute

https://mds.marshall.edu/music_perf/1197/thumbnail.jp

Tracking Cyber Adversaries with Adaptive Indicators of Compromise

A forensics investigation after a breach often uncovers network and host indicators of compromise (IOCs) that can be deployed to sensors to allow early detection of the adversary in the future. Over time, the adversary will change tactics, techniques, and procedures (TTPs), which will also change the data generated. If the IOCs are not kept up-to-date with the adversary's new TTPs, the adversary will no longer be detected once all of the IOCs become invalid. Tracking the Known (TTK) is the problem of keeping IOCs, in this case regular expressions (regexes), up-to-date with a dynamic adversary. Our framework solves the TTK problem in an automated, cyclic fashion to bracket a previously discovered adversary. This tracking is accomplished through a data-driven approach of self-adapting a given model based on its own detection capabilities. In our initial experiments, we found that the true positive rate (TPR) of the adaptive solution degrades much less significantly over time than the naive solution, suggesting that self-updating the model allows the continued detection of positives (i.e., adversaries). The cost for this performance is in the false positive rate (FPR), which increases over time for the adaptive solution, but remains constant for the naive solution. However, the difference in overall detection performance, as measured by the area under the curve (AUC), between the two methods is negligible. This result suggests that self-updating the model over time should be done in practice to continue to detect known, evolving adversaries.Comment: This was presented at the 4th Annual Conf. on Computational Science & Computational Intelligence (CSCI'17) held Dec 14-16, 2017 in Las Vegas, Nevada, US

923-3 Fluosol Reduces Myocardial Reperfusion Injury by Prolonged Suppression of Neutrophils by its Detergent Component (RheothRx) and not by Enhancing O2Delivery

Fluosol, a complex mixture of O2carrying perfluorocarbons (PFCs) emulsified by the detergent pluronic F-68 and a variety of lipids, significantly reduces myocardial reperfusion injury (RI) in animals and humans as shown in some initial clinical trials. Potential mechanisms for Fluosol include enhanced O2delivery to the reperfused tissue and modulation of various neutrophil (PMNs) functions. Recent studies in dogs and man demonstrate the same beneficial effect for treatment of Rl with the detergent component alone, RheothRx, which is currently undergoing clinical trials. We have shown that the effect of Fluosol on PMNs is related to this detergent. However, prolonged infusion (48 hrs) of detergent is required to reduce Rl to the same extent as Fluosol given over only 1 hr. Possible mechanisms for the beneficial effects of Fluosol (O2delivery vs effects on PMNs) were investigated in a model of regional ischemia utilizing rabbits undergoing 30mins of circumflex occlusion and 48 hrs of reperfusion. Infarct size (area of necrosis, AN) was determined histologically and expressed as percent of risk region (area at risk, AR). Animals received Fluosol (30cc/kg) with or without O2or saline over the first 60mins of reperfusion. AR was similar in all groups. (Mean±SEM of AN/AR (%), n=11 for all groups). The treatment with Fluosol with or without O2(44±3 and 40;±3, respectively) was significantly (p<0.05) reduced compared to control (63±4). Another group received F-I08, a larger size pluronic detergent found to be 2.5-fold more potent in suppressing PMN function in vitrocompared to F-68, during the first 3 hrs of reperfusion. This treatment did not alter the infarct size (63±5). RheothRx was found to form 4 nm micelles in solution whereas Fluosol formed particles approximately 100 times larger. Similar sized particles were formed by substituting the perfluorocarbons with mineral oil. The in vitroactivity of this pluronic/mineral oil micelle on PMN function was similar to Fluosol. Infusion of these larger oil micelles was tolerated by rabbits and used in further infarct studies.ConclusionsThese studies suggest that (1) reduction of RI by Fluosol is not due to enhanced O2delivery by the PFCs to reperfused myocardium and (2) since the Fluosol emulsion markedly reduces the clearance of the detergent F-68 (t½: Fluosol ≅ 8 hrs vs RheothRx ≅ 1.5 hrs). prolonged PMN suppression rather than potency of suppression is the mechanism whereby Fluosol ameliorates RI. Fluosol's clinical efficacy may be enhanced by prolonging its infusion to ensure an adequate blood level to suppress PMN function beyond the time of reperfusion injury. RheothRx's clinical usefulness may be facilitated by decreasing its renal clearance by delivering larger micelles of the detergent in order to produce prolonged PMN suppression with a shorter infusion time

