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Search Results: 1 - 10 of 208161 matches for " Scott P. Orr "
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Predicting post-trauma stress symptoms from pre-trauma psychophysiologic reactivity, personality traits and measures of psychopathology
Scott P Orr, Natasha B Lasko, Michael L Macklin, Suzanne L Pineles, Yuchiao Chang, Roger K Pitman
Biology of Mood & Anxiety Disorders , 2012, DOI: 10.1186/2045-5380-2-8
Abstract: Pre-trauma psychological, psychophysiological and personality variables were prospectively assessed for their predictive relationships with post-traumatic stress symptoms (PTSS). Police and firefighter trainees were tested at the start of their professional training (i.e., pre-trauma; n?=?211) and again several months after exposure to a potentially traumatic event (i.e., post-trauma, n?=?99). Pre-trauma assessments included diagnostic interviews, psychological and personality measures and two psychophysiological assessment procedures. The psychophysiological assessments measured psychophysiologic reactivity to loud tones and the acquisition and extinction of a conditioned fear response. Post-trauma assessment included a measure of psychophysiologic reactivity during recollection of the traumatic event using a script-driven imagery task.Logistic stepwise regression identified the combination of lower IQ, higher depression score and poorer extinction of forehead (corrugator) electromyogram responses as pre-trauma predictors of higher PTSS. The combination of lower IQ and increased skin conductance (SC) reactivity to loud tones were identified as pre-trauma predictors of higher post-trauma psychophysiologic reactivity during recollection of the traumatic event. A univariate relationship was also observed between pre-trauma heart rate (HR) reactivity to fear cues during conditioning and post-trauma psychophysiologic reactivity.The current study contributes to a very limited literature reporting results from truly prospective examinations of pre-trauma physiologic, psychologic, and demographic predictors of PTSS. Findings that combinations of lower estimated IQ, greater depression symptoms, a larger differential corrugator EMG response during extinction and larger SC responses to loud tones significantly predicted higher PTSS suggests that the process(es) underlying these traits contribute to the pathogenesis of subjective and physiological PTSS. Due to the low levels o
Learning to Obtain Reward, but Not Avoid Punishment, Is Affected by Presence of PTSD Symptoms in Male Veterans: Empirical Data and Computational Model
Catherine E. Myers, Ahmed A. Moustafa, Jony Sheynin, Kirsten M. VanMeenen, Mark W. Gilbertson, Scott P. Orr, Kevin D. Beck, Kevin C. H. Pang, Richard J. Servatius
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072508
Abstract: Post-traumatic stress disorder (PTSD) symptoms include behavioral avoidance which is acquired and tends to increase with time. This avoidance may represent a general learning bias; indeed, individuals with PTSD are often faster than controls on acquiring conditioned responses based on physiologically-aversive feedback. However, it is not clear whether this learning bias extends to cognitive feedback, or to learning from both reward and punishment. Here, male veterans with self-reported current, severe PTSD symptoms (PTSS group) or with few or no PTSD symptoms (control group) completed a probabilistic classification task that included both reward-based and punishment-based trials, where feedback could take the form of reward, punishment, or an ambiguous “no-feedback” outcome that could signal either successful avoidance of punishment or failure to obtain reward. The PTSS group outperformed the control group in total points obtained; the PTSS group specifically performed better than the control group on reward-based trials, with no difference on punishment-based trials. To better understand possible mechanisms underlying observed performance, we used a reinforcement learning model of the task, and applied maximum likelihood estimation techniques to derive estimated parameters describing individual participants’ behavior. Estimations of the reinforcement value of the no-feedback outcome were significantly greater in the control group than the PTSS group, suggesting that the control group was more likely to value this outcome as positively reinforcing (i.e., signaling successful avoidance of punishment). This is consistent with the control group’s generally poorer performance on reward trials, where reward feedback was to be obtained in preference to the no-feedback outcome. Differences in the interpretation of ambiguous feedback may contribute to the facilitated reinforcement learning often observed in PTSD patients, and may in turn provide new insight into how pathological behaviors are acquired and maintained in PTSD.
PFA: Program for the quantitative assessment of cell metabolism by spectral data analysis
Chris Orr,Stephen Scott,Fouad Kandeel,Kevin Ferreri
Bioinformation , 2008,
Abstract: Assessment of mitochondrial oxidative metabolism has wide-ranging importance, from pharmacokinetic analysis to studies in cell viability and apoptosis. Here, we present the Perfusion File Analyzer (PFA) application for the real-time analysis of spectral data to measure cytochrome c reduction, cytochrome a3 reduction, and other parameters important to cellular metabolism, which are collected during tissue perfusion experiments. Our current efforts are focused on quantitating changes in mitochondrial function by normalizing baseline drift of spectral data while addressing two major challenges: (1) a lack of real-time feedback from the system when aiming is compromised, and (2) an inability to adjust calculated data in the event of spectral shift. PFA has been developed to address these issues, and is currently used for quality assessment of human islets prior to clinical transplantation.
Designing Programs for Eliminating Canine Rabies from Islands: Bali, Indonesia as a Case Study
Sunny E. Townsend ,I Putu Sumantra,Pudjiatmoko,Gusti Ngurah Bagus,Eric Brum,Sarah Cleaveland,Sally Crafter,Ayu P. M. Dewi,Dewa Made Ngurah Dharma,Jonathan Dushoff,Janice Girardi,I Ketut Gunata,Elly F. Hiby,Corlevin Kalalo,Darryn L. Knobel,I Wayan Mardiana,Anak Agung Gde Putra,Luuk Schoonman,Helen ScottOrr,Mike Shand,I Wayan Sukanadi,Pebi Purwo Suseno,Daniel T. Haydon,Katie Hampson
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002372
Abstract: Background Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies. Methodology/Principal Findings Using data from Bali, we estimated the basic reproductive number, R0, of rabies in dogs, to be ~1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ~550 human lives and ~$15 million in prophylaxis costs over the next ten years. Conclusions/Significance The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.
A Meiosis-Specific Form of the APC/C Promotes the Oocyte-to-Embryo Transition by Decreasing Levels of the Polo Kinase Inhibitor Matrimony
Zachary J. Whitfield,Jennifer Chisholm,R. Scott Hawley,Terry L. Orr-Weaver
PLOS Biology , 2013, DOI: 10.1371/journal.pbio.1001648
Abstract: Oocytes are stockpiled with proteins and mRNA that are required to drive the initial mitotic divisions of embryogenesis. But are there proteins specific to meiosis whose levels must be decreased to begin embryogenesis properly? The Drosophila protein Cortex (Cort) is a female, meiosis-specific activator of the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. We performed immunoprecipitation of Cortex followed by mass spectrometry, and identified the Polo kinase inhibitor Matrimony (Mtrm) as a potential interactor with Cort. In vitro binding assays showed Mtrm and Cort can bind directly. We found Mtrm protein levels to be reduced dramatically during the oocyte-to-embryo transition, and this downregulation did not take place in cort mutant eggs, consistent with Mtrm being a substrate of APCCort. We showed that Mtrm is subject to APCCort-mediated proteasomal degradation and have identified a putative APC/C recognition motif in Mtrm that when mutated partially stabilized the protein in the embryo. Furthermore, overexpression of Mtrm in the early embryo caused aberrant nuclear divisions and developmental defects, and these were enhanced by decreasing levels of active Polo. These data indicate APCCort ubiquitylates Mtrm at the oocyte-to-embryo transition, thus preventing excessive inhibition of Polo kinase activity due to Mtrm's presence.
The Local Migration of Plant-Based Medicines from Rural Communities to Gral. E. Aquino, Paraguay  [PDF]
Noah Goyke, Blair Orr
Natural Resources (NR) , 2018, DOI: 10.4236/nr.2018.912027
Abstract: Rural Paraguay presents interesting opportunities for investigating the subtle differences in the use of medicinal plants across seasons and the urban versus rural dichotomy in a local setting. This study investigates three aspects of plant-based medicinal use in rural Paraguay: 1) seasonal differences and 2) differences between urban and rural residents and 3) the source of medicinal plants used to treat thirteen common ailments. Interviews performed in January through March 2015 and repeated in June through August 2015 revealed small differences between seasons and between places of residence but a larger homogeneity in the two populations, a homogeneity that stems from the recent migration of urban residents from nearby rural communities. We also found that the important cultural and preventive medicinal use of plant-based additions to yerba mate contributes to the similarities between the urban and rural populations. The findings suggest the continued strength of medicinal plant use going into the near future.
Mechanisms of Action of Noninvasive Monopolar Radiofrequency: Technology Review  [PDF]
Terry L. Whipple, Scott P. Steinmann
Open Journal of Orthopedics (OJO) , 2013, DOI: 10.4236/ojo.2013.31006

Tendinosis is now understood as the result of a failed tendon healing process regardless of where it occurs in the body. Current noninvasive therapeutic alternatives are anti-inflammatory in nature and outcomes are unpredictable at best. The benefit of invasive alternatives resides in the induction of the healing response as demonstrated in pre-clinical and clinical studies in cardiology and orthopaedics. A new technology that employs noninvasivemonopolar capacitive-coupled radiofrequency (mcRF), has demonstrated the ability to raise temperatures in tendons and ligaments upwards of 50°C, the temperature threshold for collagen modulation and recruitment of macrophages, fibroblasts and Heat Shock Protein factors—without damaging the overlying structures—resulting in activation of the Wound Healing Response (WHR).

Profound Hypothermia Secondary to Clobazam Use in Epilepsy: A Novel Association  [PDF]
Marc P. DiFazio, Bennet Lavenstein, Scott Demarest
Neuroscience & Medicine (NM) , 2014, DOI: 10.4236/nm.2014.51003

Clobazam, a 1-5 benzodiazepine, was introduced in the 1970s for the treatment of anxiety and agitation. Antiepileptic properties were recognized, and efficacy in a number of epilepsy syndromes was demonstrated in humans, with good tolerance. Recent reviews are generally favorable, with a relative minimum of medication-related side effects. However, a number of benzodiazepines have been associated with causing hypothermia. To date, this side effect has not been reported with clobazam. We report two cases of profound hypothermia associated with the use of this medication for the treatment of epilepsy. Both children had significant cerebral dysgenesis and were developmentally impaired, but neither had experienced hypothermia before. Temperature dysregulation was resolved with medication withdrawal after an extensive work-up for alternative causes. Hypothermia should be considered as a possible side effect of clobazam, although the exact mechanism is unknown. Appropriate monitoring of temperature is appropriate, and precautions should be offered by caregivers.

Composition and regulation of maternal and zygotic transcriptomes reflects species-specific reproductive mode
Shai S Shen-Orr, Yitzhak Pilpel, Craig P Hunter
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-6-r58
Abstract: We have used genomic data to identify and compare maternal and/or zygotic expressed genes from six different animals and find evidence for selection acting to shape gene regulatory architecture in thousands of genes. We find that mammalian maternal genes are enriched for complex regulatory regions, suggesting an increase in expression specificity, while egg-laying animals are enriched for maternal genes that lack transcriptional specificity.We propose that this lack of specificity for maternal expression in egg-laying animals indicates that a large fraction of maternal genes are expressed non-functionally, providing only supplemental nutritional content to the developing embryo. These results provide clear predictive criteria for analysis of additional genomes.Early embryos contain mRNA transcripts expressed from two distinct origins; those expressed from the mother's genome and deposited in the oocyte (maternal) and those expressed from the embryo's genome after fertilization (zygotic). Because these transcripts originate from distinct origins they are subject to distinct regulatory constraints. Maternal transcripts rely on post-transcriptional regulatory mechanisms for spatial and temporal control of their embryonic expression, and thus contain all signals that control their stability, localization and relative accessibility to the translational machinery [1-7]. In contrast, zygotically synthesized transcripts may utilize both transcriptional and post-transcriptional regulatory mechanisms to provide precise temporal and spatial expression.In all animals surveyed to date, at least 30% of protein-coding genes are detected as expressed during the transition from unfertilized oocyte to early embryo [8-13]. These may be divided into three basic groups. First, those that must be expressed exclusively from either a maternal or a zygotic origin, which include maternally expressed genes required to 'jump start' embryogenesis and zygotically expressed patterning genes whose
Improved negative selection protocol for Plasmodium berghei in the rodent malarial model
Rachael Y Orr, Nisha Philip, Andrew P Waters
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-103
Abstract: Reverse genetics in malaria parasites has been possible since the early to mid-90s [1-3] and it is now established for a number of Plasmodium species that infect a variety of hosts including human (Plasmodium falciparum), rodent (Plasmodium berghei, Plasmodium yoelii [4] and Plasmodium chabaudi [5]) primate (Plasmodium knowlesi and Plasmodium cynomolgi) as well as avian (Plasmodium gallinaceum). Typically genetically transformed parasites are positively selected in the proliferating asexual blood stages by their expression of a marker protein that confers resistance to a common antibiotic and in some cases specifically an anti-malarial drug. The number of selectable markers available for positive selection is limited, where currently five are available for use with parasites that can be cultured in vitro for long periods (i.e. P. falciparum, P. knowlesi and P. cynomolgi). However, selection in rodent malaria parasites may only be carried out in vivo as they cannot be cultured long term in vitro, reducing the number of positive selectable markers available to three: Toxoplasma DHFR-thymidylate synthase (tgDHFR-TS) and P. berghei DHFR-thymidylate synthase (pbDHFR-TS), which impart resistance to pyrimethamine and, human dihydrofolate reductase (hDHFR) which confers resistance to both pyrimethamine and WR99210. Therefore, there are only two positive selection regimes available when working with the rodent malarial model since both Apicomplexa possess genes producing DHFR-TS which confers resistance to the same anti-malarial drug, pyrimethamine. Although sequential genetic modification on P. berghei using these markers in the strict order of DHFR-TS selection with pyrimethamine followed by hDHFR selection with WR99210 [6] is possible, the number of manipulations is still limited to two. Therefore, an alternative strategy was developed using a negative selection procedure to recycle the both the positive and negative selectable markers, which could then be used multiple t
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