Supplement 75 Personal non-commercial use only

In our review, the neurobiology of fibromyalgia syndrome (FM) is discussed in the context of what is known about neural mechanisms of nociception and central mechanisms of persistent pain conditions. We present a general view of mechanisms of nociception, central temporal summation, and central sensitization, and as well compare sensory tests that examine these mechanisms in normal pain-free human subjects. We then show how amplification and other alterations of these mechanisms apply to patients with FM. NOCICEPTION, ACUTE PAIN, PERSISTENT PAIN Pain is usually related to impulse input that originates from nociceptors in somatic or visceral tissues. The impulses travel in myelinated (A-delta) and unmyelinated (C) peripheral nerves, which first project to dorsal horn nociceptor-specific neurons and wide dynamic range neurons, before these second-order neurons transmit nociceptive information to brain regions involved in pain, including the thalamus, anterior cingulate cortex (ACC), anterior insular cortex, and somatosensory cortex. Nociceptor-specific neurons are so termed because they respond predominantly to specific stimulus intensities that either cause tissue damage or would cause tissue damage if maintained over time. Wide dynamic range neurons respond differentially over a very broad range of stimulus intensities, from very gentle touch to stimuli that cause tissue damage. Brain regions that receive input from nociceptor-specific and wide dynamic range neurons are related to sensory-discriminative, cognitive-evaluative, and affective processing of somatosensory nociceptive input. The activation of these brain regions is associated with pain experience and subsequent reflex and protective behaviors. Importantly, the same brain areas are likely to be involved in both acute and persistent pain conditions. Reflex and reflective behaviors that are aimed at eliminating acute pain are not operative in chronic pain syndromes including FM. Patients with FM, like most chronic pain sufferers, do not display pain behaviors usually seen in acute pain, including increased perspiration, hypertension, hyperthermia, and tachycardia. FM patients have abnormal pain thresholds (hyperalgesia) and report amplified pain with a variety of nociceptive stimuli, including pressure, heat, and cold. Because no consistent tissue abnormalities have been detected in FM, central pain processing abnormalities need to be considered as important contributors to the heightened pain sensitivity of these patients. In our review, we also discuss recent evidence that the clinical pain of patients with FM is related to abnormal central temporal summation of pain, or "windup," evoked by repetitive stimulation of peripheral nociceptive afferent neurons. Sensory testing experiments can be used to demonstrate that abnormal windup of FM patients is related to central nervous system (CNS) mechanisms of central sensitization and persistent pain. As background to the central sensory abnormalities of FM patients, we discuss the normal role of nociceptors and the central consequences of repetitive stimulation of nociceptive neurons, and also describe how these mechanisms appear to be distorted in FM patients. DONALD D. PRICE and ROLAND STAUD ABSTRACT. Accumulating evidence suggests that fibromyalgia syndrome (FM) pain is maintained by tonic impulse input from deep tissues, such as muscle and joints, in combination with central sensitization mechanisms. This nociceptive input may originate in peripheral tissues (trauma and infection) resulting in hyperalgesia/allodynia and/or central sensitization. Evidence for abnormal sensitization mechanisms in FM includes enhanced temporal summation of delayed pain in response to repeated heat taps and repeated muscle taps, as well as prolonged and enhanced painful after-sensations in FM patients but not control subjects. Moreover, magnitudes of enhanced after-sensations are predictive of FM patients' ongoing clinical pain. Such alterations of relevant pain mechanisms may lead to longterm neuroplastic changes that exceed the antinociceptive capabilities of affected individuals, resulting in ever-increasing pain sensitivity and dysfunction. Future research needs to address the important role of abnormal nociception and/or antinociception for chronic pain in FM. (J Rheumatol 2005;32 Suppl 75:22-28