Nerve injury induces robust allodynia and ectopic discharges in Na(v)1.3 null mutant mice

Changes in sodium channel activity and neuronal hyperexcitability contribute to neuropathic pain, a major clinical problem. There is strong evidence that the re-expression of the embryonic voltage-gated sodium channel subunit Na(v)1.3 underlies neuronal hyperexcitability and neuropathic pain. Here we show that acute and inflammatory pain behaviour is unchanged in global Na(v)1.3 mutant mice. Surprisingly, neuropathic pain also developed normally in the Na(v)1.3 mutant mouse. To rule out any genetic compensation mechanisms that may have masked the phenotype, we investigated neuropathic pain in two conditional Na(v)1.3 mutant mouse lines. We used Na(v)1.8-Cre mice to delete Nav1.3 in nociceptors at E14 and NFH-Cre mice to delete Na(v)1.3 throughout the nervous system postnatally. Again normal levels of neuropathic pain developed after nerve injury in both lines. Furthermore, ectopic discharges from damaged nerves were unaffected by the absence of Na(v)1.3 in global knock-out mice. Our data demonstrate that Na(v)1.3 is neither necessary nor sufficient for the development of nerve-injury related pain

Temporal Trends in Cardiovascular Hospital Discharges Following a Mass Chlorine Exposure Event in Graniteville, South Carolina

Background: On January 6, 2005, a train derailed in Graniteville, South Carolina, releasing nearly 60,000 kg of toxic chlorine gas. The disaster left nine people dead and was responsible for hundreds of hospitalizations and outpatient visits in the subsequent weeks. While chlorine gas primarily affects the respiratory tract, a growing body of evidence suggests that acute exposure may also cause vascular injury and cardiac toxicity. Here, we describe the incidence of cardiovascular hospitalizations among residents of the zip codes most affected by the chlorine gas plume, and compare the incidence of cardiovascular discharges in the years leading up to the event (2000–2004) to the incidence in the years following the event (2005–2014). Methods: De-identified hospital discharge information was collected from the South Carolina Revenue and Fiscal Affairs Office for individuals residing in the selected zip codes for the years 2000 to 2014. A quasi-experimental study design was utilized with a population-level interrupted time series model to examine hospital discharge rates for Graniteville-area residents for three cardiovascular diagnoses: hypertension (HTN), acute myocardial infarction (AMI), and coronary heart disease (CHD). We used linear regression with autoregressive error correction to compare slopes for pre- and post-spill time periods. Data from the 2000 and 2010 censuses were used to calculate rates and to provide information on potential demographic shifts over the course of the study. Results: A significant increase in hypertension-related hospital discharge rates was observed for the years following the Graniteville chlorine spill (slope 8.2, p \u3c 0.001). Concurrent changes to CHD and AMI hospital discharge rates were in the opposite direction (slopes −3.2 and −0.3, p \u3c 0.01 and 0.14, respectively). Importantly, the observed trend cannot be attributed to an aging population. Conclusions: An unusual increase in hypertension-related hospital discharge rates in the area affected by the Graniteville chlorine spill contrasts with national and state-level trends. A number of factors related to the spill may be contributing the observation: disaster-induced hypertension, healthcare services access issues, and, possibly, chlorine-induced susceptibility to vascular pathologies. Due to the limitations of our data, we cannot determine whether the individuals who visited the hospital were the ones exposed to chlorine gas, however, the finding warrants additional research. Future studies are needed to determine the etiology of the increase and whether individuals exposed to chlorine are at a heightened risk for hypertensive heart disease

