The Clarens web services architecture

Clarens is a uniquely flexible web services infrastructure providing a unified access protocol to a diverse set of functions useful to the HEP community. It uses the standard HTTP protocol combined with application layer, certificate based authentication to provide single sign-on to individuals, organizations and hosts, with fine-grained access control to services, files and virtual organization (VO) management. This contribution describes the server functionality, while client applications are described in a subsequent talk.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 6 pages, LaTeX, 4 figures, PSN MONT00

Clarens Client and Server Applications

Several applications have been implemented with access via the Clarens web service infrastructure, including virtual organization management, JetMET physics data analysis using relational databases, and Storage Resource Broker (SRB) access. This functionality is accessible transparently from Python scripts, the Root analysis framework and from Java applications and browser applets.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics (CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, LaTeX, no figures, PSN TUCT00

Inclusion of the glucocorticoid receptor in a hypothalamic pituitary adrenal axis model reveals bistability

BACKGROUND: The body's primary stress management system is the hypothalamic pituitary adrenal (HPA) axis. The HPA axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. RESULTS: We developed a structured model of the HPA axis that includes the glucocorticoid receptor (GR). This model incorporates nonlinear kinetics of pituitary GR synthesis. The nonlinear effect arises from the fact that GR homodimerizes after cortisol activation and induces its own synthesis in the pituitary. This homodimerization makes possible two stable steady states (low and high) and one unstable state of cortisol production resulting in bistability of the HPA axis. In this model, low GR concentration represents the normal steady state, and high GR concentration represents a dysregulated steady state. A short stress in the normal steady state produces a small perturbation in the GR concentration that quickly returns to normal levels. Long, repeated stress produces persistent and high GR concentration that does not return to baseline forcing the HPA axis to an alternate steady state. One consequence of increased steady state GR is reduced steady state cortisol, which has been observed in some stress related disorders such as Chronic Fatigue Syndrome (CFS). CONCLUSION: Inclusion of pituitary GR expression resulted in a biologically plausible model of HPA axis bistability and hypocortisolism. High GR concentration enhanced cortisol negative feedback on the hypothalamus and forced the HPA axis into an alternative, low cortisol state. This model can be used to explore mechanisms underlying disorders of the HPA axis

Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) is defined by self-reported symptoms. There are no diagnostic signs or laboratory markers, and the pathophysiology remains inchoate. In part, difficulties identifying and replicating biomarkers and elucidating the pathophysiology reflect the heterogeneous nature of the syndromic illness CFS. We conducted this analysis of people from defined metropolitan, urban, and rural populations to replicate our earlier empirical delineation of medically unexplained chronic fatigue and CFS into discrete endophenotypes. Both the earlier and current analyses utilized quantitative measures of functional impairment and symptoms as well as laboratory data. This study and the earlier one enrolled participants from defined populations and measured the internal milieu, which differentiates them from studies of clinic referrals that examine only clinical phenotypes.</p> <p>Methods</p> <p>This analysis evaluated 386 women identified in a population-based survey of chronic fatigue and unwellness in metropolitan, urban, and rural populations of the state of Georgia, USA. We used variables previously demonstrated to effectively delineate endophenotypes in an attempt to replicate identification of these endophenotypes. Latent class analyses were used to derive the classes, and these were compared and contrasted to those described in the previous study based in Wichita, Kansas.</p> <p>Results</p> <p>We identified five classes in the best fit analysis. Participants in Class 1 (25%) were polysymptomatic, with sleep problems and depressed mood. Class 2 (24%) was also polysymptomatic, with insomnia and depression, but participants were also obese with associated metabolic strain. Class 3 (20%) had more selective symptoms but was equally obese with metabolic strain. Class 4 (20%) and Class 5 (11%) consisted of nonfatigued, less symptomatic individuals, Class 4 being older and Class 5 younger. The classes were generally validated by independent variables. People with CFS fell equally into Classes 1 and 2. Similarities to the Wichita findings included the same four main defining variables of obesity, sleep problems, depression, and the multiplicity of symptoms. Four out of five classes were similar across both studies.</p> <p>Conclusion</p> <p>These data support the hypothesis that chronic medically unexplained fatigue is heterogeneous and can be delineated into discrete endophenotypes that can be replicated. The data do not support the current perception that CFS represents a unique homogeneous disease and suggests broader criteria may be more explanatory. This replication suggests that delineation of endophenotypes of CFS and associated ill health may be necessary in order to better understand etiology and provide more patient-focused treatments.</p

Dual-Wavelength Imaging of Tumor Progression by Activatable and Targeting Near-Infrared Fluorescent Probes in a Bioluminescent Breast Cancer Model

Bioluminescence imaging (BLI) has shown its appeal as a sensitive technique for in vivo whole body optical imaging. However, the development of injectable tumor-specific near-infrared fluorescent (NIRF) probes makes fluorescence imaging (FLI) a promising alternative to BLI in situations where BLI cannot be used or is unwanted (e.g., spontaneous transgenic tumor models, or syngeneic mice to study immune effects)

Systematic review of patient-reported outcome measures in clinical vestibular research

Objective: To identify the most commonly used patient-reported outcome (PRO) measures in clinical vestibular research, and to assess their test characteristics and applicability to the study of age-related vestibular loss in clinical trials.Data Sources: We performed a systematic review of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases from 1950 to August 13, 2013.Study Selection: PRO measures were defined as outcomes that capture the subjective experience of the patient (eg, symptoms, functional status, health perceptions, quality of life). Two independent reviewers selected studies that used PRO measures in clinical vestibular research. Disparities were resolved with consensus between the reviewers. Of 2260 articles initially found in the literature search, 255 full-text articles were retrieved for assessment. Of these, 104 met inclusion criteria for data collection.Data Extraction: PRO measures were identified by 2 independent reviewers. The 4 most commonly used PROs were evaluated for their applicability to the condition of age-related vestibular loss. Specifically, for these 4 PROs, data were collected pertaining to instrument test-retest reliability, item domains, and target population of the instrument.Data Synthesis: A total of 50 PRO instruments were identified. The 4 most frequently used PROs were the Dizziness Handicap Inventory, Activities-specific Balance Confidence scale, Vertigo Symptom Scale-short form, and visual analog scale. Of these 4 PROs, 3 were validated for use in patients with vestibular disease and 1 was validated in community-dwelling older individuals with balance impairments. Items across the 4 PROs were categorized into 3 domains based on the International Classification of Functioning, Disability and Health: activity, participation, and body functions and structures.Conclusions: None of the most commonly used PRO instruments were validated for use in community-dwelling older adults with age-related vestibular loss. Nevertheless, the 3 common domains of items identified across these 4 PRO instruments may be generalizable to older adults and provide a basis for developing a PRO instrument designed to evaluate the effectiveness of interventions targeted toward age-related vestibular loss. (C) 2015 by the American Congress of Rehabilitation Medicin