Two-transcript gene expression classifiers in the diagnosis and prognosis of human diseases.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Identification of molecular classifiers from genome-wide gene expression analysis is an important practice for the investigation of biological systems in the post-genomic era--and one with great potential for near-term clinical impact. The 'Top-Scoring Pair' (TSP) classification method identifies pairs of genes whose relative expression correlates strongly with phenotype. In this study, we sought to assess the effectiveness of the TSP approach in the identification of diagnostic classifiers for a number of human diseases including bacterial and viral infection, cardiomyopathy, diabetes, Crohn's disease, and transformed ulcerative colitis. We examined transcriptional profiles from both solid tissues and blood-borne leukocytes. RESULTS: The algorithm identified multiple predictive gene pairs for each phenotype, with cross-validation accuracy ranging from 70 to nearly 100 percent, and high sensitivity and specificity observed in most classification tasks. Performance compared favourably with that of pre-existing transcription-based classifiers, and in some cases was comparable to the accuracy of current clinical diagnostic procedures. Several diseases of solid tissues could be reliably diagnosed through classifiers based on the blood-borne leukocyte transcriptome. The TSP classifier thus represents a simple yet robust method to differentiate between diverse phenotypic states based on gene expression profiles. CONCLUSION: Two-transcript classifiers have the potential to reliably classify diverse human diseases, through analysis of both local diseased tissue and the immunological response assayed through blood-borne leukocytes. The experimental simplicity of this method results in measurements that can be easily translated to clinical practice

Modeling of airblast propagation through an enclosed structure

The ability to model explosively formed shock waves propagating through a structure is of particular interest to engineers concerned with structural responses to blasts. Accurate peak pressure and impulse values are critical to understanding blast loads on structures and predicting the resulting structural behavior, but are sometimes difficult to determine analytically. Experiments are necessary to determine the true structural response, but the experiments alone may not identify all the details involved in an explosive event that may be important for design purposes. When tied to experiments, computational modeling of explosive events can be an invaluable tool for an engineer. The most difficult part of modeling structural response to a close-in explosive event is capturing the fluid-structure interaction of the resulting flow of the detonation products. In this paper, we compare the results of numerical simulations of an explosive experimental event in an enclosed structure, or “attic space”, using two different computational codes, CTH and DYSMAS. Both adequately model the explosive event in attic space when compared to the experiment. We also compare the two codes’ ability to produce explosive-induced pressure-time histories in the free field. The advantage of using a coupled code like DYSMAS is that structural response can be more accurately captured than by using a hydrocode like CTH alone. The differences between the two codes’ ability to model the event are analyzed and described as well as a general description of the shock wave propagation in the attic space

The Relationship between Marital Status and Psychological Resilience in Chronic Pain

We examined the relationship between marital status and a 2-stage model of pain-related effect, consisting of pain unpleasantness and suffering. We studied 1914 chronic pain patients using multivariate analysis of covariance (MANCOVA) to clarify whether marital status was a determinant factor in the emotional or ideational suffering associated with chronic pain after controlling for pain sensation intensity, age, and ethnicity. Marital status was unrelated to immediate unpleasantness (). We found a strong association with emotional suffering () but not with negative illness beliefs (). Interestingly, widowed subjects experienced significantly less frustration, fear, and anger than all other groups (married, divorced, separated, or single). A final MANCOVA including sex as a covariate revealed that the emotional response to pain was the same for both widow and widower. Only those individuals whose spouse died experienced less emotional turmoil in the face of a condition threatening their lifestyle. These data suggest that after experiencing the death of a spouse, an individual may derive some “emotional inoculation” against future lifestyle threat

Identifying Personalized Metabolic Signatures in Breast Cancer.

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism, and reactive oxygen species (ROS) detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach

Ursinus College Alumni Journal, March 1959

President\u27s page • Radioactivity detection in civil defense course • From the Dean\u27s office • University of the Air • From the Office of Admissions • The library • Industrial gift trend is up • G. E. corporate alumnus program • duPont renews $4000 grant •$2000 Esso education foundation grant • Regional groups plan meetings • Philadelphia alumni install 1959 officers • South Jersey alumni plan supper party • New York alumni plan spring dinner • Washington D.C. alumni plan annual dinner • York alumni elect new officers for 1959 • Ursinus Woman\u27s Club plans spring card party • Alumni Day, Saturday, June 6 • Donald Schultz, \u2750 wilderness medic • 1901 schoolgirl driver Rhea Duryea Johnson \u2708 • International educator, scholar and editor, Jacob Foose \u2732 • January 1959 mid year report of the Loyalty Fund Campaign • Mid campaign report • Alumni elections: Watch for your ballot in April • Requests • Football 1958 • Wrestling 1959 • Alumnae hockey 1958 • Alumnae finish undefeated for second year • Proposed amended constitution • News about ourselves • Weddings • Births • Necrology • Chase Manhattan Bank employee gift matching • Saturday, June 6, 1959: Alumni festivalhttps://digitalcommons.ursinus.edu/alumnijournal/1067/thumbnail.jp

Ursinus College Alumni Journal, July 1959

President\u27s page • D. L. Helfferich received LL.D. • 172 graduate at 90th commencement • Dr. Paul Miller commencement speaker • Dr. Sieb Pancoast resigns as Ursinus Dean of Men • Admissions office expects 250 freshmen in \u2763 class • Mr. Wilcox received doctorate from Penn • Rev. Jerry William Trexler speaker at Baccalaureate • Dean Camilla B. Stahr retires - Dean of Women since 1938 • Ralph Strassburger leaves half of his estate to charity • Ruth H. Rothenberger, \u2736 - new Dean of Women • Ursinus College has outstanding Loyalty Fund record • Rev. Richard Schellhase \u2745 - new Alumni Exec. Sec. • Festive Alumni Day brings large crowd • Paul I. Guest reelected alumni president • New York regional alumni elect new officers • The Collegeville Summer Assembly • May Day • Overseas job opportunities • Ursinus Women\u27s Club activities • Class \u2759 elects permanent officers • Old Timer\u27s Day Saturday November 7 • College teachers recognized • Baseball 1959 • 1959 track season • Ursinus girls complete undefeated spring • Lacrosse • National honors for Crosley • Softball • Tennis • News about ourselves • Weddings • Birthshttps://digitalcommons.ursinus.edu/alumnijournal/1064/thumbnail.jp

Modeling 5 Years of Subglacial Lake Activity in the MacAyeal Ice Stream (Antarctica) Catchment Through Assimilation of ICESat Laser Altimetry

Subglacial lakes beneath Antarctica’s fast-moving ice streams are known to undergo ~1km3 volume changes on annual timescales. Focusing on the MacAyeal Ice Stream (MacIS) lake system, we create a simple model for the response of subglacial water distribution to lake discharge events through assimilation of lake volume changes estimated from Ice, Cloud and land Elevation Satellite (ICESat) laser altimetry. We construct a steady-state water transport model in which known subglacial lakes are treated as either sinks or sources depending on the ICESat-derived filling or drainingrates. The modeled volume change rates of five large subglacial lakes in the downstream portion of MacIS are shown to be consistent with observed filling rates if the dynamics of all upstream lakes are considered. However, the variable filling rate of the northernmost lake suggests the presence of an undetected lake of similar size upstream. Overall, we show that, for this fast-flowing ice stream, most subglacial lakes receive \u3e90% of their water from distant distributed sources throughout the catchment, and we confirm that water is transported from regions of net basal melt to regions of net basal freezing. Our study provides a geophysically based means of validating subglacial water models in Antarctica and is a potential way to parameterize subglacial lake discharge events in large-scale ice-sheet models where adequate data are available

Ursinus College Alumni Journal, November 1958

President\u27s page • President\u27s inaugural address • Dr. D. L. Helfferich inaugurated President of Ursinus College • Ursinus College opens with 839 • The Evening School • New preceptress at 944 • Library • The Messiah • The faculty cornered • The cornered faculty turns • Tracking the Alder Flycatcher • Old Timers\u27 Day almost rained out • Face lifting on campus • Ursinus Woman\u27s Club plans holiday luncheon • Ursinus Forum, 1958-59 • A challenge for alumni giving • Fall play Joan of Lorraine • Annual alumni Schoolmen\u27s Week luncheon • Five years of alumni sponsorship completed: 1958 Loyalty Fund report • Workshop in economic education • Paul S. Craigie, class Chairman of the year • Honor roll by classes • Contributors for the 1958 Loyalty Fund campaign • Varsity football • Varsity and J.V. basketball schedule 1958-59 • Alumnae continue winning ways • Varsity wrestling schedule 1959 • Two new assistant football coaches • Varsity has strong potential • Ursinus appoints a new wrestling coach • News about ourselves • Weddings • Births • Necrology • Two Spanish majors receive honorshttps://digitalcommons.ursinus.edu/alumnijournal/1063/thumbnail.jp