Pharmacologic perturbation of neutrophils by Fluosol results in a sustained reduction in infarct size in the canine model of reperfusion

AbstractPrevious studies have demonstrated that intravenous administration of large doses of Fluosol, a perfluorochemical preparation, reduced infarct size 24 h after reperfusion, an effect that was associated with reduced neutrophil infiltration. The effect of a clinically tolerable dose of Fluosol on infarct size after a prolonged period of reperfusion and its mechanism of action on neutrophils remain unknown.Twenty-one anesthetized closed chest dogs were subjected to 90 min of proximal left anterior descending coronary artery occlusion and 72 h of reperfusion. An additional five dogs that did not undergo regional myocardial ischemia were utilized to explore the mechanism of action of Fluosol on neutrophil function. In the infarct study, animals were randomized to receive either intravenous Fluosol (n = 10) or an equivalent volume of Ringer's lactate solution (control; n = 11) at 15 ml/kg body weight during the last 30 min of occlusion and for the 1st 30 min of reperfusionFluosol significantly reduced infarct size when expressed as percent area at risk 72 h aller reperfusion (13.7 ± 2.7% vs. 38.3 ± 4.5%, respectively, p < 0.001). This reduction was associated with significant improvement in regional wall motion (18.4 ± 2.3% vs. 5.5 ± 2%, p < 0.001). Endocardial blood fiow in the ischemic bed was significantly higher 3 h after reperfusion in Fluosol-treated dogs (0.63 ± 0.08 vs. 0.34 ± 0.07 ml/min per g, p = 0.01). Reduced capillary plugging by neutrophils with relative preservation of endothelial cell structure was observed in Fluosol-treated animals. Infusion of Fluosol produced a marked transient decrease in peripheral neutrophil and platelet counts in both ischemic and nonischemic dogs and was associated with a significant reduction in total hemolytic complement levels. Studies of neutrophil function ex vivo revealed a reduction in chemotaxis and lysozyme degranulation after infusion of Fluosol. In vitro experiments showed that Fluosol produced a rapid and sustained activation of neutrophils determined by superoxide anion production.These data demonstrate that low dose intravenous Fluosol produces a sustained reduction in infarct size in the canine model. The beneficial effect may be in part due to the suppression of various neutrophil functions in the reperfused myocardium subsequent to peripheral activation by Fluosol. Such interventions may offer a novel therapy to enhance myocardial salvage by sequestration of circulating neutrophils during the critical early reperfusion period

Nicotine enemas for active Crohn's colitis: an open pilot study

BACKGROUND: Smoking has a detrimental effect in Crohn's disease (CD), but this may be due to factors in smoking other than nicotine. Given that transdermal nicotine benefits ulcerative colitis (UC), and there is a considerable overlap in the treatment of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn's colitis. AIMS: To assess the efficacy and safety of nicotine enemas in active Crohn's colitis. Patients. Thirteen patients with active rectosigmoid CD; 3 patients were excluded because they received antibiotics. METHODS: Subjects were given 6 mg nicotine enemas, each day for 4 weeks, in an open pilot study. At the beginning and end of the trial, a Crohn's disease activity index (CDAI) score was calculated, sigmoidoscopy was performed, and haematological inflammatory markers measured. RESULTS: Mean CDAI decreased from 202 to 153-the score was reduced in 6 patients, unchanged in 3, and increased in one. Frequency of bowel movements decreased in 8 patients and the sigmoidoscopy grade was reduced in 7. Mean C-reactive protein decreased from 22.0 to 12.3 mg/L. There were no withdrawals due to adverse events. CONCLUSIONS: In this relatively small study of patients with active Crohn's colitis, 6 mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe

Towards Global Consensus on Core Outcomes for Hidradenitis Suppurativa Research: An Update from the HISTORIC Consensus Meetings I and II

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings